Non-Myeloablative Allogeneic Stem Cell Transplantation in 154 Patients (pts) with Chronic Myeloid Leukaemia (CML).
Authors: Benakli Malek , Hamladji Rose-Marie , Nacer Redhouane Ahmed , Talbi Amina , Mehdid Farih , Belhadj Rachida , Rahmoune Nadia 
Published: October 2019

Background: Allogeneic stem cell transplantation using a reduced intensity or nonmyeloablative conditioning (NSCT) represents an attractive treatment modality in CML. The rationale behind such approach is to decrease toxicity while inducing the graft-versus-leukemia (GVL) effect. Because of its significantly lower cost in comparison to Imatinib mesylate, NSCT may be considered an early treatment option in countries where limited resources.

Material and Methods: Between April 2001 and December 2006, we treated 154 CML patients (131 in first chronic phase, 23 in accelerated phase) with NSCT from an HLA-identical family donor. The majority of pts has a Gratwohl score <2 prior to NSCT (n=115; 74,6%). The conditioning regimen included Fludarabine 150 mg/m2 and oral Busulfan 8 mg /kg (139 pts). GVHD prophylaxis consisted of association ciclosporine (CSA)-Mycophenolate (MMF). 15 pts received an additional prophylaxis with antithymocyte globulin (ATG). Median age was 35 (range, 18–55) years, and the sex-ratio (M/F) 0,87. The median time from diagnosis to NSCT was 11 (range, 4–50) months. All pts received G-CSF mobilised peripheral blood stem cells, median CD34+ cells count: 7,02.106/kg (range, 1,28–44,9).

Results: Leucopenia is found almost at 71 pts (46,1%). The median time to achieve ANC >500. 109/l granulocytes was 14 (range, 7–24) days, and median time of aplasia was 7 (range, 2–19) days. Transfusion requirements were significantly reduced, only 3 pts (1,9%) required red blood cells transfusions. Only 15 pts (9,7%) needed platelets transfusions. Acute GVHD was seen in 65 cases (43,6%) including 26 (17,4%) cases of grade III–IV and 32 cases (21%) of late onset acute GVHD occurring after day 100 post-NSCT. 93 pts (67,3%) had chronic GVHD, of whom 58 with an extensive form. 23 pts (15,4%) had CMV reactivation. 24 pts (16,1%) relapsed (15 in chronic phase, 7 in blast crisis and 2 with a molecular relapse), but 11 pts could be salvaged and are currently in remission (7 after immunosupression discontinuation, one after DLI and 3 after a second conventional allograft). The chimerism of donor origin (STR-PCR method) of patients in remission was at an average of 74% at day 30, 80% at d100, 93% at 6 months, 97% at 1 year, and 99% at 2 years. Fifty pts (33,5%) have died, of whom 39 (22,1%) from GVHD and 10 (6,7%) from disease relapse. Transplant Related Mortality (TRM) at 100 days was 6%, but rose to 31,5% at 3 years. At last follow-up (median, 32 (range 6–68) months), 99 pts (66,4%) are still alive, 97 (65,1%) pts in hematologic remission; of whom 76 (78,3%) in complete molecular remission evaluated by RT-PCR. Overall survival and progression-free survival at 5 years are 61% and 51,6% respectively.

Conclusion. The study demonstrates a relatively low rate of short-term toxicities after NSCT. However, long-term TRM is still high because of the GVHD. The GVL effect is well admited. The relapse can be often controled by immunomodulation (stoppage of immunosuppression, DLI) and eventually by second myeloablative allograft.