Autologous Bone Marrow Transplantation - Blog Science Connections

ABMT Timing in Lymphoma 291
in a mixture of 5% DMSO, 6% HES, and 4% human albumin can be easily
cryopreserved by placing it directly into a -80°C freezer and subsequently
transferring it into the liquid nitrogen tank (29). After rapid thawing, the
marrow is immediately infused into the patient without any additional
treatment. We obtained suitable engraftment in all our patients who survived
the immediate posttransplantation period in this study. The cell dose and
viability of the cells infused is detailed in Table 3. One patient's platelet count
took 121 days to increase to over 50,000/mm 3 , but none of the patients has
required any blood product support after the first 40 days.
Role of Marrow Purging
The therapeutic benefit of bone marrow purging in the animal model
systems is well established (30) and is easy to prove because of the availability
of inbred strains of animals and the ability to work with defined numbers of
malignant cells. Significant data are also available demonstrating the ability to
purge human marrow in vitro (33,34,52,53), but the benefit in clinical trials is
hard to prove because of the difficulty in detecting a minimal number (< 1 %) of
neoplastic cells in the bone marrow. Perhaps newer techniques, such as
preferential tumor cell growth (54,55), molecular probes, or specific antibodies
against the neoplastic hematopoietic cells will help detect small numbers
of lymphoma cells and also aid in developing better methods for
purging. Another approach to proving the clinical usefulness of purging is to
compare outcome of patients who receive purged marrow and that of those
who receive unpurged bone marrow, but such studies require large numbers
of patients and are subject to statistical uncertainties because of variability in
prognostic factors.
Among the various chemotherapy drugs we evaluated, we found 4-HC to
be the best for purging marrow of B-cell lymphoma (34) and acute myelogenous
leukemia cells (33) in vitro. Under the optimum conditions
developed, 4-HC was found to give a four- to five-log reduction of the neoplastic
cells with only moderate damage to the normal bone marrow progenitors
(32-34). We therefore decided to evaluate 4-HC for clinical phase I
purging trials. So far the number of patients entered into this ongoing clinical
trial is small, but we have found that the patients have had no problem with
bone marrow engraftment after purging with 120 ^iM of 4-HC for 30 minutes.
Clinical trials using 4-HC-purged marrow for patients with acute leukemia
have also shown encouraging results (31,37).
Our results demonstrate that intensive chemotherapy and TBI followed
by ABMT is well tolerated in the patient population treated. The therapeutic
advantage is most significant for the patients who receive ABMT after induction
therapy when they are in a CR or PR; 11 out of 14 patients in this group
remain disease free with a median follow-up of 31 + months. This group of
patients has done markedly better than our historical control group of
patients with the same unfavorable prognostic features. More intensive