autologous blood and marrow transplantation - Blog Science ...

726 Chapter 16: Summaries
use of posttransplant interferon but no definite benefit from current purging
techniques. The new flexibly designed EBMT study (by Carella and Apperley) will
randomize patients to receive interferon-based or autologous transplant-based
therapies. In the interferon arm, investigators can elect to use additional cytosine
arabinoside (Ara-C). In the autograft arm patients may be mobilized using ifosfamide,
carboplatin, etoposide (ICE) chemotherapy as used by Carella to select Ph-negative
CD34 cells or receive unmanipulated transplants. The use of improved and highly
sensitive polymerase chain reaction (PCR) techniques described by Goldman has
made it possible to precisely evaluate the clinical significance of extremely low levels
of minimal residual disease in CML after autoBMT. Patients at the lowest levels of
detection after autoBMT appear to have long disease-free intervals.
New treatment approaches
The unique susceptibility of CML to the GVL effect of alloreacting
lymphocytes makes this disease the obvious starting point for evaluating the
curative effect of nonmyeloablative transplants. The presentation by Carella of a
successful outcome after autologous stem cell transplant followed by a "mini"
allotransplant represents an important step in treatment. The success of nonmyeloablative
conditioning treatments and their low toxicity as reported by Giralt and
Slavin begs the question whether the only maneuver required to cure CML is to
establish a donor immune system using just enough conditioning to achieve full
donor lymphocyte chimerism. Another promising area is the continuing effort to
target the bcr-abl fusion product with specific tyrosine kinase inhibitors. So far
progress has been slow, and antisense strategies have fallen out of favor. However,
the tailored tyrosine kinase inhibitors (tyrophostins) described by Carlo-Stella may
soon find a place first in purging of the autograft.
FUTURE DIRECTIONS
The next few years are likely to see an explosion in the use of allogeneic stem
cell transplants using "minitransplants"—low-intensity, nonmyeloablative
preparative regimens. The preliminary data presented at this meeting establish that
such transplants are associated with low morbidity and mortality and that they may
confer a GVL effect. As technology improves, advances in immunotherapy can be
anticipated. In the field of allogeneic transplantation, improved ways of manipulating
the transplant, T cell selection and expansion, and Tk gene insertion should
make targeted T cell therapy a realistic possibility. In the autograft field,
immunologic and pharmacologic purging should become more feasible, but
perhaps more importantly, antitumor responses may be elicited using dendritic cell
therapy, gene-modified tumor vaccines, nonspecific activation with cytokines and
sophisticated humanized toxin-conjugated monoclonal antibody based treatments.