Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.

Published

Journal Article

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.

Full Text

Duke Authors

Cited Authors

  • Sung, AD; Jauhari, S; Siamakpour-Reihani, S; Rao, AV; Staats, J; Chan, C; Meyer, E; Gadi, VK; Nixon, AB; Lyu, J; Xie, J; Bohannon, L; Li, Z; Hourigan, CS; Dillon, LW; Wong, HY; Shelby, R; Diehl, L; de Castro, C; LeBlanc, T; Brander, D; Erba, H; Galal, A; Stefanovic, A; Chao, N; Rizzieri, DA

Published Date

  • June 2020

Published In

Volume / Issue

  • 95 / 6

Start / End Page

  • 662 - 671

PubMed ID

  • 32162718

Pubmed Central ID

  • 32162718

Electronic International Standard Serial Number (EISSN)

  • 1096-8652

International Standard Serial Number (ISSN)

  • 0361-8609

Digital Object Identifier (DOI)

  • 10.1002/ajh.25781

Language

  • eng