Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs). We illustrate the advantages of NK alloreactivity as demonstrated in various types of hematopoietic stem cell transplants (HSCT), such as haploidentical, human leukocyte antigen-matched related or unrelated donor and umbilical cord blood transplant. We elaborate on different models used to predict NK cell alloreactivity in these studies, which are either based on the absence of the ligands for inhibitory KIRs, presence of activating NK cell receptors and KIR genes content in donors, or a combination of these. We will review clinical studies demonstrating anti-tumor efficacy of NK cells used either as a stand-alone immunotherapy or as an adjunct to HSCT and novel genetic engineering strategies to improve the anti-tumor activity of NK cells.

phoma Group. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. Lancet Haematol. 2015;2(9):e357-e366. 7. Montesinos P, Bergua JM, Vellenga E, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775-783.

BACKGROUND: The current standard practice in North America is to cryopreserve mobilized autologous stem cells for use after high dose chemotherapy for multiple myeloma. Fresh autologous stem cell infusions are used infrequently around the world for this same purpose with comparable efficacy. This study aims to compare short term outcomes after autologous transplant with fresh versus (vs) cryopreserved (cryo) stem cells. METHODS: Sixty-four (64) consecutive patients who underwent autologous stem cells for multiple myeloma at our center between June 2018 and December 2019 were grouped based on whether fresh or cryopreserved product was used for transplantation. The primary outcomes included the number of days until neutrophil and platelet recovery. The secondary outcome was length of hospital stay (LOS). After mobilization with G-CSF with or without plerixafor, peripheral blood stem cells were harvested over 1 day. For the fresh group, the collected cells were stored at 4 °C in the cell therapy laboratory for up to 48 hours. Meanwhile, the patient underwent high-dose melphalan treatment, 24 hours following which, the autologous stem cells were infused. In the cryopreserved group, the cells were cryopreserved for variable lengths of time until their infusion 48 hours after high-dose melphalan therapy. RESULTS: Thirty-two (32) patients received fresh product and 32 received cryopreserved product. Baseline characteristics were similar between the groups and summarized in Table 1. Median CD34 count at infusion was 3.90 (range 2.83 to 5.68) million/kg in the fresh group and 4.32 (range 2.46 to 7.41) million/kg in the cryopreserved group, which was not statistically different (p= 0.07). Thirty patients in the fresh group and 27 in the cryo group received plerixafor. All the patients engrafted. The median time to neutrophil engraftment was 11 days (range 10-13 days) in the fresh group compared to 12 days (range 10-18 days) in the cryopreserved group (10.71±0.77 vs 12.18±1.71 days. P= 0.90). ANC <500 developed earlier in the fresh group vs cryopreserved group at median of 5 vs 8 days respectively (5.46±0.8 vs 7.78±1.07 days. P = <0.0001) and the duration of neutropenia was not significantly longer (6.25±1.04 vs 6.4±1.96 days. P = 0.70). The median time to platelet engraftment was 18 days (range 14-21 days) in the fresh group versus 23 days (range 16-50 days) in the cryopreserved group (16.25±4.72 vs 23±6.53 days. P < 0.0001). The median LOS was 13 days (range 10-21 days) in the fresh group versus 17 days (range 13-30) in the cryopreserved group (13.25±2.83 vs 16.59±4.18 days. P = 0.0004). CONCLUSIONS: Time to platelet engraftment and length of stay in the hospital were significantly shorter with use of fresh autologous stem cells compared to cryopreserved cell for transplantation for multiple myeloma. Despite earlier development of neutropenia in the fresh group, time to engraftment and duration of neutropenia were not significantly longer. CD34 cell dose was actually lower in the fresh group, with the difference approaching statistical significance. The use of fresh autologous product is both feasible and safe. Early hematologic recovery, particularly in terms of platelet engraftment with use of fresh product has further helped with early discharge from the transplant clinic to the referring oncologists. It has also led to subsequent utilization of this approach in performing outpatient autologous transplants at our center. Table Disclosures Randolph: Bristol Myers Squibb, Celgene: Speakers Bureau. Khaled:Celgene, Seattle Genetics, Jazz, Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for some patients with hematologic conditions. There are two main types of HSCT. This includes autologous HSCT, for which the stem cells are obtained from the patient, and allogeneic HSCT, for which the stem cells are obtained from a related or unrelated donor. The most common indications for autologous stem cell transplant are multiple myeloma and relapsed/refractory lymphoma, whereas leukemia and bone marrow failure syndromes remain the most common indications for allogeneic stem cell transplant. This chapter will review the different types, indications, processes, and main complications of HSCT. This chapter will also discuss end-of-life issues that patients and providers face when transplant patients are admitted for the intensive care unit.

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease—a major complication of allogeneic HCT—to enable the patient and clinician to assess management options in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.