PV QA 2 - Poster Viewing Q&A 2
Purpose/Objective(s): Hematopoietic stem cell transplantation (HSCT) is elective post-remission treatment for patients with intermediate-high risk acute myeloid leukemia (AML). An alternative to the matched sibling donor is the 1-haplotype mismatched relative (haploidentical HSCT), who is immediately available for 95% patients. Transplantation cures AML through the conditioning regimen’s myeloablation and the graft’s elimination of residual leukemic cells (GvL effect). In elderly patients, myeloablative conditioning regimens, which may include total body irradiation, are associated with high toxicity and non-relapse mortality rates. We hypothesized that administering total marrow/total lymphoid irradiation (TMI/TLI) by helical tomotherapy (HT) followed by low chemotherapy doses could lower regimen-related toxicity and non-relapse mortality rates in elderly AML patients.
Materials/Methods: July 2015 - October 2017: 14 AML patients (median age 62 years, 6 in first and 7 in second complete remission, 1 in partial remission) underwent haploidentical HSCT. Composite comorbidity/age scores were 1/2 in 7 patients and 3/4 in 8. TMI/TLI target volumes were skeletal bones, major lymph node chains and spleen. TMI/TLI was delivered from day -7 to day -4, in 2 daily fractions of 1.5 Gy (TMI) and 1.3 Gy (TLI) (total doses 13.5Gy and 11.7Gy respectively). Chemotherapy: tiothepa 2.5 mg/kg on days -10 and -9; fludarabine 30 mg/m2 from days -10 to -6; cyclophosphamide 15 mg/kg on days -8 and -7. Haploidentical grafts consisted of 10x106/kg purified CD34+cells, 1x106/kg conventional T cells (Tcon), 2 x106/kg freshly isolated T regulatory cells (Treg). No post-transplant immunosuppression was given.
Results: After TMI/TLI the worst regimen-related acute toxicity was G3 gastrointestinal in 1 patient. All patients sustained primary full-donor type engraftment. Grade II-IV acute graft-versus- host disease (GvHD) developed in 6 patients (43%) and chronic GvHD in none. Transplant-related causes of death in 3 patients were veno-occlusive disease (1), sepsis (1) and acute GvHD (1). Immune reconstitution was good, with peripheral blood T cells rapidly increasing. Eleven patients are alive and relapse-free at a median follow up of 18 months (minimum 6 months).
Conclusion: A conditioning regimen based on TMI/TLI, relatively low chemotherapy doses and Treg/Tcon adoptive immunotherapy was safe and successful in haploidentical transplantation for elderly AML patients. The myeloablative effect of TMI contributed to eradicate leukemia while the immunosuppressive effect of TLI ensured a high engraftment rate. The appropriate Tcon: Treg ratio was confirmed to exert a powerful T-cell dependent GvL effect in the absence of GvHD. Findings need to be supported by a larger cohort of elderly patients before extending the protocol to young AML patients.
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