Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by Human T-lymphotropic Virus type 1 (HTLV-1) infection. The disease develops in approximately 2-5% of HTLV-1 carriers after a prolonged latency of decades. ATLL is endemic in southwestern Japan, the Caribbean, parts of South America, and sub-Saharan Africa. The HTLV-1 Tax oncoprotein is the primary driver of transformation, activating NF-kappaB and CREB pathways, inducing genomic instability, and impairing DNA repair. ATLL cells characteristically display a CD4+CD25+ regulatory T-cell phenotype with flower-shaped nuclear morphology.
Ask a research question about Adult T-Cell Leukemia/Lymphoma. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Adult T-Cell Leukemia/Lymphoma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-08T16:21:17Z'
description: >-
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm
caused by Human T-lymphotropic Virus type 1 (HTLV-1) infection. The disease develops
in approximately 2-5% of HTLV-1 carriers after a prolonged latency of decades.
ATLL is endemic in southwestern Japan, the Caribbean, parts of South America,
and sub-Saharan Africa. The HTLV-1 Tax oncoprotein is the primary driver of
transformation, activating NF-kappaB and CREB pathways, inducing genomic instability,
and impairing DNA repair. ATLL cells characteristically display a CD4+CD25+ regulatory
T-cell phenotype with flower-shaped nuclear morphology.
categories:
- Hematologic Malignancy
- T-Cell Lymphoma
- Virus-Associated Cancer
parents:
- T-cell leukemia
- T-cell lymphoma
has_subtypes:
- name: Acute ATLL
description: >-
Most aggressive form with leukemic presentation, hypercalcemia, organ
infiltration, and opportunistic infections. Median survival is 6-10 months
despite treatment. Characterized by high tumor burden and poor response
to chemotherapy.
evidence:
- reference: PMID:1751370
reference_title: "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)."
supports: PARTIAL
snippet: >-
MST was 6.2 months for acute type
explanation: >-
Shimoyama classification study confirms acute ATLL has median survival
of 6.2 months, supporting the poor prognosis described.
- name: Lymphoma Type ATLL
description: >-
Presents with lymphadenopathy without significant blood involvement.
May have better prognosis than acute form if responsive to chemotherapy.
Less frequently associated with hypercalcemia.
evidence:
- reference: PMID:1751370
reference_title: "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)."
supports: PARTIAL
snippet: >-
Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and
histologically-proven lymphadenopathy with or without extranodal lesions.
explanation: >-
Shimoyama classification defines lymphoma type by lymphadenopathy without
significant blood involvement.
- name: Chronic ATLL
description: >-
Indolent presentation with mild lymphocytosis and skin involvement.
May remain stable for years before transforming to acute type.
Better prognosis with median survival of several years.
evidence:
- reference: PMID:1751370
reference_title: "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)."
supports: PARTIAL
snippet: >-
24.3 months for chronic type
explanation: >-
Shimoyama study shows chronic type has median survival of 24.3 months,
supporting the better prognosis described.
- name: Smoldering ATLL
description: >-
Most indolent form with at least 5% abnormal T lymphocytes in peripheral
blood, normal total lymphocyte count, no hypercalcemia, and often
skin-limited disease. May not require immediate treatment but requires
monitoring for transformation to aggressive disease.
evidence:
- reference: PMID:1751370
reference_title: "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)."
supports: SUPPORT
snippet: >-
Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB,
normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia
explanation: >-
Shimoyama classification defines smoldering type by at least 5% abnormal
T lymphocytes in peripheral blood, normal total lymphocyte count, and
absence of hypercalcemia.
infectious_agent:
- name: Human T-Lymphotropic Virus Type 1 (HTLV-1)
infectious_agent_term:
preferred_term: Human T-cell leukemia virus type I
term:
id: NCBITaxon:11908
label: Human T-cell leukemia virus type I
description: >-
HTLV-1 is a deltaretrovirus that infects CD4+ T cells. Transmission occurs
through breastfeeding, sexual contact, blood transfusion, and injection drug
use. After infection, HTLV-1 integrates into the host genome and establishes
lifelong persistent infection. The viral Tax protein is the major transforming
factor, activating NF-kappaB, inducing genomic instability, and promoting
T-cell proliferation. HBZ (HTLV-1 basic leucine zipper factor) expressed from
the antisense strand also contributes to leukemogenesis.
evidence:
- reference: PMID:41553980
reference_title: "CXCR3/CXCL10 Axis-Mediated T Cell Infiltration in the Lungs of Patients With HTLV-1-Associated Diseases: Implications for Subclinical Pulmonary Involvement."
supports: PARTIAL
snippet: "HTLV-1 is a retrovirus associated with adult T cell leukemia/lymphoma (ATL) and inflammatory diseases, including HTLV-1-associated myelopathy (HAM) and HTLV-1-associated bronchopneumonopathy (HAB)."
explanation: This abstract explicitly links HTLV-1 to adult T-cell leukemia/lymphoma, supporting the infectious etiology.
pathophysiology:
- name: HTLV-1 Infection and Tax Oncoprotein Expression
description: >-
HTLV-1 preferentially infects CD4+ T cells and integrates into the host genome.
The viral Tax protein is the primary driver of transformation, functioning as
a transcriptional activator that hijacks multiple cellular pathways. Tax activates
NF-kappaB, CREB/ATF, and AP-1 transcription factors, driving T-cell proliferation
and survival.
evidence:
- reference: PMID:15129647
reference_title: "HTLV-1 and associated adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: "HTLV-1 causes 2 major diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy."
explanation: "Abstract states HTLV-1 causes ATLL, supporting the infectious etiology."
- reference: PMID:15129647
reference_title: "HTLV-1 and associated adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: "Tax is a 40-kDa phosphoprotein that is encoded by the pX region of the virus."
explanation: "Abstract identifies Tax as a viral protein, supporting Tax oncoprotein expression."
cell_types:
- preferred_term: T cell
term:
id: CL:0000084
label: T cell
biological_processes:
- preferred_term: viral transcription
term:
id: GO:0019083
label: viral transcription
downstream:
- target: Tax-Mediated NF-kappaB Activation
description: Tax constitutively activates NF-kappaB signaling
- target: Genomic Instability and Accumulation of Mutations
description: Tax impairs DNA repair and induces genomic instability
- name: Tax-Mediated NF-kappaB Activation
description: >-
Tax activates both canonical and non-canonical NF-kappaB pathways through
direct interaction with IKK complex and NIK. Constitutive NF-kappaB activation
drives expression of anti-apoptotic genes (BCL-XL, cIAP, survivin), cytokines
(IL-2, IL-15), and cell cycle regulators, promoting T-cell survival and
proliferation.
biological_processes:
- preferred_term: positive regulation of NF-kappaB transcription factor activity
modifier: INCREASED
term:
id: GO:0043123
label: positive regulation of canonical NF-kappaB signal transduction
downstream:
- target: Apoptosis Resistance
description: NF-kappaB activates anti-apoptotic gene expression
- target: Uncontrolled T-Cell Proliferation
description: NF-kappaB and cytokine signaling drive proliferation
- name: Genomic Instability and Accumulation of Mutations
description: >-
Tax impairs multiple DNA repair pathways including nucleotide excision repair,
base excision repair, and double-strand break repair. This leads to accumulation
of somatic mutations over the decades-long latency period. Tax also causes
aneuploidy through centrosome amplification and mitotic checkpoint dysfunction.
biological_processes:
- preferred_term: DNA damage response
modifier: DECREASED
term:
id: GO:0006974
label: DNA damage response
downstream:
- target: Uncontrolled T-Cell Proliferation
description: Accumulated mutations in growth regulatory genes promote transformation
- name: Apoptosis Resistance
description: >-
Multiple mechanisms contribute to apoptosis resistance: NF-kappaB-mediated
upregulation of BCL-XL and cIAP, Tax-mediated p53 inhibition, and HBZ-mediated
enhancement of regulatory T-cell survival. This allows accumulation of cells
with genomic abnormalities.
biological_processes:
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
- name: Uncontrolled T-Cell Proliferation
description: >-
Combined effects of constitutive NF-kappaB activation, accumulated mutations,
and apoptosis resistance result in clonal expansion of HTLV-1-infected T cells.
ATLL cells acquire a CD4+CD25+FOXP3+ regulatory T-cell phenotype with
immunosuppressive properties.
cell_types:
- preferred_term: T cell
term:
id: CL:0000084
label: T cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
histopathology:
- name: T-Cell Lymphoproliferative Neoplasm
finding_term:
preferred_term: Adult T-Cell Leukemia/Lymphoma
term:
id: NCIT:C3184
label: Adult T-Cell Leukemia/Lymphoma
frequency: VERY_FREQUENT
description: Adult T-cell lymphoma/leukemia is a rare T-cell lymphoproliferative neoplasm.
evidence:
- reference: PMID:28796966
reference_title: "Adult T-Cell Leukemia/Lymphoma."
supports: SUPPORT
snippet: "Adult T-cell lymphoma/leukemia (ATL) is a rare T-cell lymphoproliferative"
explanation: Abstract characterizes ATL as a rare T-cell lymphoproliferative neoplasm.
phenotypes:
- category: Hematologic
name: Leukocytosis
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Elevated white blood cell count with characteristic "flower cells" showing
multilobated nuclei. Peripheral blood involvement is prominent in acute and
chronic forms.
phenotype_term:
preferred_term: Increased total leukocyte count
term:
id: HP:0001974
label: Increased total leukocyte count
- category: Lymphatic
name: Lymphadenopathy
frequency: VERY_FREQUENT
description: >-
Generalized lymphadenopathy is common, particularly prominent in
lymphoma-type ATLL.
phenotype_term:
preferred_term: Lymphadenopathy
term:
id: HP:0002716
label: Lymphadenopathy
- category: Metabolic
name: Hypercalcemia
frequency: FREQUENT
diagnostic: true
description: >-
Hypercalcemia occurs in up to 70% of acute ATLL cases due to ATLL cell
production of PTHrP (parathyroid hormone-related protein) and osteoclast-
activating cytokines. Can be severe and life-threatening.
evidence:
- reference: PMID:24714244
reference_title: "Hypercalcemic crisis due to adult T cell leukemia: a rare cause of paralytic ileus."
supports: SUPPORT
snippet: "Hypercalcemia occurs in about 70% of patients with acute adult T cell leukemia."
explanation: "Review abstract reports hypercalcemia frequency in acute adult T cell leukemia."
phenotype_term:
preferred_term: Hypercalcemia
term:
id: HP:0003072
label: Hypercalcemia
- category: Dermatologic
name: Skin Lesions
frequency: FREQUENT
description: >-
Skin involvement with erythematous papules, nodules, plaques, or
erythroderma. Prominent in smoldering and chronic forms. May resemble
mycosis fungoides.
phenotype_term:
preferred_term: Abnormal skin morphology
term:
id: HP:0011121
label: Abnormal skin morphology
- category: Abdominal
name: Hepatomegaly
frequency: FREQUENT
description: >-
Liver enlargement from leukemic infiltration, common in acute ATLL.
phenotype_term:
preferred_term: Hepatomegaly
term:
id: HP:0002240
label: Hepatomegaly
- category: Abdominal
name: Splenomegaly
frequency: FREQUENT
description: >-
Splenic enlargement from leukemic infiltration.
phenotype_term:
preferred_term: Splenomegaly
term:
id: HP:0001744
label: Splenomegaly
- category: Infectious
name: Opportunistic Infections
frequency: FREQUENT
description: >-
ATLL cells have regulatory T-cell properties causing profound
immunosuppression. Opportunistic infections including Pneumocystis,
Strongyloides, and fungal infections are common and major causes of death.
phenotype_term:
preferred_term: Recurrent infections
term:
id: HP:0002719
label: Recurrent infections
biochemical:
- name: HTLV-1 Antibodies
notes: >-
Seropositivity for HTLV-1 antibodies is required for diagnosis. ELISA
screening followed by Western blot confirmation.
- name: HTLV-1 Proviral Load
notes: >-
Quantification of HTLV-1 proviral DNA by PCR. High proviral load is
associated with increased risk of ATLL development.
- name: Soluble IL-2 Receptor (sIL-2R)
notes: >-
Markedly elevated sIL-2R reflects high tumor burden and T-cell activation.
Useful for monitoring disease activity.
genetic:
- name: HTLV-1 Tax
association: Viral Oncogene
notes: >-
Tax is the major HTLV-1 transforming protein. Activates NF-kappaB, CREB,
and AP-1 pathways; induces genomic instability; inhibits DNA repair;
and dysregulates cell cycle. Tax expression is often lost in established
ATLL due to promoter methylation, suggesting its role is primarily in
early transformation.
- name: HTLV-1 HBZ
association: Viral Oncogene
notes: >-
HBZ (HTLV-1 basic leucine zipper factor) is expressed from the antisense
strand and maintained in all ATLL cells. Promotes T-cell proliferation
and regulatory T-cell phenotype. Contributes to transformation
independently of Tax.
- name: TP53
association: Somatic Mutation
notes: >-
TP53 mutations occur in approximately 20-40% of aggressive ATLL and
are associated with poor prognosis. More common in acute than
indolent forms.
- name: CCR4
association: Gain of Function Mutation
notes: >-
CCR4 mutations occur in approximately 25% of cases and result in
receptor stabilization and enhanced signaling. Target of mogamulizumab
therapy.
treatments:
- name: Chemotherapy
description: >-
Intensive combination chemotherapy regimens including CHOP-like protocols
or more intensive regimens (VCAP-AMP-VECP). Response rates are modest
and duration is typically short in aggressive disease.
evidence:
- reference: PMID:22042945
reference_title: "Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: >-
The overall response rate ranged from 49% with chemotherapy alone to 81%
with combined first-line therapy (chemotherapy with concurrent/sequential
ZDV/IFN-α).
explanation: >-
Study shows chemotherapy alone achieves 49% response rate in aggressive
ATLL, supporting modest efficacy.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Mogamulizumab
description: >-
Anti-CCR4 monoclonal antibody approved for relapsed/refractory ATLL.
CCR4 is highly expressed on ATLL cells. Provides activity in patients
with CCR4 mutations who have particularly high expression.
evidence:
- reference: PMID:30573506
reference_title: "Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: >-
mogamulizumab treatment resulted in 11% cORR, with a tolerable safety
profile.
explanation: >-
International phase II trial showed mogamulizumab demonstrated responses
in relapsed/refractory ATLL where chemotherapy showed no activity.
treatment_term:
preferred_term: immunotherapy
term:
id: NCIT:C15262
label: Immunotherapy
therapeutic_agent:
- preferred_term: mogamulizumab
term:
id: NCIT:C62510
label: Mogamulizumab
- name: Allogeneic Stem Cell Transplantation
description: >-
Only potentially curative treatment for ATLL. Graft-versus-ATLL effect
contributes to efficacy. Reserved for younger patients with aggressive
disease who achieve remission. Long-term survival of 30-40% in selected
patients.
evidence:
- reference: PMID:30573506
reference_title: "Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: >-
Allogeneic stem cell transplantation (allo-SCT) can significantly prolong
survival, but there are few appropriate candidates
explanation: >-
Study confirms allo-SCT prolongs survival but notes limited candidates
due to age and prior treatment response requirements.
treatment_term:
preferred_term: hematopoietic stem cell transplantation
term:
id: MAXO:0000747
label: hematopoietic stem cell transplantation
- name: Interferon-alpha and Zidovudine
description: >-
Combination of interferon-alpha and zidovudine (AZT) shows activity,
particularly in leukemic subtypes. May be combined with or followed
by chemotherapy. Mechanism involves both antiviral and pro-apoptotic
effects.
evidence:
- reference: PMID:22042945
reference_title: "Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma."
supports: PARTIAL
snippet: >-
Use of ZDV/IFN-α at any time prolonged survival in acute (P < .001) and
lymphoma ATLL (P < .001) and was the sole factor associated with
reduction in risk of death in aggressive ATLL
explanation: >-
UK study demonstrated ZDV/IFN-α significantly prolonged survival in both
acute and lymphoma ATLL subtypes.
treatment_term:
preferred_term: immunotherapy
term:
id: NCIT:C15262
label: Immunotherapy
therapeutic_agent:
- preferred_term: zidovudine
term:
id: CHEBI:10110
label: zidovudine
disease_term:
preferred_term: adult T-cell leukemia/lymphoma
term:
id: MONDO:0019471
label: adult T-cell leukemia/lymphoma
classifications:
icdo_morphology:
classification_value: Lymphoma
harrisons_chapter:
- classification_value: cancer
- classification_value: hematologic malignancy
references:
- reference: DOI:10.1111/bjh.13338
title: 'Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase <scp>II</scp> study'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: 'Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase <scp>II</scp> study'
supporting_text: a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma (
evidence:
- reference: DOI:10.1111/bjh.13338
reference_title: 'Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase <scp>II</scp> study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma (
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.1111/cas.13343
title: 'Mogamulizumab for relapsed adult T‐cell leukemia–lymphoma: Updated follow‐up analysis of phase I and <scp>II</scp> studies'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: The present study sought to elucidate the prognosis of adult T‐cell leukemia–lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti‐CCR4 monoclonal antibody.
supporting_text: The present study sought to elucidate the prognosis of adult T‐cell leukemia–lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti‐CCR4 monoclonal antibody.
evidence:
- reference: DOI:10.1111/cas.13343
reference_title: 'Mogamulizumab for relapsed adult T‐cell leukemia–lymphoma: Updated follow‐up analysis of phase I and <scp>II</scp> studies'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The present study sought to elucidate the prognosis of adult T‐cell leukemia–lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti‐CCR4 monoclonal antibody.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.1111/ejh.12863
title: Effects of mogamulizumab in adult T‐cell leukemia/lymphoma in clinical practice
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: The efficacy of mogamulizumab in adult T‐cell leukemia/lymphoma (ATLL) was reported in a previous phase 2 study.
supporting_text: The efficacy of mogamulizumab in adult T‐cell leukemia/lymphoma (ATLL) was reported in a previous phase 2 study.
evidence:
- reference: DOI:10.1111/ejh.12863
reference_title: Effects of mogamulizumab in adult T‐cell leukemia/lymphoma in clinical practice
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The efficacy of mogamulizumab in adult T‐cell leukemia/lymphoma (ATLL) was reported in a previous phase 2 study.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.1182/blood-2011-03-345702
title: How I treat adult T-cell leukemia/lymphoma
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I.
supporting_text: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I.
evidence:
- reference: DOI:10.1182/blood-2011-03-345702
reference_title: How I treat adult T-cell leukemia/lymphoma
supports: SUPPORT
evidence_source: OTHER
snippet: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.1182/bloodadvances.2020003053
title: 'Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: 'Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study'
supporting_text: Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696).
evidence:
- reference: DOI:10.1182/bloodadvances.2020003053
reference_title: 'Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696).
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.1186/s12985-023-02077-0
title: 'Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy.
supporting_text: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy.
evidence:
- reference: DOI:10.1186/s12985-023-02077-0
reference_title: 'Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis'
supports: SUPPORT
evidence_source: OTHER
snippet: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.3390/biom13101543
title: 'Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL).
supporting_text: Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL).
evidence:
- reference: DOI:10.3390/biom13101543
reference_title: 'Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL).
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.3390/medicina60060872
title: 'Clinical Features and Survival Outcome in Aggressive-Type Adult T-Cell Leukemia/Lymphoma Patients: Real-Life Experience of a Single Center from an HTLV-1 Endemic Country'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1).
supporting_text: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1).
evidence:
- reference: DOI:10.3390/medicina60060872
reference_title: 'Clinical Features and Survival Outcome in Aggressive-Type Adult T-Cell Leukemia/Lymphoma Patients: Real-Life Experience of a Single Center from an HTLV-1 Endemic Country'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1).
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.3390/v16101616
title: Current State of Therapeutics for HTLV-1
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally.
supporting_text: Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally.
evidence:
- reference: DOI:10.3390/v16101616
reference_title: Current State of Therapeutics for HTLV-1
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.3390/v17050664
title: 'Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types.
supporting_text: Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types.
evidence:
- reference: DOI:10.3390/v17050664
reference_title: 'Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
- reference: DOI:10.3390/v17101333
title: 'HTLV-1 and ATLL: Epidemiology, Oncogenesis, and Opportunities for Community-Informed Research in the United States'
found_in:
- Adult_T_Cell_Leukemia_Lymphoma-deep-research-falcon.md
findings:
- statement: 'HTLV-1 and ATLL: Epidemiology, Oncogenesis, and Opportunities for Community-Informed Research in the United States'
supporting_text: Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year.
evidence:
- reference: DOI:10.3390/v17101333
reference_title: 'HTLV-1 and ATLL: Epidemiology, Oncogenesis, and Opportunities for Community-Informed Research in the United States'
supports: SUPPORT
evidence_source: OTHER
snippet: Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year.
explanation: Deep research cited this publication as relevant literature for Adult T Cell Leukemia Lymphoma.
Adult T-cell leukemia/lymphoma (ATLL; also written ATL) is a distinct mature/peripheral T-cell malignancy etiologically caused by human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2). It typically develops after a long latency (≈20–30 years) in a minority of HTLV-1 carriers and is characterized by aggressive clinical behavior in acute and lymphoma subtypes, with frequent immunosuppression and opportunistic infections (altieri2025htlv1andatll pages 7-9).
Abstract quote (etiology/risk): “Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL). … 5–10% of carriers lose this balance and develop ATL.” (Nakahata et al., Biomolecules, 2023-10; (nakahata2023understandingtheimmunopathology pages 1-2)).
Key naming and identifier fields available from retrieved evidence are summarized here:
| Field | Value | Evidence / notes | ICD-10 | ICD-11 | MeSH | MONDO | Orphanet | OMIM |
|---|---|---|---|---|---|---|---|---|
| Preferred disease name | Adult T-cell leukemia/lymphoma | Distinct mature/peripheral T-cell malignancy caused by HTLV-1; often abbreviated ATL or ATLL (tsukasaki2020diagnosticapproachesand pages 1-2, nosaka2025jshpracticalguidelines pages 1-3) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Concise disease overview | Aggressive mature T-cell neoplasm arising after long-latency HTLV-1 infection, with leukemic and/or lymphomatous presentations | Reviews/guidelines describe ATL as HTLV-1-caused, typically after decades of latency; median survival for aggressive disease remains poor (altieri2025htlv1andatll pages 7-9, nakahata2023understandingtheimmunopathology pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Common abbreviations | ATL; ATLL | Both forms are used in recent literature and guidelines (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Key synonyms / alternative names | Adult T-cell leukaemia-lymphoma; Adult T-cell leukemia-lymphoma; HTLV-1-associated adult T-cell leukemia/lymphoma | British and American spellings both appear; disease is frequently described as HTLV-1-associated ATL/ATLL (o’donnell2023integratedmolecularand pages 3-4, tsukasaki2020diagnosticapproachesand pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Causative agent | Human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) | Causal viral etiology is consistently stated across guideline and reviews (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2, nakahata2023understandingtheimmunopathology pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Typical target cell / lineage | Mature CD4+ T-cell neoplasm; commonly CD3+, CD4+, CD25+, often CCR4+ | Immunophenotypic description from overview/review sources (altieri2025htlv1andatll pages 7-9, tsukasaki2020diagnosticapproachesand pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Canonical clinical classification | Four Shimoyama subtypes: acute, lymphoma, chronic, smoldering | Current guideline retains Shimoyama clinical subtyping; acute/lymphoma and unfavorable chronic are aggressive, favorable chronic and smoldering are indolent (nosaka2025jshpracticalguidelines pages 1-3, altieri2025htlv1andatll pages 7-9, nosaka2025jshpracticalguidelines media 8f3eac9b) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Aggressive vs indolent grouping | Aggressive: acute, lymphoma, chronic with unfavorable factors; Indolent: chronic without unfavorable factors, smoldering | Unfavorable chronic defined by abnormal BUN, LDH, or low albumin in guideline summary (nosaka2025jshpracticalguidelines pages 1-3) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Latency / temporal development | Usually develops after long latency, about 20-30 years after HTLV-1 infection; many carriers remain asymptomatic for decades | Long latency emphasized in recent reviews; only a minority of carriers progress to ATL/ATLL (altieri2025htlv1andatll pages 7-9, o’donnell2023integratedmolecularand pages 3-4, nakahata2023understandingtheimmunopathology pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
| Mode of knowledge represented here | Aggregated disease-level literature and guidelines, not individual-patient EHR data | Information in this summary comes from reviews, consensus/guideline documents, and cohort studies (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2, iordan2024clinicalfeaturesand pages 1-2) | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run | Not retrieved in this run |
Table: This table summarizes the core disease naming, etiology, subtype classification, and latency concepts for adult T-cell leukemia/lymphoma. Identifier fields are included for ontology/database curation and marked as not retrieved where this evidence run did not supply them.
Note: ICD-10/ICD-11/MeSH/MONDO/Orphanet/OMIM codes were not directly retrieved from the full text evidence in this tool run; they should be added via targeted ontology/registry queries.
This report is derived from aggregated disease-level resources: reviews, guidelines/consensus documents, clinical trials, and cohort studies (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2, iordan2024clinicalfeaturesand pages 1-2). It does not include individual EHR-derived patient records.
ATLL is causally linked to HTLV-1 infection, a deltaretrovirus that persists via proviral integration and clonal expansion of infected T cells (nosaka2025jshpracticalguidelines pages 1-3, o’donnell2023integratedmolecularand pages 2-3). Viral proteins Tax and HBZ contribute to oncogenesis and immune dysregulation (o’donnell2023integratedmolecularand pages 3-4, nakahata2023understandingtheimmunopathology pages 1-2).
Infectious exposure and transmission routes: Major transmission routes include mother-to-child via breastfeeding, sexual contact, and exposure to infected blood products/transfusion (tsukasaki2020diagnosticapproachesand pages 1-2, branda2025humantlymphotropicvirus pages 10-12).
High proviral load: In a 2023 Lancet Haematology review, higher baseline proviral load strongly predicted ATLL risk; proviral load “>4 copies per 100 PBMCs” was associated with HR 3.57 (95% CI 2.25–5.68) for developing ATLL (o’donnell2023integratedmolecularand pages 3-4).
Coinfection/host immune state: Strongyloides coinfection is cited as promoting ATLL development, consistent with the concept that immune status influences progression (nakahata2023understandingtheimmunopathology pages 1-2).
Evidence in this run supports breastfeeding modification as protective against HTLV-1 transmission (see Prevention). Specific genetic protective variants were not retrieved as explicit “protective variants” in the excerpts, although host HLA influences transmission risk and immune control (o’donnell2023integratedmolecularand pages 2-3).
Host genetics (e.g., HLA concordance between mother and infant) influences HTLV-1 transmission risk, modifying how an environmental exposure (breastfeeding) translates into infection (o’donnell2023integratedmolecularand pages 2-3).
ATLL is classically divided into acute, lymphoma, chronic, and smoldering subtypes (nosaka2025jshpracticalguidelines pages 1-3, nosaka2025jshpracticalguidelines media 8f3eac9b). A 2023 Lancet Haematology review provides quantitative subtype proportions: smouldering (5–10%), chronic (10–20%), lymphoma (20–25%), with acute accounting for the remainder (o’donnell2023integratedmolecularand pages 5-6).
Smouldering ATL is defined by specific blood and laboratory thresholds: “presence of abnormal T cells with flower cell morphology in peripheral blood (≥5%)”, normal lymphocyte count (≤4×10^9/L), “no hypercalcaemia (corrected calcium concentration <2·74 mmol/L)”, and only mild LDH elevation (o’donnell2023integratedmolecularand pages 5-6).
Across guidelines and reviews, common features include: - Leukocytosis with abnormal “flower cells” (nosaka2025jshpracticalguidelines pages 1-3) - Lymphadenopathy, hepatosplenomegaly, skin rash/skin lesions (nosaka2025jshpracticalguidelines pages 1-3, altieri2025htlv1andatll pages 7-9) - Elevated LDH, hypercalcemia (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2) - Opportunistic infections (e.g., Pneumocystis, aspergillosis, candidiasis, CMV; also Strongyloides) (altieri2025htlv1andatll pages 7-9, nosaka2025jshpracticalguidelines pages 1-3)
Real-world complications documented in a 2024 Romanian cohort included cytopenias and infections in all patients; pathogens included Candida albicans, C. difficile, bacterial infections, herpes zoster, SARS-CoV-2, CMV reactivation, and BK virus; symptomatic hypercalcemia was common (iordan2024clinicalfeaturesand pages 5-6).
(These are ontology suggestions; IDs should be verified against HPO.) - Hypercalcemia (HP:0003072) (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2) - Lymphadenopathy (HP:0002716) (nosaka2025jshpracticalguidelines pages 1-3) - Hepatosplenomegaly (HP:0001433 / HP:0001744) (nosaka2025jshpracticalguidelines pages 1-3) - Skin rash / Cutaneous lesion (HP:0000988 / HP:0000951) (nosaka2025jshpracticalguidelines pages 1-3) - Elevated lactate dehydrogenase (HP:0003236) (nosaka2025jshpracticalguidelines pages 1-3) - Opportunistic infection (HP:0002719) (altieri2025htlv1andatll pages 7-9, nosaka2025jshpracticalguidelines pages 1-3) - Leukocytosis (HP:0001974) (nosaka2025jshpracticalguidelines pages 1-3)
Direct QoL instrument data (EQ-5D/SF-36/PROMIS) were not retrieved in this run; however, severe systemic symptoms, infections, and hypercalcemia complications in aggressive ATLL imply major functional and hospitalization burden (iordan2024clinicalfeaturesand pages 5-6).
Two viral gene products are repeatedly emphasized: - Tax: transiently expressed, highly immunogenic, drives proliferation/anti-apoptotic pathways and host gene dysregulation (o’donnell2023integratedmolecularand pages 3-4, nakahata2023understandingtheimmunopathology pages 1-2). - HBZ: persistently expressed antisense product with low immunogenicity; promotes clonal proliferation and immune evasion (o’donnell2023integratedmolecularand pages 3-4, o’donnell2023integratedmolecularand pages 2-3).
Abstract quote (Tax oncogenesis): “HTLV-1 encodes the viral transcription transactivator, Tax, in the pX region of its genome, which promotes oncogenesis.” (Nakahata et al., Biomolecules, 2023-10; (nakahata2023understandingtheimmunopathology pages 1-2)).
From a 2023 immunopathology review: - “~90% of ATL cases have activating TCR–NF-κB pathway mutations” (nakahata2023understandingtheimmunopathology pages 3-5). - “~40% show CpG island hypermethylation (CIMP)” (nakahata2023understandingtheimmunopathology pages 3-5). - HLA class I mutations/deletions and PD-L1 3′-UTR structural alterations that increase PD-L1 mRNA are enriched in ATL (nakahata2023understandingtheimmunopathology pages 3-5).
Single-cell features described include upregulation of immunosuppressive molecules (PD-L1, CD73, CD39) and activation markers (CD71, CD25, CD38) (nakahata2023understandingtheimmunopathology pages 3-5).
(IDs should be verified against GO.) - NF-κB signaling (nakahata2023understandingtheimmunopathology pages 3-5, o’donnell2023integratedmolecularand pages 3-4) - Regulation of T-cell activation / TCR signaling (nakahata2023understandingtheimmunopathology pages 3-5) - Immune evasion / negative regulation of immune response (nakahata2023understandingtheimmunopathology pages 3-5, o’donnell2023integratedmolecularand pages 3-4) - DNA methylation / epigenetic gene regulation (nakahata2023understandingtheimmunopathology pages 3-5)
HTLV-1 is the infectious agent underlying ATLL (nosaka2025jshpracticalguidelines pages 1-3, tsukasaki2020diagnosticapproachesand pages 1-2).
In this run, the key non-genetic exposures relate to transmission opportunities: breastfeeding, sexual exposure, contaminated blood/organ products, and injection-related exposures (altieri2025htlv1andatll pages 12-14, tsukasaki2020diagnosticapproachesand pages 1-2).
1) HTLV-1 acquisition (breastfeeding/sexual/blood) → 2) proviral integration and clonal expansion of infected CD4+ T cells with generally quiescent transcription → 3) episodic Tax expression enables spread and promotes proliferative programs but drives immune recognition → 4) selection for immune escape with Tax silencing (e.g., 5′ LTR methylation/deletion) and persistence via HBZ-driven proliferation → 5) accumulation of host genetic and epigenetic lesions (e.g., TCR–NF-κB pathway mutations, CIMP, HLA/PD-L1 alterations) → 6) emergence of malignant clone with immune evasion and systemic immunodeficiency → clinical ATLL with hypercalcemia, organ infiltration, and opportunistic infections (o’donnell2023integratedmolecularand pages 3-4, nakahata2023understandingtheimmunopathology pages 3-5, nosaka2025jshpracticalguidelines pages 1-3).
Single-cell transcriptomic observations include ATL cell upregulation of PD-L1, CD73, CD39, CD71, CD25, CD38, and dynamic HLA class II expression patterns during clonal expansion (nakahata2023understandingtheimmunopathology pages 3-5).
(IDs should be verified against UBERON.) - Peripheral blood; bone marrow; lymph node; skin; liver; spleen; central nervous system; gastrointestinal tract (tsukasaki2020diagnosticapproachesand pages 1-2, nosaka2025jshpracticalguidelines pages 1-3).
ATLL typically develops after long latency from infection (20–30 years) (altieri2025htlv1andatll pages 7-9). Aggressive subtypes have a rapid course (months), while indolent subtypes have longer median survivals (years) (nosaka2025jshpracticalguidelines pages 1-3, o’donnell2023integratedmolecularand pages 5-6).
Table 1 from the JSH guideline provides ATL diagnostic and subtype classification criteria and can be used as the primary structured reference for smoldering/chronic/lymphoma/acute definitions in routine practice (nosaka2025jshpracticalguidelines media 8f3eac9b).
HTLV-1 confirmation: The guideline states serology positive by particle agglutination, ELISA/Western blotting, or line immunoassay; confirmatory tests are recommended (nosaka2025jshpracticalguidelines pages 1-3). Where available, “Institutions capable of performing Southern blotting should do so to confirm integration of HTLV-1 provirus into ATL cells.” (nosaka2025jshpracticalguidelines pages 1-3).
Molecular assays: PCR/qPCR proviral testing and clonality analysis are referenced as diagnostic approaches (branda2025humantlymphotropicvirus pages 17-17, stUnknownyearprotocolforthe pages 5-10).
Immunophenotyping (flow cytometry): Recommended minimal panel includes CD3, CD4, CD7, CD8, CD25; typical tumor phenotype includes CD2/CD4/CD5/CD45RO/CD29/TCR with reduced CD3 and often negative for CD7, CD8, CD26 (bazarbachi2011howitreat pages 2-3).
Histology requirement at low blood tumor burden: When circulating abnormal lymphocytes are <5%, histological confirmation of neoplastic lesions is required for smoldering/chronic/acute ATL diagnosis (nosaka2025jshpracticalguidelines pages 1-3).
From a nationwide Japan survey (2010–2011) summarized in the JSH guideline: - 4-year OS: acute 16.8%, lymphoma 19.6%, chronic unfavorable 26.6%, chronic favorable 62.1%, smoldering 59.8% (nosaka2025jshpracticalguidelines pages 1-3).
From a 2023 Lancet Haematology review (median OS): - Smouldering: median OS 55 months; 4-year OS 52% (o’donnell2023integratedmolecularand pages 5-6) - Chronic: median OS 31.5 months; 4-year OS 36% (o’donnell2023integratedmolecularand pages 5-6)
A Japanese cohort (2000–2009) reported median OS: acute 8.3 months; lymphoma 10.6 months; chronic 31.5 months; smoldering 55.0 months (munakata2018adulttcellleukemialymphoma. pages 12-14).
A 2024 Romanian single-center cohort of aggressive ATLL reported median survival 6.37 months overall; lymphoma-type 8.16 months vs acute-type 3.60 months, with low response to chemotherapy (iordan2024clinicalfeaturesand pages 1-2).
A consolidated treatment evidence table from this run is provided here:
| Treatment modality | Setting | Key efficacy statistics | Safety / limitations | Publication year | URL / DOI | Evidence |
|---|---|---|---|---|---|---|
| Zidovudine + interferon-α (AZT/IFN) | Frontline, combination with chemotherapy, maintenance in selected subtypes | 2023 meta-analysis of 15 studies/1,101 patients: overall response 67% (95% CI 0.50–0.80), CR 33% (95% CI 0.24–0.44), PR 31% (95% CI 0.24–0.39); better responses when used front-line and in indolent disease; aggressive subtype pooled CR 25%, indolent pooled CR 53%; one observational analysis reported HR for death 0.23 (95% CI 0.09–0.60) in aggressive ATLL; one report cited median PFS 48 months with AZT/IFN vs 11 months after chemotherapy in CR patients | Evidence base is heterogeneous and largely non-randomized; interferon availability issues noted; some cohorts reported no significant survival difference vs chemotherapy; detailed pooled AE statistics not robustly available in retrieved evidence | 2023 | https://doi.org/10.1186/s12985-023-02077-0 | (shafiee2023zidovudineandinterferon pages 1-2, shafiee2023zidovudineandinterferon pages 4-6, shafiee2023zidovudineandinterferon pages 8-9, shafiee2023zidovudineandinterferon pages 6-7, shafiee2023zidovudineandinterferon pages 7-8) |
| Intensive multiagent chemotherapy (e.g., VCAP-AMP-VECP, modified LSG15, CHOP/CHOP-like, hyper-CVAD) | Frontline for aggressive acute/lymphoma ATL | In randomized phase II study, adding mogamulizumab to mLSG15 increased CR to 52% vs 33% with mLSG15 alone and ORR to 86% vs 75%; Romanian real-world cohort using CHOP/CHOP-like, modified LSG15, or hyper-CVAD had only 6 responses among 20 patients and median survival 6.37 months overall (8.16 months lymphoma-type, 3.60 months acute-type) | Conventional chemotherapy responses are often short; poor outcomes in aggressive disease; cytopenias/infections common in real-world practice | 2015, 2024 | https://doi.org/10.1111/bjh.13338 ; https://doi.org/10.3390/medicina60060872 | (iordan2024clinicalfeaturesand pages 1-2, iordan2024clinicalfeaturesand pages 9-10, iordan2024clinicalfeaturesand pages 2-4) |
| Mogamulizumab monotherapy | Relapsed/refractory aggressive ATL; also used prospectively in broader ATL population | Phase II relapsed aggressive ATL: median PFS 5.2 months, 1-year PFS 26%, median OS 14.4 months, 3-year OS 23%; outcomes better with rash ≥grade 2: median PFS 11.7 months, median OS 25.6 months; multicenter observational study: ORR 65%, median PFS 7.4 months, median OS 16.0 months; retrospective real-world cohort: ORR 36%, CR 17%, median PFS 1.8 months, OS 4.0 months overall, better with ≥5 courses | Rash is common and may correlate with response; fatal AEs reported; severe cutaneous reactions, HBV reactivation, infusion reactions reported; efficacy varies substantially by population and line of therapy | 2017, 2020 | https://doi.org/10.1111/cas.13343 ; https://doi.org/10.1182/bloodadvances.2020003053 ; https://doi.org/10.1111/ejh.12863 | (ishida2017mogamulizumabforrelapsed pages 1-2, sekine2017effectsofmogamulizumab pages 14-18, sekine2017effectsofmogamulizumab pages 10-14, yonekura2020mogamulizumabforadult pages 12-12) |
| Mogamulizumab + intensive chemotherapy | Frontline newly diagnosed aggressive ATL | Randomized phase II: CR 52% (95% CI 33–71) and ORR 86% with mLSG15 + mogamulizumab vs CR 33% and ORR 75% with mLSG15 alone | More grade ≥3 anemia, thrombocytopenia, lymphopenia, leukopenia, decreased appetite; CMV infection, interstitial lung disease, and skin disorders reported in combination arm | 2015 | https://doi.org/10.1111/bjh.13338 | (wang2024currentstateof pages 12-14) |
| Mogamulizumab before allogeneic HSCT | Pre-transplant exposure in transplant-eligible patients | Not a benefit row: retrieved evidence emphasizes risk rather than efficacy | Significantly increased risks of severe and steroid-refractory GVHD, non-relapse mortality, and overall mortality; 50-day washout before allo-HSCT recommended in 2024 review | 2018, 2024 | https://doi.org/10.1007/978-3-319-99716-2_7 ; https://doi.org/10.3390/v16101616 | (wang2024currentstateof pages 34-35, wang2024currentstateof pages 12-14, munakata2018adulttcellleukemialymphoma. pages 16-17) |
| Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) | Consolidation/curative-intent for eligible aggressive ATL, typically early after remission/response | Considered the only modality with curative potential in recent reviews/guidelines; exact pooled survival statistics not in retrieved 2023–2024 evidence here; Romanian cohort: only 2/20 patients underwent allo-HSCT | Limited to fit/eligible patients; transplant morbidity/mortality substantial; timing complicated by prior mogamulizumab exposure | 2023, 2024, 2025 | https://doi.org/10.3390/biom13101543 ; https://doi.org/10.3390/v16101616 ; https://doi.org/10.3390/medicina60060872 ; https://doi.org/10.1007/s12185-025-04011-2 | (nakahata2023understandingtheimmunopathology pages 2-3, nosaka2025jshpracticalguidelines pages 1-3, wang2024currentstateof pages 34-35, iordan2024clinicalfeaturesand pages 1-2, wang2024currentstateof pages 12-14) |
| Lenalidomide | Relapsed/recurrent ATL; maintenance benefit discussed in review literature | Mentioned as phase II ATLL-002 and case reports of maintenance benefit; no numeric ORR/PFS/OS values available in retrieved evidence | Quantitative efficacy not in retrieved evidence; recognized as an approved/emerging option in reviews | 2024 | https://doi.org/10.3390/v16101616 | (wang2024currentstateof pages 34-35) |
| Brentuximab vedotin | Selected CD30-positive ATL; role discussed in reviews | Not in retrieved evidence for quantitative efficacy statistics | Mentioned as an approved/newer agent in review literature, but no trial outcome numbers captured in this run | 2020 | https://doi.org/10.3389/fmicb.2020.01207 | (tsukasaki2020diagnosticapproachesand pages 1-2) |
| Valemetostat / EZH1/2-directed epigenetic therapy | Relapsed/refractory ATL; investigational/early implementation | Open-label single-arm phase II and preclinical activity mentioned; no numeric ORR/PFS/OS captured in retrieved evidence | Early-phase/limited evidence in this run; quantitative outcomes not retrieved | 2024 | https://doi.org/10.3390/v16101616 | (wang2024currentstateof pages 34-35) |
| Investigational CAR-T / gene-edited cell therapy (e.g., anti-CD7 CAR-T, CD70 allogeneic CRISPR-edited CAR-T) | Relapsed/refractory T-cell malignancies including ATL in early-phase studies | Trial programs identified: anti-CD7 CAR-T (NCT05620680; single-center phase 1, n=20) and CD70-directed allogeneic CRISPR-edited CTX131 (NCT06492304); efficacy statistics not in retrieved evidence | Early-phase, small cohorts, relapsed/refractory setting; immune toxicity and translational challenges remain | 2025 | https://doi.org/10.1016/j.leukres.2025.107642 | (epsteinpeterson2025newtreatmentsfor pages 15-15) |
| CRISPR/ZFN proviral excision / RNA-based or gene-therapy strategies | Preclinical / future therapeutic modality | No clinical efficacy statistics in retrieved evidence | Delivery efficiency, off-target effects, and safety remain major challenges; promising concept rather than established therapy | 2024, 2025 | https://doi.org/10.3390/v16101616 ; https://doi.org/10.3390/v17050664 | (branda2025humantlymphotropicvirus pages 23-25, wang2024currentstateof pages 1-2) |
Table: This table summarizes key established and emerging treatment strategies for adult T-cell leukemia/lymphoma, including clinical setting, efficacy signals, and major safety limitations. It is useful for quickly comparing frontline, relapsed, transplant, and investigational approaches using only evidence retrieved in this run.
Key points: - AZT/IFN remains a widely used antiviral/immune-modulating regimen with pooled response estimates in a 2023 meta-analysis (OR 67%, CR 33%) and signals of greater benefit in indolent disease and in frontline combination use (shafiee2023zidovudineandinterferon pages 1-2, shafiee2023zidovudineandinterferon pages 4-6). - Mogamulizumab (anti-CCR4) shows clinically meaningful activity in relapsed aggressive ATL (phase II median OS 14.4 months; PFS 5.2 months) with rash as an immune-related AE correlated with improved outcomes (ishida2017mogamulizumabforrelapsed pages 1-2). Real-world results vary (e.g., ORR 36% and OS 4.0 months in one retrospective cohort) (sekine2017effectsofmogamulizumab pages 10-14). - Chemoimmunotherapy (mLSG15 + mogamulizumab) improved CR rates compared with chemotherapy alone, but with higher toxicity and opportunistic infections (wang2024currentstateof pages 12-14). - Allo-HSCT is emphasized as the only potentially curative approach in recent reviews and depends on eligibility and timing; pretransplant mogamulizumab exposure increases GVHD and mortality risk, motivating washout periods (wang2024currentstateof pages 34-35, wang2024currentstateof pages 12-14).
(IDs should be verified against MAXO.) - Antiviral therapy (AZT/IFN) (shafiee2023zidovudineandinterferon pages 1-2) - Combination chemotherapy (iordan2024clinicalfeaturesand pages 1-2) - Monoclonal antibody therapy (mogamulizumab) (ishida2017mogamulizumabforrelapsed pages 1-2) - Hematopoietic stem cell transplantation (allo-HSCT) (nakahata2023understandingtheimmunopathology pages 2-3) - CAR T-cell therapy (investigational) (epsteinpeterson2025newtreatmentsfor pages 15-15)
ATLL prevention is largely primary prevention of HTLV-1 acquisition, because disease typically follows long-term infection.
Breastfeeding modification: Early cessation of breastfeeding reduces transmission risk “from 14% to 4%” (o’donnell2023integratedmolecularand pages 2-3). A US-focused review states refraining from breastfeeding in HTLV-1-positive mothers can prevent 87% of early-life infections; short-term breastfeeding up to 3 months is proposed when formula is infeasible (altieri2025htlv1andatll pages 12-14).
Blood donor screening: Blood-donor screening is linked to a “significant reduction in transmission through blood transfusions” (branda2025humantlymphotropicvirus pages 10-12).
Organ donor screening: Receiving an organ from an HTLV-1-positive donor was described as having “100% risk of infection” (altieri2025htlv1andatll pages 4-5).
Sexual and injection-related transmission prevention: Safe-sex practices, partner testing/counseling, and harm-reduction needle exchange programs are recommended in public-health frameworks (altieri2025htlv1andatll pages 12-14).
This run retrieved animal-model discussions relevant to experimental systems (see Model Organisms) but did not retrieve evidence of naturally occurring ATLL in non-human species.
A 2024 HTLV-1 therapeutics review summarizes multiple model systems: - Transgenic mice: Tax transgenic mice established Tax as an oncoprotein but often developed mesenchymal tumors rather than frank ATL-like disease; HBZ transgenic expression in CD4+ T cells induced leukemia/lymphoma after a long latency, aligning with HBZ constitutive expression in ATL (wang2024currentstateof pages 9-11, wang2024currentstateof pages 8-9). - Xenografts / patient-derived xenografts: NOD/SCID and NOG mice engrafted with ATL cells better recapitulate disease; the MET-1 NOD/SCID model demonstrated tumor inhibition and prolonged survival with daclizumab + depsipeptide (HDAC inhibitor) (wang2024currentstateof pages 8-9). - Humanized mice: Models (e.g., huNSG formats) allow HTLV-1 infection with rising proviral load, clonal CD25+CD4+ expansion, and ATL-like pathology; limitations include incomplete recapitulation of long-term persistence and immune context (wang2024currentstateof pages 9-11).
References
(nosaka2025jshpracticalguidelines pages 1-3): Kisato Nosaka and Takuya Fukushima. Jsh practical guidelines for hematological malignancies, 2023: ii. lymphoma 9—adult t-cell leukemia–lymphoma (atl). International Journal of Hematology, 122:177-189, Jun 2025. URL: https://doi.org/10.1007/s12185-025-04011-2, doi:10.1007/s12185-025-04011-2. This article has 3 citations and is from a peer-reviewed journal.
(tsukasaki2020diagnosticapproachesand pages 1-2): Kunihiro Tsukasaki, Ambroise Marçais, Rihab Nasr, Koji Kato, Takahiro Fukuda, Olivier Hermine, and Ali Bazarbachi. Diagnostic approaches and established treatments for adult t cell leukemia lymphoma. Frontiers in Microbiology, Jun 2020. URL: https://doi.org/10.3389/fmicb.2020.01207, doi:10.3389/fmicb.2020.01207. This article has 63 citations and is from a peer-reviewed journal.
(altieri2025htlv1andatll pages 7-9): Adrian Altieri, Sean Patrick Reilly, Abu Mansalay, Alan Soo-Beng Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, and Pierluigi Porcu. Htlv-1 and atll: epidemiology, oncogenesis, and opportunities for community-informed research in the united states. Viruses, 17:1333, Sep 2025. URL: https://doi.org/10.3390/v17101333, doi:10.3390/v17101333. This article has 6 citations.
(nakahata2023understandingtheimmunopathology pages 1-2): Shingo Nakahata, Daniel Enriquez-Vera, M. Ishrat Jahan, Kenji Sugata, and Yorifumi Satou. Understanding the immunopathology of htlv-1-associated adult t-cell leukemia/lymphoma: a comprehensive review. Biomolecules, 13:1543, Oct 2023. URL: https://doi.org/10.3390/biom13101543, doi:10.3390/biom13101543. This article has 35 citations.
(o’donnell2023integratedmolecularand pages 3-4): Jake S O’Donnell, Stewart K Hunt, and Keith J Chappell. Integrated molecular and immunological features of human t-lymphotropic virus type 1 infection and disease progression to adult t-cell leukaemia or lymphoma. The Lancet Haematology, 10:e539-e548, Jul 2023. URL: https://doi.org/10.1016/s2352-3026(23)00087-x, doi:10.1016/s2352-3026(23)00087-x. This article has 23 citations and is from a highest quality peer-reviewed journal.
(nosaka2025jshpracticalguidelines media 8f3eac9b): Kisato Nosaka and Takuya Fukushima. Jsh practical guidelines for hematological malignancies, 2023: ii. lymphoma 9—adult t-cell leukemia–lymphoma (atl). International Journal of Hematology, 122:177-189, Jun 2025. URL: https://doi.org/10.1007/s12185-025-04011-2, doi:10.1007/s12185-025-04011-2. This article has 3 citations and is from a peer-reviewed journal.
(iordan2024clinicalfeaturesand pages 1-2): Iuliana Iordan, Ana-Maria Vlădăreanu, Cristina Mambet, Minodora Onisâi, Diana Cîșleanu, and Horia Bumbea. Clinical features and survival outcome in aggressive-type adult t-cell leukemia/lymphoma patients: real-life experience of a single center from an htlv-1 endemic country. Medicina, 60:872, May 2024. URL: https://doi.org/10.3390/medicina60060872, doi:10.3390/medicina60060872. This article has 1 citations.
(o’donnell2023integratedmolecularand pages 2-3): Jake S O’Donnell, Stewart K Hunt, and Keith J Chappell. Integrated molecular and immunological features of human t-lymphotropic virus type 1 infection and disease progression to adult t-cell leukaemia or lymphoma. The Lancet Haematology, 10:e539-e548, Jul 2023. URL: https://doi.org/10.1016/s2352-3026(23)00087-x, doi:10.1016/s2352-3026(23)00087-x. This article has 23 citations and is from a highest quality peer-reviewed journal.
(branda2025humantlymphotropicvirus pages 10-12): Francesco Branda, Chiara Romano, Grazia Pavia, Viola Bilotta, Chiara Locci, Ilenia Azzena, Ilaria Deplano, Noemi Pascale, Maria Perra, Marta Giovanetti, Alessandra Ciccozzi, Andrea De Vito, Angela Quirino, Nadia Marascio, Giovanni Matera, Giordano Madeddu, Marco Casu, Daria Sanna, Giancarlo Ceccarelli, Massimo Ciccozzi, and Fabio Scarpa. Human t-lymphotropic virus (htlv): epidemiology, genetic, pathogenesis, and future challenges. Viruses, 17:664, May 2025. URL: https://doi.org/10.3390/v17050664, doi:10.3390/v17050664. This article has 19 citations.
(o’donnell2023integratedmolecularand pages 5-6): Jake S O’Donnell, Stewart K Hunt, and Keith J Chappell. Integrated molecular and immunological features of human t-lymphotropic virus type 1 infection and disease progression to adult t-cell leukaemia or lymphoma. The Lancet Haematology, 10:e539-e548, Jul 2023. URL: https://doi.org/10.1016/s2352-3026(23)00087-x, doi:10.1016/s2352-3026(23)00087-x. This article has 23 citations and is from a highest quality peer-reviewed journal.
(iordan2024clinicalfeaturesand pages 5-6): Iuliana Iordan, Ana-Maria Vlădăreanu, Cristina Mambet, Minodora Onisâi, Diana Cîșleanu, and Horia Bumbea. Clinical features and survival outcome in aggressive-type adult t-cell leukemia/lymphoma patients: real-life experience of a single center from an htlv-1 endemic country. Medicina, 60:872, May 2024. URL: https://doi.org/10.3390/medicina60060872, doi:10.3390/medicina60060872. This article has 1 citations.
(nakahata2023understandingtheimmunopathology pages 3-5): Shingo Nakahata, Daniel Enriquez-Vera, M. Ishrat Jahan, Kenji Sugata, and Yorifumi Satou. Understanding the immunopathology of htlv-1-associated adult t-cell leukemia/lymphoma: a comprehensive review. Biomolecules, 13:1543, Oct 2023. URL: https://doi.org/10.3390/biom13101543, doi:10.3390/biom13101543. This article has 35 citations.
(ishida2017mogamulizumabforrelapsed pages 1-2): Takashi Ishida, Atae Utsunomiya, Tatsuro Jo, Kazuhito Yamamoto, Koji Kato, Shinichiro Yoshida, Shigeki Takemoto, Hitoshi Suzushima, Yukio Kobayashi, Yoshitaka Imaizumi, Kenichi Yoshimura, Kouichi Kawamura, Takeshi Takahashi, Kensei Tobinai, and Ryuzo Ueda. Mogamulizumab for relapsed adult t‐cell leukemia–lymphoma: updated follow‐up analysis of phase i and ii studies. Cancer Science, 108:2022-2029, Aug 2017. URL: https://doi.org/10.1111/cas.13343, doi:10.1111/cas.13343. This article has 82 citations and is from a peer-reviewed journal.
(altieri2025htlv1andatll pages 12-14): Adrian Altieri, Sean Patrick Reilly, Abu Mansalay, Alan Soo-Beng Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, and Pierluigi Porcu. Htlv-1 and atll: epidemiology, oncogenesis, and opportunities for community-informed research in the united states. Viruses, 17:1333, Sep 2025. URL: https://doi.org/10.3390/v17101333, doi:10.3390/v17101333. This article has 6 citations.
(branda2025humantlymphotropicvirus pages 17-17): Francesco Branda, Chiara Romano, Grazia Pavia, Viola Bilotta, Chiara Locci, Ilenia Azzena, Ilaria Deplano, Noemi Pascale, Maria Perra, Marta Giovanetti, Alessandra Ciccozzi, Andrea De Vito, Angela Quirino, Nadia Marascio, Giovanni Matera, Giordano Madeddu, Marco Casu, Daria Sanna, Giancarlo Ceccarelli, Massimo Ciccozzi, and Fabio Scarpa. Human t-lymphotropic virus (htlv): epidemiology, genetic, pathogenesis, and future challenges. Viruses, 17:664, May 2025. URL: https://doi.org/10.3390/v17050664, doi:10.3390/v17050664. This article has 19 citations.
(stUnknownyearprotocolforthe pages 5-10): P St and SE London. Protocol for the use of zidovudine and interferon-alpha in the management of acute adult t-cell leukaemia/lymphoma (atll). Unknown journal, Unknown year.
(bazarbachi2011howitreat pages 2-3): Ali Bazarbachi, Felipe Suarez, Paul Fields, and Olivier Hermine. How i treat adult t-cell leukemia/lymphoma. Blood, 118 7:1736-45, Aug 2011. URL: https://doi.org/10.1182/blood-2011-03-345702, doi:10.1182/blood-2011-03-345702. This article has 225 citations and is from a highest quality peer-reviewed journal.
(munakata2018adulttcellleukemialymphoma. pages 12-14): Wataru Munakata and Kensei Tobinai. Adult t-cell leukemia-lymphoma. Cancer treatment and research, 176:145-161, Dec 2018. URL: https://doi.org/10.1007/978-3-319-99716-2_7, doi:10.1007/978-3-319-99716-2_7. This article has 12 citations.
(shafiee2023zidovudineandinterferon pages 1-2): Arman Shafiee, Niloofar Seighali, Nooshin Taherzadeh-ghahfarokhi, Shayan Mardi, Sorour Shojaeian, Shahrzad Shadabi, Mahsa Hasani, Sabahat Haghi, and Sayed-Hamidreza Mozhgani. Zidovudine and interferon alfa based regimens for the treatment of adult t-cell leukemia/lymphoma (atll): a systematic review and meta-analysis. Virology Journal, Jun 2023. URL: https://doi.org/10.1186/s12985-023-02077-0, doi:10.1186/s12985-023-02077-0. This article has 13 citations and is from a peer-reviewed journal.
(shafiee2023zidovudineandinterferon pages 4-6): Arman Shafiee, Niloofar Seighali, Nooshin Taherzadeh-ghahfarokhi, Shayan Mardi, Sorour Shojaeian, Shahrzad Shadabi, Mahsa Hasani, Sabahat Haghi, and Sayed-Hamidreza Mozhgani. Zidovudine and interferon alfa based regimens for the treatment of adult t-cell leukemia/lymphoma (atll): a systematic review and meta-analysis. Virology Journal, Jun 2023. URL: https://doi.org/10.1186/s12985-023-02077-0, doi:10.1186/s12985-023-02077-0. This article has 13 citations and is from a peer-reviewed journal.
(shafiee2023zidovudineandinterferon pages 8-9): Arman Shafiee, Niloofar Seighali, Nooshin Taherzadeh-ghahfarokhi, Shayan Mardi, Sorour Shojaeian, Shahrzad Shadabi, Mahsa Hasani, Sabahat Haghi, and Sayed-Hamidreza Mozhgani. Zidovudine and interferon alfa based regimens for the treatment of adult t-cell leukemia/lymphoma (atll): a systematic review and meta-analysis. Virology Journal, Jun 2023. URL: https://doi.org/10.1186/s12985-023-02077-0, doi:10.1186/s12985-023-02077-0. This article has 13 citations and is from a peer-reviewed journal.
(shafiee2023zidovudineandinterferon pages 6-7): Arman Shafiee, Niloofar Seighali, Nooshin Taherzadeh-ghahfarokhi, Shayan Mardi, Sorour Shojaeian, Shahrzad Shadabi, Mahsa Hasani, Sabahat Haghi, and Sayed-Hamidreza Mozhgani. Zidovudine and interferon alfa based regimens for the treatment of adult t-cell leukemia/lymphoma (atll): a systematic review and meta-analysis. Virology Journal, Jun 2023. URL: https://doi.org/10.1186/s12985-023-02077-0, doi:10.1186/s12985-023-02077-0. This article has 13 citations and is from a peer-reviewed journal.
(shafiee2023zidovudineandinterferon pages 7-8): Arman Shafiee, Niloofar Seighali, Nooshin Taherzadeh-ghahfarokhi, Shayan Mardi, Sorour Shojaeian, Shahrzad Shadabi, Mahsa Hasani, Sabahat Haghi, and Sayed-Hamidreza Mozhgani. Zidovudine and interferon alfa based regimens for the treatment of adult t-cell leukemia/lymphoma (atll): a systematic review and meta-analysis. Virology Journal, Jun 2023. URL: https://doi.org/10.1186/s12985-023-02077-0, doi:10.1186/s12985-023-02077-0. This article has 13 citations and is from a peer-reviewed journal.
(iordan2024clinicalfeaturesand pages 9-10): Iuliana Iordan, Ana-Maria Vlădăreanu, Cristina Mambet, Minodora Onisâi, Diana Cîșleanu, and Horia Bumbea. Clinical features and survival outcome in aggressive-type adult t-cell leukemia/lymphoma patients: real-life experience of a single center from an htlv-1 endemic country. Medicina, 60:872, May 2024. URL: https://doi.org/10.3390/medicina60060872, doi:10.3390/medicina60060872. This article has 1 citations.
(iordan2024clinicalfeaturesand pages 2-4): Iuliana Iordan, Ana-Maria Vlădăreanu, Cristina Mambet, Minodora Onisâi, Diana Cîșleanu, and Horia Bumbea. Clinical features and survival outcome in aggressive-type adult t-cell leukemia/lymphoma patients: real-life experience of a single center from an htlv-1 endemic country. Medicina, 60:872, May 2024. URL: https://doi.org/10.3390/medicina60060872, doi:10.3390/medicina60060872. This article has 1 citations.
(sekine2017effectsofmogamulizumab pages 14-18): Masaaki Sekine, Yoko Kubuki, Takuro Kameda, Masanori Takeuchi, Takanori Toyama, Noriaki Kawano, Kouichi Maeda, Seiichi Sato, Junzo Ishizaki, Hiroshi Kawano, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Kotaro Shide, Tomonori Hidaka, Akira Kitanaka, Kiyoshi Yamashita, Hitoshi Matsuoka, and Kazuya Shimoda. Effects of mogamulizumab in adult t‐cell leukemia/lymphoma in clinical practice. European Journal of Haematology, 98:501-507, May 2017. URL: https://doi.org/10.1111/ejh.12863, doi:10.1111/ejh.12863. This article has 19 citations and is from a peer-reviewed journal.
(sekine2017effectsofmogamulizumab pages 10-14): Masaaki Sekine, Yoko Kubuki, Takuro Kameda, Masanori Takeuchi, Takanori Toyama, Noriaki Kawano, Kouichi Maeda, Seiichi Sato, Junzo Ishizaki, Hiroshi Kawano, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Kotaro Shide, Tomonori Hidaka, Akira Kitanaka, Kiyoshi Yamashita, Hitoshi Matsuoka, and Kazuya Shimoda. Effects of mogamulizumab in adult t‐cell leukemia/lymphoma in clinical practice. European Journal of Haematology, 98:501-507, May 2017. URL: https://doi.org/10.1111/ejh.12863, doi:10.1111/ejh.12863. This article has 19 citations and is from a peer-reviewed journal.
(yonekura2020mogamulizumabforadult pages 12-12): Kentaro Yonekura, Shigeru Kusumoto, Ilseung Choi, Nobuaki Nakano, Asahi Ito, Youko Suehiro, Yoshitaka Imaizumi, Makoto Yoshimitsu, Kisato Nosaka, Eiichi Ohtsuka, Michihiro Hidaka, Tatsuro Jo, Hidenori Sasaki, Yukiyoshi Moriuchi, Masao Ogata, Hiro Tatetsu, Kenji Ishitsuka, Yasushi Miyazaki, Ryuzo Ueda, Atae Utsunomiya, and Takashi Ishida. Mogamulizumab for adult t-cell leukemia-lymphoma: a multicenter prospective observational study. Blood advances, 4 20:5133-5145, Oct 2020. URL: https://doi.org/10.1182/bloodadvances.2020003053, doi:10.1182/bloodadvances.2020003053. This article has 43 citations and is from a peer-reviewed journal.
(wang2024currentstateof pages 12-14): Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher, and Chantelle L. Ahlenstiel. Current state of therapeutics for htlv-1. Viruses, 16:1616, Oct 2024. URL: https://doi.org/10.3390/v16101616, doi:10.3390/v16101616. This article has 21 citations.
(wang2024currentstateof pages 34-35): Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher, and Chantelle L. Ahlenstiel. Current state of therapeutics for htlv-1. Viruses, 16:1616, Oct 2024. URL: https://doi.org/10.3390/v16101616, doi:10.3390/v16101616. This article has 21 citations.
(munakata2018adulttcellleukemialymphoma. pages 16-17): Wataru Munakata and Kensei Tobinai. Adult t-cell leukemia-lymphoma. Cancer treatment and research, 176:145-161, Dec 2018. URL: https://doi.org/10.1007/978-3-319-99716-2_7, doi:10.1007/978-3-319-99716-2_7. This article has 12 citations.
(nakahata2023understandingtheimmunopathology pages 2-3): Shingo Nakahata, Daniel Enriquez-Vera, M. Ishrat Jahan, Kenji Sugata, and Yorifumi Satou. Understanding the immunopathology of htlv-1-associated adult t-cell leukemia/lymphoma: a comprehensive review. Biomolecules, 13:1543, Oct 2023. URL: https://doi.org/10.3390/biom13101543, doi:10.3390/biom13101543. This article has 35 citations.
(epsteinpeterson2025newtreatmentsfor pages 15-15): Zachary D. Epstein-Peterson, Ashwath Gurumurthi, and Steven M. Horwitz. New treatments for adult t-cell leukemia/lymphoma. Leukemia Research, 149:107642, Feb 2025. URL: https://doi.org/10.1016/j.leukres.2025.107642, doi:10.1016/j.leukres.2025.107642. This article has 9 citations and is from a peer-reviewed journal.
(branda2025humantlymphotropicvirus pages 23-25): Francesco Branda, Chiara Romano, Grazia Pavia, Viola Bilotta, Chiara Locci, Ilenia Azzena, Ilaria Deplano, Noemi Pascale, Maria Perra, Marta Giovanetti, Alessandra Ciccozzi, Andrea De Vito, Angela Quirino, Nadia Marascio, Giovanni Matera, Giordano Madeddu, Marco Casu, Daria Sanna, Giancarlo Ceccarelli, Massimo Ciccozzi, and Fabio Scarpa. Human t-lymphotropic virus (htlv): epidemiology, genetic, pathogenesis, and future challenges. Viruses, 17:664, May 2025. URL: https://doi.org/10.3390/v17050664, doi:10.3390/v17050664. This article has 19 citations.
(wang2024currentstateof pages 1-2): Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher, and Chantelle L. Ahlenstiel. Current state of therapeutics for htlv-1. Viruses, 16:1616, Oct 2024. URL: https://doi.org/10.3390/v16101616, doi:10.3390/v16101616. This article has 21 citations.
(altieri2025htlv1andatll pages 4-5): Adrian Altieri, Sean Patrick Reilly, Abu Mansalay, Alan Soo-Beng Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, and Pierluigi Porcu. Htlv-1 and atll: epidemiology, oncogenesis, and opportunities for community-informed research in the united states. Viruses, 17:1333, Sep 2025. URL: https://doi.org/10.3390/v17101333, doi:10.3390/v17101333. This article has 6 citations.
(wang2024currentstateof pages 9-11): Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher, and Chantelle L. Ahlenstiel. Current state of therapeutics for htlv-1. Viruses, 16:1616, Oct 2024. URL: https://doi.org/10.3390/v16101616, doi:10.3390/v16101616. This article has 21 citations.
(wang2024currentstateof pages 8-9): Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher, and Chantelle L. Ahlenstiel. Current state of therapeutics for htlv-1. Viruses, 16:1616, Oct 2024. URL: https://doi.org/10.3390/v16101616, doi:10.3390/v16101616. This article has 21 citations.