Joanna Drozd-Sokołowska

The impact of venetoclax‐based therapies on autoimmune cytopenias (AIC) in patients with chronic lymphocytic leukemia (CLL) is largely unknown. This study aimed to evaluate preexisting and treatment‐emergent AIC in patients with CLL treated with venetoclax, focusing on the differential impact of venetoclax monotherapy versus venetoclax‐based combinations. In this retrospective multicenter study, data from 1720 patients were collected; 23.1% received venetoclax single agent and 76.9% venetoclax combinations (mostly containing anti‐CD20 monoclonal antibodies and/or BTK inhibitors). Combination regimens were used in 97.7% of treatment‐naïve (TN) patients and 65.8% of patients with relapsed/refractory (R/R) CLL. Preexisting AIC were reported in 11.7% of patients (8.7% in TN and 13.4% in R/R, P = 0.005). CLL‐related genetic risk factors and disease outcomes did not differ in patients with and without preexisting AIC. Irrespective of treatment type, venetoclax therapy resulted in AIC resolution or improvement in 63% of patients with active or controlled AIC. Treatment‐emergent AIC occurred in 2.6% of patients (2% in TN and 2.9% in R/R, not statistically significant). AIC episodes were reported in 4.3% of patients treated with venetoclax monotherapy and in 2.1% of those treated with venetoclax‐based combinations (P = 0.02). After standard management, AIC was considered resolved or controlled in 82% of the patients, with no substantial difference between treatment groups. Venetoclax‐based therapies have a beneficial impact on the outcome of CLL‐associated preexisting AIC. Treatment‐emergent AIC is a rare and generally manageable event. Although more frequent with venetoclax monotherapy in unadjusted analysis, this association was attenuated after adjustment for baseline prognostic factors.

Myelodysplastic neoplasms (MDS) relapsing after allogeneic stem cell transplantation (alloSCT) have a poor prognosis. A second alloSCT (alloSCT2) can offer durable remission, however, earlier studies reported <20% long-term survival. Here we summarize contemporary outcome and risk factors after alloSCT2 (2012-2023), particularly focusing on donor change (DoC). We included 313 adults undergoing alloSCT2 for MDS relapse. Donors for alloSCT2 were matched- related/unrelated/haploidentical in 19%/62%/19%, with DoC reported in 71%. Two-year overall-/progression-free survival (OS/PFS), cumulative relapse incidence (RI) and non-relapse mortality (NRM) from alloSCT2 were 45%/33%/37%/30%. Outcome improved over time (2y-OS/PFS: 51%/39% in years 2018-2023). In multivariable analyses, DoC was associated with lower risk of relapse (HR=0.56, 95%-CI: 0.36-0.89), a finding never observed after alloSCT2 for acute leukemia. Additionally, adverse cytogenetics were correlated with relapse risk (HR=1.93, 95%-CI: 1.18-3.17). Risk of NRM decreased in more recent years (HR=0.88, per year later) and in patients with Karnofsky performance score (KPS) ≥90 at alloSCT2 (HR=0.59). Concerning survival, remission after alloSCT1 ≥12 months (HR=0.62/0.67) and KPS ≥90 (HR=0.68/0.69) were associated with better OS/PFS. In summary, we report improved outcomes of alloSCT2 in MDS in more recent years and demonstrate superior disease control by DoC, although a trend toward increased NRM precluded a significant survival benefit.

Myelodysplastic syndromes (MDS) in young adults are uncommon and underrepresented in transplant cohorts. We evaluated 697 patients aged 18–40 years who underwent first allogeneic hematopoietic cell transplantation (allo-HCT) reported to the EBMT between 2016 and 2021. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and graft-versus-host disease (GVHD). With a median follow-up of 2.8 years, 3-year OS and PFS were 69% (95% CI, 65–73) and 62% (58–66), respectively. At 3 years, CIR and NRM were 20% (16–23) and 18% (15–21). Grade II–IV acute GVHD occurred in 28% (25–32) by day +100, while chronic GVHD and extensive chronic GVHD occurred in 38% (34–42) and 18% (14–21) at 3 years. In multivariable analysis, very-poor cytogenetic risk was associated with inferior OS (HR 2.81, 95% CI 1.77–4.45). Haploidentical donors and reduced-intensity conditioning were also associated with inferior survival. Patients younger than 30 years had superior PFS, whereas outcomes with matched sibling and matched unrelated donors were comparable. These findings support the feasibility of allo-HCT in young adults with MDS and may help inform risk-adapted transplant approaches.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults [1]. Although outcomes have improved substantially in recent years—driven in part by the introduction of multiple novel targ...

Tuberculosis (TB) is an infectious complication of hematopoietic cell transplantation (HCT). There is a paucity of data on TB after HCT. Here we present the data from a low/low-intermediate TB-burden country. This was a Retrospective analysis of adult patients who developed TB after HCT. Seventeen patients were identified, 9 (52.9%) females, the median age at TB 44 years. Five (29.4%) patients underwent auto-HCT, 12 (70.6%) allo-HCT, translating into the relative frequency of TB of 0.171% for allo-HCT, and 0.063% for auto-HCT. The median time from HCT to TB was 431 days (range, 5–973). All patients had pulmonary TB. Bacteriologically confirmed TB was diagnosed in 13 (76.5%) patients; drug susceptibility testing was performed in 3/13 (23.1%). The median duration of treatment was 6 months. Twelve out of 13 evaluable patients (92.3%) obtained treatment success. With a median follow-up of 48 months (95%CI 19–95) 1-year cumulative incidence of TB-associated death was 6.7% (95%CI 0.9–40.8%). To conclude TB is a very rare infectious complication of HCT. Most frequently TB develops late after HCT. The primary site involved is the lung with no extrapulmonary TB identified in the current analysis. TB can still result in the death of the affected patient.

The landscape of Allogeneic Haematopoietic Cell Transplantation (allo-HCT) for Chronic Myeloid Leukaemia (CML) remains dynamic with the advent of tyrosine kinase inhibitors (TKIs). There remains an absence of widely agreed evidence-based guidelines for post-transplant monitoring and relapse management. To evaluate current real-world practices for ‘high risk’ CML, the CML subcommittee of the Chronic Malignancies Working Party (CMWP) of the European Blood and Marrow Transplantation (EBMT) society developed an electronic survey, which was distributed to 39 EBMT-registered transplant centres in April 2024. Centres were chosen based on CML allo-HCT activity. Twenty-three centres (59%) responded, providing clinical perspectives into pre-transplant chemotherapy regimens, TKI use, ABL1 kinase domain mutation analysis, post-transplant monitoring, and their practice regarding sequencing/ integration of TKIs with donor lymphocyte infusions (DLI). Most centres conduct monthly BCR::ABL1 transcript monitoring during the first three months post-transplant, transitioning to quarterly assessments upon achieving a deep molecular response. TKI maintenance is widely adopted across centres, with treatment duration guided by molecular response, and TKIs are generally preferred over DLI for managing molecular relapse. However, DLI remains a valid option for TKI-refractory chronic-phase (CP)-CML relapse. Survey findings illustrate significant heterogeneity in practice, offering insights to inform research aimed at improving allo-HCT outcomes in CML.