Acute Complications of Hodgkin Lymphoma Post-Chemotherapy
The most common acute complications following chemotherapy for Hodgkin lymphoma include myelosuppression (leukopenia, anemia, thrombocytopenia), febrile neutropenia, nausea/vomiting, and infection risk, with specific toxicities varying by regimen—ABVD carries pulmonary toxicity risk from bleomycin, while BEACOPP-based regimens significantly increase risk of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and severe infections. 1
Hematologic Complications
Myelosuppression and Febrile Neutropenia
Cytopenias (leukopenia, anemia, thrombocytopenia) are the most frequent acute complications across all chemotherapy regimens used for Hodgkin lymphoma 2, 3.
Febrile neutropenia (FN) risk varies by regimen intensity: Standard ABVD carries lower FN risk compared to intensified protocols like BEACOPP 1.
G-CSF prophylaxis should be considered for patients receiving intensive regimens (BEACOPP-escalated), though evidence specifically in Hodgkin lymphoma is limited—recommendations are extrapolated from non-Hodgkin lymphoma trials where high FN risk (>40%) was demonstrated 1.
Bleeding manifestations including petechiae, purpura, epistaxis, and hemoptysis can occur secondary to thrombocytopenia 2.
Secondary Hematologic Malignancies
BEACOPP-escalated chemotherapy carries a significantly elevated risk of AML/MDS compared to ABVD-like regimens, with the 10-year cumulative incidence reaching approximately 2-3% 1, 4.
Alkylating agent-containing regimens (MOPP, BEACOPP) are the primary culprits for leukemogenesis, while modern ABVD does not appear leukemogenic 1.
Leukemia risk peaks within the first 5-10 years post-treatment and represents an early-onset secondary malignancy 1, 5.
Infectious Complications
Acute Infection Risk
Profound immunosuppression during chemotherapy creates high susceptibility to bacterial, fungal, and viral infections 1.
Anti-infectious prophylaxis (anti-fungal, Pneumocystis jiroveci) and surveillance screening (Aspergillus, EBV, CMV) should be strongly considered during active chemotherapy, particularly with intensive regimens 1.
Hepatitis B, hepatitis C, and HIV screening is mandatory before initiating therapy to identify patients requiring prophylaxis or modified treatment approaches 1.
Hemophagocytic Lymphohistiocytosis (HLH)
HLH can occur as a rare but life-threatening complication during chemotherapy-induced immunosuppression ("HLH During Chemotherapy"), often triggered by concurrent infections, particularly EBV 1, 6.
Clinical presentation mimics sepsis: prolonged fever >39.4°C, hepatosplenomegaly, cytopenias affecting ≥2 cell lines, hyperferritinemia (≥500 μg/L), hypertriglyceridemia, and hypofibrinogenemia 6.
Diagnosis requires high clinical suspicion using HLH-2004 criteria (5 of 8 parameters: fever, splenomegaly, cytopenias, hypertriglyceridemia/hypofibrinogenemia, hemophagocytosis, low NK cell activity, ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL) 6.
Management involves postponing subsequent chemotherapy cycles, treating infectious triggers rigorously, and considering glucocorticosteroids and immunoglobulins—the extent of HLH-directed therapy depends on clinical severity, balancing immunosuppression against infection control 1.
Gastrointestinal Toxicity
Nausea and vomiting are the most commonly reported acute side effects across all regimens 2.
Additional GI complications include: stomatitis, diarrhea, constipation, abdominal pain, anorexia, and rarely hematemesis or melena 2.
Hepatic dysfunction and jaundice can occur, necessitating monitoring of liver enzymes (alkaline phosphatase, transaminases) 1, 2.
Pulmonary Toxicity
Bleomycin-containing regimens (ABVD, BEACOPP) carry risk of acute pneumonitis and potentially fatal pulmonary fibrosis 2.
Pulmonary function tests are mandatory prior to treatment to identify patients at increased baseline risk 1.
Clinical monitoring for cough, dyspnea, and respiratory symptoms is essential during treatment 2.
Cardiovascular Complications
Acute cardiotoxicity from anthracyclines (doxorubicin in ABVD/BEACOPP) includes arrhythmias, hypotension, tachycardia, and rarely acute heart failure 2, 3.
Cardiac function testing is mandatory before treatment initiation to establish baseline and identify high-risk patients 1.
Cumulative doxorubicin dose monitoring is critical—cardiac toxicity risk increases substantially above 300-400 mg/m² 7.
Neurologic Toxicity
Vinca alkaloid-related neuropathy (vinblastine in ABVD, vincristine in BEACOPP) manifests as paresthesias, diminished reflexes, ataxia, and rarely foot drop 2, 3.
Procarbazine (in BEACOPP) can cause CNS depression, confusion, hallucinations, and headache 2.
Severe neurologic complications including seizures, coma, and nystagmus are rare but documented 2.
Dermatologic and Allergic Reactions
Skin manifestations include: dermatitis, pruritus, alopecia, hyperpigmentation, rash, urticaria, and flushing 2.
Generalized allergic reactions can occur and require immediate management 2.
Genitourinary and Reproductive Toxicity
Acute hemorrhagic cystitis (hematuria, urinary frequency) can occur, particularly with cyclophosphamide-containing regimens 2.
Fertility preservation counseling is mandatory before treatment initiation for all patients of reproductive age 1.
Alkylating agents cause dose-dependent gonadal toxicity: BEACOPP carries significantly higher risk of amenorrhea and azoospermia compared to ABVD 1, 2.
Drug-Specific Interactions and Precautions
Procarbazine (BEACOPP regimens)
Exhibits monoamine oxidase inhibitor activity—avoid sympathomimetic drugs, tricyclic antidepressants, tyramine-rich foods (wine, aged cheese, bananas), and alcohol (Antabuse-like reaction) 2.
CNS depressants (barbiturates, antihistamines, narcotics, phenothiazines) should be used with extreme caution 2.
Vinblastine/Vincristine
Drugs inhibiting hepatic cytochrome P450 3A (e.g., erythromycin) can cause earlier onset and increased severity of toxicity 3.
Phenytoin levels may decrease due to either reduced absorption or increased metabolism when given concurrently 3.
Critical Monitoring Parameters
Complete blood count monitoring every 3-4 months during the first two years post-treatment 1.
Thyroid function testing (TSH, FT3, FT4) is mandatory for patients receiving neck/mediastinal radiotherapy 1.
Cardiovascular monitoring should continue long-term for all patients 1.
Common Pitfalls to Avoid
Do not underestimate infection risk during nadir periods—maintain high clinical suspicion for atypical presentations of sepsis or HLH 1, 6.
Do not delay G-CSF in high-risk patients receiving intensive chemotherapy regimens 1.
Do not ignore cumulative anthracycline dosing—cardiac toxicity is dose-dependent and can manifest acutely 7.
Do not overlook drug-drug interactions, particularly with procarbazine's MAO inhibitor properties 2.
Do not proceed with bleomycin in patients with declining pulmonary function or new respiratory symptoms 2.