The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow.
The detection of residual molecular and cytogenetic disease was prospectively compared in patients with Philadelphia-chromosome (Ph1) positive first chronic phase chronic myelogenous leukemia (CML) who underwent allogeneic transplantation of unmanipulated peripheral blood stem cells (PBSCT) (n = 29) or bone marrow (BM) (n = 62) using genotypically HLA-identical sibling donors or partially HLA-matched extended family donors. A molecular relapse (MR), as defined by two consecutive positive polymerase chain reaction (PCR) assays for the detection of M-bcr-abl transcripts in a 4-week interval, was found in two of 29 (7%) patients after PBSCT compared with 20 of 62 (32%) patients after bone marrow transplantation (BMT). This corresponds to a 4-year molecular relapse estimate (+/- standard error) of 7% +/- 5% after PBSCT and of 44% +/- 8% after BMT (P <.009). With identical follow-up periods of survivors in both patient subsets between 6 and 55 months (median, 28 months), 14 of the 20 patients with MR after BMT progressed to an isolated cytogenetic (n = 10) or a hematologic (n = 4) disease recurrence, resulting in a 4-year cytogenetic relapse estimate of 47% +/- 11%, while none of the patients after PBSCT has so far relapsed (P <.006). Multivariate analysis including all potential influencial factors of posttransplant disease recurrence identified the source of stem cells (P <.02) as the only independent predictor of molecular relapse. In conclusion, this prospective comparison of molecular and cytogenetic residual disease demonstrates that peripheral blood stem cell transplants have a more pronounced activity against residual CML cells than bone marrow transplants. Prospective randomized trials comparing PBSCT and BMT in patients with first chronic phase Ph1-positive CML are strictly required to further substantiate differences in the antileukemic activity of the two stem cell sources.
Elmaagacli
A H
AH
Departments of Bone Marrow Transplantation and Internal Medicine (Tumor Research), University Hospital of Essen, Essen, Germany.
Beelen
D W
DW
Opalka
B
B
Seeber
S
S
Schaefer
U W
UW
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D016026:Bone Marrow Transplantation; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D005858:Germany / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000648:ultrastructure; D011446:Prospective Studies; D012008:Recurrence; D012306:Risk; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl