Prior COVID-19 infection may increase risk for developing endothelial dysfunction following hematopoietic cell transplantation

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

Non-Hodgkin lymphoma (NHL) is a broad entity which comprises a number of different types of lymphomatous malignancies. In the pediatric and adolescent population, the type and prognosis of NHL varies by age and gender. In comparison to adults, pediatric and adolescent patients generally have better outcomes following treatment for primary NHL. However, relapsed/refractory (R/R) disease is associated with poorer outcomes in many types of NHL such as diffuse large B cell lymphoma and Burkitt lymphoma. Newer therapies have been approved in the use of primary NHL in the pediatric and adolescent population such as Rituximab and other therapies such as chimeric antigen receptor T-cell (CAR T-cell) therapy are under investigation for the treatment of R/R NHL. In this review, we feature the characteristics, diagnosis, and treatments of the most common NHLs in the pediatric and adolescent population and also highlight the differences that exist between pediatric and adult disease. We then detail the areas of treatment advances such as immunotherapy with CAR T-cells, brentuximab vedotin, and blinatumomab as well as cell cycle inhibitors and describe areas where further research is needed. The aim of this review is to juxtapose established research regarding pediatric and adolescent NHL with recent advancements as well as highlight treatment gaps where more investigation is needed

Classical Hodgkin Lymphoma: From Past to Future—A Comprehensive Review of Pathophysiology and Therapeutic Advances

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL patients, the chance of developing secondary leukemia is manifold compared to that in the general pediatric population, and the prognosis for patients with secondary leukemia is much worse than that for patients with other hematological malignancies. Therefore, it is crucial to develop clinically useful biomarkers to stratify patients according to their risk of late malignancies and determine which require intense treatment regimens to maintain the ideal balance between maximizing survival rates and avoiding late consequences. In this article, we review HL’s epidemiology, risk factors, staging, molecular and genetic biomarkers, and treatments for children and adults, as well as treatment-related adverse events and the late development of secondary malignancies in patients with the disease

The Evolution of Chimeric Antigen Receptor T-Cell Therapy in Children, Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary treatment for pediatric, adolescent and young adult patients (AYA) with relapsed/refractory B-cell acute lymphoblastic leukemia. While the landscape of immunotherapy continues to rapidly evolve, widespread use of CAR T therapy is limited and many questions remain regarding the durability of CAR T therapy, methods to avoid CAR T therapy resistance and the role of consolidative stem cell transplant. Modified strategies to develop effective and persistent CAR T cells at lower costs and decreased toxicities are warranted. In this review we present current indications, limitations and future directions of CAR T therapy for ALL in the pediatric and AYA population

Post-Transplant Cyclophosphamide after Matched Sibling and Unrelated Donor Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acute Myeloid Leukemia

Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) and mismatched haploidentical HSCT adult recipients. However, there are no published data in pediatric patients with acute myeloid leukemia who received matched-donor HSCT with PTCy. We demonstrate, in this case series, that the use of PTCy in this population is potentially safe, effective in preventing acute GVHD, does not impair engraftment, is associated with reduced non-relapse mortality, and does not hinder immune reconstitution post HSCT

Revumenib in patients with acute leukemias: compassionate use program experience

In this compassionate use program, which included heavily pretreated pts, disease responses were observed. Several pts who started REV as maintenance post-HSCT experienced prolonged remissions. No new safety signals were reported