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).
Authors: Caballero M.D. , García-Marco J.A. , Martino R. , Mateos M.V. , Cabrera R. , Briones J. , González M. , Esteve J. , León A. , Ribera Josep Maria , Sarrá J. , de la Serna J. , San Miguel J.F. 
Published: October 2019

Abstract
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<0,05). On multivariate analysis only the latter variable remained as an independent prognostic factor (p=0,02).After 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, with a probability for TRM of 26%; Overall survival (OS) and event free survival (EFS) are 64 and 68%, respectively.
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.