Chemotherapy-Induced Neutropenia

Complex MONDO:0001475 Pathograph 6 Show in embeddings browser Hematologic Disease Iatrogenic condition

Chemotherapy-induced neutropenia is a treatment-related hematologic toxicity of cytotoxic antineoplastic therapy. Myelosuppressive chemotherapy damages proliferating hematopoietic progenitors in the bone marrow, suppressing granulopoiesis and producing a fall in the circulating neutrophil count. It is the single-lineage-predominant expression of the conserved myelosuppression mechanism, and its principal danger is febrile neutropenia and infection, which drives dose delays and reductions that can compromise antitumor treatment.

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1
Mappings
4
Pathophys.
2
Phenotypes
6
Pathograph
1
Genes
1
Medical Actions
🔗

Mappings

MONDO
MONDO:0001475 neutropenia
skos:closeMatch MONDO
Closest MONDO term available for chemotherapy-induced neutropenia in the local ontology snapshot; the dismech entry specializes it to the drug-induced, single-lineage context.
⚙

Pathophysiology

4
Cytotoxic chemotherapy exposure and hematopoietic progenitor injury
Myelosuppressive chemotherapy delivers cytotoxic drugs to the bone marrow, where rapidly proliferating hematopoietic stem and progenitor cells are preferentially injured — the conserved initiating lesion of the myelosuppression module, here viewed through its granulocytic consequence.
hematopoietic stem cell CL:0000037 hematopoietic progenitor cell CL:0008001
apoptotic process GO:0006915 ↑ INCREASED
Downstream
Bone marrow granulopoietic suppression Progenitor injury suppresses marrow output, particularly the neutrophil lineage.
Show evidence (3 references)
PMID:34307165 SUPPORT Other
"Proliferating hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are particularly susceptible to chemotherapy-induced damage."
Establishes chemotherapy injury to proliferating marrow progenitors as the initiating lesion, matching the module trigger node this disease conforms to. Evidence source is OTHER because this is a review article.
PMID:31504118 SUPPORT Human Clinical
"Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression."
A human clinical trial frames chemotherapy-induced HSPC damage as the cause of myelosuppression, of which neutropenia is the predominant lineage here.
PMID:31988457 SUPPORT In Vitro
"a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to..."
New Approach Methodology (NAM) evidence (Wyss Institute human bone-marrow organ-on-chip, the "bone marrow" example highlighted in Don Ingber's NAMeRS 2026 case study on real-world human-chip implementation). A vascularized human BM chip recapitulates clinically relevant chemotherapeutic- and radiation-induced myelosuppression of proliferating hematopoietic progenitors — and subsequent recovery — providing a human-specific microphysiological model of the initiating marrow lesion of chemotherapy-induced neutropenia without animal testing.
Bone marrow granulopoietic suppression
Loss of functional progenitors suppresses bone marrow hematopoietic output. In this entry the suppression is viewed through its effect on granulopoiesis, reducing the marrow's capacity to replace circulating neutrophils.
hematopoietic stem cell CL:0000037
hemopoiesis GO:0030097 ↓ DECREASED
Downstream
Peripheral neutropenia Suppressed granulopoiesis lowers the circulating neutrophil count.
Show evidence (1 reference)
PMID:40057216 SUPPORT Model Organism
"The resultant bone marrow suppression is a major dose-limiting side effect."
Identifies marrow suppression as the dose-limiting consequence of chemotherapy hematopoietic toxicity, matching the module central-effector node. Evidence source is MODEL_ORGANISM (mouse 5-fluorouracil study).
Peripheral neutropenia
Reduced marrow output lowers the circulating neutrophil count. This node specializes the module's multilineage-cytopenia effector to the neutrophil lineage, the predominant and most clinically consequential cytopenia for many regimens.
neutrophil CL:0000775
myeloid cell homeostasis GO:0002262 ↓ DECREASED
Downstream
Febrile neutropenia and infection susceptibility A low neutrophil count raises the risk of infection and febrile neutropenia.
Show evidence (1 reference)
PMID:34307165 SUPPORT Other
"one of the most common side effects of chemotherapy is myelosuppression, which typically manifests as neutropenia, anemia, thrombocytopenia, and/or lymphopenia"
Lists neutropenia among the manifestations of chemotherapy-induced myelosuppression, the lineage specialized in this node. Evidence source is OTHER because this is a review article.
Febrile neutropenia and infection susceptibility
Neutropenia impairs host defense, raising the risk of infection and febrile neutropenia — the principal driver of morbidity and mortality and the reason chemotherapy doses are delayed or reduced.
neutrophil CL:0000775
leukocyte mediated immunity GO:0002443 ↓ DECREASED
Show evidence (2 references)
PMID:21095116 SUPPORT Other
"Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment."
Establishes neutropenia as the driver of infection-related morbidity and as a dose-limiting toxicity, the consequence captured by the module node. Evidence source is OTHER because this is a guideline document.
PMID:38587388 SUPPORT Other
"Neutropenia increases infection risk, and anemia frequently results in debilitating fatigue."
Maps neutropenia to its characteristic infection complication. Evidence source is OTHER because this is a review article.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Chemotherapy-Induced Neutropenia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

2
Blood 1
Neutropenia Decreased total neutrophil count HP:0001875
Show evidence (1 reference)
PMID:34307165 SUPPORT Other
"one of the most common side effects of chemotherapy is myelosuppression, which typically manifests as neutropenia, anemia, thrombocytopenia, and/or lymphopenia"
Names neutropenia among the defining manifestations of chemotherapy-induced myelosuppression. Evidence source is OTHER because this is a review.
Immune 1
Recurrent infections Recurrent infections HP:0002719
Show evidence (1 reference)
PMID:21095116 SUPPORT Other
"Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment."
Establishes infection-related morbidity and mortality as the principal complication of chemotherapy-induced neutropenia. Evidence source is OTHER because this is a guideline document.
🧬

Genetic Associations

1
UGT1A1 pharmacogenomic susceptibility (Reduced-function UGT1A1 variants increase irinotecan-associated neutropenia risk)
Gene: UGT1A1 hgnc:12530 relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (1 reference)
PMID:11990381 SUPPORT Human Clinical
"screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity."
Human pharmacokinetic evidence links UGT1A1*28 to greater irinotecan bone marrow toxicity, of which neutropenia is the principal manifestation.
💊

Medical Actions

1
Granulocyte colony-stimulating factor (G-CSF)
Action: Pharmacotherapy NCIT:C15986
Agent: filgrastim NCIT:C1474
Prophylactic or therapeutic G-CSF (filgrastim, lenograstim, pegfilgrastim) reduces the incidence and duration of chemotherapy-induced neutropenia and febrile neutropenia.
Show evidence (1 reference)
PMID:21095116 SUPPORT Other
"prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia"
The EORTC guideline identifies prophylactic G-CSF as the standard intervention to reduce chemotherapy-induced neutropenia. Evidence source is OTHER because this is a guideline document.
{ }

Source YAML

click to show 
name: Chemotherapy-Induced Neutropenia
creation_date: "2026-06-24T00:00:00Z"
category: Complex
categories:
- Treatment-Related Disorder
- Hematologic Toxicity
- Adverse Drug Reaction
synonyms:
- CIN
- chemotherapy-induced neutropenia
description: >-
  Chemotherapy-induced neutropenia is a treatment-related hematologic toxicity of
  cytotoxic antineoplastic therapy. Myelosuppressive chemotherapy damages
  proliferating hematopoietic progenitors in the bone marrow, suppressing
  granulopoiesis and producing a fall in the circulating neutrophil count. It is
  the single-lineage-predominant expression of the conserved myelosuppression
  mechanism, and its principal danger is febrile neutropenia and infection, which
  drives dose delays and reductions that can compromise antitumor treatment.
parents:
- Hematologic Disease
- Iatrogenic condition
disease_term:
  preferred_term: chemotherapy-induced neutropenia
  term:
    id: MONDO:0001475
    label: neutropenia
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0001475
      label: neutropenia
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      Closest MONDO term available for chemotherapy-induced neutropenia in the
      local ontology snapshot; the dismech entry specializes it to the
      drug-induced, single-lineage context.
pathophysiology:
- name: Cytotoxic chemotherapy exposure and hematopoietic progenitor injury
  conforms_to: "myelosuppression#Cytotoxic Insult to Proliferating Hematopoietic Progenitors"
  description: >-
    Myelosuppressive chemotherapy delivers cytotoxic drugs to the bone marrow,
    where rapidly proliferating hematopoietic stem and progenitor cells are
    preferentially injured — the conserved initiating lesion of the
    myelosuppression module, here viewed through its granulocytic consequence.
  role: trigger
  cell_types:
  - preferred_term: hematopoietic stem cell
    term:
      id: CL:0000037
      label: hematopoietic stem cell
  - preferred_term: hematopoietic progenitor cell
    term:
      id: CL:0008001
      label: hematopoietic precursor cell
  biological_processes:
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
    modifier: INCREASED
  evidence:
  - reference: PMID:34307165
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Proliferating hematopoietic stem and progenitor cells (HSPCs) in the bone
      marrow are particularly susceptible to chemotherapy-induced damage.
    explanation: >-
      Establishes chemotherapy injury to proliferating marrow progenitors as the
      initiating lesion, matching the module trigger node this disease conforms
      to. Evidence source is OTHER because this is a review article.
  - reference: PMID:31504118
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Chemotherapy-induced damage of hematopoietic stem and progenitor cells
      (HSPC) causes multi-lineage myelosuppression.
    explanation: >-
      A human clinical trial frames chemotherapy-induced HSPC damage as the cause
      of myelosuppression, of which neutropenia is the predominant lineage here.
  - reference: PMID:31988457
    reference_title: "On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      a vascularized human BM-on-a-chip (BM chip) supports the differentiation
      and maturation of multiple blood cell lineages over 4 weeks while improving
      CD34+ cell maintenance, and that it recapitulates aspects of BM injury,
      including myeloerythroid toxicity after clinically relevant exposures to
      chemotherapeutic drugs and ionizing radiation, as well as BM recovery after
      drug-induced myelosuppression
    explanation: >-
      New Approach Methodology (NAM) evidence (Wyss Institute human bone-marrow
      organ-on-chip, the "bone marrow" example highlighted in Don Ingber's
      NAMeRS 2026 case study on real-world human-chip implementation). A
      vascularized human BM chip recapitulates clinically relevant
      chemotherapeutic- and radiation-induced myelosuppression of proliferating
      hematopoietic progenitors — and subsequent recovery — providing a
      human-specific microphysiological model of the initiating marrow lesion of
      chemotherapy-induced neutropenia without animal testing.
  downstream:
  - target: Bone marrow granulopoietic suppression
    description: >-
      Progenitor injury suppresses marrow output, particularly the neutrophil
      lineage.
- name: Bone marrow granulopoietic suppression
  conforms_to: "myelosuppression#Bone Marrow Hematopoietic Suppression"
  description: >-
    Loss of functional progenitors suppresses bone marrow hematopoietic output.
    In this entry the suppression is viewed through its effect on granulopoiesis,
    reducing the marrow's capacity to replace circulating neutrophils.
  role: central_effector
  cell_types:
  - preferred_term: hematopoietic stem cell
    term:
      id: CL:0000037
      label: hematopoietic stem cell
  biological_processes:
  - preferred_term: hemopoiesis
    term:
      id: GO:0030097
      label: hemopoiesis
    modifier: DECREASED
  evidence:
  - reference: PMID:40057216
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The resultant bone marrow suppression is a major dose-limiting side effect.
    explanation: >-
      Identifies marrow suppression as the dose-limiting consequence of
      chemotherapy hematopoietic toxicity, matching the module central-effector
      node. Evidence source is MODEL_ORGANISM (mouse 5-fluorouracil study).
  downstream:
  - target: Peripheral neutropenia
    description: >-
      Suppressed granulopoiesis lowers the circulating neutrophil count.
- name: Peripheral neutropenia
  conforms_to: "myelosuppression#Multilineage Peripheral Cytopenias"
  description: >-
    Reduced marrow output lowers the circulating neutrophil count. This node
    specializes the module's multilineage-cytopenia effector to the neutrophil
    lineage, the predominant and most clinically consequential cytopenia for many
    regimens.
  role: effector
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: myeloid cell homeostasis
    term:
      id: GO:0002262
      label: myeloid cell homeostasis
    modifier: DECREASED
  evidence:
  - reference: PMID:34307165
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      one of the most common side effects of chemotherapy is myelosuppression,
      which typically manifests as neutropenia, anemia, thrombocytopenia, and/or
      lymphopenia
    explanation: >-
      Lists neutropenia among the manifestations of chemotherapy-induced
      myelosuppression, the lineage specialized in this node. Evidence source is
      OTHER because this is a review article.
  downstream:
  - target: Febrile neutropenia and infection susceptibility
    description: >-
      A low neutrophil count raises the risk of infection and febrile
      neutropenia.
- name: Febrile neutropenia and infection susceptibility
  conforms_to: "myelosuppression#Cytopenia-Related Clinical Complications"
  description: >-
    Neutropenia impairs host defense, raising the risk of infection and febrile
    neutropenia — the principal driver of morbidity and mortality and the reason
    chemotherapy doses are delayed or reduced.
  role: consequence
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: leukocyte mediated immunity
    term:
      id: GO:0002443
      label: leukocyte mediated immunity
    modifier: DECREASED
  evidence:
  - reference: PMID:21095116
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Chemotherapy-induced neutropenia is a major risk factor for
      infection-related morbidity and mortality and also a significant
      dose-limiting toxicity in cancer treatment.
    explanation: >-
      Establishes neutropenia as the driver of infection-related morbidity and as
      a dose-limiting toxicity, the consequence captured by the module node.
      Evidence source is OTHER because this is a guideline document.
  - reference: PMID:38587388
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Neutropenia increases infection risk, and anemia frequently results in
      debilitating fatigue.
    explanation: >-
      Maps neutropenia to its characteristic infection complication. Evidence
      source is OTHER because this is a review article.
phenotypes:
- name: Neutropenia
  description: >-
    Reduced circulating neutrophil count, the defining laboratory abnormality of
    this toxicity.
  phenotype_term:
    preferred_term: Neutropenia
    term:
      id: HP:0001875
      label: Decreased total neutrophil count
  evidence:
  - reference: PMID:34307165
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      one of the most common side effects of chemotherapy is myelosuppression,
      which typically manifests as neutropenia, anemia, thrombocytopenia, and/or
      lymphopenia
    explanation: >-
      Names neutropenia among the defining manifestations of chemotherapy-induced
      myelosuppression. Evidence source is OTHER because this is a review.
- name: Recurrent infections
  description: >-
    Increased susceptibility to infection, including febrile neutropenia,
    downstream of the low neutrophil count.
  phenotype_term:
    preferred_term: Increased susceptibility to infection
    term:
      id: HP:0002719
      label: Recurrent infections
  evidence:
  - reference: PMID:21095116
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Chemotherapy-induced neutropenia is a major risk factor for
      infection-related morbidity and mortality and also a significant
      dose-limiting toxicity in cancer treatment.
    explanation: >-
      Establishes infection-related morbidity and mortality as the principal
      complication of chemotherapy-induced neutropenia. Evidence source is OTHER
      because this is a guideline document.
genetic:
- name: UGT1A1 pharmacogenomic susceptibility
  gene_term:
    preferred_term: UGT1A1
    term:
      id: hgnc:12530
      label: UGT1A1
  association: Reduced-function UGT1A1 variants increase irinotecan-associated neutropenia risk
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  notes: >-
    Reduced UGT1A1 activity limits SN-38 glucuronidation after irinotecan
    exposure, increasing bone marrow toxicity including neutropenia.
  variants:
  - name: UGT1A1*28
    description: >-
      Promoter repeat allele associated with lower SN-38 glucuronidation and
      increased irinotecan myelotoxicity susceptibility.
  evidence:
  - reference: PMID:11990381
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      screening for UGT1A1*28 polymorphism may identify patients with lower
      SN-38 glucuronidation rates and greater susceptibility to irinotecan
      induced gastrointestinal and bone marrow toxicity.
    explanation: >-
      Human pharmacokinetic evidence links UGT1A1*28 to greater irinotecan bone
      marrow toxicity, of which neutropenia is the principal manifestation.
treatments:
- name: Granulocyte colony-stimulating factor (G-CSF)
  description: >-
    Prophylactic or therapeutic G-CSF (filgrastim, lenograstim, pegfilgrastim)
    reduces the incidence and duration of chemotherapy-induced neutropenia and
    febrile neutropenia.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: filgrastim
      term:
        id: NCIT:C1474
        label: Filgrastim
  evidence:
  - reference: PMID:21095116
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      prophylactic treatment with granulocyte-colony stimulating factors
      (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim
      or pegfilgrastim is available to reduce the risk of chemotherapy-induced
      neutropenia
    explanation: >-
      The EORTC guideline identifies prophylactic G-CSF as the standard
      intervention to reduce chemotherapy-induced neutropenia. Evidence source is
      OTHER because this is a guideline document.