Matthias Stelljes

Chronic graft-versus-host disease (GvHD) is a significant risk factor for late morbidity and mortality after allogeneic stem cell transplantation. In Europe, so far there were no standard treatment options available after failure of corticosteroids and ruxolitinib. The selective ROCK-2 inhibitor belumosudil, a novel FDA-, and recently EMA-approved agent, has shown efficacy in phase-2 trials and had been made available to German and Austrian patients within a managed-access program (MAP). In a retrospective multicenter study, we analyzed 144 patients with predominately severe chronic GvHD (72%) receiving belumosudil within the MAP after a median of four prior therapeutic agents. The objective response rate at one and six months was partial remission or better in 53 and 52 patients (37% and 56%). Responses were observed across all organ systems. Median time to response was 1.3 months. At six months, steroids could be discontinued in 35% and reduced in 33% of patients. Failure-free survival was 81.9% and 75.8% at six and nine months. Six months overall survival was 96.9%. Treatment-emergent adverse reactions CTCAE grade III-IV were mostly infectious complications and occurred in 28 patients (22%). This retrospective analysis of a large real-world cohort demonstrates efficacy and safety of belumosudil in refractory chronic GvHD patients.

Objectives: Primary plasma cell leukemia (pPCL) is a rare disease with poor outcomes. As data on randomized phase‐III trials are lacking, treatment recommendations are predominately based on retrospective analyses incorporating time periods with outdated therapies. Thus, the optimal consolidation strategy remains to be defined. Methods: We conducted a retrospective, multi‐center analysis with 49 transplant‐eligible patients diagnosed with pPCL between 2011 and 2025 focusing on different stem cell transplantation (SCT) strategies as consolidation treatment in first remission: single autologous (auto) or single allogeneic (allo) SCT versus patients with tandem cell therapy strategies (auto‐auto, allo‐auto, auto‐chimeric antigen receptor therapy). Results: The median follow‐up after first SCT was 31 months. The cumulative incidence of initiating next treatment was lower after tandem cell therapy compared to single SCT (at 12 months: 42% vs. 57%, p = 0.006). Moreover, in a multivariable analysis incorporating cytogenetic risk and response to induction therapy, tandem transplantation strategies tended to be the only independent predictor for prolonged time to next treatment (TTNT, p = 0.077). Noteworthy, differences in TTNT between patients with a single SCT and patients with tandem cell therapy did not translate into an improved overall survival, possibly due to potent salvage therapies. Conclusions: Our data support recent recommendations advising treating patients with tandem transplantation regimes.

There are very limited data on treosulfan (Treo)-based conditioning before allogeneic hematopoietic stem cell transplantation (alloHSCT) in acute lymphoblastic leukemia. We aimed to compare fludarabine with Treo (FluTreo) or total body irradiation (FluTBI) in this setting. The final matched-pair analysis included ALL patients transplanted in complete remission after FluTreo (n = 153) or FluTBI (n = 431). The median patient age was 56.5 and 54.1 years, respectively. The allograft was derived from an unrelated (54.2% in FluTreo and 52% FluTBI group), matched sibling (30.7% and 32.5%) or haploidentical donor (15% and 15.5%). The incidence of acute graft-versus-host disease (GVHD) grade II-IV was 26.6% in the FluTreo and 30% in the FluTBI group (p = 0.43). The 2-year incidence of chronic GVHD was 33.5% and 40.7%, respectively (p = 0.23). The 2-year incidence of relapse and non-relapse mortality was 28.1% and 25.6% in the FluTreo and 25.1% and 20.4%, respectively, in the FluTBI group (p = 0.15 and p = 0.38). Leukemia-free survival and overall survival was 46.2% and 55% in the FluTreo and 54.5% and 61.3%, respectively, in the FluTBI group (p = 0.1 and p = 0.22). GVHD-free and relapse-free survival was 33.7% and 40.8%, respectively, in FluTreo and FluTBI patients (p = 0.06). In conclusion, there were no significant differences in transplant outcomes between the studied groups.

Allogeneic hematopoietic cell transplantation (allo-HCT) can cure acute leukemia, but relapse and non-relapse mortality restrict its success. Existing models focus on single prognostic areas and are not designed to predict leukemia-free survival (LFS), the outcome that best reflects allo-HCT’s curative intent. In this large retrospective cohort of allografted AL patients ( N = 24,317), we combined key pre-transplant patient, disease, and treatment factors into a practical holistic H-score to predict post–allo-HCT LFS. Component weights were derived from Cox-regression hazard ratios in a training cohort ( N = 19,029). The model was validated in a geographically split testing cohort (N = 4760), with outcomes assessed using Kaplan-Meier analysis and multivariate Cox models. In the overall cohort ( N = 24,317), 2-year overall survival and LFS were 64% and 56%, respectively. The H-score stratified patients into four risk groups, with 2-year LFS ranging from 66.2% in the low-risk group to 32.0% in the very high-risk group. The H-score was the strongest independent predictor of LFS ( p < 0.0001), outperforming individual indices and offering more refined risk stratification. The H-score was also an independent predictor of overall survival, relapse, and non-relapse mortality. While individual prediction is limited, the H-score aids patient counseling and provides a useful baseline for comparing new transplant treatments.

The optimal conditioning intensity for allogeneic hematopoietic stem cell transplantation (allo-HCT) in elderly acute myeloid leukemia (AML) remains elusive. We retrospectively analyzed 2900 AML patients aged ≥65 in complete remission who underwent allo-HCT from 2004 to 2021. Conditioning was classified as reduced-intensity conditioning (RIC: fludarabine with busulfan, melphalan, or treosulfan) or non-myeloablative (NMA: fludarabine with total body irradiation). Primary endpoints were overall survival (OS) and leukemia-free survival (LFS); secondary endpoints included non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and GVHD/relapse-free survival (GRFS). With follow-up censored to account for differences between arms, OS, LFS, and NRM at 2 years were similar between RIC and NMA on multivariable analysis. Peripheral blood stem cells (PBSC) were independently associated with superior OS (HR 0.67, p = 0.002) and LFS (HR 0.71, p = 0.008) versus bone marrow grafts. GRFS was equivalent between conditioning intensities, although RIC was associated with higher acute GVHD and NMA with higher extensive chronic GVHD. In exploratory analysis, OS and LFS were similar across RIC regimens (Flu/Bu2 as reference: Flu/Mel OS HR 0.91, p = 0.53; Flu/Treo OS HR 0.89, p = 0.42). In older AML patients in remission, RIC and NMA yield comparable survival and NRM; PBSC grafts may be associated with superior outcomes although this warrants validation.

The International Prognostic Index (IPI) is an essential prognostic tool for patients with large B-cell lymphoma (LBCL). To compare outcomes after chimeric antigen receptor T-cell (CART) therapy and allogeneic stem cell transplantation (alloSCT) in relation to IPI risk factors, we analyzed 515 LBCL patients receiving CART (n = 303) or alloSCT (n = 212) as ≥third-line treatment, registered with EBMT (2016–2021). Patients treated with CART were older (median 62.4 vs 51.1 years), had higher IPI scores (48.2% vs 20.8% high/high-intermediate risk), and a higher incidence of refractory disease (84.1% vs 34.6%). At 24 months, overall survival (OS) was 49% vs 41%, progression-free survival (PFS) was 37% vs 32%, relapse-incidence (RI) was 56% vs 38%, and non-relapse-mortality (NRM) was 7% vs 30%, respectively. In multivariate analysis, CART therapy showed superior OS primarily due to significantly lower NRM, while RI was higher. The survival benefit of CART was significant in patients with low/low-intermediate IPI (OS HR 0.43, 95% CI 0.31-0.60), but not observed in high-risk patients. Elevated LDH eliminated the PFS advantage of CART over alloSCT. Poor outcomes after CART in patients with high-risk disease support early preparation for alloSCT for eligible patients.

Tabelecleucel (tab-cel) is an allogeneic Epstein-Barr virus (EBV)–specific T-cell therapy approved in the European Union for relapsed or refractory (R/R) EBV-associated posttransplantation lymphoproliferative disorder (PTLD) after rituximab or immunochemotherapy failure. Despite its promise as the first approved option for treating the disorder, real-world evidence remains limited. The aim of this study was to investigate the scope of use and outcomes of tab-cel treatment in the real-world setting across Germany, Austria, and Switzerland. Eleven patients with EBV+ PTLD or other EBV-associated lymphoproliferative disorders (LPD) from 9 academic centers were included for a detailed analysis of baseline characteristics and survival parameters. Of these, 8 patients with PTLD (6 after solid organ transplantation and 2 after allogeneic hematopoietic cell transplantation) and 3 patients with EBV-associated LPDs were treated with a median of 2 cycles of tab-cel (range, 1-3). After a median follow-up of 15.1 months, 6 of 11 (55%) patients remained alive. Initially, 7 of 11 patients (64%) achieved an objective response, with best response occurring at a median of 31 days after the first tab-cel infusion (ie, end of cycle 1). Relapse and progression after tab-cel occurred in 7 of 11 (64%) patients. The estimated median overall survival was 13.4 months (confidence interval, 4.4-14.7), likely because of successful subsequent salvage treatments. Immunotherapy-related adverse events were rare. Tab-cel showed efficacy and low toxicity in patients with R/R PTLD/LPD, a vulnerable cohort of immunodeficient or patient who underwent transplantations. These real-world data help elucidate the optimal integration of tab-cel in the management of R/R PTLD.