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Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research Inc., 2016.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....cbdafaff4833a7e0ebdac70510f7766b