ABSTRACT
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.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adult , Humans , Transplantation, Homologous , Neoplasm Recurrence, Local , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Transplantation Conditioning/adverse effectsSubject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Aged , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Mutation , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Prognosis , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
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.
