autologous blood and marrow transplantation - Blog Science ...

Giralt, Khouri, and Champlin
seven évaluable patients had cytogenetic progression during the first 3 months after
transplant, one patient remains in complete cytogenetic remission 6 months after
transplant, and the other relapsed 9 months posttransplant. All five of the
progressing patients had immunosuppression withdrawn and received further
infusion of donor lymphocyte with no responses reported to date.
These preliminary results suggest that the combination of fludarabine,
idarubicin and Ara-c, although effective in achieving remissions, may not be
optimal for CML. However, further study in more patients in nontransformed
phases and longer follow-up is needed.
To try to improve on disease control, at M.D. Anderson Cancer Center we have
explored the combination of the purine analogs fludarabine or 2-CDA with
melphalan for patients with advanced hematologic malignancies who were
considered poor candidates for a conventional allogeneic progenitor cell
transplant. 11
From February 1996 to April 1998, a total of 63 patients with a variety
of hematologic malignancies have been treated. Patient and treatment characteristics
are summarized in Table 2. All patients received unmanipulated donor bone marrow
or stem cells and FK506/methotrexate combinations for GVHD prophylaxis.
Fifty-six patients had neutrophil recovery at a median of 14 days (range 9-35),
and 40 patients recovered platelet transfusion independence at a median of 22 days
(range 9-118). All engrafting patients except one had documentation of >80%
donor cell engraftment by day 30, with one instance of autologous reconstitution
and one case of secondary graft failure. In this group of very poor prognosis
patients ineligible for conventional transplant, the 100-day transplant-related
mortality (TRM) was 50% (31 of 63), with four of eight patients in the 2-
CDA/melphalan arm dying from multiorgan failure, leading us to close this
treatment arm. The overall survival for patients in CR1 or untreated first relapse
was 68% at 1 year, vs. 9% for patients with more advanced or refractory disease
(Fig. 2). We concluded that fludarabine/melphalan combinations can allow
engraftment of allogeneic progenitor cells including cells obtained from matched
unrelated donors. Furthermore, this strategy can produce long-term disease control
in patients with hematologic malignancies early in the course of their disease at an
acceptable risk and toxicity in patients ineligible for conventional myeloablative
transplant therapies. Treatment-related mortality and disease recurrence limits the
usefulness of this approach in patients with refractory disease.
MINITRANSPLANTS FOR LYMPHOID MALIGNANCIES
The use of allogeneic transplantation is limited in patients with lymphoid
malignancies, such as chronic lymphocytic leukemia or lymphomas, because they
typically are older. We have evaluated the induction of graft-vs.-leukemia as
primary therapy for patients with lymphoid malignancies who are considered poor
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