Imatinib Maintenance Following Allogeneic Hematopoietic Cell Transplantation (Hct) For Patients With Philadelphia Chromosome Positive (Ph Plus ) Acute Lymphoblastic Leukemia (All)

The addition of tyrosine kinase inhibitors (TKI) to conventional ALL therapy has significantly improved outcome for Ph+ patients, resulting in more patients being able to receive HCT in remission. Maintenance therapy with TKI following HCT may additionally improve outcomes. We performed a retrospective chart review on transplants since 2001 when TKI first became available for use following HCT. From March 2001 through June 2009, 66 patients with median age 37 years (range 3-61) received an allogeneic HCT for Ph+ ALL in CR1 (n=56) or CR2 (n=10); 28 patients were in complete molecular remission at time of HCT. Patients received matched related (n=30) or matched unrelated (n=27) peripheral blood (n=35), bone marrow (n=22), or mismatched cord blood cells (n=9) following a myeloablative TBI-based (n=48) or nonTBI-based (n=18) transplant conditioning regimen. GVHD prophylaxis was tacrolimus-based. All patients received TKI prior to HCT. Patients were eligible to receive TKI maintenance following HCT if they had hematologic recovery defined by an unsupported platelet count >50,000/uL and absolute neutrophil count >1500/uL. Forty-seven percent (n=31) of patients received TKI in the form of imatinib at median dose 300 mg (range 100-800) initiated at median of 2 months (range 1-12) following HCT. Median duration of imatinib use post HCT was 13 months (range 1-91). The most common reason for treatment discontinuation was physician preference followed by disease progression. Cytopenias and gastrointestinal discomfort were the most common imatinib-related toxicities. With a median follow-up of 4 years among survivors (range 0.3-7.7), 2-year overall survival (OS) and progression-free survival (PFS) were 55% and 50%, respectively. Day 100, 1-year, and 2-year non-relapse mortality (NRM) rates were 11%, 26%, and 28%, respectively. The cumulative incidence of grade 2-4 and 3-4 acute GVHD were 48% and 16%, respectively; the incidence of chronic extensive GVHD was 19%. In univariate analysis, imatinib maintenance led to significantly better OS (HR 0.3, 95% CI 0.1-.8, p=0.02) and NRM (HR 0.3, 95%CI 0.1-1.1, p=0.07). Additionally, age>40 years and CR2 vs CR1 led to significantly worse OS; molecular remission did not reach statistical significance. Large, multicenter trials in Ph+ ALL are in progress to confirm the benefit of TKI maintenance following HCT.