Chronic graft-versus-host disease (cGVHD) represents a major complication after allogeneic stem cell transplantation (alloHSCT). In 2009 and 2018 a survey among German, Austrian, and Swiss transplant centers was performed showing a homogeneous 1st-line treatment practice, while 2nd-line treatment as well as management of progressive onset type and bronchiolitis obliterans syndrome (BOS) displayed significant heterogeneity. Since the last survey, ruxolitinib (rux) has been approved and other agents are explored in treatment of cGVHD. Therefore, we conducted a new survey in 2024 to document the impact of recent approvals and new agents on treatment practice focusing on management of 2nd-line treatment, progressive onset type, BOS, and sclerotic manifestations. Methods: A paper-and-pencil-based questionnaire on current clinical practice in cGVHD care was sent electronically to 60 German speaking centers performing alloHSCT. Nineteen centers responded, representing 41% of the patients receiving an alloHSCT in 2023 in Germany. Results: In 1st-line treatment of classical standard risk cGVHD, single agent prednisolone represents standard of care (13/19 centers) which may be combined with calcineurin inhibitor (CNI) (4/19), while rux is used in selected cases only. In 2nd-line treatment rux is used by the majority of centers (17/19). In the presence of cytopenia, rux (10 - 20mg/d) is the preferred agent (10/19) while extracorporeal photopheresis (ECP) is applied in patients with cytopenia especially in steroid-dependent cGVHD in 7 of 19 centers. In case of active infections, ECP is preferred by 14 of 19 centers and both agents are regarded as steroid-sparing agents in 2nd-line treatment of steroid-dependent cGVHD. Rux would be applied in the presence of active infections by 5/19 centers only. Moreover, rux (15/19) and ECP (5/19) are also preferred treatment modalities in treatment of progressive onset cGVHD. For BOS, systemic and inhalative corticosteroids, montelukast and azithromycin (FAM), rux (14/19), ECP (16/19), CNI (9/19), and abatacept (9/19) are frequently applied agents, while belumosudil (7/19), imatinib (5/19) and ibrutinib (2/19) are used as salvage option in selected patients. In case of new sclerotic manifestations after failure of 2nd line treatment including steroids, CNI and rux, most centers would use ECP (13/19), whereas subsequent or alternative salvage treatment of sclerotic manifestations remains heterogenous comprising belumosudil (12/19), ibrutinib (5/19), imatinib (5/19), rituximab (4/19), cyclosporine (3/19), tacrolimus (3/19), everolimus (3/19), sirolimus (3/19), MTX (3/19) and MMF (3/19). Belumosudil is generally considered effective in treatment of cGVHD but remains to be used in selected patients only most likely due to the lack of EMA approval. The preferred taper sequence of immunosuppressive agents in case of response applied in 11/19 centers is primary taper of steroids, followed by taper of CNI and final termination of rux. Conclusion: The survey documents the effect of evidence and approval on clinical care with single agent prednisolone representing the standard of care in 1st-line treatment while rux combined with steroids defines the new standard for 2nd line treatment of cGVHD. ECP is used in case of contraindication for rux and both agents are also used in progressive onset cGVHD. In contrast, treatment of BOS and sclerotic cGvHD remains heterogeneous after failure of 2nd-line treatment with new agents being integrated in the treatment landscape.

Therapeutic drug monitoring (TDM) of busulfan (Bu) is well-established in pediatric hematopoietic stem cell transplantation (HSCT), but its use in adults is limited due to a lack of clear recommendations and scarcity of evidence regarding its utility. GSTA1 promoter variants are reported to affect Bu clearance in both adults and pediatric patients. This study aimed to evaluate the value of preemptive genotyping GSTA1 and body composition (obesity) in individualizing Bu dosing in adults, through pharmacokinetic (PK) modeling and simulations. A population pharmacokinetic (PopPK) model was developed and validated with data from 60 adults who underwent HSCT. Simulations assessed different dosing scenarios based on body size metrics and GSTA1 genotypes. Due to the limited number of obese patients in the cohort, the effect of obesity on Bu pharmacokinetics (PK) was evaluated in silico using a physiologi- cally -based pharmacokinetic (PBPK) model and relevant virtual populations from Simcyp software. Patients with at least 1 GSTA1*B haplotype had 17% lower clearance on average. PopPK simulations indicated that adjusting doses based on genotype increased the probabil- ity of achieving the target exposure (3.7 to 5.5 mg.h/L) from 53% to 60 % in GSTA1*A homozy- gous patients, and from 50% to 61% in *B carriers. Still, Approximately 40% of patients would not achieve this therapeutic window without TDM. A 2 -sample optimal design was validated for routine model -based Bu first dose AUC 0- 1 estimation, and the model was implemented in the Tucuxi user-friendly TDM software. PBPK simulations con firmed body surface area - based doses of 29 to 31 mg/m 2 / 6 h as the most appropriate, regardless of obesity status. This study emphasizes the importance of individualized Bu dosing strategies in adults to achieve therapeutic targets. Preemptive genotyping alone may not have a signi ficant clinical impact, and routine TDM may be necessary for optimal transplantation outcomes. (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to qualify comorbidities to predict non-relapse mortality (NRM) of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HSCT procedures continue to improve. Therefore, the predictive value of HCT-CI needs to be re-evaluated. Our study is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n = 1102) undergoing allo-HSCT from 2006-2021. HCT-CI was classified as low (HCT-CI 0), intermediate (HCT-CI 1–2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI group was 21.0%, 26.0%, and 25.8% (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001), but not between intermediate to high-risk HCT-CI (p = 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (HR = 1.73, p = 0.02) and OS (HR = 1.77, p < 0.001). All other individual organ comorbidities influenced NRM to a lesser extent. Further, donor (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM. Improvement in transplant techniques and supportive care may have improved outcome with respect to comorbidities.

Busulfan (Bu) combined with cyclophosphamide (Cy) is commonly used as a myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). There is inter-individual variability of Bu pharmacokinetics (PK) and hence in toxicity and efficacy. The introduction of therapeutic drug monitoring (TDM) of Bu has decreased toxicity of the regimen. Hepatic metabolism of Bu is mediated through Glutathione-S-Transferases (GSTs), mainly GSTA1. Patients with GSTA1*A variants are considered normal metabolizers and GSTA1*B corresponds to poor metabolism, defined by nucleotide changes at −52 or −69 locus in GSTA1 promoter region. The aim of the study was to explore the correlation between GSTA1 polymorphisms and Bu-PK in 60 adult patients receiving an allo-HCT in the BuCyBu clinical study (ClinicalTrials.gov I, ID NCT01779882) comparing the sequence BuCy to CyBu. DNA samples prior to conditioning were genotyped for candidate variants at −52 (rs3957356) and −69 (rs3957357) loci in the GSTA1 promoter. Thirty-three % of patients were GSTA1*A*A, 49% GSTA1*A*B and 18% GSTA1*B*B. In GSTA1*A*A patients, median Bu-AUC was 3.6 ± 0.7 mg*h/L, in GSTA1*A*B 4.5 ± 1.6 and in GSTA1*B*B 4.9 ± 1.4 (AUC 35% higher than GSTA1*A*A, p = 0.03), with a similar significant correlation with Bu-clearance (p = 0.04). The correlation between GSTA1 polymorphism and AUC remained significant in multivariate linear regression analysis. There was a trend for lower non-relapse mortality (NRM) in patients with low AUC. We could not demonstrate a correlation between GSTA1 polymorphisms and NRM, acute graft-versus-host disease (aGvHD) in this small cohort, but there is a trend of higher aGvHD incidence in GSTA1*B*B patients.

Introduction Therapy of relapsed and refractory multiple myeloma (MM) with Ide-Cel is superior to alternative treatments, but availability is lower than the number of patients in need. Treatment slots are distributed by the manufacturer per country. Their allocation to individual patients is a medical, logistical and ethical challenge. Ideally, such allocation should be inclusive, fair, transparent, effective, and base on prospectively confirmed objective outcome criteria. Methods Swiss Blood Stem Cell Transplantation and Cellular Therapy (SBST) has established the national SBST-CAR-T MM board for allocation of Ide-Cel treatment slots. Allocation process and triage criteria were developed by clinical experts in exchange with the ethical board of the Swiss academy for medical sciences and health insurers, approved by all JACIE-accredited national centers for cellular therapies, and agreed that Ide-Cel therapy in Switzerland is only available through this allocation system. Patients are registered in parallel with request for insurance coverage in one key document. Patients had to meet qualifying approval criteria for Ide-Cel in Switzerland (relapsed and refractory MM, >2 prior therapy lines, triple-class-exposed). Reaching CR after Ide-Cel is associated with superior PFS. We therefore developed an algorithm to select patients with high likelihood for CR. Patient factors negatively associated with CR derived from the KarMMa trial were complemented by factors prospectively associated with inferior overall survival after CAR-T in malignant lymphoma. High tumor burden (bone marrow infiltration > 50% or high tumor load by PET-CT), inflammatory activity (increasede ferritin or D-dimers), ECOG patient status and comorbidities were used as negative predictive factors and combined to a sum score of 0-4. All registered patients are presented at the monthly virtual meeting and ranked according to this score. Ranking is refined based on availability of alternative treatment options, resulting in a final national ranking agreed by all board members. Because no patients with severe comorbidities were registered, this dimension was later excluded. Results Between May 2022 and April 2023 all 48 Ide-Cel regular treatment slots in Switzerland were allocated in 12 virtual meetings lasting median 55 minutes (25-70) with the participation of median 7 centers (6-8), 8 physicians (6-15), discussing in total 72 patients (median 5.5 per meeting, range 4-10) to distribute 4 slots monthly. All therapy slots were successfully allocated, including short-notice changes in availability of slots or patients requiring immediate allocation of substituting patients. 74.2% of all patients registered with the SBST CART MM board received Ide-Cel. Patient, treatment and outcome parameters were centrally collected to SBST database from 37 treated patients per April 2023. (1 patient each had cell collection failure, Ide-Cel production failure, missing outcome data). Patients were 65% triple refractory, 65 % penta refractory, 14% received prior BCMA-targeted therapy, 8% prior bispecifc antibodies and 67% had high risk cytogenetics. Best response achieved so far was CR or better in 57% of patients, PR-VGPR 16%, PD 13%, not stated/too early 13%. A low SBST-MM CAR-T Score was prospectively associated with CR (table 1, p=0.048). Each scoring dimension (ECOG, tumor load, inflammation) significantly correlated inversely with CR, while conventional characteristics for poor MM outcomes (HR CG, penta refractory disease) did not correlate. PFS and OS data is pending. Cross cohort comparison with the Real-World Experience from the US Myeloma CAR-T Consortium (Hansen et al., JCO 2023) revealed a strong trend towards higher CR rates (57% vs. 23%, p=0.10). Conclusion This algorithm prospectively selects MM patients for BCMA-CAR-T treatment to maximize CR rate. Also, this national real world cohort demonstrates the feasibility of triaging the allocation of CAR-T therapy slots based on a, fair, objective, transparent, consensual algorithm using predefined criteria. The SBST scoring system prospectively reflects differential likelyhood of CR (100>64>53>33%), and the scoring dimensions (ECOG, tumor load, inflammation) prospectively correlate with a CR rate of 57 %, supporting the selection process. The SBST CAR-T scoring system may be used to allocate CAR-T treatment slots to maximize benefit from this treatment.

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.

Busulfan (Bu) is widely used in conditioning regimens before allogeneic hematopoietic cell transplantation, with variable metabolism due to interindividual differences of pharmacokinetics (PK). The purpose of this study was to correlate pharmacokinetics and clinical outcomes. Lower-AUC, in range-AUC and higher-AUC were defined as ±25% of the targeted Bu-AUC. In 2019, we changed Bu dosing from 4×/day (Bu-4) to 1×/day (Bu-1) for ease of application. AUC-target range was reached in 46% of patients; 40% were in low-AUC and 14% in high-AUC. Among all toxicities, viral and fungal infections were significantly more frequent in high-AUC compared with low-AUC (20% vs. 8%; p = 0.01 and 37% vs. 17%; p = 0.03). Bu-1 showed lower PK values (66% vs. 36% of Bu-4 in low-AUC; p < 0.01) and higher incidence of mucositis ( p = 0.02). Long-term outcomes at 2 years showed a higher non-relapse mortality (NRM) ( p < 0.01) and higher relative risk of death in the high-AUC group compared to the other groups. Cumulative incidence of relapse and acute/chronic GvHD were not significantly different. The optimal cut-off in Bu-AUC associated with low NRM was 969 µmol/l*min (ROC AUC 0.67, sensitivity 0.86 and specificity 0.47) for Bu-4. In conclusion, low-AUC BU-PK seems of benefit regarding NRM and survival.

Abstract Background Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood. Methods We investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison. Results Both regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT patients can elicit potent antibody responses. However, an unrelated donor, absolute lymphocyte counts below the normal range, and treatment with calcineurin inhibitors lowered the odds of responding. Conclusions HSCT patients show a highly heterogeneous vaccine response but, overall, patients benefited from the booster shot and can acquire seroprotective antibodies over the years after transplantation. Several common patient factors lower the odds of responding, urging identification of additional preventive strategies in the poorly responding groups. Clinical Trials Registration NCT03467074.

To assess the response to vaccination, quantity (concentration) and quality (avidity) of neutralizing antibodies are the most important parameters. Specifically, an increase in avidity indicates germinal center formation, which is required for establishing long-term protection. For influenza, the classical hemagglutination inhibition (HI) assay, however, quantifies a combination of both, and to separately determine avidity requires high experimental effort. We developed from first principles a biophysical model of hemagglutination inhibition to infer IgG antibody avidities from measured HI titers and IgG concentrations. The model accurately describes the relationship between neutralizing antibody concentration/avidity and HI titer, and explains quantitative aspects of the HI assay, such as robustness to pipetting errors and detection limit. We applied our model to infer avidities against the pandemic 2009 H1N1 influenza virus in vaccinated patients (n = 45) after hematopoietic stem cell transplantation (HSCT) and validated our results with independent avidity measurements using an enzyme-linked immunosorbent assay with urea elution. Avidities inferred by the model correlated with experimentally determined avidities (ρ = 0.54, 95% CI = [0.31, 0.70], P < 10-4). The model predicted that increases in IgG concentration mainly contribute to the observed HI titer increases in HSCT patients and that immunosuppressive treatment is associated with lower baseline avidities. Since our approach requires only easy-to-establish measurements as input, we anticipate that it will help to disentangle causes for poor vaccination outcomes also in larger patient populations. This study demonstrates that biophysical modelling can provide quantitative insights into agglutination assays and complement experimental measurements to refine antibody response analyses.

HLA compatibility is a key factor for survival after unrelated hematopoietic stem cell transplantation (HSCT). HLA-A, -B, -C, -DRB1, and -DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent, although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Because classical DPB1 allele mismatches are often unavoidable, however, several biological models have been developed to predict the optimal DPB1 mismatch combination for less graft-versus-host disease (GVHD) and better overall survival. In 909 recipient/donor pairs, we analyzed the role of 3 biological models: T-cell epitopes (TCEs) based on the immunogenicity of DPB1, cell surface expression of DPB1 molecules based on a single-nucleotide polymorphism located in the 3' untranslated region, and the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model based on the presentation of allogeneic peptides derived from mismatched HLA, compared with the classical allele mismatch. Matching for both DPB1 alleles remains the best option to prevent acute GVHD. In the situation of one DPB1 allele mismatch, the donor associated with the lowest acute GVHD risks is mismatched for an allele with a low expression profile in the recipient, followed by a permissive TCE3/4 mismatch and/or the absence of PIRCHE II potential against the recipient. In the context of 2 DPB1 mismatches, the same considerations apply for a permissive TCE3/4 mismatch and no PIRCHE II. By combining the biological models, the most favorable DPB1 constellation can be defined. This approach will help optimize donor selection and improve post-HSCT complications and patient prognosis.

Quantitative and molecular analysis have been performed on two main polymorphs of buspirone hydrochloride (BUS-HCl). Quantitative analysis of solid-state composition of pharmaceutical powders is necessary to ensure safety and efficacy of drug substance and to validate the production processes. In this study, X-ray powder diffraction and differential scanning calorimetry have been used for the quantitative analysis of two polymorphic forms of BUS-HCl. In addition, single crystal X-ray study of Form 1 revealed its crystal structure, however, a similar study on Form 2 was not possible due to the difficulties encountered in producing it. Molecular analysis including partial charge analysis has been performed by using Gaussian simulation package to find the electro-negativity pattern in molecule. 1H and 13C solid-state NMR spectra of polymorphs were recorded and also regression equations and QM theory were developed to predict the 1H and 13C NMR spectra through the use of atomic environmental descriptors. The NMR differences between the two polymorphs were discussed by using prediction and experimental results and description of each NMR shift for carbon and hydrogen atoms.

In this issue of Blood, a randomized clinical trial reported by Kennedy et al(1) showed that adding the monoclonal interleukin-6 (IL-6) receptor antibody tocilizumab to standard graft-versus-host disease (GVHD) prophylaxis had only a modest effect on the incidence of acute GVHD (aGVHD).

Background and Summary: Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD. Key Messages: ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.

BACKGROUND:Infections are an important complication after allogeneic hematopoietic cell transplantation (allo-HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo-HCT patients, as well as associated risk factors for infections and for one-year non-relapse mortality.METHODS:This is a retrospective cohort study using STCS and EBMT databases to assess the one-year incidence rate of infection, as well as risk factors for infections and for one-year non-relapse mortality among adult allo-HCT patients transplanted between 2010 and 2014 in Switzerland. Univariable and multivariable quasi-Poisson and multivariable Cox regression models were used.RESULTS:Of 553 patients included, 486 had an infection with a global incidence rate of 3.66 infections per patient-year. Among a total of 1534 infections analyzed, viral infections were predominant (n = 1138, 74.2%), followed by bacterial (n = 343, 22.4%) and fungal (n = 53, 3.5%) infections. At one year, the cumulative incidence of relapse and non-relapse mortality was 26% and 16%, respectively. 195 (35.3%) of patients had at least one episode of severe graft-versus-host-disease (GvHD). A center effect was observed, and underlying disease, donor type, cytomegalovirus serological constellation, and GvHD were also associated with the incidence rate of infections. There was an increased risk for one-year non-relapse mortality associated with all pathogens, specifically within two months of infection, and this remained true beyond 2 months of a fungal infection.CONCLUSION:Despite advances to limit infections in this population, they still occur in most allo-HCT patients with a major impact on survival at 1 year.

Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (p = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, p = 0.05) was lower and survival (63% versus 43%, p = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (p = 0.21), acute and chronic graft-versus-host disease (p = 0.40; 0.36), and relapse (p = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome.

Acute myeloid leukemia (AML) with FLT3- mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3 -mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft versus host disease (GVHD) grades II–IV and III–IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, NPM1 -mutation, transplantation in CR1, in vivo T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. In vivo T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care.