Eppendorf Group

Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo‐HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry‐based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX‐ and MMF‐based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX‐ or MMF prophylaxis in combination with a CNI. Endpoints after allo‐HCT were overall survival, relapse‐free survival (RFS), relapse incidence, non‐relapse mortality (NRM), and Grades 2–4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow‐up was 42.8 months (IQR 19.8–74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81–0.95, p = 0.001) and NRM (HR 0.86, 95% CI 0.78–0.96, p = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94–1.14, p = 0.53) or RFS (HR 0.95, 95% CI 0.88–1.01, p = 0.12). There was a reduced risk of Grades 2–4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo‐HCT. In conclusion, MTX‐complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.

In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin’s lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting. We included 257 allo-HCT patients (n = 172 ≥ 18 years) with B-ALL or B-NHL, treated with anti-CD19 CAR T-cells (tisagenlecleucel n = 184, brexucabtagene autoleucel n = 43 and axicabtagene ciloleucel n = 30), between 2018 and 2022. Three patients developed aGvHD, whereas 6 patients developed cGvHD after CAR T-cell. The 100-day cumulative incidence (CI) of new aGvHD was 1.6% and the 12-month CI of new cGvHD was 2.8%. The 1-year GvHD relapse-free survival and non-relapse mortality were 52.1% and 4.7%, respectively. Last, with a median follow up of 18.8 months, the 1-year overall survival was 76.8%. In summary, the GvHD rate in allo-HCT patients treated with CAR T-cell therapy is relatively low. Our data support the view that GvHD is not a major safety issue in this setting.

Analytes, from sample preparation, until entering an analytical instrument, are prone to adsorb to surfaces, driven by the chemical properties of the surface and the liquids they are dissolved in. This problem can be addressed with internal standards when a single or few known analytes are quantified that are usually not available in omics. However, minimal to no loss of analytes is the aim. Here, we present a novel assay for qualifying and quantifying interactions responsible for adsorption of molecules to surfaces (APS) by using LC–MS/MS‐based differential quantitative analysis. To reflect a broad range of chemical interactions with surfaces, a reference mixture of thousands of tryptic peptides, with known compositions was selected, representing a variety of different chemical characteristics. The assay was tested by investigating the adsorption properties of several different vials with different surface chemistries. A significant number of hydrophobic peptides adsorbed to conventional polypropylene vials. In contrast, only few peptides adsorbed to polypropylene vials, assigned as low‐protein‐binding. The highest number of peptides adsorbed to glass vials driven by electrostatic interactions. In summary, the new assay is suitable to characterize adsorption properties of different surfaces and to approximate the loss of analytes during sample preparation.

The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred. Nine patients self‐reported mild adverse events during flight (13%), while after landing, 12 patients reported events (20%). Solely one patient (2%) had an adverse event leading to medical consultation. In patients with PH and World Health Organization functional classes II and III, air travel was safe.

We compared relapse incidence (RI) post‐unrelated transplantation with post‐transplant cyclophosphamide (PTCy) versus no PTCy graft‐versus‐host disease (GVHD) prophylaxis, in 7049 acute myeloid leukemia (AML) patients in remission, 707 with PTCy, and 6342 without (No PTCy). The patients in the PTCy group were younger, 52.7 versus 56.6 years (p < .001). There were more 9/10 donors in the PTCy group, 33.8% versus 16.4% (p < .001), and more received myeloablative conditioning, 61.7% versus 50.2% (p < .001). In the No PTCy group, 87.7% of patients received in vivo T‐cell depletion. Neutrophil and platelet engraftment were lower in the PTCy versus No PTCy group, 93.8% and 80.9% versus 97.6% and 92.6% (p < .001). RI was not significantly different in the PTCy versus the No PTCy group, hazard ratio (HR) of 1.11 (95% confidence interval [CI] 0.9–1.37) (p = .31). Acute GVHD grades II–IV and III–IV, were significantly lower in the PTCy versus the No PTCy group, HR of 0.74 (95% CI 0.59–0.92, p = .007) and HR = 0.56 (95% CI 0.38–0.83, p = .004), as were total and extensive chronic GVHD, HRs of 0.5 (95% CI 0.41–0.62, p < .001) and HR = 0.31 (95% CI 0.22–0.42, p < .001). Non‐relapse mortality (NRM) was significantly lower with PTCy versus the No PTCy group, HR of 0.67 (95% CI 0.5–0.91, p = .007). GVHD‐free, relapse‐free survival (GRFS) was higher in the PTCy versus the No PTCy group, HR of 0.69 (95% CI 0.59–0.81, p = .001). Leukemia‐free survival (LFS) and overall survival (OS) did not differ between the groups. In summary, we observed comparable RI, OS, and LFS, significantly lower incidences of GVHD and NRM, and significantly higher GRFS in AML patients undergoing unrelated donor‐hematopoietic stem cell transplantation with PTCy versus No PTCy GVHD prophylaxis.

There is a high risk of GVHD and non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) from unrelated donors. Prophylaxis with rabbit anti-thymocyte globulin (rATG) is standard in Europe but post-transplantation Cyclophosphamide (PTCy) is an emerging alternative. We analyzed outcomes of rATG (n = 7725) vs. PTCy (n = 1039) prophylaxis in adult patients with hematologic malignancies undergoing peripheral blood alloSCT from 10/10 antigen-matched unrelated donors (MUD) between January 2018 and June 2021 in the EBMT database. The provided P-values and hazard ratios (HR) are derived from multivariate analysis. Two years after alloSCT, NRM in the PTCy group was 12.1% vs. 16.4% in the rATG group; p = 0.016; HR 0.72. Relapse was less frequent after PTCy vs. rATG (22.8% vs. 26.6%; p = 0.046; HR 0.87). Overall survival after PTCy was higher (73.1% vs. 65.9%; p = 0.001, HR 0.82). Progression free survival was better after PTCy vs. rATG (64.9% vs. 57.2%; p < 0.001, HR 0.83). The incidence of chronic GVHD was lower after PTCy (28.4% vs. rATG 31.4%; p = 0.012; HR 0.77), whereas the incidence and severity of acute GVHD were not significantly different. GVHD-free relapse-free survival was significantly higher in the PTCy arm compared to the rATG arm (2 y incidence: 51% vs. 45%; HR: 0.86 [95% CI 0.75–0.99], p = 0.035). In the absence of evidence from randomized controlled trials, our findings support a preference for the use of PTCy in adult recipients of peripheral blood alloSCTs from MUD.

Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3–63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9–11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54–77) and 39% (27–51) and 53% (41–65) and 29% (18–40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs. 21%, p = 0.032). Cumulative incidences of grade II–IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29–53) and chronic GVHD at 3 years was 53% (95% CI 41–65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26–50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline “Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus—version 3.1” is to provide practical and evidence‐based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well‐established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage‐appropriate therapy after the initial diagnosis of esophageal cancer. In high‐grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD‐L1 and/or Her2 expression.

In the 2022 European LeukemiaNet classification, patients with nucleophosmin 1 (NPM1)‐mutated acute myeloid leukemia (AML) were classified in the adverse‐risk category in the presence of high‐risk cytogenetics (CG). Nonetheless, the impact of various CG aberrations on posttransplant outcomes remains to be unraveled. This registry study analyzed adult patients with NPM1‐mutated de novo AML who underwent their first allogeneic hematopoietic cell transplantation in the first complete remission from 2005 to 2021. A total of 3275 patients were identified, 2782 had normal karyotype, 493 had chromosomal aberrations including 160 with adverse‐risk CG, 72 patients had complex karyotype (CK), and 66 monosomal karyotype (MK). Overall, 2377 (73%) patients had FLT3‐ITD. On univariate analysis, only FLT3‐ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72, p = .009). In the subgroup of 493 patients with aberrant CG, the 2‐year leukemia‐free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p = .025; and 1.99, p = .003 respectively) and worse LFS (HR 1.62, p = .018; and 1.64, p = .011 respectively) while FLT3‐ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91, p = .002). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1‐mutated AML. Nevertheless, even for this subgroup, a significant proportion of patients can achieve long‐term posttransplant survival.

Although CMML since long has been separated from MDS, many studies continue to evaluate the outcomes of both diseases after hematopoietic cell transplantation (allo‐HCT) together. Data evaluating outcomes of a large CMML cohort after allo‐HCT compared to MDS are limited. We aim to compare outcomes of CMML to MDS patients who underwent allo‐HCT between 2010 and 2018. Patients ≥18 years with CMML and MDS undergoing allo‐HCT reported to the EBMT registry were analyzed. Progression to AML before allo‐HCT was an exclusion criterion. Overall survival (OS), progression/relapse‐free survival (PFS), relapse incidence (including progression) (REL), and non‐relapse mortality (NRM) were evaluated in univariable and multivariable (MVA) Cox proportional hazard models including interaction terms between disease and confounders. In total, 10832 patients who underwent allo‐HCT were included in the study, there were a total of 1466 CMML, and 9366 MDS. The median age at time of allo‐HCT in CMML (median 60.5, IQR 54.3–65.2 years) was significantly higher than in the MDS cohort (median 58.8, IQR 50.2–64.5 years; p < .001). A significantly higher percentage of CMML patients were male (69.4%) compared to MDS (61.2%; p < .001). There were no clinically meaningful differences in the distribution of Karnofsky score, Sorror HCT‐CI score at allo‐HCT, and donor type, between the CMML and MDS patients. RIC platforms were utilized in 63.9% of CMML allo‐HCT, and in 61.4% of MDS patients (p = .08). In univariable analyses, we found that OS, PFS, and REL were significantly worse in CMML when compared with MDS (all p < .0001), whereas no significant difference was observed in NRM (p = .77). In multivariable analyses, the HR comparing MDS versus CMML for OS was 0.81 (95% CI, 0.74–0.88, p < .001), PFS 0.76 (95% CI 0.70–0.82, p < .001), relapse 0.66 (95% CI 0.59–0.74, p < .001), and NRM 0.87 (95% CI 0.78–0.98, p = .02), respectively. The association between baseline variables and outcome was found to be similar in MDS and CMML (all interaction p > .05) except for a decreasing trend over time of the risk of relapse in CMML (HR allo‐HCT per year later 0.94, 95% CI 0.90–0.98), whereas no such trend was observed in MDS (HR 1.00, 95% CI 0.98–1.02). The poor outcome observed for CMML could be related to variables not measured in this study or to factors inherent to the disease itself. This study demonstrates that outcomes of CMML patients after allo‐HCT are significantly worse compared to MDS. The results of this study may contribute to future recommendations for allo‐HCT in CMML patients.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5–65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45–56%) and relapse free survival (RFS) 45% (95% CI 40–51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

Microbes – bacteria, archaea, unicellular eukaryotes, and viruses – play an important role in human and environmental health. Growing awareness of this fact has led to a huge increase in microbiological research and applications in a variety of fields. Driven by technological advances that allow high-throughput molecular characterization of microbial species and communities, microbiological research now offers unparalleled opportunities to address current and emerging needs. As well as helping to address global health threats such as antimicrobial resistance and viral pandemics, it also has a key role to play in areas such as agriculture, waste management, water treatment, ecosystems remediation, and the diagnosis, treatment and prevention of various diseases. Reflecting this broad potential, billions of euros have been invested in microbiota research programs worldwide. Though run independently, many of these projects are closely related. However, Germany currently has no infrastructure to connect such projects or even compare their results. Thus, the potential synergy of data and expertise is being squandered. The goal of the NFDI4Microbiota consortium is to serve and connect this broad and heterogeneous research community by elevating the availability and quality of research results through dedicated training, and by facilitating the generation, management, interpretation, sharing, and reuse of microbial data. In doing so, we will also foster interdisciplinary interactions between researchers. NFDI4Microbiota will achieve this by creating a German microbial research network through training and community-building activities, and by creating a cloud-based system that will make the storage, integration and analysis of microbial data, especially omics data, consistent, reproducible, and accessible across all areas of life sciences. In addition to increasing the quality of microbial research in Germany, our training program will support widespread and proper usage of these services. Through this dual emphasis on education and services, NFDI4Microbiota will ensure that microbial research in Germany is synergistic and efficient, and thus excellent. By creating a central resource for German microbial research, NDFDI4Microbiota will establish a connecting hub for all NFDI consortia that work with microbiological data, including GHGA, NFDI4Biodiversity, NFDI4Agri and several others. NFDI4Microbiota will provide non-microbial specialists from these consortia with direct and easy access to the necessary expertise and infrastructure in microbial research in order to facilitate their daily work and enhance their research. The links forged through NFDI4Microbiota will not only increase the synergy between NFDI consortia, but also elevate the overall quality and relevance of microbial research in Germany.

The current incidence, diagnostic policy, management, and outcome of VOD/SOS at EBMT centers were studied. All centers that had performed allogeneic HSCTs in adult patients within one defined year were invited to the study. Seventy-one centers participated with a total of 2886 allogeneic transplantations and 93 cases of VOD/SOS in 2018. The cumulative incidence of VOD/SOS at day 21 was 1.8% and at day 100 2.4%. Of 67 cases with detailed data, 52 were classical and 15 (22%) late onset (>day 21). According to the EBMT criteria, 65/67 patients had at least two VOD/SOS risk factors. The severity grades were: mild 0, moderate 3, severe 29, very severe 35. Fifty-four patients were treated with defibrotide. VOD/SOS resolved in 58% of the patients, 3/3 with moderate, 22/28 with severe, and 12/33 with very severe grade (p < 0.001). By day 100, 57% of the patients were alive; 3/3 with moderate, 22/29 with severe, and 13/35 with very severe VOD/SOS (p = 0.002). In conclusion, the incidence of VOD/SOS was low. Severe and very severe grades dominated. Very severe grade predicted poor outcome compared to severe grade further supporting the concept of early diagnosis and treatment to avoid a dismal outcome.

In the setting of a first relapse of multiple myeloma (MM), a second autologous stem cell transplant (ASCT) following carfilzomib-lenalidomide-dexamethasone (KRd) is an option, although there is scarce data concerning this approach. We performed a retrospective study involving 22 EBMT-affiliated centers. Eligible MM patients had received a second-line treatment with KRd induction followed by a second ASCT between 2016 and 2018. Primary objective was to estimate progression-free survival (PFS) and overall survival (OS). Secondary objectives were to assess the response rate and identify significant variables affecting PFS and OS. Fifty-one patients were identified, with a median age of 62 years. Median PFS after ASCT was 29.5 months while 24- and 36-months OS rates were 92.1% and 84.5%, respectively. Variables affecting PFS were an interval over four years between transplants and the achievement of a very good partial response (VGPR) or better before the relapse ASCT. Our study suggests that a relapse treatment with ASCT after KRd induction is an effective strategy for patients with a lenalidomide-sensitive first relapse. Patients with at least four years of remission after a frontline ASCT and who achieved at least a VGPR after KRd induction appear to benefit the most from this approach.

Background To assess whether cardiac T1 mapping for detecting myocardial fibrosis enables preoperative identification of patients at risk for early left ventricular dysfunction after surgery of aortic regurgitation. Methods 1.5 Tesla cardiac magnetic resonance imaging was performed in 40 consecutive aortic regurgitation patients before aortic valve surgery. Native and post-contrast T1 mapping was performed using a modified Look-Locker inversion-recovery sequence. Serial echocardiography was performed at baseline and 8 ± 5 days after aortic valve surgery to quantify LV dysfunction. Receiver operating characteristic analysis was performed to determine the diagnostic accuracy of native T1 mapping and extracellular volume for predicting postoperative LV ejection fraction decrease >−10% after aortic valve surgery. Results Native T1 was significantly increased in patients with a postoperatively decreased LVEF ( n = 15) vs. patients with a preserved postoperative LV ejection fraction ( n = 25) (i.e., 1,071 ± 67 ms vs. 1,019 ± 33 ms, p = .001). Extracellular volume was not significantly different between patients with preserved vs. decreased postoperative LV ejection fraction. With a cutoff-of value of 1,053 ms, native T1 yielded an area under the curve (AUC) of .820 (95% CI: .683–.958) for differentiating between patients with preserved vs. reduced LV ejection fraction with 70% sensitivity and 84% specificity. Conclusion Increased preoperative native T1 is associated with a significantly higher risk of systolic LV dysfunction early after aortic valve surgery in aortic regurgitation patients. Native T1 could be a promising tool to optimize the timing of aortic valve surgery in patients with aortic regurgitation to prevent early postoperative LV dysfunction.

Allogeneic hematopoietic cell transplant (allo‐HCT) provides the only potential route to long‐term remission in patients diagnosed with blast phase transformation of myeloproliferative neoplasm (BP‐MPN). We report on a large, retrospective European Society for Blood and Marrow Transplantation registry‐based study of BP‐MPN patients undergoing allo‐HCT. BP‐MPN patients undergoing first allo‐HCT between 2005 and 2019 were included. A total of 663 patients were included. With a median follow‐up of 62 months, the estimated 3‐year overall survival (OS) was 36% (95% confidence interval [CI], 32–36). Factors associated with lower OS were Karnofsky Performance Score (KPS) <90 (hazard ratio [HR] 1.65, p < .001) and active disease at allo‐HCT (HR 1.45, p < .001), whereas patients undergoing allo‐HCT more recently associated with a higher OS (HR 0.96, p = .008). In a selected patient's population, the 3‐year OS of patients undergoing allo‐HCT in complete response (CR) and with a KPS ≥90 was 60%. KPS < 90 (HR 1.4, p = .001) and active disease (HR 1.44, p = .0004) were associated with a lower progression‐free survival (PFS). Conversely, most recent allo‐HCT associated with a higher PFS (HR 0.96, p = .008). Active disease at allo‐HCT (HR 1.34, p = .03) was associated with a higher cumulative incidence of relapse (RI) and allo‐HCT in earlier calendar years (HR 0.96, p = .02) associated with a lower RI. Last, KPS < 90 (HR 1.91, p < .001), active disease (HR 1.74, p = .003) and allo‐HCT from mismatched related donors were associated with a higher non‐relapse mortality (HR 2.66, p = .003). In this large series of BP‐MPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo‐HCT in the more recent era, with a KPS ≥90 and in CR at transplant had a better prognosis.

Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo‐HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo‐HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched‐pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non‐relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia‐free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2–4 acute graft‐versus‐host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3–4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse‐free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo‐HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2–4 acute GVHD and encouraging survival rates.

Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documented with endogenously expressed envelopes in humans. We report that the human genome harbors a large pool of envelope-derived sequences with the potential to restrict retroviral infection. To test this, we characterized an envelope-derived protein, Suppressyn. We found that Suppressyn is expressed in human preimplantation embryos and developing placenta using its ancestral retroviral promoter. Cell culture assays showed that Suppressyn, and its hominoid orthologs, could restrict infection by extant mammalian type D retroviruses. Our data support a generalizable model of retroviral envelope co-option for host immunity and genome defense.

Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD ( p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% ( p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5–4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III–IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD ( p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24–3.0)], and HR [3.5(1.5–8.1)]. The median age of HD 37 (IQR 30–47) years was significantly lower than sibling donors 56 (IQR 49–62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it’s use when no better donor is available.