New research in older patients with acute myeloid leukemia (AML) validates the use of microtransplantation from human leukocyte antigen (HLA)-identical family donors. This novel transplant protocol maintains the anti-leukemia benefits of traditional allogeneic hematopoietic stem cell transplantation (HSCT) while minimizing the risk of adverse events.
Anthony D. Sung, MD, on behalf of his research team at the Duke Cancer Institute, presented preliminary results from an ongoing study at the American Society of Hematology's 59th Annual Meeting & Exposition, December 9 to 12, 2017, in Atlanta, GA.
Older patients with AML tend to respond poorly to standard allogeneic HSCT due to a high prevalence of poor-risk cytogenetics and other adverse prognostic factors. Compared with younger patients and those with more favorable disease features, older patients with AML have lower rates of complete remission (CR), worse survival, and a higher risk of graft-versus-host disease (GVHD).
Sung and his team are conducting a pilot study of microtransplantation as an alternative treatment approach for older patients with newly diagnosed high-risk AML. The current analysis includes findings from the first 17 patients enrolled in the study.
The median patient age was 73 years (range, 61-78 years). The majority of patients (71%) were classified as having poor-risk AML due to high-risk cytogenetics (59%), antecedent hematologic disorder (29%), and/or therapy-related AML (6%). Two patients (12%) had intermediate-risk AML. The 3 patients (18%) with favorable-risk AML all harbored the NPM1 mutation, which is associated with a better prognosis in patients with AML.
Patients received induction chemotherapy with cytarabine and idarubicin, followed by microtransplantation within 24 to 48 hours. The microtransplantation procedure involved a minimum infusion of 1 x 108 CD3+ cells/kg from an HLA-haploidentical family donor. Together, this protocol of induction followed by microtransplantation is referred to as 7+3+MST.
After the first round of 7+3+MST, patients who achieved CR received 2 cycles of consolidation therapy with high-dose cytarabine, followed by a second microtransplantation procedure. Patients who did not achieve CR after the first microtransplantation were able to undergo a second repeat cycle of 7+3+MST.
In total, 16 patients completed at least 1 round of the 7+3+MST protocol. Due to a case of sepsis following induction chemotherapy, 1 patient did not receive the microtransplant.
With a median follow-up of 248 days (range, 37-887 days), results support the safety and feasibility of microtransplantation in older patients with AML.
Microtransplantation was associated with a high CR rate (Table). Of the 16 patients who received a microtransplant, 10 (62.5%) achieved CR. This includes a CR rate of 100% among patients with intermediate- or favorable-risk AML.
TABLE. CRs Following Microtransplantation in AML
|Patients||CR, n (%)|
|All patients receiving microtransplantation (n = 16)||10 (62.5%)|
|Intermediate- or favorable-risk AML (n = 4)||4 (100%)|
|Poor-risk AML (n = 12)||6 (50%)|
AML = acute myeloid leukemia; CR = complete remission.
The estimated overall survival was 67% at 6 months and 34% at 1 year.
The microtransplantation procedure was safe, with no cases of treatment-related mortality. Moreover, there were no cases of GVHD. The absence of GVHD suggests that the procedure was effective in avoiding substantial engraftment, defined as more than 2% donor chimerism.
Sung and colleagues are planning several additional studies to better understand the anti-leukemia mechanisms of microtransplantation. The team will examine the potential immunomodulatory effects of microtransplant, including T-cell exhaustion and effects on natural killer cell function. Future studies will also assess the depth of response following microtransplant, measured by minimal residual disease, as well as the persistence of donor cells and microchimerism.
Overall, preliminary findings support the use of microtransplantation in older patients with AML. Research is ongoing to better understand the potential role of microtransplantation across subgroups of patients with AML, including those with poor-risk disease.
Source: Sung AD, de Castro CM, LeBlanc TW, et al. Clinical outcomes of microtransplantation for older adults with acute myeloid leukemia. Presented at: American Society of Hematology 59th Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 3853.