Nonmyeloablative Allogeneic

The major focus of clinical transplant research in CLL has shifted to non-myeloablative allogeneic SCT. Ideally, the GVL effect of allogeneic SCT can be har nessed, while reducing TRM from acute GVHD, acute infection and organ toxicity associated with myeloablative SCT. Although many reports of non-myeloablative SCT have included CLL with other indolent lympho-proliferative diseases, such as follicle center lymphoma, several studies have specifically examined CLL.00-00 Fludarabine, busulfan, and ATG were administered to 30 German CLL patients; the stem cell source was a matched related (n = 15) or unrelated (n = 15) donor.00-00 Grade 2-4 acute GVHD was observed in 56% patients, while 75% developed chronic GVHD.00-00 Responses were seen in 93% patients, with 40% achieving CR. Of note, it took up to 2 years for patients to achieve CR, suggesting a GVL effect. All patients achieved a molecular CR by PCR, but only six patients were in continued molecular CR after a median follow-up of two years. Two-year TRM, PFS, and OS were 15%, 67%, and 72%, respectively.00-00

The EBMT retrospectively examined 77 CLL patients who received a variety of non-myeloablative conditioning regimens, followed by allogeneic SCT. 00-00 Median follow-up was 18 months. Complete chimerism and best response were achieved a median of 3 months post-SCT. One-year TRM was 18%, and the 2-year probability of relapse was 31%. Two-year DFS and OS were 56% and 72%, respectively. Nineteen patients received donor lymphocyte infusion (DLI) for relapse or incomplete donor chimerism, but only seven responded to DLI (37%). Unfortunately, the interpretation of this study was compromised by the heterogeneity of conditioning regimens, and the use of ATG or Campath-1H for T-cell depletion in 40% of patients.

A recent, small German study indicated that non-myeloablative allogeneic SCT may be superior to autologous SCT in obtaining clinical and molecular remissions in high-risk CLL patients with unmutated IgVH, due to a GVL effect. Seven of nine patients (78%) became negative by PCR for allele-specific IgVH after day + 100 post-SCT; attainment of molecular CR occurred after DLI or development of chronic GVHD. In contrast, only six of 26 control CLL patients (23%) achieved a PCR-negative state after autologous SCT. 00-00 Thus, an immunological GVL effect appears to be important in CLL and may confer a long-term survival advantage for allogeneic over autologous SCT, given sufficient time. Finally, the MD Anderson administered fludarabine and cyclophosphamide to 17 patients, 10 of whom also received rituximab, followed by allogeneic SCT. 00-00 Ten patients subsequently received DLI for persistent CLL; 7 achieved a CR, and 2 a PR. Of the 17 patients, 12 achieved a CR and 4 a PR, for an overall response rate of 94%. Interestingly, OS was 100% for patients who received rituximab with conditioning, compared to 14% for patients who did not. Although these results were intriguing, this was a small study, and it is unclear how rituximab may augment or facilitate the GVL effect of allogeneic SCT in CLL.

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