Acute Leukemias - Republican Scientific Medical Library

a 17.6 · Long-Term Complications of Allogeneic SCT 225
Table 17.5. Risk of relapse following non-T-cell depleted allogeneic transplantation in ALL
Study No. patients Risk of relapse (%)
Doney, 1991 [20] 192 (SCT in CR2) No GVHD
80
Grade II-IV GVHD
40
Sullivan, 1989 [72] 200
(SCT in CR) No GVHD 56
Acute GVHD 27
Acute & chronic GVHD 22
(SCT in relapse) No GVHD 81
Acute GVHD 39
Acute & chronic GVHD 43
Horowitz, 1990 [73] 349 (SCT in CR1) No GVHD 44
(IBMTR) Acute GVHD 17
Chronic GVHD 20
Acute & chronic GVHD 15
Direct and indirect evidence suggests that donor T
cells and NK cells are primary mediators of GVM.
The target antigens for the GVM response are unknown.
It is difficult to generate a T-cell response to lymphoblasts.
ALL cells do not express costimulatory molecules
and are poor stimulators of T-cell reactivity.
G-CSF mobilized PBSC have also been investigated
as a source of donor lymphocytes for adoptive therapy.
The numbers of T cells and NK cells found in PBSC are
comparable to those present in a DLI. Eleven patients
(four CML, five AML, one ALL) received PBSC postrelapse;
all patients with acute leukemia received cytoreductive
therapy prior to PBSC. All six patients with
acute leukemia achieved a CR, with median remission
duration of 24 weeks [77]. Perhaps the success noted
in this study resulted, in part, from the cytoreduction
prior to DLI, which may play an important role in the
DLI efficacy. DLI has been combined with IL-2 in an attempt
to augment efficacy in ALL patients. Four patients
with relapsed ALL were treated with this approach
and all responded [77]. No conclusions can be drawn
from such small series of patients. However, these results
are intriguing, and suggest that adoptive cell therapy
and associated immunomodulatory therapy may be
further developed as a treatment modality, and may
eventually become a viable salvage option for ALL relapses
following allogeneic transplants.
17.6 Long-Term Complications of Allogeneic SCT
Socie et al. analyzed the characteristics of 6691 patients
listed in the IBMTR who underwent allogeneic SCT for
AML, ALL, CML, or aplastic anemia between January
1980 and December 1993 [78]. The median duration of
follow-up was 80 months. Mortality rates in this cohort
were compared with those of an age-, sex-, and nationality-matched
general population. All patients were free
of disease 2 years posttransplant, with 89% survival at
5 years. Mortality rates remained significantly higher
than the general population throughout the study
among patients who underwent transplantation for
ALL or CML, and through the ninth year for patients
who had AML. Specifically, for patients with ALL, the
relative mortality rate was 20.1 2 years after transplantation,
25.9 5 years after transplantation, and 15.4 10 years
after transplantation. Not surprisingly, recurrent leukemia
was the chief cause of death for patients who underwent
SCT for leukemia and GVHD among those in
either disease category, followed by infection, new cancer,
and organ failure. Older age was associated with an
increased risk of relapse in the ALL group, with 48% relapse
observed in ALL compared with 11% relapses in
the overall group. Chronic GVHD was the second leading
cause of death overall, with 23% observed in the ALL
cohort. A low incidence of secondary cancer was reported
overall (6%), with a slightly higher rate observed