title: Prolonged haematological toxicity from the hyper-CVAD regimen: manifestations, frequency, and natural history in a cohort of 125 consecutive patients.
abstract: The hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) regimen has impressive efficacy in several haematological malignancies but is associated with considerable short-term haematological toxicity. Secondary myelodysplasia (MDS) or acute myeloid leukaemia (AML) also occurs. In this retrospective study, we also describe other prolonged haematological sequelae of this regimen. One hundred and twenty-five patients were treated with a median of six hyper-CVAD cycles and followed for a median of 28 months. Follow-up for cytopenias was censored at the next cytotoxic therapy. At 3 months post-therapy, 77 patients were evaluable. Cytopenias persisted in 59% of patients. Requirement for dose attenuation was the only factor significantly associated with persisting cytopenias (p<0.05). The median time to normalisation of counts for those with post-treatment cytopenias in the respective lineages was 9 months (range, 6-12) for anaemia, 6 months (range, 6-30) for neutropenia and 9 months (range, 6-30) for thrombocytopenia. MDS/AML was diagnosed in four patients at 4, 21, 24 and 37 months after therapy with a cumulative incidence rate of 4.43% at 4 years. These results indicate a considerable rate of prolonged haematological toxicity after hyper-CVAD and a modest rate of MDS at this limited follow-up. These findings likely reflect cumulative damage to haematopoietic stem cells.
authors.affiliation: Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Victoria 8006, Australia.
authors.forename: Saar
authors.initials: S
authors.lastname: Gill
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lane
authors.forename: Julie
authors.initials: J
authors.lastname: Crawford
authors.forename: Gavin
authors.initials: G
authors.lastname: Cull
authors.forename: David
authors.initials: D
authors.lastname: Joske
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
authors.forename: Peter N
authors.initials: PN
authors.lastname: Mollee
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000532:radiotherapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000209:etiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide