Autologous Bone Marrow Transplantation - Blog Science Connections

76 ABMT in AML With Monoclonal Antibodies
patients) or high-dose cytarabine. Two of these patients recently underwent a
second ABMT, with busulfan and cyclophosphamide used as induction
therapy (16). At the present time, both patients have engrafted and are
surviving disease free at 2 and 4 months posttransplantation. The three
patients who received transplants during CR1 are all disease free 1, 5, and 7
months later, the latter two with normal blood counts. The first patient is early
in the posttransplantation course but is demonstrating engraftment.
Since patients 6 to 16 are a relatively homogeneous group (in CR2 and
CR3), their survivals were analyzed separately (17). Survival curves (relapse
free and overall) for these patients are shown in Figures 1 and 2. Actuarial
median relapse-free survival was 21 months. Overall actuarial median
survival has not been attained.
DISCUSSION
High-dose chemotherapy, with or without TBI, with bone marrow rescue
offers patients with AML a greater chance of cure than other treatment
combinations. Although it has not been proved that autologous bone marrow
must be treated in some manner to remove residual leukemic cells, this
conclusion is supported by the high relapse rates found in previous studies
(18). The results reported here indicate that successful engraftment can be
accomplished by using the particular MAbs (plus C) that we selected for
marrow treatment. Although 2 of the 16 patients did not demonstrate
adequate recovery of platelets, in general, engraftment of the three major
hematopoietic lines was within acceptable time limits in most patients. It is
difficult in an uncontrolled phase I and II study to draw conclusions regarding
the efficacy of the marrow treatment in preventing relapse. The relapse rate in
allogeneic BMT during first relapse or CR2 is as high as 50% (4). Our 46%
actual relapse rate, albeit with a relatively small sample is consistent with that
of other studies. A recent report from the Johns Hopkins Oncology Center
about the use of 4-hydroperoxycyclophosphamide to treat marrow from AML
patients in CR2 or CR3 showed an actuarial relapse rate of 43% in 25 patients
(6). Final conclusions regarding the relative efficacy of ABMT with and
without marrow treatment will depend on sample size, length of follow-up,
and ultimately on randomized controlled studies that minimize selection bias.
A trial of ABMT in CR1 is attractive because a lower rate of relapse from
allogeneic BMT has been documented in CR1, demonstrating that successful
eradication of the leukemic clone by the preparative regimen is more effective
then. Thus, we are directing our efforts to early institution in CR1 of ABMT
with MAb and C treatment. Again, long follow-up and, ultimately, controlled
studies will probably be necessary to prove conclusively the efficacy of this
procedure. Cooperative group studies may offer the setting for such studies.
Since we used an immunologic method in our in vitro purging protocol, a
question could be raised about the escape of antigen-negative variants of the