TY - JOUR
T1 - Vaccination with autologous myeloblasts admixed with GM-K562 cells in patients with advanced MDS or AML after allogeneic HSCT
AU - Ho, Vincent T.
AU - Kim, Haesook T.
AU - Bavli, Natalie
AU - Mihm, Martin
AU - Pozdnyakova, Olga
AU - Piesche, Matthias
AU - Daley, Heather
AU - Reynolds, Carol
AU - Souders, Nicholas C.
AU - Cutler, Corey
AU - Koreth, John
AU - Alyea, Edwin P.
AU - Antin, Joseph H.
AU - Ritz, Jerome
AU - Dranoff, Glenn
AU - Soiffer, Robert J.
N1 - Funding Information:
Acknowledgments This work was supported by the National Institutes of Health, National Cancer Institute (grants R01 CA183559, R01 CA183560, and P01 CA142106), the John B. Fisher Fund, and the Ted and Eileen Pasquarello Research Fund.
Publisher Copyright:
© 2017 by The American Society of Hematology
PY - 2017/11/14
Y1 - 2017/11/14
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2017009084
DO - 10.1182/bloodadvances.2017009084
M3 - Article
C2 - 29296875
AN - SCOPUS:85048715023
SN - 2473-9529
VL - 1
SP - 2269
EP - 2279
JO - Blood Advances
JF - Blood Advances
IS - 24
ER -