title: Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia.
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.
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Jihlavska 20, Brno, Czech Republic. mkrejci@fnbrno.cz
authors.forename: Marta
authors.initials: M
authors.lastname: Krejci
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Olga
authors.initials: O
authors.lastname: Stehlikova
authors.forename: Jana
authors.initials: J
authors.lastname: Chovancova
authors.forename: Boris
authors.initials: B
authors.lastname: Tichy
authors.forename: Hana Skuhrova
authors.initials: HS
authors.lastname: Francova
authors.forename: Milan
authors.initials: M
authors.lastname: Navratil
authors.forename: Miroslav
authors.initials: M
authors.lastname: Tomiska
authors.forename: Ondrej
authors.initials: O
authors.lastname: Horky
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D012008:Recurrence; D012306:Risk; D000069283:Rituximab; D016879:Salvage Therapy; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014750:Vincristine / Q000008:administration & dosage; D014916:Whole-Body Irradiation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D003561:Cytarabine; D000074323:Alemtuzumab; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D011239:Prednisolone; D014740:Vidarabine; C024352:fludarabine