Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML
| العنوان: | Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML |
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| المؤلفون: | Lotta Hansson, Lisa L. Liu, Kristina I. Wikstrom, Ebba Sohlberg, Andreas T. Björklund, Jeffrey S. Miller, Monika Klimkowska, Marie Schaffer, Mattias Carlsten, Trevor Clancy, Björn E. Wahlin, Pontus Blomberg, Marzia Palma, Karl-Johan Malmberg, Per Ljungman, Sarah Cooley, Emma Watz, Hans-Gustaf Ljunggren, Eva Hellström-Lindberg, Mohsen Karimi |
| المصدر: | Clinical Cancer Research. 24:1834-1844 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Myeloid, Cyclophosphamide, medicine.medical_treatment, Hematopoietic stem cell transplantation, Lymphocyte Activation, Immunophenotyping, Clonal Evolution, Cell therapy, 03 medical and health sciences, Internal medicine, Humans, Medicine, Aged, Transplantation Chimera, business.industry, Graft Survival, Remission Induction, Middle Aged, medicine.disease, Adoptive Transfer, Combined Modality Therapy, Fludarabine, Killer Cells, Natural, Transplantation, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Myelodysplastic Syndromes, Transplantation, Haploidentical, Cytokines, Female, business, Biomarkers, medicine.drug |
| الوصف: | Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell–based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2–activated haploidentical NK cells. Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients. Six patients achieved objective responses with complete remission (CR), marrow CR, or partial remission (PR). Five patients proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Three patients are still free from disease >3 years after treatment. All evaluable patients with objective responses (5/5 evaluable) had detectable donor NK cells at days 7/14 following infusion and displayed reduction of tumor cell clones, some of which carried poor prognosis mutations. Residual lin−CD34+CD123+CD45RA+ blast cells in responders had increased total HLA class I and HLA-E expression. Responding patients displayed less pronounced activation of CD8+ T cells and lower levels of inflammatory cytokines following NK-cell infusion. Intriguingly, despite omission of systemic IL2, all patients displayed increased frequencies of activated Ki-67+CD127−FoxP3+CD25hiCD4+ Treg cells of recipient origin following NK-cell therapy. Conclusions: Overall, this study suggests that high-risk MDS is responsive to NK-cell therapy and supports the use of haploidentical NK-cell infusions as a bridge to HSCT in refractory patients. Objective clinical responses and reduction of high-risk clones were associated with detectable donor-derived NK cells, immunoediting of residual blast cells, and less pronounced host immune activation. Clin Cancer Res; 24(8); 1834–44. ©2018 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::764612f6fa568b1f463e11fe6f8ec0b5Test https://doi.org/10.1158/1078-0432.ccr-17-3196Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....764612f6fa568b1f463e11fe6f8ec0b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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