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Key Points Ofatumumab with glucocorticoid therapy for cGVHD resulted in 62.5% ORR at 6 months and 53% FFS at 12 months.Safety was observed with ofatumumab plus glucocorticoid for initial therapy., Visual Abstract, Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01680965.

We conducted a prospective study of adult allogeneic hematopoietic cell transplantation (HCT) recipients to assess pre- and post-HCT physical function. Baseline measurements included a wrist actigraphy, a 6 min walk test (6MWT), an international physical activity questionnaire (IPAQ), and a Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) as well as serial post-HCT assessments of 6MWT, IPAQ, and FACT-BMT. Forty-seven patients were evaluable for functionality assessments, with a median follow-up of 54.5 months for surviving recipients. No patients demonstrated vigorous or very vigorous activity at any time during monitoring by wrist actigraphy; patients spent a median of 6 h daily sedentary. Self-reported activity via the IPAQ showed 36%, 43%, and 21% of subjects reporting light, moderate, and vigorous activity prior to HCT, respectively. Post-HCT 6MWTs on day +30 demonstrated the greatest association with subsequent survival and non-relapse mortality. A decline in 6MWT distance over time also demonstrated worsened overall survival. This study shows the feasibility of fitness assessments and the ability to risk stratify for subsequent mortality, particularly using the 6MWT on the day +30 single time point assessment and change scores from baseline to day +30 post HCT. These pilot findings suggest important targets for future study.

The world is presently infected by the biological fever of COVID-19 caused by SARS-CoV-2 virus. The present study is mainly related to the airborne transmission of novel coronavirus through airway. Similarly, our mother planet is suffering from drastic effects of air pollution. There are sufficient probabilities or evidences proven for contagious virus transmission through polluted airborne-pathway in formed aerosol molecules. The pathways and sources of spread are detailed along with the best possible green control technologies or ideas to hinder further transmission. The combined effects of such root causes and unwanted outcomes are similar in nature leading to acute cardiac arrest of our planet. To maintain environmental sustainability, the prior future of such emerging unknown biological hazardous air emissions is to be thoroughly researched. So it is high time to deal with the future of hazardous air pollution and work on its preventive measures. The lifetime of such an airborne virus continues for several hours, thus imposing severe threat even during post-lockdown phase. The world waits eagerly for the development of successful vaccination or medication but the possible outcome is quite uncertain in terms of equivalent economy distribution and biomedical availability. Thus, risk assessments are to be carried out even during the post-vaccination period with proper environmental surveillance and monitoring. The skilled techniques of disinfection, sanitization, and other viable wayouts are to be modified with time, place, and prevailing climatic conditions, handling the pandemic efficiently. A healthy atmosphere makes the earth a better place to dwell, ensuring its future lifecycle., Graphical abstract, Highlights • Causes and sources of air-borne transmission of SARS-CoV-2 virus • Pathways of airborne transmission via indoor and outdoor atmosphere • Combined effects of SARS-CoV-2 and air particulate emission over the environment • Control mechanism for aerosol particulate transmission of novel coronavirus • Potential future risk linked with COVID-19, air pollution and population

Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n = 293) to MTX/TAC (n = 414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II–IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P = 0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI ⩾ 4 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14–3.04, P = 0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48–1.26, P = 0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II–IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI ⩾ 4.

We hypothesized that tobacco usage is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). To evaluate the impact of tobacco usage in this population, we identified patients diagnosed with MDS in our Center’s MDS database and reviewed individual charts retrospectively. Of the 767 MDS patients identified, 743 patients (97%) had a known tobacco usage history. Given that the majority of tobacco users were smokers, we stratified patients as having never smoked (never-smoker group) versus current or former smokers (ever-smoker group). Greater than 60% of ever-smokers were risk stratified as having low or intermediate-1 (int-1) risk at diagnosis based on the International Prognostic Scoring System for MDS. In patients with lower-risk MDS, we found that ever-smokers had an increased proportion of poor-risk karyotypes (8.8%) compared with never-smokers (2.4%) (P = 0.003). The adverse effect of smoking was greatest in the low-risk and int-1-risk groups, where median overall survival was 69 months (95% CI 42–96) in never-smokers versus 48 months (95% CI 41–55) in ever-smokers (P = 0.006). The median overall survival for never-smokers, former smokers, and current smokers was 69 months (95% CI 42–96), 50 months (95% CI 43–57), and 38 months (95% CI 23–53), respectively, in patients risk stratified as lower-risk MDS (P = 0.01). Our findings suggest that tobacco usage negatively impacts overall survival in patients with lower-risk MDS.

Standard primary therapy for chronic graft-versus-host disease (GVHD) is incompletely effective. Based on biologic insights implicating pathogenic B cells, we conducted a phase I trial examining the combination of standard (1 mg/kg/day prednisone) glucocorticoid therapy with ofatumumab, a humanized anti-CD20 monoclonal antibody, for primary chronic GVHD therapy. Patients ages ≥ 18 with National Institutes of Health Consensus moderate-to-severe chronic GVHD newly requiring 1 mg/kg/day prednisone were treated at 3 escalating dose levels (300 mg, 700 mg, and 1000 mg) of i.v. ofatumumab on days 1 and 14 of initial glucocorticoid therapy. Dose-limiting toxicity (DLT) was defined by grade 4 infusion reactions, related grade 4 constitutional symptoms, related grade ≥ 3 organ toxicities, or grade 4 neutropenia lasting > 14 days. A total of 12 patients (median age 54; range, 25 to 72) were treated (dose level 1: n = 3; level 2: n = 3; level 3: n = 6). At enrollment, overall chronic GVHD was moderate (n = 7) or severe (n = 5), with diverse organ involvement (skin: n = 8; mouth: n = 8; eye: n = 8; lung: n = 4; gastrointestinal: n = 3; liver: n = 5; genital: n = 2; joint/fascia: n = 5). Infusion of ofatumumab was well tolerated, and no DLT was observed. From the total number of adverse events (n = 29), possibly related adverse events (n = 4) included grade 1 fatigue, grade 1 transaminitis, and 2 infusion reactions (grades 2 and 3). Infectious complications were expected, and there were no cases of hepatitis B reactivation or progressive multifocal leukoencephalopathy. Ofatumumab in combination with prednisone is safe and a phase II examination of efficacy is ongoing.