Outcome in Allo- SCT in Patients with Refrectory Acute Lymphoblastic Leukemia with Non TBI Conditioning Regimens

Background: Despite intensive remission induction chemotherapy, up to 5–10% AYAs with acute lymphoblastic leukemia (ALL) are primarily refractory.1,2 Of those that achieve a remission, as much as 70–80% fail consolidation largely due to relapse or sustained aplasia. Allogeneic stem-cell transplantation (allo-SCT) remains the only salvage option with curative potentials available, but the long-term benefits of the procedure and whether all patients should benefit from it remains controversial. There has always been a discussion about best conditioning regimen for ALL transplants especially in resource limited situation where TBI is not available. We analyzed our data on allo-transplants for ALL, wherein we had used non-TBI protocols for conditioning.

Study: This study retrospectively analyzes the outcome in 32 patients ( 19 females & 13 males) who underwent Allo-SCT for refractory acute lymphoblastic leukemia at our center between 2000-2013. The median age was 28 years (range, 7–26). 14 patients had relapse, 8 failed re-induction, 5 in partial remission & 7 patients had high risk disease ( Ph+ disease). All patients were in a state of bone marrow remission at the time of transplantation. All received myeloablative conditioning using busulfan( BU) & cyclophosphamide( CY). The stem cell harvesting was done by peripheral G-mobilized stem cell collection from related donors. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. Infection prophylaxis & supportive care was provided as per standard protocols. The median cell dose was 5.4 MNCx10 ^7/Kg (3.8-7.6) & CD34 cells 3.7x10⁵/Kg. 31 patients engrafted successfully by median day 12(7-23) for White cells & median day 38 ( 27-48) for platelets. One patient experienced late graft failure. 21 patients developed Gd-II acute-GVHD, 11 of them progressed to severe form( Gd-III). 5 pateints had severe grade IV Ac GVHD. 3 of them died chronic-GVHD appeared in 14 patients,. 19 patients (58%%) remain alive after a median of 60 months (range, 6–174); with 13 deaths, mostly from relapse (n=10) and infections (n=3). Overall survival (OS) and progression-free survival (PFS) at 5 years was 53% and 48%, respectively. OS and PFS were significantly better with blasts 20% and time to transplant 1 year.

Conclusions: We conclude that patients with refractory leukemia can benefit from allogeneic BMT, if they are transplanted in a state of remission, by using non-TBI based protocols. Thus in a resource limited situation, the outcome in refractory ALL can still be improved by improvisation of protocols without using TBI in conditioning regimens.