Vaccination with autologous myeloblasts admixed with GM-K562 cells in patients with advanced MDS or AML after allogeneic HSCT

Vincent T. Ho, Haesook T. Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C. Souders, Corey Cutler, John Koreth, Edwin P. Alyea, Joseph H. Antin, Jerome Ritz, Glenn Dranoff, Robert J. Soiffer

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with $5% marrow blasts underwent myeloblast collection before HSCT. At approximately day 130, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (;day 100). Thirty-three patients with AML (25) and MDS (8) enrolled, 16 (48%) had $5% marrow blasts at transplantation. The most common vaccine toxicity was injection site reactions. One patient developed severe eosinophilia and died of eosinophilic myocarditis. With a median follow-up of 67 months, cumulative incidence of grade 2-4 acute and chronic GVHD were 24% and 33%, respectively. Relapse and nonrelapse mortality were 48% and 9%, respectively. Progression-free survival (PFS) and overall survival (OS) at 5 years were 39% and 39%. Vaccinated patients who were transplanted with active disease ($5% marrow blasts) had similar OS and PFS at 5 years compared with vaccinated patients transplanted with,5% marrow blasts (OS, 44% vs 35%, respectively, P 5 .81; PFS, 44% vs 35%, respectively, P 5 .34). Postvaccination antibody responses to angiopoietin-2 was associated with superior OS (hazard ratio [HR], 0.43; P 5 .031) and PFS (HR, 0.5; P 5 .036). Patients transplanted with active disease had more frequent angiopoeitin-2 antibody responses (62.5% vs 20%, P 5 .029) than those transplanted in remission. GM-K562/leukemia cell vaccination induces biologic activity, even in patients transplanted with active MDS/AML. This study is registered at www.clinicaltrials.gov as #NCT 00809250.

Original languageEnglish (US)
Pages (from-to)2269-2279
Number of pages11
JournalBlood Advances
Volume1
Issue number24
DOIs
StatePublished - Nov 14 2017
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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