Survival Advantage of Cell Therapy Over Cytotoxic Therapy Alone in Adult Patients with Relapsed AML After Allogeneic Hematopoietic Stem Cell Transplantation

The prognosis of acute myelogenous leukemia (AML) relapsing after allogeneic hematopoietic stem cell transplantation (allo HCT) remains poor and the treatment options are limited. There is no standard of care for these patients (pts) and treatment primarily aimed towards rapid tapering of immunosuppressant medications to induce graft versus leukemia effect. Salvage chemotherapy alone post allo HCT for relapsed AML is seldom curative with the overall survival (OS) at 2 years 9% as reported by the European Blood and Marrow Transplant Group (EBMT). The addition of cell therapy, such as donor lymphocyte infusion (DLI) or stem cells (second transplant) may improve response rate however, long term survival rate remains poor.

To asses the factors contributing to outcomes after relapse post allo HCT; we conducted a retrospective analysis of 85 adult pts with relapsed AML from 2004 to 2011 at our institution. Our study was designed to evaluate the efficacy of different therapies with focus on an intent-to-treat analysis. Therapy groups were defined as: cytotoxic therapy, including hypomethylating agents (HMA) or other forms of chemotherapy (CH); cell therapy (CT), including chemotherapy followed by DLI or CD34⁺ stem cells; and supportive care. The median time from transplant to relapse was 4.3 (range: 0.6–45) months (m) and the median post HCT follow up was 9 (range: 2–85) m.

The median age was 50 (range: 19–69) years, 39 were females and 45 males. 41 (47%) pts had secondary AML, 44 (51%) with de novo AML. At diagnosis 31 (36%) pts were positive for adverse cytogenetics, 33 (38%) pts had intermediate-1(INT-I), 17 (20%) pts had INT-II and 4 (5%) pts with favorable cytogenetics. CIBMTR Risk stratification: 35 (41%) low, 24(28%) intermediate and 26 (30%) high. At time of HCT 55 (64%) pts had bone marrow (BM) blasts < 5%, 7 (12%) pts with minimal residual disease; 30 (35%) had BM blasts > 5% and 4 pts (13%) had BM blasts > 30%. Eighty three (97%) received mobilized CD34⁺cells from peripheral blood, 36 (42%) pts previously received HCT were from matched related donors, 34 (40%) from matched unrelated donors and 14(16%) from a mismatched unrelated donors. At relapse post HCT, 28 (32%) pts received cytotoxic therapy (HMA or CH), 21 (24%) pts received CT. Thirty-six (42%) pts received supportive care only.

In pts who received salvage therapy the complete remission (CR) rate was 43%. For the CT group 71% achieved CR compared to 21% who received cytotoxic therapy (p=0.002). No significant difference was noted in the CR rate between HMA or CH group 31% versus 9% respectively (p=0.27). The median time to relapse after achieving CR for all pts was approximately 13 m with 14%, 40% and 70% relapsed by 6, 12 and 24 months respectively. The median time of survival from time of relapse post HCT for all pts was 3.7 m with the best outcome noted in the CT group at 10.2 m compared to 4.7 m and 2.6 m for those received HMA and CH respectively. The OS at 1 year from the time of relapse post allo HCT was 24% for all pts, 43% for CT, 29% for cytotoxic therapy (HMA 31%, CH 27%) and 8% for those received supportive care (P<0.001).

These data suggest that pts who are able to receive CT preceded by cytotoxic therapy have the best chance of prolonged OS. Cytotoxic therapy alone does not improve survival over supportive care. Our findings suggest that future approaches should focus on giving cytotoxic therapy followed by CT to achieve maximal response for AML pts after relapse post HCT.

No relevant conflicts of interest to declare.