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Die allogene hamatopoetische Stammzelltransplantation (HSZT) stellt fur viele Patienten mit maligner, aber auch nichtmaligner hamatologischer Grunderkrankung die einzige Chance auf Heilung dar. Dies gilt insbesondere fur Patienten, die genetisch bedingt ein hohes Rezidivrisiko haben oder sich refraktar auf eine konventionelle Therapie zeigen. Durch die allogene HSZT eroffnet sich fur diese Patienten eine Langzeitperspektive bei ansonsten infauster Prognose. Diese Therapieform ist jedoch mit einer nicht unerheblichen Morbiditat und Mortalitat assoziiert. Ein Teil der Patienten wird aufgrund von infektiosen, immunologischen und/oder toxischen Komplikationen intensivpflichtig. Nach wie vor ist unklar, ob Patienten in solchen klinischen Situationen von einer Intensivtherapie mit mechanischer Beatmung und Nierenersatztherapie profitieren, da die Mortalitat der Betroffenen hoch ist. Diese Arbeit beschreibt die wichtigsten Komplikationen und mogliche Behandlungsstrategien von allogen blutstammzelltransplantierten Patienten auf der Intensivstation.

Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020. Four hundred forty patients with active disease at transplantation from the European Society for Blood and Marrow Transplantation database were analyzed (291 [66.1%] with intermediate-risk [AMLint] and 149 [44.1%] with adverse-risk cytogenetics [AMLadv]). Impact of baseline cytogenetic risk on various transplantation outcomes was evaluated. Pre-transplantation disease status was relapse in 48.1% and 26.8% and primary refractory in 51.9% and 73.2% of the patients with AMLint and AMLadv, respectively (P.0001). Two-year leukemia-free survival (LFS, 35.5% versus 15.5%, P = .001) and overall survival (OS, 39.2% versus 20.1%, P = .001) were better in AMLint versus AMLadv. In multivariate analysis, the relapse rate was significantly higher (hazard ratio [HR] = 2.17 [95% confidence interval {CI} 1.57-3.0]) and LFS (HR = 1.71 [95% CI, 1.31-2.22]) and OS (HR = 1.69 [95% CI, 1.29-2.22]), significantly lower for patients with AMLadv compared to AMLint, conditioning intensity did not affect leukemia relapse rate. Non-relapse mortality (HR = 1.1 [95% CI, 0.7-1.74]) and graft-versus-host disease-free, relapse-free survival (HR = 1.37 [95% CI, 1.06-1.77]) did not differ significantly between the risk groups. Disease status before transplant (primary refractory versus relapsed) or conditioning intensity did not impact main transplant outcomes. Baseline cytogenetic risk remains a key prognostic factor for patients with R/R AML with persistent disease before non-T-cell-depleted Haplo-HCT.

BACKGROUND The successful initiation of enteral nutrition is frequently hampered by various complications occurring in patients treated in the intensive care unit (ICU). Successful placement of a nasojejunal tube by CORTRAK enteral access system (CEAS) has been reported to be a simple bedside tool for placing the postpyloric (PP) feeding tube. METHODS We evaluated the efficacy and side effects using CEAS to establish EN in patients with critical illness, thrombocytopenia, and/or anticoagulation. RESULTS Fifty-six mechanically ventilated patients were analyzed. Twenty-four of them underwent prior hematopoietic stem cell transplantation (SCT). Sixteen patients received extracorporeal membrane oxygenation treatment because of acute respiratory distress syndrome. The median platelet count at PP placement was 26 g/L (range, 4-106 g/L); 16 patients received therapeutic anticoagulation (activated partial thromboplastin time, 50-70 s). CEAS-assisted placement of a PP nasojejunal tube was performed successfully in all patients. The most frequent adverse event was epistaxis in 27 patients (48.2%), which was mostly mild (Common Terminology Criteria for Adverse Events grade 1, n = 21 [77.8%], and grade 2, n = 6). A significant association between a low platelet count and bleeding complications was observed (P

Familial exudative vitreoretinopathy (FEVR) is a human disease characterized by defective retinal angiogenesis and associated complications that can result in vision loss. Defective Wnt/β-catenin signaling is an established cause of FEVR, whereas other molecular alterations contributing to the disease remain insufficiently understood. Here, we show that integrin-linked kinase (ILK), a mediator of cell-matrix interactions, is indispensable for retinal angiogenesis. Inactivation of the murine Ilk gene in postnatal endothelial cells results in sprouting defects, reduced endothelial proliferation and disruption of the blood-retina barrier, resembling phenotypes seen in established mouse models of FEVR. Retinal vascularization defects are phenocopied by inducible inactivation of the gene for α-parvin (Parva), an interactor of ILK. Screening genomic DNA samples from exudative vitreoretinopathy patients identifies three distinct mutations in human ILK, which compromise the function of the gene product in vitro. Together, our data suggest that defective cell-matrix interactions are linked to Wnt signaling and FEVR., Integrin-linked kinase (ILK) is an important mediator of integrin signaling. Here Park et al. show that mice with endothelial-specific deletion of Ilk develop vascular defects that resemble familial exudative vitreoretinopathy, and identify mutations in ILK in patients with exudative vitreoretinopathy suggesting a potential role in human pathogenesis.

Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.

ZusammenfassungIn der allogenen Blutstammzelltransplantation bezeichnet „haploidentisch“ einen Spender aus der Familie, der genetisch in den HLA-Merkmalen nur zu 50% mit seinem Empfänger übereinstimmt. Diese „Disparität“ stellt eine große immunologische Barriere für die Transplantation dar, die schwere Komplikationen wie Transplantatabstoßung, GvHD und Infektionen zur Folge haben kann. Dieses im Vergleich zur HLA-gematchten Transplantation erhöhte Risiko sowie aufwendige Herstellungsverfahren (In-vitro-Manipulation des Blutstammzellpräparats zur T-Zell-Depletion) zur Reduktion der aggressiven Immunogenität des Transplantats limitierten die Anwendung der HLA-haploidentischen Stammzelltransplantation bisher. Die unmanipulierte Haplo-HSZT mit Einsatz von Posttransplantations-Cyclophosphamid zur GvHD-Prophylaxe stellt ein neueres, simples und sicheres haploidentisches Transplantationsverfahren mit geringer Abstoßungsrate, guter hämatopoetischer Rekonstitution, wenig GvHD sowie günstiger Immunrekonstitution und wenig Infektionen dar. Somit ist bei niedriger TRM eine sichere Überwindung der HLA-Barriere mit guter Kontrolle der bidirektionalen Alloreaktivität möglich. Behandlungsergebnisse ähnlich wie bei einer HLA-kompatiblen Transplantation können erreicht werden. Andere alternative Transplantationsverfahren, wie die der MMUD-T, manipulierten Haplo-HSZT und CBT, treten aufgrund schlechterer Spenderverfügbarkeit und Verträglichkeit sowie aufwendiger Herstellungsverfahren in den Hintergrund. Die Verwendung eines sequenziellen Therapiekonzepts, das eine intensive Chemotherapie vor Start der Konditionierung zur Haplo-HSZT zur Reduktion der Leukämielast vorsieht, führt auch in der unmanipulierten Haplo-HSZT mit PTCY zu einer verbesserten Erkrankungskontrolle bei Patienten mit rezidivierter und refraktärer hämatologischer Erkrankung ohne Erhöhung der TRM..

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using T-cell-replete grafts and post-transplantation cyclophosphamide (PTCY) provides a popular curative approach for older patients (pts) with high-risk (HR) MDS/AML. The sequential therapeutic concept herein, is used to optimize disease control and gain time, especially in patients suffering from active disease at time of haplo-HSCT. Yet, sequential conditioning regimens prior to haplo-HSCT are often associated with a considerable risk of severe adverse events especially in older comorbid patients. Previous studies in the HLA-matched setting have demonstrated feasibility and safety of treosulfan-based reduced intensity conditioning (RIC) by stable engraftment and low non-relapse mortality (NRM). However, data for treosulfan-based conditioning in the unmanipulated HLA-haplo-HSCT setting in HR AML/MDS pts are rare, especially in the context of sequential conditioning. Here we report on a matched-pair analysis of 26 patients treated with either a treosulfan- or melphalan-based sequential conditioning for haplo-HSCT using PTCY as GvHD prophylaxis in HR MDS/AML. We retrospectively analyzed the outcome and toxicity profile of 26 patients undergoing sequential haplo-HSCT at our center between January 2009 and June 2019. Thirteen patients with HR AML/MDS and >54 years old who underwent sequential haplo-HSCT using treosulfan (3x10g/m2) for RIC were considered for potential matching with recipients (n=30) of a sequential melphalan-based RIC regimen. Matching criteria comprised (1) disease activity (blast yes or no), (2) disease status (relapse, refractory, high-risk cytogenetics), (3) HCT-CI and (4) age (+/- 5 years). Post-grafting immunosuppression consisted of cyclophosphamide, tacrolimus and MMF. Thirteen patients undergoing treosulfan-haplo-HSCT were successfully pair-matched with thirteen recipients of melphalan-based haplo-HSCT, respectively ((1) p=1.0; (2) p=1.0; (3) p=1.0; (4) p=0,76). Median age of the entire cohort was 63 years (54-71). Each group consisted of two MDS patients and eleven AML patients. All recipients treated with treosulfan showed neutrophil engraftment with a median of 20 days while only 69% of the melphalan treated patients engrafted (median=19 days, p= 0.9). In the melphalan group one graft rejection occurred, three patients died in early aplasia. Acute GvHD °II-IV occurred in 23% and 44% of the patients treated with treosulfan or melphalan, respectively. Severe (°III-IV) non-hematologic regimen-related toxicities were seen in 2/13 pts of the treosulfan and 7/13 pts of the melphalan group, predominately affecting the GI-tract in both. NRM at day +100 was 0% and 31% (p=0.06) for the treosulfan and melphalan group, respectively. Thereby, infections made up for most NRM events. Conversely, CI of relapse at one year was 23% vs 0 % (p=0.004) for treosulfan vs melphalan. OS at 1-year (treosulfan group: 69% vs melphalan gropup: 62%) and PFS at 1-year (treosulfan group: 69% vs melphalan group: 62%) did not differ significantly between the groups (p=0.72) Sequential haplo-HSCT using treosulfan and PTCY in older advanced MDS/AML patients is safe, resulting in lower NRM at the expense of higher relapse incidence compared to the melphalan-based sequential conditioning approach. Treosulfan-based RIC in haplo-HSCT though might be an alternative in older pts with low leukemic burden. However for disease control its intensity should be reconsidered and all available post-grafting mantainance strategies applied. Disclosures Fraccaroli: Medac: Other: Travel Grant. Buecklein:Celgene: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; Gilead: Consultancy, Research Funding; Novartis: Research Funding.

Objective To evaluate the prognostic effect of allogenic red blood cell transfusion (RBT) and preoperative anemia in patients with oral squamous cell carcinoma (OSCC) undergoing primary tumor resection. Methods We retrospectively analyzed a cohort of 621 patients, diagnosed with OSCC receiving tumor resection in curative intention. Preoperative anemia and perioperative RBT were evaluated according to WHO definition. Overall survival (OAS) as well as recurrence-free survival (RFS) was evaluated in transfused and non-transfused as well as in anemic and non-anemic patients. In addition, outcome parameters were calculated for distinct amounts of perioperatively administered RBTs. Data analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.3 years. Results Preoperative anemia was diagnosed in 29% of OSCC patients. Anemic patients displayed a significantly decreased five-year OAS (44%) in comparison to non-anemic equivalents (69%). 70% of non-transfused OSCC patients were alive after five years, whereas in case of RBT five-year OAS was 41%. These findings were substantiated by subgroup analysis in patients without preoperative anemia. For anemic patients however, no deleterious effect on survival in case of perioperative RBT was seen. Increasing numbers of received RBTs were shown to worsen outcome of OSCC patients in a dose-dependent manner. Conclusion Preoperative anemia and RBT are significantly associated with impaired long-term outcome of patients suffering from OSCC. Future studies are needed to evaluate differentiated effects of RBTs in anemic and non-anemic OSCC patients and accordingly providing individual transfusion strategies to ameliorate outcome of patients suffering from OSCC.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for many malignant high-risk hematological diseases. The Graft-vs.-Tumor (GvT) effect is the major hallmark of this treatment approach. However, disease relapse remains a major limitation. Boosting the GvT effect by checkpoint inhibitors (CI) is an attractive option in this desperate situation although potentially triggering Graft-vs.-Host Disease (GvHD). Early reports in patients with Hodgkin’s lymphoma support the idea that CI therapy after HSCT is feasible and effective. We have retrospectively analyzed CI therapy for treatment of disease recurrence after allo-HSCT other than Hodgkin’s lymphoma including 21 patients from eight German transplant centers. The median follow-up was 59 days. The overall response rate (ORR) was 43%. Patients receiving donor lymphocyte infusion (DLI) in combination with CI had superior response (ORR 80%). Severe acute GvHD grade III–IV and moderate to severe chronic GvHD were observed in 29% of all patients. Taken together, CI therapy in relapsed patients after HSCT, especially in combination with DLI, is effective but induces severe GvHD in a considerable proportion of patients. Thus, prospective trials or EBMT registry-based validation of different dosing and application schedules including immunosuppressive regimens in those patients are urgently needed.

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option.

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related toxicities (grade III-IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow-up of 36 months, the estimated 1- and 3-year overall survival was 56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is an effective salvage treatment providing high anti-leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.

Supplemental Digital Content is available in the text., Rationale: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein α-parvin (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known. Objective: To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms. Methods and Results: We deleted the α-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of α-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of α-pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of α-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, α-pv–deficient ECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell–extracellular matrix adhesion structures and an altered actin cytoskeleton. Conclusions: Endothelial α-pv is essential for vessel sprouting and for vessel stability.

Transplant-associated microangiopathy (TAM) is a life-threatening complication after allogeneic transplantation, related to endothelial toxicity caused by chemoradiotherapy, infections, immunosuppressive drugs and GvHD. Clinical manifestations include severe thrombocytopenia, microangiopathic hemolysis and organ dysfunction (e.g. renal, neurological) in the absence of disseminated intravascular coagulation. The reported incidence of TAM after allogeneic hematopoietic stem cell transplantation (HSCT) varies between 0,5 to 70%. Data for TAM occurrence and outcome in the context of HLA-haploidentical transplantation (haplo-HSCT) are rare. Here, we report our experience on TAM incidence, disease manifestation, treatment and outcome in T-cell-replete haplo-HSCT using PTCY as GvHD prophylaxis. We retrospectively analyzed the treatment course of 148 adult patients undergoing haplo-HSCT with regard to the incidence of TAM at our center from January 2012 to April 2019. The diagnosis of TAM required the fulfillment of the criteria as defined by Ruutu et al., Haematologica 2007. Median age of the entire cohort was 54 years (23-74). The majority of patients was transplanted for myeloid disease (60%). Postgrafting immunosuppression consisted of PTCY, CNI and MMF in all patients. Median follow-up time upon survivors was 3 years (4 months - 7 years). Twenty of 148 patients developed TAM, with a cumulative incidence of 10% at day 100. Median interval from haplo-HSCT to TAM onset was 63 days (23-295 days), with seven patients showing TAM after day +100. Median platelet count at diagnosis was 20 x 109/L (range: 6-116), predominantly de novo or worsening thrombocytopenia. Median LDH level was 437 IU/L (305-1445 IU/L). Serum haptoglobin levels were decreased in 85% of the TAM patients. 12/20 patients had active infection at the time of TAM diagnosis, most commonly viral (10/12). All but three patients presented with concurrent active acute GvHD requiring systemic steroid treatment in 16 patients Renal function abnormalities were diagnosed in 55% of the patients affected by TAM, with 4 patients requiring hemodialysis. Nine patients developed grade III hypertension and three patients showed neurologic dysfunction. Upon diagnosis of TAM, CNI dose was reduced (7 patients) or temporarily discontinued (7 patients). No switch to another CNI was performed. FFPs were transfused in nine patients, three patients underwent plasma exchange therapy without any effect. In four patients rituximab was applied. With a CI of 18% vs 2% (p0.002) using a PBSC graft was a risk factor for TAM development when compared to BM. Neither origin of disease (myeloid/lymphoid) nor sex of patient/donor or conditioning intensity (RIC/MAC) influenced the incidence significantly. Estimated one-year and three-year overall survival did not differ between the TAM and the non-TAM cohort (61% vs 61% and 46% vs 47%, p=0.9). Only one patient died because of TAM. With an incidence of 10% at day +100 at our center TAM is a serious but not rare complication after haplo-HSCT using PTCY, CNI and MMF for GvHD prophylaxis. However, in our cohort disease course was moderate with low TAM-associated mortality. The use of a PBSC graft was the only factor influencing TAM incidence. Disclosures Hiddemann: F. Hoffmann-La Roche: Research Funding.

Sequential conditioning regimens, comprising cytoreductive chemotherapy shortly applied prior to reduced intensity conditioning are successfully used for high-risk (HR) AML/MDS in matched related and unrelated donor hematopoietic stem cell transplantation. However, few data are available for sequential conditioning in the context of HLA-haploidentical transplantation (haplo-HSCT), especially in the elderly. To investigate the relative merits of sequential haplo-HSCT in the elderly we retrospectively analyzed the outcome of thirty-five patients (pts) with advanced AML/MDS (>=50 years old). Thirty-three pts suffering from HR AML, defined by refractory, relapsed or secondary leukemia, or complete remission with adverse-risk genetics according to ELN criteria and two pts with HR MDS according to IPSS-R, who underwent T-cell-replete haplo-HSCT at our institution between January 2009 and November 2016 were included. Disease was active in 29 pts while 6 had achieved CR. Pre-transplantation risk factors were scored using the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) which was ≥3 in 13 pts (median HCT-CI:2, range 0-8). A sequential therapeutic concept using either FLAMSA (n=26) or clofarabine (n=9) for cytoreduction was used prior to RIC in all pts. Bone marrow (54%) and peripheral blood stem cells (46%) were both used as graft source. Post-grafting immunosuppression consisted of high-dose cyclophosphamide, tacrolimus and MMF in all pts. Median age was 60 years (50-70). One graft rejection occurred. Three pts died early in aplasia. Neutrophil and platelet engraftment was achieved in 95% and 77% of evaluable pts, respectively at a median of 16,5 (13-89) and 31,5 (11-103) days.Acute GvHD grade I-III occurred in 25/32 of the pts (grade III n=2); no patient developed grade IV aGvHD. Chronic GvHD was observed in 13/29 pts and was most frequently assessed as mild (n=6) or moderate (n=5) while 2 pts developed severe cGvHD. No GvHD related death was observed. CI of NRM at day 100, 1-year and 3-years was 11%, 23% and 23%, respectively. CI of relapse at 1- and 3-years was 15% and 27%, with a median time to relapse of 152 days (20-413). At a median follow up of 27 months (4-74), estimated one- and three-year overall survival (OS) was 62% and 52% respectively. One- and three-year leukemia-free survival (LFS) was 59% and 52%. Our results suggest that using a sequential therapeutic concept in PTCY-based haplo-HSCT is safe and properly tolerated while it provides a favorable disease control when treating elderly HR MDS/AML pts. Thus, sequential haplo-HSCT seems to be a valuable alternative in pts who lack a conventional donor or are in urgent need for prompt transplantation. Disclosures Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board.