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Supplementary Information from Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients

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posted on 2023-03-31, 20:25 authored by Harry Dolstra, Mieke W.H. Roeven, Jan Spanholtz, Basav N. Hangalapura, Marleen Tordoir, Frans Maas, Marij Leenders, Fenna Bohme, Nina Kok, Carel Trilsbeek, Jos Paardekooper, Anniek B. van der Waart, Peter E. Westerweel, Tjeerd J.F. Snijders, Jan Cornelissen, Gerard Bos, Hans F.M. Pruijt, Aniek O. de Graaf, Bert A. van der Reijden, Joop H. Jansen, Arnold van der Meer, Gerwin Huls, Jeannette Cany, Frank Preijers, Nicole M.A. Blijlevens, Nicolaas M. Schaap

Supplementary materials and methods, Supplementary Tables and Supplementary Figures File Supplementary Table 1. Characteristics of HSPC-NK cell products. Supplementary Table 2. Functional activity of HSPC-NK cell products. Supplementary Table 3. Adverse events associated with Cy/Flu regimen.

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ARTICLE ABSTRACT

Purpose: Older acute myeloid leukemia (AML) patients have a poor prognosis; therefore, novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting a unique scalable NK-cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPC) from partially HLA-matched umbilical cord blood units.Experimental Design: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30 × 106/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1 × 104 T cells/kg and <3 × 105 B cells/kg body weight. HSPC-NK cells were well tolerated, and neither graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting being given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL15 plasma levels. Moreover, donor chimerism up to 3.5% was found in bone marrow. Interestingly, in vivo HSPC-NK cell maturation was observed, indicated by the rapid acquisition of CD16 and KIR expression, while expression of most activating receptors was sustained. Notably, 2 of 4 patients with minimal residual disease (MRD) in bone marrow before infusion became MRD negative (<0.1%), which lasted for 6 months.Conclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential “off-the-shelf” translational immunotherapy approach in AML. Clin Cancer Res; 23(15); 4107–18. ©2017 AACR.

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