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 l...

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Bibliographic Details
Published in:	International journal of hematology Vol. 75; no. 5; pp. 493 - 498
Main Authors:	OKAMOTO, Shinichiro, WATANABE, Reiko, ASANO, Shigetaka, IKEDA, Yasuo, TAKAHASHI, Satoshi, MORI, Takehiko, IZEKI, Tohru, NAGAYAMA, Hitomi, ISHIDA, Akaru, TAKAYAMA, Nobuyuki, YOKOYAMA, Kenji, TOJO, Arinobu
Format:	Journal Article
Language:	English
Published:	Tokyo Springer 01-06-2002 Springer Nature B.V
Subjects:	Adult Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - toxicity Biological and medical sciences Bone Marrow Transplantation - methods Bone marrow, stem cells transplantation. Graft versus host reaction Cyclophosphamide - administration & dosage Cytarabine - administration & dosage Female Follow-Up Studies Graft Survival Granulocyte Colony-Stimulating Factor - administration & dosage Hematologic and hematopoietic diseases Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Pilot Projects Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Conditioning - methods Transplantation, Homologous - methods Transplantation, Isogeneic Treatment Outcome Whole-Body Irradiation Human Total body irradiation Prognosis Stem cell Hematopoietic cell Homograft Malignant hemopathy Non myeloablative treatment Myeloproliferative syndrome Chronic Cyclophosphamide Granulocyte colony stimulating factor Oxazaphosphinane derivatives Treatment Nitrogen mustard Chronic myelocytic leukemia Bone marrow Graft Cytosine Conditioning Age
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Summary:	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.
ISSN:	0925-5710 1865-3774
DOI:	10.1007/BF02982112