Outcomes of Allogeneic Stem Cell Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Introduction: Philadelphia chromosome (PH) positive (+) acute lymphoblastic leukemia (ALL) is incurable without undergoing allogeneic hematopoietic stem cell transplant (HCT). Ideally patients should be in complete remission (CR) prior to HCT without minimal residual disease (MRD). Center for International Blood and Marrow Research data shows that  ALL patients ≥20 years of age receiving matched sibling HCT  between 2001-2011, the 3-year survival probabilities were 53% ± 1%, 32% ± 2%, and 23% ± 2% for patients with early, intermediate, and advanced disease, respectively. Corresponding probabilities among the 3,929 recipients of unrelated donor HCT were 50% ± 1%, 34% ± 2%, and 18% ± 2%. Recognizing that patients with PH + ALL have aggressive disease we questioned if there were factors that would predict relapse or prevent relapse post HCT in this cohort. Methods: The HCT database at Mayo Clinic Arizona was used to identify patients with Ph + ALL underdoing transplant from January 1994 through December 2013. 20 PH+ patients were identified. Demographic and HCT data were taken from this database. Data on tyrosine kinase inhibitor (TKI) use and chimerism were obtained retrospectively from the patient record.  Results: 6 (30%) patients relapsed and 5 died from their disease. 1 patient died from transplant related mortality. 5 year survival rate was 59.5%.  Of the 6 patients who relapsed none were MRD positive pre HCT, 3 had 100% donor chimerism at day 100 and 3 started a TKI  post HCT. The 3 who started a TKI did so at day 80, 169 and 172.  Conditioning regimen for these 6 patients consisted of: Fludarabine/ Melphalan/Busulfan (2), Fludarabine/Melphalan (1), Etoposide /Cyclophosphamide/Total Body Irradiation (1) and Cyclophosphamide/Total Body Irradiation (1 ). At HCT 2 patients were in CR1, 1  in CR2 and 1 in CR3. 1 patient came to HCT in relapse but did not relapse after. 15 of the 20 patients were placed on a TKI post HCT. No statistically significant factor was detected to impact relapse or overall survival. Discussion: PH + ALL is a disease with a poor prognosis. This study shows a 60% overall survival at 5 years post HCT  which is better than has been reported. We had hypothesized that if patients were not started on a TKI, had PH + MRD  pre or post HCT, did not reach 100% chimerism at day 100 or did not receive radiation as part of the conditioning regimen it would impact relapse. Though this is a small descriptive study it is notable that there were no trends observed. In the era where we have many TKIs to choose from  perhaps our outcomes in PH positive ALL are improving. Future research should focus on conditioning regimen for ALL (full versus reduced intensity, radiation versus no radiation), optimal time to start a TKI post HCT and does  MRD  by PCR pre and post HCT matte.r Certainly in this study of 20 patients none of these factors were statistically significant. Future study of a larger population would be prudent.