title: Phase I-II study of high-dose busulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation for hematological malignancies: toxicities and hematopoietic recovery.
abstract: In a phase I-II study, we evaluated toxicities, tolerability, pace of engraftment, and tumor responses to high-dose bulsulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with hematological malignancies. We treated 51 patients with various hematological malignancies involving the bone marrow with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of autologous peripheral blood stem cells. Stem cells were previously collected during hematopoietic recovery after cyclophosphamide (100 mg/kg) and etoposide (600 mg/m2) followed by G-CSF (5 micrograms/kg/day). Neutrophil recovery (>0.5 x 10(9)/I) was rapid in the majority of patients (median 10 days after transplant, range 7-91 days), resulting in a low number of days with severe neutropenia (median 7 days, range 5-85 days) and with fever (median 5 days, range 1-13 days). Platelet recovery, however, was delayed in 60% of patients. There was one acute transplant-related death (2%). Four patients died of late, presumed infections, pulmonary complications (interstitial pneumonia). Tumor responses were documented in a significant proportion of these patients with high-risk hematological malignancies. We conclude that peripheral blood stem cell transplantation results in rapid recovery of neutrophils but variable recovery of platelets after high-dose busulfan and cyclophosphamide, when stem cells are harvested following priming with cyclophosphamide/etoposide and G-CSF. The regimen is well-tolerated with limited non-hematological toxicities and transplant-related mortality. While significant tumor responses were documented in this trial, the ultimate efficacy of the regimen needs to be further defined.
authors.affiliation: Department of Internal Medicine, University of South Florida, H Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
authors.forename: O F
authors.initials: OF
authors.lastname: Ballester
authors.forename: D P
authors.initials: DP
authors.lastname: Agaliotis
authors.forename: J W
authors.initials: JW
authors.lastname: Hiemenz
authors.forename: W E
authors.initials: WE
authors.lastname: Janssen
authors.forename: K K
authors.initials: KK
authors.lastname: Fields
authors.forename: P E
authors.initials: PE
authors.lastname: Zorksy
authors.forename: S C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: J B
authors.initials: JB
authors.lastname: Perkins
authors.forename: G J
authors.initials: GJ
authors.lastname: Elfenbein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D015993:Life Tables; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan