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Article: NKAML: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia

TitleNKAML: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia
Authors
Issue Date2010
Citation
Journal of Clinical Oncology, 2010, v. 28, n. 6, p. 955-959 How to Cite?
AbstractPurpose: To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). Patients and Methods: Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day -7) and fludarabine (25 mg/m2/d on days -6 through -2), followed by killer immunoglobulin-like receptor-human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 × 106/kg NK cells) and six doses of interleukin-2 (1 million U/m2). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results: All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). Conclusion: Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML. © 2010 by American Society of Clinical Oncology.
Persistent Identifierhttp://hdl.handle.net/10722/294433
ISSN
2020 Impact Factor: 44.544
2015 SCImago Journal Rankings: 9.204
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRubnitz, Jeffrey E.-
dc.contributor.authorInaba, Hiroto-
dc.contributor.authorRibeiro, Raul C.-
dc.contributor.authorPounds, Stanley-
dc.contributor.authorRooney, Barbara-
dc.contributor.authorBell, Teresa-
dc.contributor.authorPui, Ching Hon-
dc.contributor.authorLeung, Wing-
dc.date.accessioned2020-12-03T08:22:43Z-
dc.date.available2020-12-03T08:22:43Z-
dc.date.issued2010-
dc.identifier.citationJournal of Clinical Oncology, 2010, v. 28, n. 6, p. 955-959-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/294433-
dc.description.abstractPurpose: To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). Patients and Methods: Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day -7) and fludarabine (25 mg/m2/d on days -6 through -2), followed by killer immunoglobulin-like receptor-human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 × 106/kg NK cells) and six doses of interleukin-2 (1 million U/m2). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results: All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). Conclusion: Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML. © 2010 by American Society of Clinical Oncology.-
dc.languageeng-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titleNKAML: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1200/JCO.2009.24.4590-
dc.identifier.pmid20085940-
dc.identifier.pmcidPMC2834435-
dc.identifier.scopuseid_2-s2.0-77949898005-
dc.identifier.volume28-
dc.identifier.issue6-
dc.identifier.spage955-
dc.identifier.epage959-
dc.identifier.eissn1527-7755-
dc.identifier.isiWOS:000274653200011-
dc.identifier.issnl0732-183X-

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