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The optimal prognostication model for outcome following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) remains undefined. To establish a prognostic scoring system, 466 consecutive AML patients undergoing allo-HSCT from 2014 to 2023 were analyzed as a training cohort. Six donor, leukemia and recipient related factors were identified as prognostically significant and assigned weighted scores, respectively 1 point each for donor cytomegalovirus seropositivity, Hemopoietic Cell Transplantation-specific Comorbidity Index ≥ 2, secondary AML, not in first complete remission, and low-intensity induction therapy; 3 points for inv(3)/t(3;3)(q21;q26) or KMT2A rearrangement; 4 points for − 5/del(5q) or TP53 mutation; 0 point for CEBPA bZIP in-frame mutation or core-binding factor AML; and 1 point for all other genetic risk groups. Scores were grouped into four risk categories: favorable (0–1), intermediate (2–3), poor (4–5), and very poor (≥ 6); constituting the HATS prognostication model. The corresponding 2-year overall survivals of favorable, intermediate, poor and very poor risk groups were 92%, 78%, 50%, and 7.4% (log-rank P  < 0.001). An external validation cohort comprising 395 patients was similarly analyzed. With concordance statistics, HATS outperformed all six existing prognostication models. In conclusion, HATS represents a novel prognostication model devised for AML patients undergoing allo-HSCT. Clinicaltrials.gov identifier: NCT06702111.

Chronic graft versus host disease (cGVHD) affects 30–50% of allogeneic hematopoietic stem cell transplantation recipients, with those failing standard therapy including ruxolitinib constituting an important unmet medical need. We retrospectively analyzed the use of the ROCK2 inhibitor belumosudil in moderate to severe cGVHD that had failed ≥ 2 lines of systemic therapies, in order to evaluate its efficacy and safety in routine practice. Eighteen men and thirteen women at a median age of 50 (21–68) years with cGVHD (moderate, N  = 12; severe, N  = 19) that had failed a median of 3 (2–6) lines of systemic therapy were studied. Twenty-eight patients (90%) had failed prior ruxolitinib therapy, with seventeen patients (55%) continuing ruxolitinib despite unsatisfactory response. Among 29 patients evaluable, overall response rate was 52% (complete response:7%; partial response: 45%). Median time to response was 2.1 months (95% confidence interval, CI: 1.6–5.7), and was significantly shorter in patients older than 50 years ( P  = 0.008) and having received < 4 lines of therapy ( P  = 0.007). Median duration of response was 36.8 weeks (95% CI: 16.4 weeks to not reached). Median time to reduction of immunosuppressants by ≥ 50% was 6.7 months (95% CI: 2.3–12.2). Grade ≥ 3 adverse events occurred in 13% (4/31) of patients. Six patients (19%) discontinued treatment. At 12 months, overall survival and failure-free survival were 95% and 55%. Concomitant ruxolitinib significantly increased the probability of immunosuppressant reduction ( P  = 0.007). Belumosudil showed promising efficacy and safety in cGVHD patients in routine practice.

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.

Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19–63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21–64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.

Background: Detection of measurable residual disease (MRD) is becoming the standard of care in the prognostication of acute myeloid leukaemia post-chemotherapy, but its role in early post-haematopoietic stem cell transplantation (HSCT) is less defined. Objectives: This study aims to examine the role of MRD detection by molecular tools in early post-HSCT settings and its significance in prognostication among other clinicopathologic factors. Design: It is a retrospective cohort study. Methods: We examined MRD early post-HSCT (median: 26 days) in patients receiving allogeneic HSCT at complete remission by droplet digital PCR or next-generation sequencing targeting leukaemia-associated mutations. The effect of MRD positivity and other clinicopathologic variables on post-HSCT leukaemia-free survival (LFS), overall survival (OS) and cumulative incidence of relapse (CIR) were investigated. Results: One hundred fifty-nine patients were included, and the median follow-up time was 6 years. Early post-HSCT MRD positivity was observed in 36% patients and was associated with higher CIR (37.1% vs 13.2% at third year, p = 0.0005), inferior LFS (median: 3.8 years vs not reached, p = 0.002) and OS (median: 10.6 years vs not reached, p = 0.019). It was the only significant factor associated with inferior post-HSCT LFS, CIR and OS in both univariate and multivariate analyses. Conclusion: This study demonstrated that early MRD positivity was predictive of a higher risk of relapse, and inferior LFS and OS post-HSCT. This information laid the foundation for designing MRD-guided strategies early post-HSCT to prevent haematological relapse.

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18–86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.