Hashmi, Shahrukh K.

Abstract Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

The current paper seeks to inform healthcare professionals on how adapting various components of return to work (RTW) programs that are already in use by other musculoskeletal rehabilitation settings can help optimize return to work process for patients with or without musculoskeletal manifestations, posthematopoietic cell transplantation. Since there is no universally agreed RTW structure for hematopoietic cell transplant patients, a narrative approach has been taken utilizing evidence from the existing musculoskeletal return to work assessment publications to help draw parallel for the hematopoietic cell transplant patients. Databases were searched including PUBMED, CINHAL, AMED, SCOPUS, and Cochrane using keywords RTW, functional restoration program, hematopoietic cell transplant, bone marrow transplant, stem cell transplant, and musculoskeletal functional assessment. The authors have managed to outline and propose a structured RTW assessment and monitoring program which can aid in getting patients back to employment by utilizing the functional capacity and job evaluation to help hematopoietic cell transplantation patients reintegrate socially. Patients undergoing hematopoietic cell transplant require additional support and a robust assessment system to allow safe RTW. The proposed model of RTW assessment can prove to be beneficial in helping patients return to work safely. Clinical Significance. To acknowledge the individuality in functional limitation is important in determining not only the rehab needs but also the RTW capabilities. The proposed RTW plan not only promotes an individualized approach to patients but also provides a structure for return to work assessments for hematopoietic cell transplantation patients, thus, eliminating the need for guess work by healthcare professionals. In line with the International Classification of Functioning, Disability, and Health (ICF) recommendations, a RTW assessment combined with a job evaluation helps healthcare professionals and stakeholders to understand the unique challenges and strengths of a patient and thereby design an individualized therapy approach.

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder, and eculizumab and ravulizumab are its two approved therapies. Only few case series/reports have reported the outcomes of pregnancies in patients with PNH despite the increased risk of thrombosis. Similarly, there is limited knowledge regarding the effect of the approved treatments on conception and pregnancy outcomes. Here, we report the first series of pregnancies in PNH patients from the Middle Eastern region from our tertiary care hospital. Ten pregnancies in four females after diagnosis with PNH were identified. In terms of PNH management, only eculizumab was used, as the safety of ravulizumab use in pregnancies has not yet been established. In the antepartum period, the patients had variable symptoms that ranged from mild symptoms including epistaxis, tea-colored urine and vaginal bleeding to life-threatening vessel thrombosis. Further, red blood cell and platelet transfusions were required because of bleeding and hemolysis in four pregnancies. The pregnancy outcomes varied, but based on these, the safety of eculizumab use during pregnancy remained inconclusive. The postpartum period was complicated in one case by portal vein thrombosis and was managed accordingly. In conclusion, pregnant females with PNH are at an increased risk for complications due to PNH, and thus experienced hematologists and obstetricians should be involved jointly in their care.

AbstractSecondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy‐related AML. Large registry‐based data identified sAML as an independent poor‐outcome type of AML post allogeneic hematopoietic cell transplantation (allo‐HCT). In our study, we tried to define factors affecting outcomes of sAML post allo‐HCT, and identify patients with sAML who may truly benefit from allo‐HCT. We retrospectively analyzed the data of 64 patients aged (14‐61 years) with sAML who received allo‐HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor‐risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease‐free survival (DFS; P‐value = .009, and .004, respectively). The cumulative incidence of chronic graft‐versus‐host disease (cGVHD) was significantly lower in sAML patients with poor‐risk cytogenetics (P‐value = .003) resulting in a high risk of death without cGVHD in this group of patients (P‐value = .02). Besides, GVHD relapse‐free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II‐IV cGVHD in the first 2 years post allo‐HCT. We conclude that sAML patients with poor‐risk cytogenetics have a significantly lower DFS post allo‐HCT with a high risk of death without active cGVHD.

Objective Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. Methods We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. Results The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). Conclusions We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction

The COVID-19, due to SARS-CoV-2, has uncovered many real-world issues when it comes to healthcare management and has led to a widespread mortality. Observations thus far from the reports of COVID-19 have indicated that certain risk groups for example, those with pre-existing cardiovascular (CV) disease, hypertension, diabetes, chronic kidney disease and tobacco use are prone to disease development and specifically development of severe disease and possible fatality. It is increasingly evident that many CV conditions occur frequently. These include myopericarditis, acute coronary syndromes, thrombosis, arrhythmias, hypertension and heart failure. Many professional organisations and societies related to cardiology have produced guidelines or recommendations on most of the above-mentioned aspects. Given these rapid developments, the aims of this review manuscript were to summarise and integrate recent publications with newly developed guidelines and with the first-hand experience of frontline physicians and to yield a pragmatic insight and approach to CV complications of COVID-19. We emphasise on a strategic tier-based approach for initial assessment and management of COVID-19, and then delve into focused areas within CV domains, and additionally highlighting the role of point-of-care ultrasound especially lung ultrasound, echocardiography and electrocardiography, in the management of these patients. We hope this paper will serve as a useful tool in the CV management of COVID-19 for clinicians practicing in both developing and developed countries.

Abstract Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

BackgroundThe association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.MethodsThis study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014‐2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.ResultsThe median age was 55 years (range, 18‐83 years). The median PCS was –0.21 (range, –1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was –0.13 (range, –1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00‐1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00‐1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02‐1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM.ConclusionsPatients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.