Myeloablative Allogeneic

Allogeneic SCT offers several theoretical advantages over autologous SCT in CLL. First, contamination of the stem cell source and inadequate stem cell collection are not obstacles for allogeneic SCT. Secondly, the use of an allogeneic donor allows for an immunological graft-versus-leukemia (GVL) effect. Although GVL is not as pronounced in allogeneic SCT for CLL as it is for CML, studies have demonstrated that this immunological effect is still important.00-00 Limited data suggest that TBI-containing conditioning regimens are superior to busulphan and cytotan (BuCy) in CLL. A small study of 25 patients by the Seattle group revealed a 100-day TRM of 57% for BuCy (n = 7), compared to 17% for TBI regimens (n = 18). Five-year actuarial survival was 56% for 14 patients transplanted with TBI regimens from 1992 to 19 9 9.00-00 An MD

Anderson study of Cy/TBI in 28 CLL patients observed a 100-day TRM of 11%. Five-year PFS and OS were 78% and 78%, respectively, for chemo-sensitive patients, compared to 26% and 31% for refractory patients.00-00 Thus, TBI-containing myeloablative regimens offer the potential of long-term survival with acceptable TRM. Although results are superior for chemo-sensitive patients, myeloablative allogeneic SCT benefits a substantial minority of refractory patients.

Although prospective studies of myeloablative allo-geneic SCT for CLL have been limited by small sample size and inadequate follow-up, large, retrospective multi-center registry analyses have examined the use of allogeneic SCT in large numbers of CLL patients.00-00 A retrospective EBMT study of 135 patients showed a 54% 3-year OS and 40% 100-day TRM.00-00 Similar findings were reported by the IBMTR, with a 45% 3-year OS and 30% 100-day TRM in 242 patients. 00-00 Although patients in these analyses were relatively young (median age 45 and 47), with a median of only two prior therapies, the high TRM may be explained in part by the late stage of the disease in many of these patients. Median time from diagnosis to SCT was 41 and 46 months in the two studies, respectively,00-00 and 37% of patients in the EBMT study were chemo-refractory entering transplant.00-00 Although there are no randomized studies, a retrospective comparison showed a 3-year DFS of 57% for allogeneic SCT, versus 24% for purged autologous SCT.00-00

Thus, myeloablative allogeneic SCT may offer superior DFS in CLL, compared to autologous SCT. Although 3-year DFS after allogeneic SCT is approximately 50%,00-00 longer follow-up is needed to determine if this disease remission proves durable over time. However, the advantage in markedly decreased relapse rates with allogeneic SCT is offset by a higher TRM,00-00 decreasing enthusiasm for this treatment modality in CLL, which is often an indolent disease. Limited data indicate that Bu/Cy may be particularly toxic in this population; in contrast, TBI regimens appear to induce acceptable TRM.00-00 In order to preserve the immunological GVL effect while reducing TRM, the focus of clinical SCT research in CLL has turned to non-myeloablative allogeneic SCT in recent years (discussed below). However, the ability of mye-loablative allogeneic SCT to achieve DFS in a significant minority of chemo-refractory patients indicates that a full allogeneic SCT should be considered for this group of patients. Cy/TBI or a similar TBI regimen should be considered for any CLL patient undergoing full alloegeneic SCT.

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