Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

eceived a second tk-DLI after GCV discontinuation. T cell engraftment was documented
in all patients, with a kinetic comparable to the first infusion. Two patients
of this series received unmodified DLI and died of refractory GvHD.
15.9
Reduced Intensity versus Conventional Conditioning Regimens
The use of allogeneic BMT is limited by the high treatment-related mortality. The
toxicity of the conditioning regimen plays a crucial role in the development of most
of the transplant-related complications. The intensity of conditioning regimen is critical
in determining organ toxicity and damage to the mucosal barrier; both these
side effects of conventional intensity conditioning regimen have also been correlated
with an increased incidence of acute GvHD. The occurrence of GvHD plays a crucial
role in influencing treatment-related morbidity/mortality. The incidence of GvHD in
patients older than 45 years undergoing allogeneic transplantation with conventional
conditioning is around 50±60 % [33]. In addition, it should emphasized that treatment
mortality as high as 80 % has been reported after conventional allografting in
patients failing a previous autograft [34].
Very recently, the use of non-ablative regimens has been proposed as an alternative
strategy for selected patients with advanced hematologic malignancies. The relatively
low toxicity profile of this approach has allowed the treatment of older patients with
concomitant organ dysfunction. Analysis of preliminary data has shown that such a
strategy has proven to be effective in giving a sustained engraftment and in producing
some complete responses; in particular, in low-grade, mantle cell lymphomas,
Hodgkin's disease and multiple myeloma. In cohorts of high-risk patients, many
authors have shown that treatment-related mortality was lower than expected with
conventional conditioning regimens [35±43].
Solid tumors represent an area of major interest in which the antitumor effect is under
investigation. After sporadic reports of GvT after allogeneic transplants in breast
cancer, some phase II trials are ongoing in metastatic renal, ovarian, colon and prostate
cancer [44, 45]. More than 150 patients have been reported to the EBMT registry
and the first available results in renal carcinomas are encouraging. However, the efficacy
of this procedure remains uncertain for other potential indications.
References
1 Ringden O, Horowitz MM, Gale RP,
et al. Outcome after allogeneic bone
marrow transplant for leukemia in
older adults. J Am Med Ass 1993; 270:
57±60.
2 Armitage JO. Bone marrow transplantation.
N Engl J Med 1994; 330: 827±
838.
References
3 Klingemann HG, Storb R, Fefer A,
et al. Bone marrow transplantation in
patients aged 45 years and older. Blood
1986; 67: 770±776.
4 Appelbaum FR. Hematopoietic cell
transplantations immunotherapy. Nature
2001; 411: 385±389.
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