1. BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning
- Author
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Chiara Gentilini, Thoralf Lange, Effie W. Petersdorf, R. Krahl, U Hegenbart, Haifa Kathrin Al-Ali, Sabine Leiblein, Michael W. Deininger, Ronald Brand, Dietger Niederwieser, Rainer Storb, L Uharek, Wolfram Poenisch, and University of Groningen
- Subjects
Male ,Oncology ,Cancer Research ,Transplantation Conditioning ,Fusion Proteins, bcr-abl ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,VERSUS-HOST-DISEASE ,RNA, Neoplasm ,BCR-ABL ,Hematology ,Reverse Transcriptase Polymerase Chain Reaction ,CHRONIC MYELOGENOUS LEUKEMIA ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Middle Aged ,CHIMERISM ,Prognosis ,Combined Modality Therapy ,Fludarabine ,nonmyeloablative ,Cyclosporine ,Female ,Vidarabine ,Whole-Body Irradiation ,medicine.drug ,medicine.medical_specialty ,FUSION TRANSCRIPT ,QUANTITATIVE RT-PCR ,POLYMERASE-CHAIN-REACTION ,Hematopoietic System ,MINIMAL RESIDUAL DISEASE ,Biology ,Philadelphia chromosome ,Sensitivity and Specificity ,stem cell transplantation ,IMATINIB ,GvL effect ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,RNA, Messenger ,KINETICS ,Imatinib ,Mycophenolic Acid ,medicine.disease ,Minimal residual disease ,BONE-MARROW-TRANSPLANTATION ,Transplantation ,clinical results in chronic leukemia ,Cancer research ,Neoplasm Recurrence, Local ,Chronic myelogenous leukemia - Abstract
Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2Gy total-body irradiation in combination with (n = 14) or without (n = 3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 x 5mg (n = 2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman(R) RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P = 0.02) and slow reduction of BCR-ABL transcripts at day 28 (P = 0.006) and day 56 (P = 0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.
- Published
- 2004