Allogeneic Stem Cell Transplantation In Chronic Myeloid Leukemia In TKIs Era

Tyrosine kinase inhibitors (TKIs) have largely replaced allogeneic hematopoietic stem cell transplantation (HSCT) as first line treatment option in chronic phase chronic myeloid leukemia (CML) yet due to the need for continued administration the cost becomes prohibitive in majority of patients without any health insurance coverage. Therefore allogeneic stem cell transplant remains a reasonable treatment option for such patients especially in resource constrained countries. It is also useful treatment modality in children, CML in accelerated phase and in patients intolerant to TKIs. We report results of 64 consecutive patients undergoing HLA matched sibling allo HSCT at our center from April 2002 to September 2012.

Patients with Philadelphia positive CML were categorized into standard and high risk based on age >40 years, disease duration > 12 month from diagnosis to transplant and accelerated phase. Conditioning regimens used were oral busulphan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu16/Cy200), Bu16/Cy120, Bu16/Cy120/Etoposide30 and Bu16/Cy120/ATG. Source of stem cell was peripheral blood stem cells (PBSC) or bone marrow (BM) infusion. GVHD prophylaxis consisted of ciclosporin, short methotrexate (10 mg/m² on day +1, 8 mg/m² on day +3 & 6) ± prednisolone. Statistical calculations included Fisher’s exact test, Kaplan-Meier for survival analysis, and Cox regression for multivariate analysis.

Median age of the patients was 28 years (range 7 – 54). Female donor to male recipient was seen in 12 cases while 20 patients had major blood group mismatch. Forty seven patients were standard risk while 17 were categorized as high risk. Bu16/Cy120 was the most common conditioning regimen given in 34 cases followed by Bu16/Cy200 in 19 cases. Fifty four patients received PBSC while BM was given in 8 cases. Grade I/II acute GVHD was seen in one-third of the cases while 7 (11%) had grade III/IV GVHD. Extensive chronic GVHD was seen in 10 (16%) cases while 12 (19%) patients had limited chronic GVHD. Complications observed were hemorrhagic cystitis (7), VOD (4), CMV infection (2) and septicemia (3). Five (8%) patients had disease relapse. The overall survival was 70.3% (median 1627 days) while disease free survival was 62.5% (median 1547 days). Nineteen patients died of various complications like extensive GVHD (n=5), septicemia (n=3), VOD (n=3), CMV infection (n=3) and disseminated aspergillosis (n==2).

A significant difference was observed among patients bearing standard risk compared with those in high risk group in terms of overall survival (79% versus 47% , p=0.013), disease free survival (72% versus 35%, p=0.031) and incidence of acute GVHD (34% versus 71%, p=0.01) in univariate analysis. Age >40 year was the only factor associated with adverse outcome in multivariate Cox-regression model.

Early allogeneic HSCT in CML patients <40 years of age is associated with long term disease free survival in about 70% of cases. It is a reasonable treatment option in situations where TKIs cannot be employed as first line therapy due to various reasons.

No relevant conflicts of interest to declare.