autologous blood and marrow transplantation - Blog Science ...

Champlin, Khouri, and Girat 701
and eight have achieved complete remission. Maximal responses are slow to
develop and gradually occur over a period of several months to 1 year.
The success of nonablative regimens for GVL induction using allogeneic
transplantation requires engraftment of the donor immunocompetent cells and
sufficient time to develop an effective antileukemic response. This approach has
not been successful in patients with refractory acute leukemias; in this setting, the
leukemia generally recurs and progresses rapidly. This strategy may be useful,
however, for consolidation of remission in patients at high risk to relapse. 62
The optimal intensity of the preparative regimen is uncertain, and several factors
must be considered, including aggressiveness of the underlying malignancy,
immunocompetence of the recipient, and genetic disparity between donor and
recipient (Fig. 1). Slavin and co-workers reported use of a more intensive
preparative regimen consisting of busulfan 8 mg/kg, fludarabine, and antithymocyte
globulin, with encouraging preliminary results. 63
This regimen produces marked
myelosuppression and has not been administered without hematopoietic transplantation.
Other lower-dose or nonablative regimens have been proposed. 64
Immunocompromised patients, such as those with advanced CLL, will likely
require less immunosuppressive therapy to achieve engraftment than a fully
immunocompetent recipient. Indolent malignancies may not require cytoreduction,
but it appears necessary to achieve at least a short-term remission in patients with
highly proliferative malignancies, such as acute leukemias and aggressive
lymphomas, to allow development of an effective GVL response.
The optimal use of posttransplant immunosuppressive therapy is also uncertain.
Acute GVHD does occur with these nonablative regimens but has been relatively
mild and controllable. Immunosuppressive therapy given early posttransplant to
6 5
prevent GVHD likely also affects GVL. Effective strategies to separate GVHD
from GVL are critical for the success of this approach to treatment.
The role for nonmyeloablative preparative regimens and induction of GVL is
uncertain. This strategy allows treatment of older and medically infirm patients
Standard dose Maximally
chemotherapy Tolerated
w/o BMT Needs BMT High dose
Flag-ida
FC
PFA
Indolent
Malignancies
t MF BEAM Bu 8/F/ATG Bul6/Cy
Cy/TBI
Aggressive
Malignancies
Figure 1. Intensity of preparative regimen.