The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.

Prior mechanical circulatory support and the acute need for CRRT may predispose OHT patients to an infection early in the post-operative period. Evaluation of peri-operative antimicrobial prophylaxis, based on an individual center's resistance panels, may be warranted.

Limited guidance exists for dosing melphalan for autologous stem cell transplantation (ASCT) in the obese patient population, because the current literature reports conflicting clinical outcomes between obese and nonobese patients. In 2014, the American Society for Blood and Marrow Transplantation published conditioning chemotherapy dosing guidelines for obese patients and recommended dosing of melphalan using actual body weight (ABW) in the body surface area calculation. The practice at Barnes-Jewish Hospital has consistently been to dose melphalan using adjusted body weight (AdBW), with a 20% correction when a patient weighs ≥120% of his or her ideal body weight (IBW). The purpose of this study was to compare outcomes of melphalan ASCT in patients with multiple myeloma between obese (≥120% IBW) and nonobese (<120% IBW) populations. This retrospective, single-center study included adult patients with multiple myeloma undergoing first ASCT with melphalan conditioning between January 2009 and December 2012. Patient demographic data, transplantation characteristics, and clinical outcomes were collected. The primary outcome was 3-year event-free survival (EFS). Secondary outcomes included response at 100 days post-transplantation, 3-year overall survival, treatment-related mortality (TRM), time to neutrophil engraftment, and hospital length of stay (LOS). To ensure that melphalan dosage adjustment in the obese population did not impact efficacy, the primary outcome was assessed using a noninferiority design, with a predetermined noninferiority margin of 7%. Assuming a 70% 3-year EFS in the nonobese population, a noninferiority margin of 7%, a power of 80%, and an α value of .05, an analysis of 280 patients was required. A total of 270 patients, including 171 (63%) obese patients and 99 (37%) nonobese patients, met our inclusion criteria. Baseline characteristics were well matched between the 2 cohorts, including high-risk cytogenetics, disease severity at diagnosis, and use of maintenance therapy, with the only detectable differences related to weight itself. The 3-year EFS was 41% for the total cohort, with fewer events occurring in the obese cohort compared with the nonobese cohort (51% versus 40%; P = .0025). The 95% lower confidence limit established noninferiority. High-risk cytogenetics, disease severity at diagnosis, and therapy response pre- and post-ASCT were all associated with significantly shorter EFS. No between-group differences in TRM, time to engraftment, or hospital LOS were noted. This retrospective, single-center study found that using AdBW to dose melphalan in obese patients was not inferior to the nonobese population in terms of 3-year EFS. This study adds to the limited evidence on melphalan dosing and suggests that transplantation efficacy is not affected by AdBW dosing in obese patients. Further studies are needed to provide additional insight into the pharmacokinetic differences and best dosing practices for obese patients.

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