autologous blood and marrow transplantation - Blog Science ...

50 Chapter 1 : AML
occur within the first year, and IL-2-responsive lymphocytes have been detected in
the circulation within 2 or 3 weeks after transplantation of autologous marrow or
peripheral blood stem cells, IL-2 has been administered early after the patients have
recovered from transplant-related toxicities at a time when the tumor burden is still
minimal. Several phase I studies have identified the maximum tolerated dose of IL-
2 that can be administered after autologous transplant and have documented that
these doses have immunostimulomodulatory effects. 1718
We therefore conducted
this study to determine the feasibility of giving high-dose IL-2 after a radiationbased
transplant regimen early after transplant and have observed tolerable
toxicities and encouraging disease-free survival for such patients. Patients usually
exhibit transient early lymphopenia followed by a rebound of lymphocytosis after
stopping IL-2, something that was also observed in our own patient population.
This rise reflects an increase in the number of cells expressing CD8-positive T cells
and CD16-positive and CD56-positive activated natural killer cells with
concomitant enhanced cytotoxicity for in vitro tumor targets.
In our previous studies with autologous transplant using marrow, the diseasefree
survival was 49% for those patients on the intent-to-treat analysis and 61% for
those patients who actually underwent transplantation. 15
Disease-free survival in
that study was not correlated with cytogenetic results of the leukemia at the time of
diagnosis. Patients who required two courses of induction therapy had an inferior
outcome to those patients with good risk cytogenetics. To try to improve the
efficacy of the autologous transplant procedure, several modifications were made
in the current protocol. The first was the addition of idarubicin to high-dose Ara-C
consolidation. Most patients on the study reported here underwent consolidation
with Ara-C and idarubicin in an attempt to provide a better in vivo purge before the
collection of peripheral blood stem cells. Although some investigators hypothesized
that peripheral blood stem cells have a higher relapse rate than marrow, this
was not seen in our own study, and is consistent with observations from other
studies. 19
One of the issues in this study was the feasibility of collecting adequate
numbers of stem cells in patients who underwent consolidation of this intensity.
Approximately 50% of the patients had also received induction chemotherapy with
high-dose Ara-C. The fact that most patients could undergo collection of stem cells
suggests that this is a feasible way of reducing the tumor burden in a patient who
is undergoing stem cell collection in preparation for autologous transplant.
Once patients had completed cell collection, they were treated with an
autologous stem cell transplant regimen using total body irradiation, VP-16, and
cyclophosphamide, a program that we have used in our previous study that is
tolerable for patients up to the age of the early 60s. As noted in the Results, the
recovery rate after hematopoietic cell transplantation was relatively short, with
good recovery of neutrophils and adequate recovery of platelets. The delay in
platelet recovery (to >50,000) reflects the thrombocytopenic effect of IL-2 given