ABSTRACTAlthough post‐transplant cyclophosphamide (PTCY)‐based prophylaxis has become a widely adopted strategy for preventing graft‐versus‐host disease (GVHD) in 9 out of 10 HLA‐mismatched unrelated donors (MMUDs), allogeneic hematopoietic cell transplants (allo‐HCTs), data on the safety and efficacy of PTCY in this setting remain limited. This single‐center study investigates the outcomes of 94 adults with hematological malignancies undergoing MMUD allo‐HCT with PTCY and tacrolimus (Tac) (PTCY‐Tac) between 2014 and 2023. The median age was 53 years, and 60.6% were male. Peripheral blood stem cells were infused in all cases. By Day +100, the cumulative incidence of Grades II–IV and Grades III and IV acute GVHD were 33.0% and 9.7%, with 2‐year incidence of moderate‐to‐severe chronic GVHD at 12.6%. By Day +30, 40.8% of patients experienced bacterial bloodstream infections, and 52.4% had cytomegalovirus (CMV) reactivation before letermovir prophylaxis. With letermovir's introduction, CMV reactivation rates dropped significantly, with only one case reported. At 3 years, overall survival was 60.8%, non‐relapse mortality was 23%, and the cumulative incidence of relapse was 24.5%. HLA Class I or II mismatches did not affect key outcomes or GVHD rates. These findings demonstrate that PTCY‐Tac offers effective GVHD prevention and favorable outcomes in MMUD allo‐HCT, supporting its application for patients without fully matched donors.

Although chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are the same biologic disease entity and warrant identical treatment approaches, patients with SLL have frequently been excluded from clinical trials in CLL. This study assessed the representation of patients with SLL among Phase II or III clinical trials cited in the 2024 National Comprehensive Cancer Network (NCCN) treatment guidelines. Patients with SLL were explicitly eligible for only 21 (38%) of the 56 clinical trials for CLL, comprising 222 (6%) of the 3440 enrolled patients. Notably, 380 patients with SLL were enrolled in 16 separate non-CLL clinical trials alongside patients with indolent B-cell lymphomas such as follicular lymphoma. In CLL trials, patients with SLL were included in a greater proportion of studies evaluating BTK inhibitors (67%) or BTK/BCL2 inhibitor combinations (67%) compared to BCL2 inhibitors (0%) or chemoimmunotherapy (0%). Although recent and upcoming trials show a promising trend toward the inclusion of patients with SLL, further advocacy is needed to raise awareness of the biological similarities between CLL and SLL and to promote the representation of patients with SLL in CLL/SLL clinical research.

Relapsed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) are associated with a poor prognosis. It is unknown which re-induction therapy provides the highest chance of durable remission. Commonly used therapies are high dose cytarabine (HiDAC) and triple therapy consisting of fludarabine, cytarabine, and idarubicin combined with granulocyte colony-stimulating factor (FLAG-IDA). Two patient cohorts with relapsed AML or HR-MDS treated with HiDAC or FLAG-IDA between October 2015 and December 2021 in two academic hospitals in the Netherlands were retrospectively analyzed. Patients were treated with either HiDAC (n=22) or FLAG-IDA (n=25). Rates of CR (71% vs. 74%, P=0.85), 1-year OS (47% vs. 51%, P=0.99) and EFS (38% vs. 35%, P=0.71) were comparable between HiDAC and FLAG-IDA. Durations of neutropenia (median 24 days (IQR 20-26) vs. 30 days (IQR 22-39), P=0.014) and thrombocytopenia (22 days (IQR 17-26) vs. 36 days (IQR 26-53)) were significantly shorter in the HiDAC group than in the FLAG-IDA group. While remission rates and survival outcomes were similar, FLAG-IDA was associated with longer periods of myelosuppression and transfusion dependency compared to HiDAC in these two cohorts. HiDAC can be considered as a salvage chemotherapyfor relapsed AML/HR-MDS based on our study.

Venetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in a retrospective cohort of 100 consecutive AML patients treated with venetoclax and HMA. Thirty four patients developed laboratory Cairo Bishop TLS; 8 of these met criteria for clinical Cairo Bishop TLS. Only 6 of patients met Howard TLS criteria. Fourteen patients had spontaneous TLS. Ninety two out of 100 patients had a white blood cell count (WBC) < 25 000 cells/μL at treatment start. Prophylaxis like the original venetoclax trial with allopurinol (56%), intravenous fluids (21%), and frequent lab monitoring (56%) was less common. There was a trend toward increased Cairo Bishop TLS in patients with WBC ≥ 15 000 cells/μL. In our study Howard TLS criteria better identified patients with significant TLS. Aggressive TLS prophylaxis was uncommon in our cohort and is likely unnecessary for most patients at low risk of TLS.

Thalassemia is not currently conceived per se as a disability, but it can be a disability-inducing condition if poorly treated or as complications increase with age. People living with thalassemia do not wish, on the one hand, to be considered disabled persons to avoid stigma and loss of opportunities to achieve social inclusion in all paths of life while, on the other, they are in need of lifelong appropriate, disease-specific health and social care, including disability allowances and schemes, in order to be able to smoothly integrate into society and achieve professional, educational, personal, and social goals. The ongoing debate on whether thalassemia is a disability or not is thus complex and inconclusive and has created a vast heterogeneity of policies and approaches across the globe. Given that the risk to develop disabilities is subject to individualised assessment, the thalassemia International Federation (TIF) proposes a specific disability risk assessment model for thalassaemia (DRAM-Thal), based on the findings of a targeted literature review and of the TIF survey 2022-2023. This model considers both clinical features and social parameters and is addressed to national healthcare and social services and all other relevant stakeholders. At the same time, this work prompts further research on this understudied topic that heavily affects the rights and daily life of people living with the disease.

A few shave identified systemic and hematologic risk factors for Proliferative Sickle Cell Retinopathy (PSR) development. The relevance of healthcare utilization as a risk factor for PSR has not been defined. This study evaluates patterns of healthcare utilization among patients with sickle cell disease (SCD) and retinopathy. A retrospective study of adults with SCD, using EMR, was conducted from January 2017 to December 2019, seen at the Montefiore Medical Center eye clinic. Four hundred twelve patients with SCD were included in this analysis (65.8% HbSS (SS)) and 34.2% HbSC (SC). HBSS patients had higher utilization of hematology outpatient visits and inpatient admissions than HBSC. For individuals with either HBSC or HBSS disease, higher outpatient healthcare utilization was associated with higher number of inpatient admissions. The prevalence of retinopathy was 24% and 55% in SS and SC patients respectively, with PSR in 60% SS and 87.6% SC of these patients. Patients with HBSC with higher outpatient visits and inpatient admissions experienced significantly lower PSR rates. In contrast, for patients with HBSS, higher outpatient visits were significantly associated with higher PSR prevalence. Healthcare utilization patterns in individuals with HBSS and HBSC varied according to their prevalence of PSR. These differences may be useful in stratifying patients' risk for retinopathy development and in deciding follow-up eye examination frequency.

Large B-cell lymphoma (LBCL) taxonomy has moved in the direction of a molecular classification, but further clinical experience is needed. We present high-risk gene mutations, which predict outcome in an exploratory study of a consecutive real-world cohort of patients with primary LBCL treated with R-CHOP or R-CHOP-like therapy. The study was a Registry Study Research Project. Sixty-one patients with LBCL, who had a diagnostic tumor sample successfully examined with a 59-gene next-generation sequencing (NGS) panel as a part of routine clinical work, were included in an otherwise unselected cohort. Data were extracted from patient files and pathology reports. Mutations in NOTCH2 (HR 9.69; 95% CI [2.46-38.11]; p = 0.0012), PRDM1 (HR 3.54; 95% CI [1.03-12.22]; p = 0.045), and TP53 (HR 5.89; 95% CI [1.71-20.32]; p = 0.005) were significantly associated with inferior survival in patients with primary LBCL treated with intention to cure with at least three series of R-CHOP or R-CHOP-like therapy. Neither MYD88 (HR 0.66; 95% CI (0.17-2.49), p = 0.54) nor CD79B (HR 0.84;95% CI (0.18-3.88), p = 0.82) mutations were associated with inferior survival. With a targeted gene panel and NGS methodology feasible in daily diagnostic routine, we identified high-risk gene mutations with a significant prognostic impact of which TP53 mutations were reproducible across validation cohorts.

Budd-Chiari syndrome (BCS) is managed by interventions aimed at relieving hepatic venous obstruction and anticoagulation. Despite robust data supporting the tolerability and efficacy of direct oral anticoagulants (DOACs) in patients with other venous thromboembolism, its utility in BCS is not well documented. This study aims to evaluate the efficacy and tolerability of DOACs in Primary BCS from the available literature. Published studies that reported data on patients with BCS treated with DOACs were included. Two retrospective studies and nine case reports met the criteria for inclusion. The combined data from these two retrospective studies include 58 patients administered DOAC and 101 patients treated with VKA/LMWH. The combined re-stenosis or failure rates after percutaneous endovascular intervention, angioplasty, TIPS, or OLT were 17.2% for the DOAC group and 15.8% for the LMWH/VKA group. The incidence of major bleeding was 8.62% in the DOAC group and 5.94% in the LMWH/VKA group, while minor bleeding rates were 20.7% and 4.95%, respectively. Procedure-related bleeding was 4.5% in DOAC group and 12.8% in VKA/LMWH group. Nine case reports using apixaban in 3, rivaroxaban in 5, and one with dabigatran- described patients tolerating the treatment well and experiencing no major adverse events. DOACs appear to be at least equally effective to LMWH/VKA for the anticoagulation of patients with BCS. We believe DOACs to be preferred over LMWH/VKA for the anticoagulation of patients with BCS due to the known advantages in administration, but randomized trials might be needed to answer this question.

To report the long-term safety and efficacy of BAY 81-8973 in the LEOPOLD Kids extension phase. Patients received BAY 81-8973 (25-50 IU/kg) at least twice weekly. The primary endpoint was safety, assessed in all patients who entered the extension phase (n = 82). Efficacy endpoints were assessed in patients without high-titre inhibitors/immune tolerance induction (n = 67). Children (n = 82) received BAY 81-8973 for a median of 3.1 years per patient and a median of 405 exposure days per patient. Long-term BAY 81-8973 treatment was well tolerated, with no cases of de novo inhibitor development in the extension phase. Annualised bleeding rates (ABRs) within 48 h of prophylaxis were low for all bleeds (median [IQR], 0.7 [0-1.9]; mean, 1.4 [SD, 2.1]) and for joint bleeds (median [IQR], 0 [0-0.7]; mean, 0.5 [SD, 1.1]) (n = 67). Twenty-one of 67 patients (31.3%) had zero bleeds within 48 h of prophylaxis; the treatment response was 'good'/'excellent' in 87.9% of bleeds, and most bleeds resolved with ≤ 2 BAY 81-8973 infusions (83.5%). Long-term BAY 81-8973 treatment is well tolerated and maintains low ABRs for all bleeds and joint bleeds in children with severe haemophilia A. ClinicalTrials.gov identifier: NCT01311648.