Field Of Hematopoietic Cell Transplantation Research Articles

Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection

The current coronavirus disease 2019 (COVID 19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. The full impact of the COVID 19 pandemic, caused by the SARS CoV 2, on the field of hematopoietic cell transplantation (HCT) is unknown. Here, we report a rare case of a 21-year-old male patient known to have chronic myeloid leukemia (CML) with progression to T-cell lymphoblastic lymphoma as extramedullary blast crisis of CML. The patient was treated by pediatric chemotherapy regimen then. He underwent haploidentical stem cell transplantation. Posttransplantation, on day +7, he developed SARS-CoV-2 after receiving stem cell graft from a donor who was diagnosed with SARS-CoV-2 on the day of stem cells harvesting. The case elaborates complications and outcome of a patient receiving stem cell transplant from a donor with SARS-CoV-2 infection.

Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice

The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies that include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34+ selection and post-transplantation cyclophosphamide with tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of chronic GVHD relapse-free survival among the 3 approaches. The trial did not demonstrate a superior approach compared with Tac/MTX; however, it did highlight several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real-world practices. Here we review the results of BMT CTN 1301 and their implications for clinical practice and future clinical trial design.

American Society for Transplantation and Cellular Therapy Guidelines for Fellowship Training in Hematopoietic Cell Transplantation and Immune Effector Cell Therapy

Rapid advances in the field of hematopoietic cell transplantation (HCT), as well as the advent of immune effector cell therapy (IEC), have resulted in an increasing number of patients undergoing these therapies and an increasing level of expertise required to manage them. Previous guidelines for the training of HCT physicians were last published in 2012. In recognition of the expanding knowledge base and increasing skill set essential to the delivery of these treatment modalities, the American Society for Transplantation and Cellular Therapy Committee on Education has updated these guidelines to reflect nearly a decade of new knowledge in the field of HCT, as well as the evolution of IEC from an experimental modality to a widely used and mainstream therapy. The resulting document reflects the Committee on Education's recommended educational structure for programs engaged in the training, evaluation, and mentorship of HCT/IEC trainees.

Changes in Hematopoietic Cell Transplantation Practices in Response to COVID-19: A Survey from the Worldwide Network for Blood & Marrow Transplantation

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.

A Systematic Review of Machine Learning Techniques in Hematopoietic Stem Cell Transplantation (HSCT).

Machine learning techniques are widely used nowadays in the healthcare domain for the diagnosis, prognosis, and treatment of diseases. These techniques have applications in the field of hematopoietic cell transplantation (HCT), which is a potentially curative therapy for hematological malignancies. Herein, a systematic review of the application of machine learning (ML) techniques in the HCT setting was conducted. We examined the type of data streams included, specific ML techniques used, and type of clinical outcomes measured. A systematic review of English articles using PubMed, Scopus, Web of Science, and IEEE Xplore databases was performed. Search terms included “hematopoietic cell transplantation (HCT),” “autologous HCT,” “allogeneic HCT,” “machine learning,” and “artificial intelligence.” Only full-text studies reported between January 2015 and July 2020 were included. Data were extracted by two authors using predefined data fields. Following PRISMA guidelines, a total of 242 studies were identified, of which 27 studies met the inclusion criteria. These studies were sub-categorized into three broad topics and the type of ML techniques used included ensemble learning (63%), regression (44%), Bayesian learning (30%), and support vector machine (30%). The majority of studies examined models to predict HCT outcomes (e.g., survival, relapse, graft-versus-host disease). Clinical and genetic data were the most commonly used predictors in the modeling process. Overall, this review provided a systematic review of ML techniques applied in the context of HCT. The evidence is not sufficiently robust to determine the optimal ML technique to use in the HCT setting and/or what minimal data variables are required.

Addressing the Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Hematopoietic Cell Transplantation: Learning Networks as a Means for Sharing Best Practices.

The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.

Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era

Background The management of adult acute lymphoblastic leukemia (ALL) has evolved over the last five years with the FDA approval of targeted immunotherapies, routine incorporation of minimal residual disease, and uptake of the pediatric regimen in young adults. However, allogeneic hematopoietic cell transplantation (HCT) remains an important treatment modality for this population and progress has concomitantly occurred in the field of HCT. We hypothesized that a combination of these advancements would translate into significant improvements in post-HCT survival in adult ALL. Methods Successive patients >= 18 years who had undergone first allogeneic HCT for ALL at Stanford University between January 1, 2005 and January 30, 2019 were included and were categorized as Cohort 1 or Cohort 2 based upon time period of HCT: 2005-2013 vs 2014-2019, respectively. For survival analyses, patient post-HCT follow-up times in Cohort 1 were truncated to the maximum follow-up time in Cohort 2 (approximately 5 years) in order to account for differences in long-term follow-up between the cohorts. Results 308 adults (163 in Cohort 1; 145 in Cohort 2) with ALL underwent HCT. The median follow-up from HCT was 738 and 588 days in Cohorts 1 and 2, respectively. Median age was 39 years (range, 19-70) and did not differ between groups; 50-55% were men and 30-35% were Hispanic across time periods. Most patients (79-85% across time periods) received myeloablative conditioning (MAC) with a TBI-based regimen; a slight increase in non-TBI based MAC was observed in Cohort 2. Relative to Cohort 1, patients transplanted in Cohort 2 received cord blood units more frequently and were also more likely to enter HCT in CR1. The estimated six month, one, and two-year HCT outcomes are depicted in Table 1. The 2-year cumulative incidence of relapse (31% vs 25%) and TRM (23% vs 17%) were not significantly different between the two time cohorts but trended in favor of Cohort 2. Significant improvement in OS following HCT was observed in Cohort 2 (Figure 1) with estimated 2-year OS of 51% vs 70% in Cohorts 1 and 2, respectively. Conclusions In this large single center analysis of adult ALL outcomes following HCT over time, we demonstrate that OS following HCT has substantially improved since 2014, coinciding with a number of advancements in the fields of ALL and HCT. These data, if confirmed in a multi-center analysis, should provide new benchmarks for outcomes following HCT in adult ALL.

Worldwide Network for Blood and Marrow Transplantation (WBMT) perspective: the role of biosimilars in hematopoietic cell transplant: current opportunities and challenges in low- and lower-middle income countries.

Health care costs attributed to biologics have increased exponentially in the recent years, thus biosimilars offer a possible solution to limit costs while maintaining safety and efficacy. Reducing expenditure is vital to health care especially in developing countries where affordability and access to health care is a major challenge. We discuss the opportunities and the challenges of biosimilars in the field of hematopoietic cell transplantation (HCT) in low- and lower-middle income countries. Developing countries can potentially invest in the forecasted costs reduction by utilizing biosimilars. This can be used to decrease the costs of procedures such as HCT, which is a rapidly growing field in many developing regions. The introduction of biosimilars in the developing regions faces many challenges which include, but are not limited to: legal and regulatory issues, lack of research infrastructure, and the presence of educational barriers. Thus, collaborative efforts are needed to ensure an effective and safe introduction of biosimilars into low- and lower-middle income countries.

A Phase I Study of Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide and/or Bendamustine

Background The nearly universal donor accessibility afforded by haploidentical bone marrow transplantation (haplo-BMT) is salient for our program, as half of the patients undergoing hematopoietic cell transplantation (HCT) are ethnic or racial minorities. This highlights the need for effective haplo-BMT regimens and improvements in graft-versus-host disease (GvHD) prophylaxis. Balancing GvHD prevention with the maintenance of graft-versus-leukemia (GvL) is an ongoing challenge in the field of HCT. We have previously shown in mice that bendamustine (BEN) can safely replace cyclophosphamide (CY) as post-transplant (PT) GvHD prophylaxis following haplo-BMT, with comparable protection from GvHD and superior GvL effects. Based on our preclinical data, we have initiated a Phase I/II study to replace PT-CY (given on days +3 and +4) with PT-BEN following haplo-BMT. Methods Phase I is a standard 3 + 3 dose escalation design with six dose level cohorts. The first three cohorts (1-3) consist of a combination of sequentially reduced doses of CY and increased doses of BEN on day +4 post-BMT with the dose of CY on day +3 remaining unchanged. The next three cohorts (4-6) will involve progressive substitution of CY with BEN on day +3. We are enrolling patients ages 8-60 years with a diagnosis of acute leukemia, chronic myeloid leukemia, myelodysplastic syndrome, Hodgkin's or non-Hodgkin's lymphoma who do not have a readily available HLA-matched (10/10) donor. Myeloablative busulfan, fludarabine, and melphalan or TBI and fludarabine are used as conditioning regimens. Engraftment, immune reconstitution, T-cell receptor β (TRB) diversity, GvHD, infections, relapse, non-relapse mortality (NRM), event-free survival (EFS) and overall survival (OS) are monitored. Patients undergoing haplo-BMT (using the same conditioning regimens) who do not wish to receive PT-BEN are consented as PT-CY controls for the clinical endpoints and immune reconstitution studies. Results We have enrolled through Cohort 2 with no dose-limiting toxicities. Cohort 2 of PT-BEN had significantly earlier neutrophil engraftment than PT-CY controls (median day +13 compared to +17), with >5-fold higher neutrophil to lymphocyte ratios through day +100. PT-BEN patients displayed higher CD4 to CD8 ratio and demonstrated significantly greater TRB diversity than PT-CY only patients through 1 year following transplant. Patients receiving PT-BEN had a trend toward a lower incidence of CMV reactivation, 33% compared to 100% in PT-CY controls. No PT-BEN patient has developed grade III-IV acute GvHD or chronic GvHD. Conclusions PT-BEN has been well-tolerated, with patients demonstrating early engraftment. Preliminary data with PT-BEN indicate potential differences in immune reconstitution and TRB diversity. This may be advantageous in viral control, as well as in GvHD and GvL responses.

Artificial Intelligence Approaches in Hematopoietic Cell Transplantation: A Review of the Current Status and Future Directions

The evidence-based literature on healthcare is currently expanding exponentially. The opportunities provided by the advancement in artificial intelligence (AI) tools such as machine learning are appealing in tackling many of the current healthcare challenges. Thus, AI integration is expanding in most fields of healthcare, including the field of hematology. This study aims to review the current applications of AI in the field of hematopoietic cell transplantation (HCT). A literature search was done involving the following databases: Ovid MEDLINE, including In-Process and other non-indexed citations, and Google Scholar. The abstracts of the following professional societies were also screened: American Society of Hematology, American Society for Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation. The literature review showed that the integration of AI in the field of HCT has grown remarkably in the last decade and offers promising avenues in diagnosis and prognosis in HCT populations targeting both pre- and post-transplant challenges. Studies of AI integration in HCT have many limitations that include poorly tested algorithms, lack of generalizability, and limited use of different AI tools. Machine learning techniques in HCT are an intense area of research that needs much development and extensive support from hematology and HCT societies and organizations globally as we believe that this will be the future practice paradigm.

Peer review in hematopoietic cell transplantation: are we doing our fair share?

Peer review is believed to be important in maintaining the quality and integrity of research in academic endeavors. Recently, the value of the current peer review process, which is more than 100 years old has come into question. In the field of hematopoietic cell transplantation (HCT), peer review was unable to prevent the publication of the largest and most notorious scientific fraud in our field. In order to assess how the HCT community views and how engaged it is with the peer review process, the American Society of Blood and Marrow Transplantation conducted a survey of all of its members in 2014. The survey was sent to all active members through multiple email communications in August and September 2014. Of a total of 1183 members, 149 responded. Almost all of the respondents had participated in the peer review process, with few respondents declining ever to review manuscripts. The most common cause for declining review requests was lack of time. Most respondents (68%) thought that the current peer review process was relatively fair and unbiased, whereas only 9% of the respondents stated that they did not believe in the peer review process. In conclusion, among the respondents of this survey most felt the peer review process to be valuable and fair, however, the lack of response suggests that further study into improving the peer review process in the field of HCT is warranted in the era of electronic publishing and communication.

HLA-identical siblings versus haploidentical donors: full match still beats half match

The resurgence of haploidentical donor transplantation over the past decade is a major advance in the field of hematopoietic cell transplantation (HCT). Several platforms have been described, such as ex vivo T-cell depletion techniques with positive-CD34+ selection, ‘mega-dose’ of purified CD34+ cells, or selective depletion of T-cells, and T-cell replete approaches that include use of intensified immune suppression or post-transplant high-dose cyclophosphamide.1, 2, 3 It is safe to say that haploidentical transplantation has become a well-accepted alternative donor source, with several studies reporting survival comparable to umbilical cord blood and matched unrelated donors.4, 5, 6, 7, 8 Ongoing clinical trials such as the BMT CTN 1101 (double cord versus haplo) will further clarify where haploidentical donors factor into the donor selection process.

Allogeneic hematopoietic cell transplantation: the state of the art

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. The field has evolved substantially over the past decade, with advances in patient and donor selection, stem cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens. As a result, the indications for HCT and the pool of eligible patients have expanded significantly. In this article, we provide an overview of the major aspects of allogeneic HCT, and focus specifically on areas of active research and on novel approaches to challenges in the field. Specifically, we will discuss approaches to reduce the toxicity of the preparative regimen, with the goal of increasing the safety and applicability of HCT. The availability of suitable donors may be an obstacle to wider application of HCT. We review three major approaches to broadening the donor pool: the use of HLA-mismatched unrelated donors, umbilical cord blood and HLA-haploidentical family donors. Graft-versus-host disease remains a major cause of morbidity and mortality after HCT. We review recent advances in the understanding of this phenomenon, and novel prophylactic and therapeutic approaches that hold the promise of further improving the safety of the procedure. We conclude with a speculative outline of the next 5 years of research in the field of HCT.

Improving Hematopoietic Cell Transplant Outcomes in a New Era of Genomic Research

Based upon the recent advances in genetic association studies, the age of genetically based personalized medicine may be finally arriving in the near future for many diseases. The field of hematopoietic cell transplantation (HCT) is well ahead of this curve. In the entire field of medicine, there is no better demonstration of the power of personalized medicine than the use of patient-donor histocompatibility antigen (HLA) matching to improve stem cell transplant outcomes. Nevertheless, even the HCT field will benefit significantly from the latest developments in genetic association studies, which has allowed expanded analyses of the human genome beyond the major histocompatibility complex (MHC).

The management and outcome of chronic graft‐versus‐host disease

Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT). It is the leading cause of non-relapse mortality in transplant survivors and has a significant impact upon their functional status and quality of life. Despite significant advances being made in the field of HCT over the past 25 years, there has been little change in the incidence, morbidity and mortality of cGVHD. This is partly because of a lack of understanding about the pathogenesis of the disorder but also because a lack of well validated grading systems and outcome measures has hindered clinical research. Strategies for prophylaxis have largely been unsuccessful and may compromise the graft-versus-leukaemia (GVL) effect. Standard primary treatment remains a combination of corticosteroids and calcineurin inhibitors. There is no standard therapy for those who fail to respond to corticosteroids. Many agents have been studied but there is an urgent need for systematic research to compare the efficacy of different approaches. Infection is the leading cause of death among patients with cGVHD so antimicrobial prophylaxis is mandatory. A multidisciplinary approach to the care of patients with cGVHD is essential to adequately address its effects on both physical and psychological functioning.

Promise and Challenges of Human Regulatory T Cells in the Clinic

Regulation of immune reactions is critical in ealth and disease. Nowhere is this clearer than folowing allogeneic hematopoietic cell transplantation HCT). Here the beneficial effects of graft-versusumor reactions are clearly demonstrated, as well as he detrimental morbidity and mortality of unconrolled graft-versus-host disease (GVHD). Control of mmune reactions is complex and involves many facors including blood flow, micro-environmental interctions, cytokines, chemokines and both pro-inflamatory and anti-inflammatory molecules. In addition t has become well recognized that specialized popuations of cells, termed regulatory T cells, are critically nvolved in controlling immune reactions. Although he field of regulatory T cell biology has been exlored for many years, the more recent identification f specific populations of cells capable of regulating mmune responses with defined phenotype has opened ur re-examination of the potential impact of these ellular populations on immune function. To date, a umber of different cell populations have been charcterized with defined ability to regulate immune rections, which include two major cell populations, amely those of CD4 CD25 regulatory T cells Treg) [1] and abTCR NK-T cells which express an nvariant T cell receptor and are CD1 reactive [2]. hese cellular populations have generated enormous nterest in the field of HCT since animal models have emonstrated the potential benefit of regulatory T ell biology.

Nutrient support in hematopoietic cell transplantation.

High-dose cytoreduction and hematopoietic stem cell infusion form the basis for treatment of hematologic cancers, defects or failure of hematopoiesis, and some solid tumors. As an antitumor therapy, allogeneic hematopoietic cell transplantation (HCT) is superior to autologous HCT by induction of a graft-vs-tumor effect. However, recipients of allografts suffer higher transplant-related mortality owing to graft-vs-host disease (GVHD). Nutrition support research must recognize that HCT is a heterogeneous modality whose short and long-term outcomes are affected by transplant type, preparative regimens, diagnosis, disease stage, age, and nutritional status. The field of HCT will diversify further as lower dose cytoreduction and mixed chimerism grafts allow expansion of the technique to older patients and to other diseases.