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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 384-389
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
Ahmet H. Elmaagacli,
Dietrich W. Beelen,
Bertram Opalka,
Siegfried Seeber, and
Ulrich W. Schaefer
From the Departments of Bone Marrow Transplantation and Internal
Medicine (Tumor Research), University Hospital of Essen, Essen,
Germany.
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.
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