Graft-Versus-Leukemia Effect after Haplo-Identical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Patients with AML- No Association with Graft-Versus-Host Disease (GVHD): A Study on Behalf of the Acute Leukemia Working Party of EBMT.

Introduction Allogeneic stem-cell transplantation (SCT) is curative therapy in AML by providing intensive chemotherapy and enhancing a graft-versus-leukemia (GVL) effect. The GVL effect is usually closely associated with GVHD. The use of haploidentical SCT (haploSCT) is rapidly increasing due to the introduction of non-T depleted methods, in particular with post-transplant cyclophosphamide (PTCy), with similar outcomes as following other donor sources. There is no data whether GVL after haploSCT is associated with GVHD as in matched donor SCT. Methods We assessed the impact of acute and chronic GVHD on SCT outcomes following non-T depleted haploSCT with PTCy, by using a series of landmark analyses. Results The study included 605 patients with AML in CR1 (73%) or CR2 (27%) after haploSCT with PTCy, given during the years 2009-2016. The median age was 53 years (18-76). The overall rate of acute GVHD grade II-IV and III-IV was 28.4% and 8.0%, respectively. The rates of chronic GVHD all grades and extensive were 32.7% and 12.3%, respectively. The 2-year leukemia-free survival (LFS) was 59.9%. 509 patients were alive and leukemia-free 100 days after SCT; 366 had no prior acute GVHD at this landmark, 107 had acute GVHD grade II and 36 had grade III-IV. The subsequent relapse rate was 20.3%, 18.3% and 11.9%, respectively (P=0.60). The subsequent non-relapse mortality (NRM) rate was 10.3%, 19.0% and 35.7%, respectively (P Conclusions Acute and chronic GVHD of any grade were not associated with subsequent relapse. Acute GVHD grade III-IV and extensive chronic GVHD were associated with higher NRM and lower LFS. GVL is thus not closely associated with GVHD after non T-depleted haploSCT with PTCy. Future novel strategies for prevention of significant GVHD are warranted

abo mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia a report from the alwp of the ebmt

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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

Patients experienced serious adverse reactions within one hour of hematopoietic stem-cell infusion

© 2022 Société française de transfusion sanguine (SFTS)Methods: SARs were examined occurred within 1 hour after initiating HSC product infusions in all HSCT done in Turkey's Anadolu Medical Center Hospital accredited for HSCTs between 2013 and 2015, targeting 315 patients. Results: SARs were carefully evaluated in this study based on a comparison of the amount of stem cells infused, age, frozen sample (FS) / non-frozen samples (NFS) between HSCs sources. Rate of SARs is significantly higher in FS infusions supports the hypothesis that DMSO plays an important role in the development of SAR. Conclusion: The rate of SARs is significantly higher in infusions given using FSs confirms the hypothesis that the preservative agent DMSO plays an important role in the development of SAR. Our study provides guidance for future studies on the necessity of reducing the amount of DMSO in the HSCT product and using other alternative freezing agents instead of DMSO

Disease-Modifying Antirheumatic Drugs Increase Serum Adiponectin Levels in Patients With Rheumatoid Arthritis

Background: Adiponectin is an adipocyte-derived adipokine with immunosuppressive and anti-inflammatory properties. It also decreases expression of adhesion molecules. In terms of its relationship with acute-phase reactants, there are conflicting results in patients with rheumatoid arthritis (RA)

Review of therapeutic options and the management of patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a poorly understood group of disorders caused by one or more genetic aberrations in the bone marrow-derived cell line responsible for hematopoiesis. Recent advances in genetic medicine have offered new insights into the epigenesis as well as the prognosis of MDS, but have not resulted in new or improved curative treatment options. Bone marrow transplantation, introduced before the advent of genetic medicine, is still the only potential cure. Advances in other medical and pharmaceutical areas have broadened the scope of supportive care and disease-modifying therapies, and treating physicians now have a broad range of disease management options depending on a patient's likely prognosis. There is now clear evidence that appropriate supportive care and therapeutic intervention can improve progression-free and overall survival of MDS patients