Allogeneic Transplant with Reduced Intensity Conditioning Regimens (RIC) Could Reverse Poor Prognosis of Unmutated Igvh, 11q- or 17p- Abnormalities in B-Cell Chronic Lymphocytic Leukemia (B-CLL).

In the present study we have evaluated the outcome of reduced intensity conditioning allogeneic transplant (RIC) in 31 patients with symptomatic B-CLL. 74% of the patients were older than 50 years, and 70% had previously received purine analogues, with 38% of them relapsing or progressing after treatment. At transplant, 83% had active disease. Data from VH homology, FISH analysis, CD38 expression and ZAP 70 expression was available in 21, 27,12 and 2 patients, respectively. 21 out of 31 were conditioned with melphalan plus fludarabine according to our GETH 99–051 protocol; the other patients received other fludarabine-containing regimens. All patients engrafted. Early complete donor chimerism (CDC) (days +28) in Bone Marrow (BM) was observed in 67% of patients; all except two relapsing patients remained CDC after day +180. With a median follow up of 36 months (1–63), 9 patients have died, two of them due to disease progression and seven (22%) due to TRM. In the univariate analysis age older than 55 years, aGVHD and more than two lines of previous chemotherapy significantly influenced TRM (p 23 patients are evaluable for response: CR ( no CD19/CD5/CD23 + cells in BM) was 90% in transplanted patients with active or progressive disease −21 cases−. In 68% of patients, the response was time related to the development of GVHD; with the two latest responses observed at days +240 and +360. Regarding biological characteristics, 12 of the analyzed patients showed unmutated IgVH. The CR rate, EFS and OS of these patients did not differ from that of mutated IgVH patients . In this series 11 patients showed poor prognosis cytogenetics abnormalities (11q- in 7 and 17 p- in 4) and 5 of them had also unmutated IgVH. This group of patients showed a similar outcome to that of patients with normal cytogenetics. CD38 overexpression was detected in 7 out of 10 patients and only one has relapsed. Two patients died due to progression, one was unmutated with normal FISH and the other was 17 p- and CD38+; eight patients had at least two of the above mentioned abnormalities, including 3 with 17p-, and 7 of them, remained in CR between 20 and 63 months. According to this data, a GVL effect associated with GVHD appears to exist in CLL patients receiving RIC allograft Our data demonstrates the efficacy of RIC related allogeneic transplantation in patients with B-CLL and adverse prognostic features. Moreover, our data suggests that CLL could be cured with RIC allograft, avoiding the high TRM of myeloablative regimens.