Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia

• Published in: Bone marrow transplantation (Basingstoke) Vol. 22; no. 11; pp. 1029 - 1033
• Main Authors: KRÖGER, N, KRÜGER, W, DE WIT, M, SCHUCH, G, BARTELS, H, BRAUMANN, D, KUSE, R, KABISCH, H, ERTTMANN, R, ZANDER, A. R, WACKER-BACKHAUS, G, HEGEWISCH-BECKER, S, STOCKSCHLÄDER, M, FUCHS, N, RÜSSMANN, B, RENGES, H, DÜRKEN, M, BIELACK, S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-12-1998
• Subjects: Abl protein; Acute lymphoblastic leukemia; Adolescent; Adult; Antineoplastic agents; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Phytogenic - administration & dosage; Autografts; BCR protein; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - adverse effects; Busulfan; Child; Child, Preschool; Chromosomes; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Conditioning; Cyclophosphamide; Cyclophosphamide - administration & dosage; Disease-Free Survival; Etoposide; Etoposide - administration & dosage; Female; Fusion protein; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation; Humans; Irradiation; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Lymphatic leukemia; Male; Medical sciences; Middle Aged; Mucositis; Patients; Pharmacology. Drug treatments; Philadelphia chromosome; Radiation; Recurrence; Stem cell transplantation; Stem cells; Survival; Toxicity; Transcription; Transplantation; Transplantation Conditioning - methods; Transplantation, Autologous; Transplantation, Homologous; Transplants; Whole-Body Irradiation; Chromosomal aberration; Antineoplastic agent; Prognosis; Stem cell; Hematopoietic cell; Homograft; Intensification; Blood; Autograft; Isomerases; Lymphoproliferative syndrome; Bone marrow; Genetics; Graft; Whole body; Acute lymphocytic leukemia; Antimitotic; Chromosome translocation; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Acute; Etoposide; Enzyme inhibitor; Malignant hemopathy; Radiotherapy; Philadelphia chromosome; Podophyllotoxine derivatives; Alkylating agent; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Nitrogen mustard; Cytogenetics; Abnormal chromosome; Combined treatment
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1701498

We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30-45 mg/kg) and cyclophosphamide (120 mg/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan (16 mg/kg) instead of TBI. Nineteen patients were transplanted in 1CR, two in 2CR, one in 1PR and two in relapse. Major toxicity was mucositis grade II according to the Bearman scale in all patients. The treatment-related mortality was 25%, mainly due to infection or GVHD after allogeneic transplantation. After a median follow-up of 45 months (range 2-93), nine patients (37.5%) remain alive in CR. Nine patients (37.5%) relapsed and eight (33.3%) of these subsequently died. After autologous transplantation, four of five patients (80%) relapsed and died. Late relapse was seen after allogeneic, as well as autologous transplantation, at 33 and 59 months, respectively. The Kaplan-Meier estimate of leukemia-free survival for all patients is 38% at 3 years (95% CI: 18-58%) and 35% at 5 years (95% CI: 15-55%). For allogeneic transplants in first CR (n = 15) the estimate of disease-free survival was 46% at 3 years (95% CI: 19-73%) and 34% at 5 years (95% CI: 17-51%). Patients aged below 30 years had a better estimated overall survival at 3 years (61% vs 11%, P < 0.001). The bcr-abl fusion transcript (p210 vs p190 vs p210/190) did not affect disease-free or overall survival. In our experience, an intensified conditioning regimen seems to improve the results of bone marrow transplantation in patients with Ph+ acute lymphoblastic leukemia. However, the high relapse rate warrants novel approaches to enhance anti-leukemic efficacy.