Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median followup of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 10 9/L ) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.

Administration of immune effector cell (IEC) therapy is a complex endeavor requiring extensive coordination and communication of various healthcare and administrative teams. Chimeric antigen receptor (CAR) T cells are the most established IEC therapy available. As of July 2018 two commercial gene therapy products, tisagenlecleucel and axicabtagene ciloleucel, have been approved by the US Food and Drug Administration. To gain insight into the infrastructure and practices across the country, the American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group conducted an electronic survey on the current administrative, logistic, and toxicity management practices of CAR T cell therapy across the United States. This survey consists of 52 responses from institutions of varying sizes, most of which (»80%) had previous investigational experience with CAR T cell therapy. Absorbing the energy of this exciting new treatment has challenged hematopoietic cell transplant programs across the country to strengthen department infrastructure, develop new committees and policies, and implement significant education to ensure safe administration. With the variety of experience with CAR T cell therapy, we hope this survey can contribute to the existing published literature and provide support and consensus to established and developing IEC programs and practice guidelines.

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Resistant gram-positive infections, specifically methicillin-resistant Staphylococcus aureus (MRSA), carry an increased risk for morbidity and mortality. Historically, MRSA has been a cause of nosocomial infections, although recent reports have noted an increased prevalence in community-acquired MRSA infections. Vancomycin is the preferred agent to treat MRSA. However, cases of S. aureus with reduced susceptibility to vancomycin have been reported, prompting the need for alternative treatment options. In this review, we discuss the currently available agents with MRSA activity and those in development. Linezolid and quinupristin/dalfopristin have been demonstrated as effective although potential toxicities must be taken into consideration before their use. Daptomycin, tigecycline, telavancin, and ceftaroline are well tolerated but lack the clinical data to support a superior place in treatment over vancomycin. Several new agents in various stages of development have also demonstrated MRSA activity. Currently, vancomycin remains the gold-standard treatment option for MRSA infections. In situations that limit its use, consideration of patient-specific parameters, cost, and relevant clinical data demonstrating drug safety and efficacy should be employed for the selection of the appropriate alternative agent.

Treatment strategies have changed for patients with advanced melanoma with the use of ipilimumab and vemurafenib as first-line agents. Increased clinical experience and further published data with these and investigational agents will guide the development of treatment algorithms outlining optimal drug selection and sequencing as well as improve management of their novel adverse events.