Background: In allogeneic hematopoietic stem cell transplantation (HSCT), Anti-T-Lymphocyte Globulin (ATLG) may be used for the prevention of severe graft-versus-host disease (GVHD). ATLG targets both the recipient’s lymphocytes and those transferred with the graft. Assuming an inverse relation between the recipient’s absolute lymphocyte count (ALC) and exposure of remaining ATLG to the graft, we aim to evaluate the impact of the recipient’s ALC before the first ATLG administration on the benefits (prevention of GVHD and GVHD-associated mortality) and potential risks (increased relapse incidence) associated with ATLG. Methods: In recipients of HLA-matched, ATLG-based HSCT (n = 311), we assessed the incidence of acute GVHD, GVHD-related mortality and relapse, as well as other transplant-related outcomes, in relation to the respective ALC (divided into tertiles) before ATLG. Results: The top-tertile ALC group had a significantly increased risk of aGVHD (subhazard ratio (sHR) 1.81; [CI 95%; 1.14–2.88]; p = 0.01) and aGVHD-associated mortality (sHR 1.81; [CI 95%; 1.03–3.19]; p = 0.04). At the highest ATLG dose level (≥45 mg/kg), recipients with lowest-tertile ALC had a trend towards increased relapse incidence (sHR 4.19; [CI 95%; 0.99–17.7]; p = 0.05, n = 32). Conclusions: ATLG dosing based on the recipient’s ALC may be required for an optimal balance between GVHD suppression and relapse prevention.

(1) Background: mRNA COVID-19 vaccines are effective but show varied efficacy in immunocompromised patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients. (2) Methods: A retrospective study on 167 HSCT recipients assessed humoral response to two mRNA vaccine doses, using the manufacturer cut-off of ≥7.1 BAU/mL, and examined factors affecting non-response. (3) Results: Twenty-two percent of HSCT recipients failed humoral response. Non-responders received the first vaccine a median of 10.2 (2.5–88.9) months post-HSCT versus 35.3 (3.0–215.0) months for responders (p < 0.001). Higher CD19 (B cell) counts favored vaccination response (adjusted odds ratio (aOR) 3.3 per 100 B-cells/microliters, p < 0.001), while ongoing mycophenolate mofetil (MMF) immunosuppression hindered it (aOR 0.04, p < 0.001). By multivariable analysis, the time from transplant to first vaccine did not remain a significant risk factor. A total of 92% of non-responders received a third mRNA dose, achieving additional 77% seroconversion. Non-converters mostly received a fourth dose, with an additional 50% success. Overall, a cumulative seroconversion rate of 93% was achieved after up to four doses. (4) Conclusion: mRNA vaccines are promising for HSCT recipients as early as 3 months post-HSCT. A majority seroconverted after four doses. MMF usage and low B cell counts are risk factors for non-response.

(1) Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the only treatment with the potential for cure in patients with myelofibrosis (MF). However, the risk of graft rejection, which is particularly high in MF, and the risk of significant non-relapse mortality must be considered. (2) Methods: In this retrospective, single-center study, we compared allo-HSCT outcomes in 36 adult patients with MF transplanted at two-time intervals (2001–2015 versus 2016–2021). (3) Results: The estimated median overall survival was 48.9 months (95%CI 0.00–98.2) in the cohort transplanted before 2016 and not reached in the more recent years (p = 0.04) due to markedly lower non-relapse mortality (p = 0.02). The 3-year relapse incidence was low in both cohorts (11.1% and 12.5%, p > 0.99). When comparing only subgroups within the more recent cohort based on the presence or absence of total body irradiation (TBI) or the use of sequential regimens, OS and PFS were comparable. (4) Conclusion: Pretreatment with ruxolitinib, intensified conditioning, and the preferential use of haploidentical related instead of mismatched unrelated donors for patients lacking an HLA-identical donor are most likely responsible for the improved outcome after allo-HCT in MF in recent years.

Cyclosporin A (CsA) remains a major component of immunosuppressive regimens applied in allogeneic hematopoietic stem cell transplantation (HSCT). The impact of CsA trough levels during the first weeks after HSCT has not yet been investigated specifically in anti-T-lymphocyte globulin (ATLG)-based HSCT from matched related and unrelated donors. To address this issue, we have retrospectively examined 307 consecutive matched related (n = 145) and unrelated (n = 162) HSCTs, using peripheral blood stem cells or bone marrow. HSCTs for active, uncontrolled malignancies were excluded. The initial three weeks' average mean CsA trough levels were analyzed in landmark and multi-state models, using a cut-off of 200 ng/mL. CsA levels >200 ng/mL were associated with a reduced risk of acute graft-versus-host disease (GVHD) grade 3-4 at the first-week landmark (subdistribution hazard ratio [SHR] 0.59, P = 0.03) and the second-week landmark (SHR 0.48, P = 0.004), whereas there was no impact at the third-week landmark (HR 0.87, P = 0.69). This was supported by a multi-state model, in which week 1 (hazard ratio [HR] 0.53, P = 0.006) and week 2 (HR 0.48, P = 0.003), but not week 3 (HR 0.80, P = 0.44) CsA levels >200 ng/mL were associated with a reduced acute GVHD 3-4 risk. Relapse incidence was not significantly affected by week 1 through 3 CsA levels. Despite ATLG's inherent GVHD-preventive properties, week 1 CsA trough levels >200 ng/mL following ATLG-based HSCT (n = 220) were associated with a significantly reduced risk of non-relapse mortality (SHR 0.52, P = 0.02) and improved overall survival (HR 0.61, P = 0.02). Our findings emphasize the continuing importance of ensuring CsA levels ≥200 ng/mL immediately post-transplant in the setting of ATLG-based HSCT.

Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin inhibitor (CNI) are used as the backbone of GVHD prophylaxis. The efficacy of ATLG in combination with CNI and mycophenolate mofetil (MMF) has not been investigated as much, particularly in terms of a direct comparison with its effects when combined with CNI/MTX. A total of 401 HSCTs from two Austrian transplant centers were retrospectively evaluated. We included peripheral blood transplants from early- or intermediate-stage (excluding advanced/refractory) hematological diseases from matched siblings or 10/10 or 9/10 matched unrelated donors with CNI/MTX or CNI/MMF prophylaxis, either without (n = 219) or with ATLG (n = 182). Overall, ATLG significantly reduced the risk for all-cause mortality by multivariate Cox analysis (HR 0.53; p = 0.002). Stratification by postgrafting prophylaxis type revealed a significant survival advantage for ATLG in the CNI/MMF cohort (HR 0.49; p = 0.001; n = 193), while its effect on survival in the CNI/MTX cohort was not significant (HR 0.87; p = 0.56; n = 208). In unrelated HSCT with CNI/MMF prophylaxis, ATLG exhibited its greatest survival benefit (HR 0.34; p = 0.001; n = 104). In the context of CNI/MMF, ATLG may provide even greater benefits than in the setting of CNI/MTX for post-grafting immunosuppression. Future prospective studies on ATLG should therefore focus on CNI/MMF-based transplants, which are widely performed in elderly or comorbid patients not expected to tolerate a standard course of MTX.

Background: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. Methods: This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022. Survival outcomes, relapse incidence, and non-relapse mortality were calculated according to remission status, date of allo-HSCT, cytogenetic risk status, timing, and number of previous autologous HSCTs. Results: The median PFS was 13.6 months (95% CI, 7.7–30.4) and the median OS was 51.4 months (95% CI, 23.5–NA) in the overall cohort. The cumulative incidence of relapse at 3 years was 57%, and non-relapse mortality was 16%. The median PFS and OS were significantly longer in patients with very good partial remission (VGPR) or better compared to patients with less than VGPR at the time of allo-HSCT (mPFS 29.7 months (95% CI, 13.7–NA) vs. 6.5 months (95% CI, 2.6–17.0); p = 0.009 and mOS not reached vs. 18.6 months (95% CI, 7.0–NA); p = 0.006). Conclusion: For selected patients, allo-HSCT may result in favorable overall survival, in part by providing an appropriate hemato-immunological basis for subsequent therapies.