The Management of Relapsed AML or MDS Following a T-Cell Depleted Allogeneic Stem Cell Transplant

BACKGROUND: Relapse is a major cause of treatment failure of allogeneic stem cell transplant (SCT) for AML. Most retrospective analyses describing the natural history of relapse have not included recipients of T-cell depleted transplants (TCD). We hypothesized that response to therapy may be different in recipients of TCD-SCT and that they may be more amenable to graft versus leukemia effects. Thus we performed a retrospective analysis of our patients who relapsed after a TCD-SCT. Materials and Methods: From 2003 until 2012 we identified 42 patients with AML or MDS who relapsed after a TCD-SCT at MSKCC. Patients were divided into four groups based on management of relapse: supportive care (n=7), chemotherapy only (n=17), chemotherapy plus DLI (n=8), and chemotherapy plus 2^nd SCT (n=10). Patient and disease characteristics were compared across the four groups using Fisher’s exact test when categorical and the Kruskal-Wallis test when continuous. Kaplan-Meier methods were used to estimate survival probabilities and the log-rank test evaluated differences in survival between groups. Of the 10 patients who underwent a second HSCT, 8 received T-cell replete and 2 underwent another TCD-SCT.  RESULTS: Across groups, there were no significant differences in sex (p=0.086), donor type (related vs unrelated; p=0.082), percentage of blasts on relapse (median 25%; p=0.317), and all cause mortality (p=0.088). There was a statistically significant difference in the age of patients (p=0.010); youngest in the chemo plus 2^nd SCT group (median 41.5 yrs). The median follow up time amongst survivors was 24.4 months (range, 13.6 - 69.8 m). There were 34 all cause mortality events; 4 due to NRM. Median survival for all groups was 16 months (95% CI, 11.8-27.1). At 12 month follow up, the probability of survival in supportive care, chemo only, chemo plus DLI, and chemo plus 2^nd SCT group were 43%, 41%, 88%, and 70%, respectively. There was no statistically significant difference in overall survival (OS) between the groups (p=0.088). Patients in the chemo plus DLI and chemo plus 2^nd SCT groups had the longest median OS of 28.6 months and 20.2 months, respectively. The median survival of patients who received any salvage chemotherapy was 19.3 months (95% CI, 10.5-28.6) compared to 20.2 months (95% CI, 11.9-NA) for those receiving chemo plus 2^nd SCT (p=0.180). Complete remission was achieved at any time in 5 patients in chemo plus 2^nd SCT, 3 patients in chemo plus DLI, and none of the patients in chemo only group (p=0.003). Use of hypomethylating agents versus other salvage chemotherapy at any point in treatment did not improve OS (p=0.745). CONCLUSIONS: AML patients relapsing after a TCD-SCT can be successfully treated, however long term disease control is rare. Due to the small number of patients we were not able to demonstrate statistically significant difference in outcomes among different salvage strategies.