BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning.
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 2 Gy 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 5 mg (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.
Lange
T
T
Division of Hematology and Oncology, University of Leipzig, Germany. langet@medizin.uni-leipzig.de
Deininger
M
M
Brand
R
R
Hegenbart
U
U
Al-Ali
H
H
Krahl
R
R
Poenisch
W
W
Uharek
L
L
Leiblein
S
S
Gentilini
C
C
Petersdorf
E
E
Storb
R F
RF
Niederwieser
D
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006413:Hematopoietic System / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016572:Cyclosporine; D016044:Fusion Proteins, bcr-abl; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine