Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients
| Autor: | Mariangela Lecciso, Valeria Giudice, Maria Rosa Motta, Giuseppe Bandini, Loredana Ruggeri, Andrea Velardi, Russel Edward Lewis, Darina Očadlíková, Francesca Bonifazi, Sara Trabanelli, Simonetta Rizzi, Cristina Papayannidis, Andrea Bontadini, Roberto M. Lemoli, Giovanni Martinelli, Michele Cavo, Elena Urbani, Sarah Parisi, Elisa Dan, F. Fruet, Antonio Curti |
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| Přispěvatelé: | Curti, Antonio, Ruggeri, Loredana, Parisi, Sarah, Bontadini, Andrea, Dan, Elisa, Motta, MARIA ROSA, Rizzi, Simonetta, Trabanelli, Sara, Ocadlikova, Darina, Lecciso, MARIANGELA STEFANIA, Giudice, Valeria, Fruet, Fiorenza, Urbani, Elena, Papayannidis, Cristina, Martinelli, Giovanni, Bandini, Giuseppe, Bonifazi, Francesca, Lewis, RUSSEL EDWARD, Cavo, Michele, Velardi, Andrea, M. Lemoli, Roberto |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid Male Isoantigens Cancer Research Oncology medicine.medical_treatment Age Factors Aged Combined Modality Therapy Female Genotype Haplotypes Histocompatibility Testing Humans Immunophenotyping Killer Cells Natural Leukemia Myeloid Acute Middle Aged Phenotype Prospective Studies Receptors KIR3DL1 Recurrence Treatment Outcome Immunotherapy Tissue Donors 0302 clinical medicine Receptors Killer Cells Leukemia Myeloid leukemia Fludarabine medicine.anatomical_structure 030220 oncology & carcinogenesis Natural medicine.drug Cyclophosphamide Acute 03 medical and health sciences KIR3DL1 medicine business.industry medicine.disease Transplantation 030104 developmental biology Immunology business |
| Popis: | In acute myeloid leukemia (AML), alloreactive natural killer (NK) cells are crucial mediators of immune responses after haploidentical stem cell transplantation. Allogeneic NK cell infusions have been adoptively transferred with promising clinical results. We aimed at determining whether the composition of NK graft in terms of frequency of alloreactive NK cells influence the clinical response in a group of elderly AML patients undergoing NK immunotherapy. Purpose: In acute myeloid leukemia (AML), alloreactive natural killer (NK) cells are crucial mediators of immune responses after haploidentical stem cell transplantation. Allogeneic NK cell infusions have been adoptively transferred with promising clinical results. We aimed at determining whether the composition of NK graft in terms of frequency of alloreactive NK cells influence the clinical response in a group of elderly AML patients undergoing NK immunotherapy. Experimental Design: Seventeen AML patients, in first complete remission (CR; median age 64 years, range 53-73) received NK cells from haploidentical KIR-ligand-mismatched donors after fludarabine/cyclophosphamide chemotherapy, followed by IL2. To correlate donor NK cell activity with clinical response, donor NK cells were assessed before and after infusion. Results: Toxicity was moderate, although 1 patient died due to bacterial pneumonia and was censored for clinical follow-up. With a median follow-up of 22.5 months (range, 6-68 months), 9 of 16 evaluable patients (0.56) are alive disease-free, whereas 7 of 16 (0.44) relapsed with a median time to relapse of 9 months (range, 3-51 months). All patients treated with molecular disease achieved molecular CR. A significantly higher number of donor alloreactive NK cell clones was observed in responders over nonresponders. The infusion of higher number of alloreactive NK cells was associated with prolonged disease-free survival (0.81 vs. 0.14, respectively; P = 0.03). Conclusions: Infusion of purified NK cells is feasible in elderly AML patients as post-CR consolidation strategy. The clinical efficacy of adoptively transferred haploidentical NK cells may be improved by infusing high numbers of alloreactive NK cells. |
| Databáze: | OpenAIRE |
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