Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia in Era of Tyrosine Kinase Inhibitors -a Single Centre Experience from India

Abstract

Background Transplant remains most curative option for patients with TKI resistant disease or in advanced phase of CML. We retrospectively analyzed transplant outcome of CML patients in era of TKI from our centre. Methods All patients who underwent allogeneic stem cell transplant for CML between Aug 2010 to Sept 2016 were included. Conditioning regimens included Flu-Mel (67.5%), Bu-Cy (10%), Flu- 7.2 Gy TBI (15%), or Flu-treo-2GyTBI (7.5%). For matched sibling (MSD) or unrelated donor (MUD) transplants, GVHD prophylaxes were cyclosporine (CsA) with methotrexate in 26(65%) or mycophenolate(MMF) in 8 (20%) patients respectively . Post transplant cyclophosphamide (PtCy) with CSA / tacrolimus with MMF was used in 6 (15%) patients who underwent haploidentical transplant (HIT) .Disease Risk Index (DRI), HCT-CI and EBMT scores at transplant were calculated for all . Overall survival (OS) was calculated from date of transplant to date of death or last follow up while relapse-free survival (RFS) was calculated till date of molecular relapse (>0.1% BCR-ABL),death or LFU if in MMR. Prognostic factors evaluated were duration from diagnosis to transplant ( 2 years), EBMT score (≤3 vs>3), acute and chronic GVHD, type of transplant and DRI index. Results Median age was 30 years (12-55) of which 30 (75%) were male. TKI failure was the commonest reason for transplant (95%) .T315I mutation was seen in 17.5% of patients . Twenty-six (65%) were in CP, 8 in AP and 6 in BC at diagnosis. The median EBMT and HCT-CI score were 3 and 2 respectively. Twelve (30%) patients had high DRI. MSD transplant was performed in 33 (82.5%), 6 (15%) underwent HIT and 1 MUD transplant. All except 1 patient received PBSC graft. Grade III/IV mucositis and diarrhea were seen in 19 (47.5%) and 4 (10%) patients respectively. Median time to neutrophil and platelet engraftment were 16 and 13.5 days respectively. Incidence of grade III/IV acute GVHD and chronic GVHD was 50% and 60% respectively. At 1 year post transplant >4.5 log reduction (DMR) was attained in 25 (62.5%) while 5 (12.5%) patients were in MMR. Five patients received DLI (3 patients for clinical relapse,2 for slippage of chimerism). Median follow up was 36 months. Non relapse mortality was seen in 8 (20%) patients. (GVHD-7, Myocarditis1). OS and RFS at 5 years were 70 % and 57 % respectively. In multivariate analysis for RFS, EBMT score≤ 3 and time from diagnosis to transplant > 2 years were independent prognostic factors for better RFS. For OS, presence of chronic and absence of acute GVHD were independent prognostic factors for better survival. Conclusion The long term survival in TKI resistant and advanced CML with transplant is promising. Along with other factors, transplant after 2 years from diagnosis was an independent prognostic factor for better survival contrary to transplant within 1 year of diagnosis in the pre TKI era .This may be due to better disease control with advent of TKIs.