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

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

doi:10.1182/bloodadvances.2017009084

Cited by 18 publications

(20 citation statements)

References 27 publications

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“…Ho et al vaccinated 33 patients with advanced MDS or AML after allo‐HSCT with autologous myeloblasts admixed with GMK562 cells. Five‐year PFS and OS was 39% and 39%, respectively (NCT 00809250) . The GVAX vaccine, composed of whole tumor cells, genetically modified to secrete GM‐CSF is in phase II clinical trial for AML, MDS, and chronic myelomonocytic leukemia (CMML) patients given 30 −45 days post‐allo‐HSCT(NCT01773395).…”

Section: Cellular Therapiesmentioning

confidence: 99%

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

2019

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Acute myeloid leukemia (AML) is a disease with heterogeneous prognosis based on the clinical, cytogenetic, and molecular profile of the patient. Despite high post-induction remission rates in adult patients up to 40% of patients relapse. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and potentially curative post-remission treatment for AML. 1 The antileukemic effect of allo-HSCT depends on the cytotoxicity of the pretransplant conditioning therapy and the posttransplant graft versus leukemia (GVL) effect. In a meta-analysis, allo-HSCT significantly improves survival in patients in first complete remission (CR) with poor-risk and intermediate-risk cytogenetic abnormalities (poor-risk: HR -0.73; 95% CI, 0.59-0.90); (intermediate-risk AML: HR, 0.83%-95% CI, 0.74-0.93). 2,3 The introduction of non-myeloablative (NMA) and reduced intensity conditioning (RIC) regimens, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have allowed for a larger application of allo-HSCT to older patients and those with comorbidities. Although Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). Reduced intensity regimens, alternative graft sources, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have led to a wider application of allo-HSCT to eligible patients. Unfortunately, 30-40% of patients with AML will relapse after transplant and this is the major cause of treatment failure. Careful consideration should be paid in choosing the type of graft, graft source, and conditioning regimen to minimize the risk of disease recurrence. In addition, maintenance therapy following allo-HSCT is a potential method to keep the disease in remission, especially in those with high-risk disease characteristics. Pharmacological targeted agents with low side effect profile such as tyrosine kinase inhibitors, hypomethylating agents (HMAs), HDAC inhibitors, antibody drug conjugates (ADCs), isocitrate dehydrogenase inhibitors, and hedgehog inhibitors may prevent relapse in posttransplant setting and are under investigation. Immunological therapies including donor lymphocyte infusions (DLIs), natural killer (NK) cell therapy, peptide vaccine targeting tumor antigens, and adoptive T-cell therapies all hold promises in this area as well. As targeted agents and immunotherapies continue to be developed, patients at high risk of recurrence may benefit from prophylactic maintenance therapy. Here we review the current landscape in this rapidly evolving clinical setting. K E Y W O R D S Acute myeloid leukemia, Allogeneic Transplant, Immunotherapy, Posttransplant relapse, Targeted agents

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Section: Cellular Therapiesmentioning

confidence: 99%

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

2019

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“…As the mechanism of this phenomenon, we hypothesized that the dissemination of tumor cells in the peritoneal cavity caused some immune reaction resembling the immunotherapy using autologous cells. Recently, a number of cancer vaccinations administering autologous tumor cells are being explored for different neoplasms, and the induction of tumor reactive T cells, and therapeutic efficacy in mouse models and clinical practice were reported 5 - 13 . The present patient exhibited high grade fever and elevated CRP and uric acid levels after the first and the second ASRs.…”

Section: To the Editormentioning

confidence: 67%

Atraumatic splenic ruptures triggered both remission and death in a single case of blastic plasmacytoid dendritic cell neoplasm

Daitoku

Onimaru

Tanimoto

et al. 2019

JCEH

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“…One strategy is to generate individualized vaccines using a patient’s own cancer cells, which has been tested previously in a small cohort of MDS/AML patients post-BMT. [27,28] However, having a universal product that can be used for patients of any HLA type, such as GVAX, would be advantageous. In contrast with vaccines derived from autologous cells, GVAX has the advantage of being an “off the shelf” product for any patient without lead-time required for reagent generation and is less costly than generating an individualized vaccine for each patient.…”

Section: Discussionmentioning

confidence: 99%

Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients

Robinson

Prince

Thoburn

et al. 2018

Leukemia & Lymphoma

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Currently, approved drugs are given with non-curative intent as the only known cure is allogeneic bone marrow transplantation, which relies on the donor's immune system driving an allogeneic effect. Previous efforts to harness the endogenous immune system have been less successful. We present the results of a pilot study of K562/GM-CSF (GVAX) whole-cell vaccination in MDS patients. The primary objective of safety was met as there were no serious adverse events. One patient had a decrease in transfusion requirements and another demonstrated hematologic improvement suggesting a signal for clinical activity. In vitro correlative studies indicated biological effects on immune cells following vaccination. Although only a pilot study, results are encouraging that an immunotherapeutic approach with a whole-cell vaccine may be feasible in MDS patients.

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

Cited by 18 publications

References 27 publications

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

Atraumatic splenic ruptures triggered both remission and death in a single case of blastic plasmacytoid dendritic cell neoplasm

Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients

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