mercaptopurine and Bacteremia

Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment-related morbidity and mortality. Herein, we investigate how pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals receiving curative-intent induction chemotherapy with cytarabine and an anthracycline ("7 + 3"; n = 175) or a "7 + 3"-like regimen (n = 30). Among the entire cohort, baseline grade 4 neutropenia (i.e., absolute neutrophil count <500 cells/µL) was associated with development of fever (P = 0.04), documented infection (P < 0.0001), and bacteremia (P = 0.002) but not requirement for intensive care unit-level care; after exclusion of the 30 patients who received "7 + 3"-like induction, baseline grade 4 neutropenia remained associated with documented infection (P < 0.0001) and bacteremia (P = 0.0005). Among patients achieving a complete remission with the initial treatment cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery (P < 0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04-3.34; P=0.04)-fold, 4.95 (2.20-11.16; P<0.001)-fold, and 3.14 (0.99-9.98; P=0.05)-fold higher in patients with initial grade 4 neutropenia. Together, our studies identify severe baseline neutropenia as a risk factor for infection-associated adverse events after induction chemotherapy and may provide the rationale for the risk-adapted testing of myeloid growth factor support in this high-risk AML/MDS patient subset.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Blood Cell Count; Critical Care; Cyclophosphamide; Cytarabine; Daunorubicin; Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunocompromised Host; Infections; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Proportional Hazards Models; Remission Induction; Retrospective Studies; Young Adult

A 66-year-old woman with malignant lymphoma became neutropenic during chemotherapy and developed cryptococcemia. After amphotericin B had been commenced, she developed significant hypokalemia and polyuria, though her renal function remained stable. The laboratory findings showed no evidence of renal tubular acidosis. With vigorous water and potassium replacement, amphotericin B had been continued until the cumulative dose reached 2.5 g. After the cessation of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on theses findings, she was diagnosed as nephrogenic diabetes insipidus with hypokalemia and without renal tubular acidosis due to amphotericin B. This complication is usually reversible, and vigorous water and potassium replacement may allow completion of treatment by amphotericin B, though careful monitoring of body water balance and renal function is of importance.

Topics: Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; Antimetabolites, Antineoplastic; Bacteremia; Cryptococcosis; Cryptococcus neoformans; Diabetes Insipidus, Nephrogenic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lymphoma; Mercaptopurine; Tomography, X-Ray Computed