Abstract
Reduced-intensity allogeneic hematopoietic cell transplantation (HCT) is increasingly considered as a therapeutic option for young patients with advanced chronic lymphocytic leukemia (CLL). We report 59 consecutive CLL patients who underwent allogeneic HCT following fludarabine and melphalan conditioning at four different institutions. For graft-versus-host disease (GVHD) prophylaxis, 38 patients (Cohort 1) received alemtuzumab (20–100 mg) and cyclosporine; and 21 patients (Cohort 2) received cyclosporine plus methotrexate or mycophenolate. Donors were 47 HLA-matched siblings and 12 unrelated volunteers, 6 of whom were mismatched. Median age at transplant was 53 (range, 34–64) years and median number of previous chemotherapy regimens was 3 (1–6), with 39% of patients being refractory to fludarabine. Nine patients had previously failed an autologous HCT. Fluorescent in-situ hybridization and IgVH mutation status data were available in 33 (56%) and 31 (53%) patients, respectively, being unfavorable (17p- or 11q-) in 22 (67%) and unmutated in 24 (77%) of them. All but 1 patient engrafted, and the median interval to neutrophil recovery (> 0.5 × 109/l) was 14 (range, 10–36) days. Twenty patients (34%), mostly from Cohort 1, received escalated donor lymphocyte infusions due to mixed chimerism or disease relapse. The overall complete response rate among 53 patients with measurable disease at the time of transplantation was 70%, whereas 21% had stable disease. Grade II-IV acute GVHD was observed in 14 (37%) and 12 (57%) patients from Cohorts 1 and 2, respectively (P = 0.17). Extensive chronic GVHD was observed in 3 (8%) and 10 (48%) patients from Cohorts 1 and 2, respectively (P < 0.01). The incidence of cytomegalovirus reactivation was not significantly different between cohorts (67% vs 47%, P = 0.23). With a median follow-up of 36 (range, 3–99) months for survivors, 18 (30%) patients have died, 3 of progressive disease and 15 of transplant-related complications. The 3-year overall survival (OS), progression-free survival (PFS) and non-relapse mortality were 66% (95% CI 48–84%), 38% (20–56%) and 21% (8–34%), respectively, for Cohort 1 and 65% (44–86%), 54% (32–76%) and 29% (10–48%) for Cohort 2 (P = 0.66; P = 0.33; and P = 0.53). Despite low patient numbers, alemtuzumab seemed particularly effective for unrelated donor recipients, with a 3-year OS and PFS of 54% and 40% for Cohort 1; and 33% and 0% for Cohort 2 (P = 0.02 and P = 0.07). In conclusion, results with reduced-intensity allogeneic HCT are promising for these poor-prognosis patients. Furthermore, the alemtuzumab-based regimen was effective in reducing the chronic GVHD rate with no negative effect on NRM, PFS or OS.
Tandem Autologous and Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation (HCT) from HLA-matched Related Or Unrelated Donors for Advanced Lymphoma Or Chronic Lymphocytic Leukemia (CLL)
