Effect of HLA-matching recipients to donor non-inherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy

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Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Allogeneic haemopoietic cell transplant services in Australia and New Zealand in the first year of the COVID-19 pandemic: a report from Australia and New Zealand transplant and cellular therapies

Background The COVID-19 pandemic has caused major disruption to health systems, with allogeneic haemopoietic cell transplant (alloHCT) services a particularly vulnerable area. Ongoing provision of alloHCT has required dynamic responses at national and local levels. In Australia and New Zealand (ANZ), a high reliance on unrelated donors from overseas registries has posed an additional challenge. Aims To describe the impact of COVID-19 on alloHCT services in ANZ in the first year of the pandemic. Methods Data from the national alloHCT patient and unrelated donor registries were extracted for a 2-year time frame. Comparisons were made between a pre-pandemic period of 1 March 2019 to 29 February 2020 and the corresponding dates during the pandemic, 1 March 2020 to 28 February 2021. Results There was a 13% decrease in the number of allogeneic transplants, a reversal of steady increases in previous years, with the largest decrease in unrelated donor transplants. Local donors supplied a greater proportion of unrelated stem cell products. With a switch to universal cryopreservation, the time from request of a product to infusion increased by a median of 25.5 days for overseas products and 14 days for local products. There was a significant increase in the number of products collected but not used. Conclusions A strong public health response and coordinated transplant community activities allowed for safe provision of alloHCT in ANZ; however, our data suggest that the timely delivery of allogeneic transplants was affected by the COVID-19 pandemic. Continued dedicated efforts are required to minimise further impacts

Viral infection in hematopoietic stem cell transplantation: an International Society for Cell & Gene Therapy Stem Cell Engineering Committee review on the role of cellular therapy in prevention and treatment

Despite recent advances in the field of HSCT, viral infections remain a frequent causeof morbidity and mortal-ity among HSCT recipients. Adoptive transfer of viral specific T cells has been successfully used both as pro-phylaxis and treatment of viral infections in immunocompromised HSCT recipients. Increasingly, precise risk stratification of HSCT recipients with infectious complications should incorporate not only pretransplant clinical criteria, but milestones of immune reconstitution as well. These factors can better identify those at highest risk of morbidity and mortality and identify a population of HSCT recipients in whom adoptive ther-apy with viral specific T cells should be considered for either prophylaxis or second line treatment early after inadequate response to first line antiviral therapy. Broadening these approaches to improve outcomes for transplant recipients in countries with limited resources is a major challenge. While the principles of risk stratification can be applied, early detection of viral reactivation as well as treatment is challenging in regions where commercial PCR assays and antiviral agents are not readily available.(c) 2022 Published by Elsevier Inc. on behalf of International Society for Cell &amp; Gene Therapy. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Transplant for non-malignant disorders: an International Society for Cell & Gene Therapy Stem Cell Engineering Committee report on the role of alternative donors, stem cell sources and graft engineering

: Hematopoietic stem cell transplantation (HSCT) is curative for many non-malignant disorders. As HSCT and supportive care technologies improve, this life-saving treatment may be offered to more and more patients. With the development of new preparative regimens, expanded alternative donor availability, and graft manipulation techniques, there are many options when choosing the best regimen for patients. Herein the authors review transplant considerations, transplant goals, conditioning regimens, donor choice, and graft manipulation strategies for patients with non-malignant disorders undergoing HSCT