Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase.
Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.
Okamoto
Shinichiro
S
Department of Medicine, Keio University School of Medicine, Tokyo, Japan. okamoto@sc.itc.keio.ac.jp
Watanabe
Reiko
R
Takahashi
Satoshi
S
Mori
Takehiko
T
Izeki
Tohru
T
Nagayama
Hitomi
H
Ishida
Akaru
A
Takayama
Nobuyuki
N
Yokoyama
Kenji
K
Tojo
Arinobu
A
Asano
Shigetaka
S
Ikeda
Yasuo
Y
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D016026:Bone Marrow Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide