Publications by authors named "Shahrukh K Hashmi"

133 Publications

Recommendations on service delivery to help reduce suffering and anxiety in patients and caregivers post-hematopoietic cell transplantation: a case report.

J Med Case Rep 2021 Nov 5;15(1):549. Epub 2021 Nov 5.

Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Background: The aim of this study is to highlight the importance of having a central case managing team and to make some strong recommendations that can have a positive impact on the lives of hematopoietic stem cell transplantation survivors.

Case Presentation: A 2-year-old white child who was diagnosed with acute myeloid leukemia and underwent hematopoietic stem cell transplantation in May 2014 relapsed in March 2017, and underwent a second hematopoietic stem cell transplantation in July 2017, at which point he suffered from graft-versus-host disease. This case report presents his journey and that of his caregivers, and the challenges they faced as patient and parents in pursuit of optimal quality of life during the survivorship period. The case study emphasizes not only the challenges faced by patients but also identified gaps in post-hematopoietic cell transplantation care service delivery. Furthermore, the case study also highlights the importance of involving caregivers in post-transplant care and having a better communication process and service facilitation process throughout the journey of the patient and their carer.

Conclusions: Transplant centers have a duty of care, and a proactive approach with a well-defined pathway is needed for managing post-transplant complications and reducing stress and anxiety for patients and their caregivers.
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http://dx.doi.org/10.1186/s13256-021-03126-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569970PMC
November 2021

Blockchain Integration With Digital Technology and the Future of Health Care Ecosystems: Systematic Review.

J Med Internet Res 2021 11 2;23(11):e19846. Epub 2021 Nov 2.

Division of Hematology, Mayo Clinic, Rochester, MN, United States.

Background: In the era of big data, artificial intelligence (AI), and the Internet of Things (IoT), digital data have become essential for our everyday functioning and in health care services. The sensitive nature of health care data presents several crucial issues such as privacy, security, interoperability, and reliability that must be addressed in any health care data management system. However, most of the current health care systems are still facing major obstacles and are lacking in some of these areas. This is where decentralized, secure, and scalable databases, most notably blockchains, play critical roles in addressing these requirements without compromising security, thereby attracting considerable interest within the health care community. A blockchain can be maintained and widely distributed using a large network of nodes, mostly computers, each of which stores a full replica of the data. A blockchain protocol is a set of predefined rules or procedures that govern how the nodes interact with the network, view, verify, and add data to the ledger.

Objective: In this article, we aim to explore blockchain technology, its framework, current applications, and integration with other innovations, as well as opportunities in diverse areas of health care and clinical research, in addition to clarifying its future impact on the health care ecosystem. We also elucidate 2 case studies to instantiate the potential role of blockchains in health care.

Methods: To identify related existing work, terms based on Medical Subject Headings were used. We included studies focusing mainly on health care and clinical research and developed a functional framework for implementation and testing with data. The literature sources for this systematic review were PubMed, Medline, and the Cochrane library, in addition to a preliminary search of IEEE Xplore.

Results: The included studies demonstrated multiple framework designs and various implementations in health care including chronic disease diagnosis, management, monitoring, and evaluation. We found that blockchains exhibit many promising applications in clinical trial management such as smart-contract application, participant-controlled data access, trustless protocols, and data validity. Electronic health records (EHRs), patient-centered interoperability, remote patient monitoring, and clinical trial data management were found to be major areas for blockchain usage, which can become a key catalyst for health care innovations.

Conclusions: The potential benefits of blockchains are limitless; however, concrete data on long-term clinical outcomes based on blockchains powered and supplemented by AI and IoT are yet to be obtained. Nonetheless, implementing blockchains as a novel way to integrate EHRs nationwide and manage common clinical problems in an algorithmic fashion has the potential for improving patient outcomes, health care experiences, as well as the overall health and well-being of individuals.
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http://dx.doi.org/10.2196/19846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596226PMC
November 2021

Current status and future perspectives on the Internet of Things in oncology.

Hematol Oncol Stem Cell Ther 2021 Oct 18. Epub 2021 Oct 18.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Medicine, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates. Electronic address:

The Internet of Things (IoT) has penetrated many aspects of everyday human life. The use of IoT in healthcare has been expanding over the past few years. In this review, we highlighted the current applications of IoT in the medical literature, along with the challenges and opportunities. IoT use mainly involves sensors and wearables, with potential applications in improving the quality of life, personal health monitoring, and diagnosis of diseases. Our literature review highlights that the current main application studied in the literature is physical activity tracking. In addition, we discuss the current technologies that would help IoT-enabled devices achieve safe, quick, and meaningful data transfer. These technologies include machine learning/artificial intelligence, 5G, and blockchain. Data on current IoT-enabled devices are still limited, and future research should address these devices' effect on patients' outcomes and the methods by which their integration in healthcare will avoid increasing costs.
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http://dx.doi.org/10.1016/j.hemonc.2021.09.003DOI Listing
October 2021

Historical perspective and a glance into the antibody-based conditioning regimens: A new era in the horizon?

Blood Rev 2021 Oct 16:100892. Epub 2021 Oct 16.

Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, UAE; Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

The hematopoietic cell transplantation practice has changed significantly over the years. More than 1500 centers around the globe are offering transplant for different types of diseases. This growth was driven by improving the efficacy and the safety of the procedure and the ability to use alternate donors. These improvements made the procedure feasible in virtually all patients in need for it. With the availability of novel therapies and targeted agents, we may be witnessing a new transplant-era. These agents may help to circumvent some of the remaining limitations of the procedure and open the doors for new indications. Herein, we review historical transplant milestones, the accomplishments that led to the modern transplant practice and we discuss the idea of minimal-intensity conditioning and the possibility to adopt chemotherapy and radiation-free preparative regimens in the near future.
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http://dx.doi.org/10.1016/j.blre.2021.100892DOI Listing
October 2021

Machine Learning Applications in the Diagnosis of Benign and Malignant Hematological Diseases.

Clin Hematol Int 2021 Mar 21;3(1):13-20. Epub 2020 Dec 21.

Department of Medicine, Mayo Clinic, Rochester, MN, USA.

The use of machine learning (ML) and deep learning (DL) methods in hematology includes diagnostic, prognostic, and therapeutic applications. This increase is due to the improved access to ML and DL tools and the expansion of medical data. The utilization of ML remains limited in clinical practice, with some disciplines further along in their adoption, such as radiology and histopathology. In this review, we discuss the current uses of ML in diagnosis in the field of hematology, including image-recognition, laboratory, and genomics-based diagnosis. Additionally, we provide an introduction to the fields of ML and DL, highlighting current trends, limitations, and possible areas of improvement.
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http://dx.doi.org/10.2991/chi.k.201130.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432325PMC
March 2021

Understanding the Process and Challenges for Return-to-Work Post-Hematopoietic Cell Transplantation from a Musculoskeletal Perspective: A Narrative Review.

Occup Ther Int 2021 6;2021:5568513. Epub 2021 Jul 6.

Rehabilitation Association for Hematopoietic Cell Transplantation, Gloucester, UK.

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. . 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.
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http://dx.doi.org/10.1155/2021/5568513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277503PMC
July 2021

Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.

Transplant Cell Ther 2021 08;27(8):642-649

West Virginia University, Morgantown, West Virginia.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.
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http://dx.doi.org/10.1016/j.jtct.2021.04.007DOI Listing
August 2021

Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.

N Engl J Med 2021 07;385(3):228-238

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Background: Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD.

Methods: This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24.

Results: A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups.

Conclusions: Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).
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http://dx.doi.org/10.1056/NEJMoa2033122DOI Listing
July 2021

Post-Marketing Analysis of Peripheral Neuropathy Burden with New-Generation Proteasome Inhibitors Using the FDA Adverse Event Reporting System

Turk J Haematol 2021 08 30;38(3):218-221. Epub 2021 Jun 30.

Mayo Clinic, Department of Medicine, Rochester, USA

Proteasome inhibitors (PIs) are an integral component of multiple myeloma therapies. Peripheral neuropathy (PN) is a well-knownconsequence of PIs, most frequently reported with earlier generations such as bortezomib (BTZ). There is a paucity of data highlighting the risk of developing PN with the new-generation PIs carfilzomib (CFZ) and ixazomib (IZB). This study evaluated reports of PN encountered with all three PIs using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS). Signal disproportionality analysis was reported using the reporting odds ratio (ROR) with 95% confidence interval (CI). PN was reported in a total of 2.1%, 5.0%, and 10.9% of AEs with CFZ, IZB, and BTZ, respectively. The ROR (95% CI) for PN secondary to BTZ, CFZ, and IZB was 34.10 (32.76-35.49), 6.37 (5.50-7.37), and 14.97 (13.63-16.44), respectively. Compared to BTZ, CFZ and IZB have lower rates of reported PN, with RORs of 0.19 (0.16-0.22) and 0.48 (0.43-0.54), respectively.
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http://dx.doi.org/10.4274/tjh.galenos.2021.2021.0052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386311PMC
August 2021

Methods to Assess Disease Activity and Severity in Cutaneous Chronic Graft-versus-Host Disease: A Critical Literature Review.

Transplant Cell Ther 2021 09 6;27(9):738-746. Epub 2021 Jun 6.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Chronic graft-versus-host disease (cGVHD), a potentially debilitating complication of hematopoietic cell transplantation, confers increased risk for mortality. Whereas treatment decisions rely on an accurate assessment of disease activity/severity, validated methods of assessing cutaneous cGVHD activity/severity appear to be limited. In this study, we aimed to identify and evaluate current data on the assessment of disease activity/severity in cutaneous cGVHD. Using modified PRISMA methods, we performed a critical literature review for relevant articles. Our literature search identified 1741 articles, of which 1635 were excluded as duplicates or failure to meet inclusion criteria. Of the included studies (n = 106), 39 (37%) addressed clinical and/or histopathologic parameters, 53 (50%) addressed serologic parameters, 8 (7.5%) addressed imaging parameters, and 6 (5.5%) addressed computer-based technologies. The only formally validated metric of disease activity/severity assessment in cutaneous cGVHD is the National Institutes of Health consensus scoring system, which is founded on clinical assessment alone. The lack of an objective marker for cGVHD necessitates further studies. An evaluation of the potential contributions of serologic, imaging, and/or computer-based technologies is warranted.
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http://dx.doi.org/10.1016/j.jtct.2021.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719782PMC
September 2021

Breaking the Age Barrier: Physicians' Perceptions of Candidacy for Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Transplant Cell Ther 2021 07 6;27(7):617.e1-617.e7. Epub 2021 Apr 6.

City of Hope, Duarte, California.

Despite continuing increases in the use of allogeneic hematopoietic cell transplantation (alloHCT) in older adults, no standardized geriatric assessment (GA) has been established to risk stratify for transplantation-related morbidity. We conducted a survey of transplant physicians to determine perceptions of the impact of older age (≥60 years) on alloHCT candidacy, and utilization of tools to gauge candidacy. This 23-item online cross-sectional survey was distributed to HCT physicians caring for adults in the United States between May and July 2019. Of the 770 invited HCT physicians, 175 (22.7%) completed the survey. The majority of respondents were age 41 to 60 years and male and practiced in a higher-volume teaching hospital. When considering regimen intensity, 29 physicians (17%) stated they would consider a myeloablative regimen for patients age ≥70 years, and 141 (82%) would consider reduced-intensity/nonmyeloablative conditioning for patients age ≥70 years. Almost all (90%) endorsed the need for a specialized assessment of pre-HCT vulnerabilities to guide candidacy decisions for older adults. Most physicians reported that their centers rarely (33%) or never (46%) use a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates age ≥60 years. Common barriers to performing a GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff. Many alloHCT physicians will consider alloHCT in patients up to age 75 years and not uncommonly in patients older than that. However, the application of tools and domains to assess candidacy in older adults varies widely. Incorporation of a standardized pretransplantation health assessment tool for risk stratification is a significant unmet need.
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http://dx.doi.org/10.1016/j.jtct.2021.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254775PMC
July 2021

Systematic Review/Meta-Analysis on Efficacy of Allogeneic Hematopoietic Cell Transplantation in Sickle Cell Disease: An International Effort on Behalf of the Pediatric Diseases Working Party of European Society for Blood and Marrow Transplantation and the Sickle Cell Transplantation International Consortium.

Transplant Cell Ther 2021 02 10;27(2):167.e1-167.e12. Epub 2020 Dec 10.

Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, Florida. Electronic address:

Sickle cell disease (SCD) affects more than 300,000 children annually worldwide. Despite improved supportive care, long-term prognosis remains poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole validated curative option, resulting in sustained resolution of the clinical phenotype. The medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated allo-HCT efficacy in adults. Here, we conducted a systematic review/meta-analysis to assess the totality of evidence on the efficacy, or lack thereof, of allo-HCT in treating SCD. We performed a comprehensive literature search using PubMed/Medline, Embase, and Cochrane library databases on November 13, 2019. Four authors independently extracted data on clinical outcomes related to benefits (overall survival [OS] and disease-free survival [DFS]) and harms (acute graft-versus-host disease [aGVHD], chronic graft-versus-host disease [cGVHD], nonrelapse mortality [NRM], and graft failure [GF]). Our search identified a total of 1906 references. Only 33 studies (n= 2853 patients) met our inclusion criteria. We also performed a subset analysis by age. Analyses of all-age groups showed pooled rates of 96% for OS, 90% for DFS, 20% for aGVHD, 10% for cGVHD, 4% for NRM, and 5% for GF. In the pediatric population, pooled rates for OS, DFS, aGVHD, cGVHD, NRM, and GF were 97%, 91%, 26%, 11%, 5%, and 3%, respectively. In adults, pooled rates for OS, DFS, aGVHD, cGVHD, NRM, and GF were 98%, 90%, 7%, 1%, 0%, and 14%, respectively. Our data show that allo-HCT is safe and effective, yielding pooled OS rates exceeding 90%. The high GF rate of 14% in adults is concerning and emphasizes the need to evaluate new strategies.
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http://dx.doi.org/10.1016/j.jtct.2020.10.007DOI Listing
February 2021

Worldwide Network for Blood and Marrow Transplantation (WBMT) Recommendations Regarding Essential Medications Required To Establish An Early Stage Hematopoietic Cell Transplantation Program.

Transplant Cell Ther 2021 03 16;27(3):267.e1-267.e5. Epub 2020 Dec 16.

Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.
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http://dx.doi.org/10.1016/j.jtct.2020.12.015DOI Listing
March 2021

Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions.

Hematol Oncol Stem Cell Ther 2021 Dec 7;14(4):290-301. Epub 2021 Mar 7.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment.
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http://dx.doi.org/10.1016/j.hemonc.2021.02.001DOI Listing
December 2021

Awareness of myeloma care and the global impact of treatment: An international internet-based prospective study.

J Oncol Pharm Pract 2021 Mar 9:10781552211001928. Epub 2021 Mar 9.

Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL, USA.

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.
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http://dx.doi.org/10.1177/10781552211001928DOI Listing
March 2021

Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease

Transplant Cell Ther 2021 02 21;27(2):177.e1-177.e8. Epub 2020 Dec 21.

Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, PA.

Variation in the gastrointestinal (GI) microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD risk in pediatric patients undergoing HCT for acute leukemia. We performed a retrospective analysis in a dataset merged from 2 sources: (1) the Center for International Blood and Marrow Transplant Research, an observational transplantation registry, and (2) the Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to 3 classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) antipseudomonal penicillins, and (3) carbapenems. The primary outcome was grade II-IV aGVHD; secondary outcomes were grade III-IV aGVHD and lower GI GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (subcohort) included transplantation characteristics, GVHD risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2550 patients at 36 centers; the subcohort included 1174 patients. In adjusted models, carbapenems were associated with an increased risk of grade II-IV aGVHD in the full cohort (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.02 to 1.51) and subcohort (sub hazard ratio [HR], 1.31; 95% CI, 0.99 to 1.72), as well as with an increased risk of grade III-IV aGVHD (subHR, 1.77; 95% CI, 1.25 to 2.52). Early carbapenem exposure (before day 0) especially impacted aGVHD risk. For antipseudomonal penicillins, the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad-spectrum antibiotics, should be used judiciously in pediatric HCT recipients to minimize aGVHD risk. Further research is needed to clarify the mechanism underlying this association.
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http://dx.doi.org/10.1016/j.jtct.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946150PMC
February 2021

Association of graft-versus-host-disease with neurologic complications: clinical paradigm and future directions.

Bone Marrow Transplant 2021 06 9;56(6):1471-1473. Epub 2021 Feb 9.

Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1038/s41409-021-01216-xDOI Listing
June 2021

Epidemiology, Risk Factors, and Outcomes of Diffuse Alveolar Hemorrhage After Hematopoietic Stem Cell Transplantation.

Chest 2021 06 9;159(6):2325-2333. Epub 2021 Jan 9.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Background: Diffuse alveolar hemorrhage (DAH) is an uncommon complication of hematopoietic stem cell transplantation (HCT) that carries high morbidity and mortality. Limited contemporary data are available regarding the incidence, outcomes, and risk factors for DAH.

Research Question: What are the incidence, outcomes, and risk factors for DAH developing after HCT?

Methods: This was a single-center retrospective cohort study of patients who underwent HCT between January 1, 2005, and December 31, 2016. The incidence and outcomes of DAH development were evaluated. A multivariate logistic regression model was used to analyze differences between survivors and nonsurvivors.

Results: Of 4,350 patients undergoing first-time HCT, DAH was diagnosed in 99 (2.3%). DAH was seen in 40 of 3,536 autologous HCT recipients (1.1%) and 59 of 814 allogeneic HCT recipients (7.2%). Mean age was 53 ± 13 years, and median time of DAH diagnosis was 126 days (interquartile range, 19-349 days) after HCT. In-hospital mortality and mortality 1 year after DAH diagnosis were 55.6% and 76.8%, respectively. DAH diagnosis more than 30 days after transplantation (OR, 7.06; 95% CI, 1.65-30.14), low platelet count (OR, 0.98; 95% CI, 0.96-1.0; P = .02), elevated international normalized ratio (INR; OR, 4.08; 95% CI, 0.64-25.88; P = .046) and need for invasive mechanical ventilation (OR, 8.18; 95% CI, 1.9-35.21) were associated with higher in-hospital mortality. Steroid treatment did not alter mortality (P = .80) or length of stay (P = .65). However, among those who received steroids, survival was higher in whose who received modest-dose steroids (< 250 mg methylprednisolone equivalent/d) compared with those who received high-dose steroids (≥ 250 mg methylprednisolone equivalent/d; OR, 0.21; 95% CI, 0.07-0.72).

Interpretation: The mortality of DAH after HCT remains high, and DAH can occur long after transplantation. Later development of DAH (>30 days after HCT), need for invasive mechanical ventilation, thrombocytopenia, and elevated INR are all associated with worse outcomes.
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http://dx.doi.org/10.1016/j.chest.2021.01.008DOI Listing
June 2021

Free of malignancy but not of fears: A closer look at Damocles syndrome in survivors of hematologic malignancies.

Blood Rev 2021 07 1;48:100783. Epub 2020 Dec 1.

Division of Hematology, Dept. of Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Fear of cancer recurrence (FoR) is an important yet underestimated long term sequela that many cancer survivors suffer from. The continuous state of uncertainty the survivors might go through can lead to a serious impact on their quality of life (QoL), which is collectively referred to as Damocles syndrome. Given the increasing numbers of cancer survivors, it is crucial to understand the different psychological issues that face them, including Damocles syndrome. Herein, we review the current literature of Damocles syndrome specifically in hematologic cancer survivors. Although with inconsistent terms, current literature demonstrates the impact and the prevalence of Damocles syndrome on QoL of survivors of leukemia, lymphoma, and hematopoietic cell transplant. Interventional studies are very limited in this area. Moreover, hematologic malignancy survivors can also meet the diagnostic criteria of other psychiatric diseases, including depression, anxiety, and post-traumatic stress disorder, wherein they should be managed accordingly. It is important to increase the awareness about Damocles syndrome and screen patients for it and other related psychological disorders. Additionally, this review has shown the need for standardization of Damocles syndrome definitions. Finally, the lack of interventional studies that target survivors' psychosocial challenges calls for prospective research to better address this rising problem.
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http://dx.doi.org/10.1016/j.blre.2020.100783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166938PMC
July 2021

Screening for SARS-CoV-2: Health Policy Implications in Low- and Middle-Income Countries.

Mayo Clin Proc 2020 12 15;95(12):2606-2608. Epub 2020 Oct 15.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561345PMC
December 2020

Role of testosterone in COVID-19 patients - A double-edged sword?

Med Hypotheses 2020 Nov 17;144:110287. Epub 2020 Sep 17.

Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

COVID-19 affects males twice as frequently as females with significantly increased severity and mortality. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. The gradual decline in total and free testosterone levels has a direct correlation with serious pulmonary complications requiring advanced care (ICU, ventilators, ECMO, etc.). SARS-CoV-2 utilizes Angiotensin-Converting Enzyme II (ACE2) for entry in the host cell, and Transmembrane Protease, Serine 2 (TMPRSS2) to prime spike protein of SARS-CoV-2. Testosterone induces ACE-2 expression, a critical pulmonary protective enzyme. Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome (ARDS, duration of ICU stay, mortality). On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients. A critical evaluation of the serum testosterone and its relevance to COVID-19 is warranted to re-evaluate strategies to effectively triage, prioritize, and manage high-risk patients for ICU admission, survival outcomes, targeted solutions, and operational algorithms.
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http://dx.doi.org/10.1016/j.mehy.2020.110287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494488PMC
November 2020

Risk of relapse in patients receiving azithromycin after allogeneic HSCT.

Bone Marrow Transplant 2021 04 31;56(4):960-962. Epub 2020 Oct 31.

Department of Hematology, Mayo Clinic, Rochester, MN, USA.

Following publication of the ALLOZITHRO trial, the FDA released a safety announcement warning that azithromycin should not be given long-term to prevent BOS in patients with a blood or lymph cancer who have undergone allogeneic HSCT. Our site typically initiated azithromycin when patients were diagnosed with BOS post-transplant rather than empirically as prevention. The purpose of our study was to discern whether the use of azithromycin at the time of diagnosis of BOS increased risk of disease relapse in patients who received an allogeneic HSCT for malignant disease. We retrospectively reviewed 432 patients in 3 cohorts: Cohort (1) patients who received greater than or equal to 2 weeks of azithromycin therapy (n = 98); Cohort (2) patients who received azithromycin therapy for less than 2 weeks (n = 63); and Cohort (3) patients who never received azithromycin therapy (n = 271). Neither patients in Cohort 1 (HR 0.44; 95% CI, 0.12-1.53, P = 0.19) nor Cohort 2 (HR 0.66; 95% CI, 0.2-2.19, P = 0.49) were associated with an increased risk of relapse when compared to those who had never received azithromycin. Our data indicate that the prolonged use of azithromycin after allogeneic HSCT is not associated with an increased rate of hematologic relapse.
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http://dx.doi.org/10.1038/s41409-020-01095-8DOI Listing
April 2021

Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis.

Lancet Haematol 2020 Nov;7(11):e816-e826

Division of Haematology, Mayo Clinic, Rochester, MN, USA; Department of Immunology, Mayo Clinic, Rochester, MN, USA; T-Cell Engineering, Mayo Clinic, Rochester, MN, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in patients with refractory or relapsed acute lymphocytic leukaemia. Various anti-CD19 CAR T-cell constructs have been trialled and responses vary widely among different studies. We aimed to systematically analyse the outcomes of patients with acute lymphocytic leukaemia treated with anti-CD19 CAR T cells and identify factors associated with differences in outcomes.

Methods: We did a systematic review and meta-analysis of published and unpublished clinical trials that reported data on the outcomes of adult or paediatric patients that were treated with anti-CD19 CAR T cells for relapsed or refractory B-cell acute lymphocytic leukaemia, reported between Jan 1, 2012, and April 14, 2020. Studies with two patients or fewer were excluded and summary data were extracted from the reports. The primary outcome was the number of patients who had complete remission at any time after anti-CD19 CAR T-cell infusion. This study is not registered in PROSPERO.

Findings: From 1160 studies, we identified 40 potentially appropriate studies, 35 (88%) of which met the eligibility criteria and were included in the final analysis (n=953 patients). The pooled complete remission was 80% (95% CI 75·5-84·8) and heterogeneity between studies was moderate (I=56·96%). In the prespecified subgroup analyses, 195 (75% [95% CI 66·9-82·9, I=35·22%]) of 263 patients in adult studies and 242 (81% [72·9-87·2, I=54·45%]) of 346 patients in paediatric studies achieved complete remission, p=0·24. The pooled complete remission did not significantly differ with anti-CD19 CAR T-cell construct type or single-chain variable fragment clone, but was higher with autologous T-cell origin (727 [83%, 78·5-86·5, I=44·34%] of 901 patients), compared with allogeneic T-cell origin (29 [55%, 30·6-79·0, I=62·64%] of 52 patients; p=0·018). 242 (26% [95% CI 18·5-34·1]) of 854 patients developed grade 3 or worse cytokine release syndrome and 97 (12% [6·6-19·2]) of 532 developed grade 3 or worse neurotoxicity. There was no difference in the proportion of patients who achieved complete remission or who had cytokine release syndrome or neurotoxicity between different anti-CD19 CAR T-cell constructs. The risk of bias was assessed as low in 17 studies and moderate in 18 studies.

Interpretation: The high response rates after anti-CD19 CAR T-cell therapy can be used to guide the use of therapy in patients with relapsed or refractory acute lymphocytic leukaemia. Comparison studies are required to further determine differences in efficacy between different anti-CD19 CAR T-cell constructs in the setting of relapsed or refractory acute lymphocytic leukaemia.

Funding: National Cancer Institute, National Comprehensive Cancer Network, Mayo Clinic K2R Research Pipeline, and Mayo Clinic Center for Individualized Medicine.
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http://dx.doi.org/10.1016/S2352-3026(20)30277-5DOI Listing
November 2020

Management of chemotherapy-induced alopecia (CIA): A comprehensive review and future directions.

Crit Rev Oncol Hematol 2020 Dec 22;156:103093. Epub 2020 Sep 22.

Division of Hematology, Dept. of Medicine, Mayo Clinic, Rochester, MN, USA; Sheikh Shakhbout Medical City / Mayo Clinic, Abu Dhabi, United Arab Emirates. Electronic address:

Objectives: To review and summarize the available literature on the management of chemotherapy-induced alopecia (CIA) including complementary and alternative medicine (CAM), and to present CIA's effect on quality of life (QoL).

Methods: Nine databases were searched for CIA-related keywords, including the effect on QoL, and management options. Among 1019 articles found, 54 articles focusing on treatment/prevention or QoL were retrieved. References of selected articles were also checked manually.

Results: CIA was found to negatively affect QoL and body image, regardless of head covering status (i.e., for cultural or religious reasons). Most studies related to treatment/prevention of CIA reported on the use of scalp-cooling. The efficacy of CAM treatments was found to be questionable.

Conclusion: A high incidence rate of CIA exists with certain chemotherapies, and it significantly impairs QoL. Preventive and treatment strategies are incompletely effective. Additional literature is needed to explore potential preventive or therapeutic options for CIA.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103093DOI Listing
December 2020

Thank You for Not Smoking.

Mayo Clin Proc 2020 10;95(10):2062-2064

Division of General Internal Medicine, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528948PMC
October 2020

Pride and Prejudice during the COVID-19 Pandemic: The Misfortune of Inappropriate Clinical Trial Design.

J Epidemiol Glob Health 2021 03 7;11(1):15-19. Epub 2020 Aug 7.

College of Medicine, Alfaisal University, Riyadh, KSA.

Coronavirus Disease 2019 (COVID-19) is a rapidly evolving global pandemic for which more than a thousand clinical trials have been registered to secure therapeutic effectiveness, expeditiously. Most of these are single-center non-randomized studies rather than multi-center, randomized controlled trials. Single-arm trials have several limitations and may be conducted when spontaneous improvement is not anticipated, small placebo effect exists, and randomization to a placebo is not ethical. In an emergency where saving lives takes precedence, it is ethical to conduct trials with any scientifically proven design, however, safety must not be compromised. A phase II or III trial can be conducted directly in a pandemic with appropriate checkpoints and stopping rules. COVID-19 has two management paradigms- antivirals, or treatment of its complications. Simultaneous assessment of two different treatments can be done using 2 × 2 factorial schema. World Health Organization's SOLIDARITY trial is a classic example of the global research protocol which can evaluate the preferred treatment to combat COVID-19 pandemic. Short of that, a trial design must incorporate the practicality of the intervention used, and an appropriate primary endpoint which should ideally be a clinical outcome. Collaboration between institutions is needed more than ever to successfully execute and accrue in randomized trials.
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http://dx.doi.org/10.2991/jegh.k.200729.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958277PMC
March 2021

Hematopoietic Cell Transplantation in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia: An Evidence-Based Review from the American Society of Transplantation and Cellular Therapy.

Transplant Cell Ther 2021 01 20;27(1):6-20. Epub 2020 Sep 20.

EBMT Paris Study Office, Paris, France; Chaim Sheba Medical Center, Tel Hashomer, Israel.

The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML expert panel, consisting of both transplant and nontransplant experts, was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by the American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate- and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed.
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http://dx.doi.org/10.1016/j.bbmt.2020.09.020DOI Listing
January 2021

The Increasing Trends in Cases of the Most Common Cancers in Saudi Arabia.

J Epidemiol Glob Health 2020 12 22;10(4):258-262. Epub 2020 May 22.

Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, KSA.

Background: Cancer epidemiology in Saudi Arabia (SA) differs from that of the USA with respect to types of common malignancies. Hematologic malignancies are among the top five cancers prevalent in SA, including lymphoma and leukemia. Most common malignancies in SA also include breast, thyroid, and colorectal cancer. We sought to evaluate the current trends of these most common cancers in SA.

Methods: Electronic search analysis pertaining to Hodgkin's lymphoma, leukemia, breast, colorectal, and thyroid cancer were carried out from two databases: The Saudi Cancer Registry (SCR) and the Surveillance, Epidemiology, and End Results (SEER). Data on prevalence and incident frequency were collected. Trends from 2001 to 2014 were calculated and compared between SCR and SEER.

Findings: Leukemia is the most common cancer type among males in SA, followed by colorectal cancer. Hodgkin's lymphoma has become the third most common malignancy among Saudi males. Percentage of women's breast cancer and thyroid cancer among total cancer cases have increased by 10.5% and 1.7% respectively from 2001 to 2014, making them the first and second most common cancers in women respectively. Trends of thyroid cancer among males has been stable. Colorectal cancer stands as third most common among Saudi females.

Interpretations: There have been significant changes in trends of incidence rate of the most common cancers in SA among both males and females over the past decade. Breast cancer rates have risen at an alarming pace. More epidemiological studies need to be conducted to evaluate etiological factors at environmental, molecular, and genetic levels.
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http://dx.doi.org/10.2991/jegh.k.200515.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758845PMC
December 2020

Promising role for mesenchymal stromal cells in coronavirus infectious disease-19 (COVID-19)-related severe acute respiratory syndrome?

Blood Rev 2021 03 13;46:100742. Epub 2020 Aug 13.

Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address:

Mesenchymal stromal cells (MSC) have immune regulatory and tissue regenerative properties. MSCs are being studied as a therapy option for many inflammatory and immune disorders and are approved to treat acute graft-versus-host disease (GvHD). The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic and associated coronavirus infectious disease-19 (COVID-19) has claimed many lives. Innovative therapies are needed. Preliminary data using MSCs in the setting of acute respiratory distress syndrome (ARDS) in COVID-19 are emerging. We review mechanisms of action of MSCs in inflammatory and immune conditions and discuss a potential role in persons with COVID-19.
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http://dx.doi.org/10.1016/j.blre.2020.100742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425550PMC
March 2021
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