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Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen– Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory.

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Presentation on theme: "Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen– Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory."— Presentation transcript:

1 Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen– Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia  Inpyo Choi, Suk Ran Yoon, Soo-Yeon Park, Hanna Kim, Sol-Ji Jung, You-Lee Kang, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Jae- Lyun Lee, Han-Seung Park, Eun-Ji Choi, Young-Shin Lee, Young-A. Kang, Mijin Jeon, Miee Seol, Seunghyun Baek, Sung-Cheol Yun, Hwa Jung Kim, Kyoo-Hyung Lee  Biology of Blood and Marrow Transplantation  Volume 22, Issue 11, Pages (November 2016) DOI: /j.bbmt Copyright © 2016 The American Society for Blood and Marrow Transplantation Terms and Conditions

2 Figure 1 Treatment paradigm. (A) Outline of the treatment paradigm of the current study of HLA-haploidentical HCT and subsequent DNKI. Patients received conditioning therapy for HCT with busulfan, fludarabine, and antithymocyte globulin between days −7 and −1. Hematopoietic cell donors underwent 2 sessions of cell collection. For the first session, the donors received daily G-CSF starting on day −10 and underwent large-volume leukapheresis on day −7. For the second session of cell collection, beginning on day −3, the donor received G-CSF daily for 5 to 6 days and underwent daily leukapheresis for 2 to 4 days beginning on day 0. Mononuclear cells collected during the first 1 to 3 days of the second session were infused into patients through central venous catheters on the same day for the purpose of HCT. Cells collected in the first session and on the last day of the second session were transported to the laboratory, where they were depleted of CD3+ cells and differentiated into NK cells ex vivo. The donor NK cells generated were infused into patients 4 times on days 6, 9, 13, and 20 of HCT. (B) Treatment paradigm of the haploidentical HCT and DNKI of the previous study from this hospital [28] where the cell donors underwent only 1 session of leukapheresis and the patients received ex vivo–generated donor NK cells twice, 2 and 3 weeks after HCT. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2016 The American Society for Blood and Marrow Transplantation Terms and Conditions

3 Figure 2 Frequency and outcomes of toxicity observed during donor-derived NK cell infusions after HLA-haploidentical HCT. Of 45 evaluated patients, 33 (73%) showed experienced DNKI-associated toxicity with fever (>38.3°C), along with body weight increase (>5%) and/or hyperbilirubinemia (>2 mg/dL). MOF indicates mutiorgan failure. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2016 The American Society for Blood and Marrow Transplantation Terms and Conditions

4 Figure 3 Engraftment, GVHD, leukemia progression, NRM, and patient survival after HLA-haploidentical HCT with subsequent infusion of donor-derived NK cells. Cumulative incidence curves are depicted for (A) donor cell engraftment, (B) acute and chronic GVHD, and (C) leukemia progression and NRM. (D) Kaplan-Meier plots of event-free and overall survival outcomes are also depicted. Red lines represent the current study cohort of patients (n = 51) while black lines represent the historical cohort (n = 40). (This figure is available in color online at Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2016 The American Society for Blood and Marrow Transplantation Terms and Conditions

5 Figure 4 Leukemia progression and patient survival in the entire cohort of 91 patients who underwent HLA-haploidentical HCT with subsequent infusion of donor-derived NK cells. Cumulative incidence of leukemia progression according to (A) diagnosis (AML versus ALL), (B) requirement for cytoreductive chemotherapy before HCT, and (C) NKp30 expression of donor NK cells (≤90% versus >90%). (D) Kaplan-Meier plots of EFS and OS according to the requirement for cytoreductive chemotherapy before HCT. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2016 The American Society for Blood and Marrow Transplantation Terms and Conditions


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