Outcomes of 475 consecutive patients undergoing first allogeneic transplantation for hematologic malignancy performed using T-replete HLA-haploidentical donors and post-transplantation cyclophosphamide (HIDT; n = 116) were compared with contemporaneous patients transplanted from 10 of 10 HLA allele-matched unrelated donors (MUDT; n = 178) or HLA-identical sibling donors (MRDT; n = 181). Uniform supportive care measures and assessments were used. Median follow-up was 45 months. HIDT patients were more likely than MUDT patients to be black (44% versus 2%; P < .001). At 2 years after transplantation, estimates of overall survival were 57% for HIDT, 59% for MUDT, and 72% for MRDT (P not significant [NS] for HIDT versus MUDT; P = .02 for HIDT versus MRDT); corresponding disease-free survival rates were 54%, 50%, and 56% (P NS for both comparisons). The respective cumulative incidences (CIs) of nonrelapse mortality were 17%, 16%, 14%, and those of relapse were 29%, 34%, and 30% (P NS for all). The respective CIs of acute graft-versus-host disease (GVHD) grade II-IV were 41%, 48%, and 28% (P = NS for HIDT versus MUDT; P = .005 for HIDT versus MRDT). At 2 years, the respective CIs of moderate/severe chronic GVHD were 31%, 47%, and 44% (P = .004 for HIDT versus MUDT; P = .032 for HIDT versus MRDT) and 19% of HIDT recipients, 42% of MUDT recipients, and 35% of MRDT recipients were on systemic immunosuppressive treatment (P = .007 for HIDT versus MUDT). In recipients of peripheral blood stem cell grafts, the incidence of moderate-severe chronic GVHD was significantly lower in HIDT recipients compared with MUDT recipients (2-year CI, 25% versus 48%; P = .002). In a multivariate analysis incorporating Disease Risk Index and other significant covariates, survival (hazard ratio [HR], 1.31; P = .15) and disease-free survival (HR, 0.96; P = .79) were not significantly different between HIDT and MUDT recipients, but the incidence of chronic GVHD was lower in HIDT recipients (moderate-severe, HR, 0.59; P = .007). HIDT produced similar long-term survival with lower rates of chronic GVHD than optimally matched MUDT. HIDT should be considered a standard of care option for patients lacking a matched sibling donor.

The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, because multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age were 52 years (range, 19 to 75) and 38 years (range, 15 to 73), peripheral blood stem cell was the stem cell source in 66%, and myeloablative conditioning was used in 41%. Median follow-up for surviving patients was 33 months (range, 7 to 130). Donor variables analyzed included age, sex, relationship, cytomegalovirus (CMV) status, ABO compatibility, HLA disparity, and several natural killer (NK) alloreactivity models. Multivariate Cox analysis was used to adjust for known patient, disease, and transplant covariates. Donor characteristics independently associated with improved survival included presence of HLA-DR mismatch, HLA-DP nonpermissive mismatch, killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch, and KIR B/x haplotype with KIR2DS2. Donor characteristics associated with inferior survival included parental donor relationship and the use of a CMV-seronegative donor for a CMV-seropositive patient. Increased HLA disparity (≥4/10 HLA allelic mismatches [graft-versus-host direction]) resulted in relapse protection at the expense of increased nonrelapse mortality with no associated survival effect. We further propose a donor risk factor scoring system to permit a more evidence-based selection algorithm for potential haplo donors. This large, single-institution analysis demonstrates the importance of HLA-DR/HLA-DP disparity, NK alloreactivity, and other clinical variables in the haplo donor selection process and suggests that KIR and HLA-DP genotyping should be performed routinely for haplo donor selection.

Particulates from air pollution are implicated in causing or exacerbating respiratory and systemic cardiovascular diseases and are thought to be among the leading causes of morbidity and mortality. However, the contribution of ambient particulate matter to diseases affecting the pulmonary circulation, the right heart, and especially pulmonary hypertension is much less documented. Our own work and that of other groups has demonstrated that prolonged exposure to antigens via the airways can cause severe pulmonary arterial remodeling. In addition, vascular changes have been well documented in a typical disease of the airways, asthma. These experimental and clinical findings link responses in the airways with responses in the lung's vasculature. It follows that particulate air pollution could cause, or exacerbate, diseases in the pulmonary circulation and associated pulmonary hypertension. This perspective details the literature for support of this concept. Data regarding the health effects of particulate matter from air pollution on the lung's vasculature, with emphasis on the lung's inflammatory responses to particulate matter deposition and pulmonary hypertension, are discussed. A deeper understanding of the health implications of exposure to ambient particulate matter will improve our knowledge of how to improve the management of lung diseases, including diseases of the pulmonary circulation. As man-made ambient particulate air pollution is typically linked to economic growth, a better understanding of the health effects of exposure to particulate air pollution is expected to integrate the global goal of achieving healthy living for all.

Since its recent discovery, Bourbon virus has been isolated from a human and ticks. To assess exposure of potential vertebrate reservoirs, we assayed banked serum and plasma samples from wildlife and domestic animals in Missouri, USA, for Bourbon virus–neutralizing antibodies. We detected high seroprevalence in raccoons (50%) and white-tailed deer (86%).

Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft. For MRD, MUD and HID transplants respectively, 2-year estimates of non-relapse mortality (17, 23, and 9%), relapse (32, 34, and 33%), overall survival (OS) (62, 55, and 67%) and disease-free survival (DFS) (51, 43, and 58%) were not significantly different. Maximum cumulative incidences of grade 2-4 acute GVHD were not different (27, 37, 39%), but incidences of NIH grade moderate to severe (39, 35, 15%, p = 0.028 MUD vs. HID, p = 0.026 MRD vs. HID) and severe chronic GVHD (9, 12, 0%, p = 0.030 MUD vs. HID, p = 0.009 MRD vs. HID) were significantly higher in MRD and MUD than in HID transplants. On multivariable analysis, donor type was not a significant determinant of OS, DFS, TRM, or relapse. However, male gender and high/very high Disease Risk Index (DRI) were associated with significantly higher rates of relapse (HR 1.94, p = 0.047 for male gender, HR 2.48, p = 0.004 for high/very high DRI) and lower OS (HR 1.94, p = 0.018 for male gender, HR 1.80, p = 0.025 for high/very high DRI). HIDs are an acceptable alternative to matched donors in older patients with AML and MDS.