T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and leukemic relapse. In human transplants, we show that donor-versus-recipient natural killer (NK)-cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against GVHD. In mice, the pretransplant infusion of alloreactive NK cells obviated the need for high-intensity conditioning and reduced GVHD. NK cell alloreactivity may thus provide a powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.

Because of the expression of inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I allotypes, a person’s natural killer (NK) cells will not recognize and will, therefore, kill cells from individuals lacking his/her KIR epitopes. This study investigated the role of NK cell alloreactivity in human HLA haplotype-mismatched hematopoietic stem cell transplantation and, specifically, the role of the three major NK specificities, ie, those for HLA-C group 1, HLA-C group 2, and HLA-Bw4 alleles. In 20 of 60 donor-recipient pairs, KIR epitope incompatibility and functional analyses of donor NK cell clones predicted donor NK cells could cause graft-versus-host (GVH)/graft-versus-leukemia (GVL) reactions. NK cell clones of donor origin were obtained from transplanted recipients and tested for lysis of recipient’s cryopreserved pretransplant lymphocytes. Despite the absence of GVH disease, we detected high frequencies of NK clones which killed recipient’s target cells. Lysis followed the rules of NK cell alloreactivity, being blocked only by the MHC class I KIR epitope which was missing in the recipient. The alloreactive NK clones also killed the allogeneic leukemia. Transplants from these KIR epitope incompatible donors had higher engraftment rates. Therefore, a GVL effector and engraftment facilitating mechanism, which is independent of T-cell–mediated GVH reactions, may be operational in HLA mismatched hematopoietic cell transplants.

Aspergillus and cytomegalovirus are major causes of morbidity/mortality after haploidentical hematopoietic transplantation. The high degree of mismatching makes cell immunotherapy impossible as it would result in lethal graft-versus-host disease (GvHD). We generated large numbers of donor T-cell clones specific for Aspergillus or cytomegalovirus antigens. We identified clones potentially responsible for causing GvHD by screening them for cross-reactivity against recipient mononuclear cells. Nonrecipient reactive, pathogen-specific clones were infused soon after transplantation. They were CD4 ؉ and produced high levels of interferon-␥ and low levels of interleukin-10. In 46 control transplant recipients who did not receive adoptive therapy, spontaneous pathogen-specific T cells occurred in low frequency 9 to 12 months after transplantation and displayed a nonprotective low interferon-␥/high interleukin-10 production phenotype.

Onychomycosis is a fungal infection of the nail, causing discoloration and thickening of the affected nail plate, and is the most common nail infection worldwide. Onychomycosis was initially thought to be predominantly caused by dermatophytes; however, new research has revealed that mixed infections and those caused by non‐dermatophyte moulds (NDMs) are more prevalent than previously thought, especially in warmer climates. Microscopy and fungal culture are the gold standard techniques for onychomycosis diagnosis, but high false‐negative rates have pushed for more accurate methods, such as histology and PCR. As NDMs are skin and laboratory contaminants, their presence as an infectious agent requires multiple confirmations and repeated sampling. There are several treatment options available, including oral antifungals, topicals and devices. Oral antifungals have higher cure rates and shorter treatment periods than topical treatments, but have adverse side effects such as hepatotoxicity and drug interactions. Terbinafine, itraconazole and fluconazole are most commonly used, with new oral antifungals such as fosravuconazole being evaluated. Topical treatments, such as efinaconazole, tavaborole, ciclopirox and amorolfine have less serious side effects, but also have generally lower cure rates and much longer treatment regimens. New topical formulations are being investigated as faster‐acting alternatives to the currently available topical treatments. Devices such as lasers have shown promise in improving the cosmetic appearance of the nail, but due to a high variation of study methods and definitions of cure, their effectiveness for onychomycosis has yet to be sufficiently proven. Recurrence rates for onychomycosis are high; once infected, patients should seek medical treatment as soon as possible and sanitize their shoes and socks. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurrence.