Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia

Ann Hematol. 2013 Jan;92(2):249-54. doi: 10.1007/s00277-012-1579-y. Epub 2012 Sep 27.

Abstract

Allogeneic stem cell transplantation (SCT) is a treatment option for patients with poor-risk chronic lymphocytic leukemia (CLL). Sequential use of chemotherapy and reduced-intensity conditioning has been proposed to improve the treatment outcomes. Fludarabine (30 mg/m(2)/day) and cytarabine (2 g/m(2)/day) for 4 days (combination of fludarabine with cytarabine; FAraC) were used for cytoreduction. After 3 days of rest, reduced intensity conditioning (RIC) was carried out consisting of 4 Gy total body irradiation, 10-20 mg/kg/day antithymocyte globulin for 3 days, and 40-60 mg/kg/day cyclophosphamide for 2 days. The median time of neutrophil engraftment was 16 days. The most frequent toxicities were grades III/IV infections in 12 of 15 cases and gastrointestinal toxicities in 8 of 15 cases. Remission (complete remission + partial remission) was achieved in 14 of 15 patients (93 %), minimal residual disease negativity according to flowcytometric analysis was observed in 10 patients. Nonrelapse mortality after 1 and 2 years was 7 and 13 %, respectively. After the median follow-up from SCT of 30 months, 80 % of patients were alive (12/15), three patients have died, and three relapses occurred. The FAraC-RIC protocol seems to be a promising approach to the treatment of poor-risk CLL with a high response rate of 93 % and favorable progression-free survival and overall survival of 70 and 85 % at 2 years after SCT, respectively. Other prospective clinical trials are needed to confirm the results of this novel therapeutic strategy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / surgery
  • Male
  • Middle Aged
  • Neoplasm, Residual
  • Peripheral Blood Stem Cell Transplantation* / adverse effects
  • Prednisolone / administration & dosage
  • Prospective Studies
  • Recurrence
  • Risk
  • Rituximab
  • Salvage Therapy
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Vincristine / administration & dosage
  • Whole-Body Irradiation

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Immunosuppressive Agents
  • Cytarabine
  • Alemtuzumab
  • Rituximab
  • Vincristine
  • Dexamethasone
  • Cyclophosphamide
  • Prednisolone
  • Vidarabine
  • fludarabine