autologous blood and marrow transplantation - Blog Science ...

Martin, Atta, and Hoelzer 85
adult ALL patients are characterized by the presence of the t(9;22) Philadelphia
translocation and/or the corresponding BCR-ABL rearrangement as a diseasespecific
clonal marker. 1,3_6
Conventional chemotherapy induces complete
morphologic remissions in 60-70% of patients but does not achieve stable longterm
remissions, with few, if any exceptions. 2,6
Most patients with BCR-ABLpositive
ALL who do not proceed to bone marrow or stem cell transplantation
rapidly relapse and eventually succumb to their disease. Allogeneic bone marrow
transplantation, accepted as the treatment of choice if an HLA-matched family
donor is available, cures about 30-40% of patients. 7-9
Few, but encouraging data
with 45% long-term disease-free survivors and low relapse rates are reported after
transplantation from matched unrelated donors (MUD) in young patients with a
median age of 25 years, supporting evidence that a graft-vs.-leukemia-effect is
likely to contribute to preventing relapse. 10
However, the median age of 45 years
in BCR-ABL-positive ALL patients as documented in the German multicenter
adult ALL (GMALL) 2,6
and other large multicenter studies precludes a majority of
patients from receiving MUD-transplants. Thus, for older patients without a
matched sibling donor, autologous transplantation remains the best chance of cure.
In 1992, the GMALL study group initiated a prospective autograft program
including in vitro purging and sequential monitoring of residual disease by
semiquantitative RT-PCR for patients with BCR-ABL +
ALL without a compatible
HLA-identical donor. 6,11
PATIENTS AND METHODS
Patients
From 1992 through 1998, a total of 42 patients with BCR-ABL-positive ALL in
morphologic complete remission and a median age of 45 years were recruited from
a total of 25 referring hospitals participating in the GMALL trials 04/89 or 05/93. 2
Autologous bone marrow was harvested in 20 patients, 12,13
whereas PBSCs were
collected after induction phase II (high-dose cytosine arabinoside and
mitoxantrone) in 22 patients. 14
Thirty-four patients with a median age of 44 years
proceeded to either single (n=25) or double (n=9) autologous transplantation as
detailed in Fig. 1.
Quantification of residual BCR-ABL-positive cells
Residual BCR-ABL-positive cells were determined using a semiquantitative
limiting-log dilution RT-PCR as described in detail previously. 12,14
The level of
residual BCR-ABL-positive cells before and after purging was expressed as log 10
of the highest dilution with a positive PCR signal.