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Isavuconazole, an antifungal azole used to treat invasive fungal diseases (IFDs), is approved as a first-line treatment for invasive aspergillosis and can be used as an alternative treatment for mucormycosis [...]

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10-5 and HR 1.71, p < 10-5, respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10-5), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions. [ABSTRACT FROM AUTHOR]

Background: Three different scoring systems have been developed to assess pre‐transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo‐HSCT): the Hematopoietic Cell Transplantation‐Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease‐free survival (DFS) survivals and non‐relapse mortality (NRM) in patients receiving HLA‐matched Allo‐HSCT, but their performance has scarcely been studied in the haploidentical Allo‐HSCT setting with post‐transplant cyclophosphamide, a procedure in constant expansion worldwide. Methods: To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo‐HSCT in four different centers. Results: With a median follow‐up of 35.6 months, 3‐year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI (p < 0.001), an older age of recipients (≥55 years old, p = 0.02) and of donors (≥40 years old, p = 0.005). Older donor age was also associated with lower DFS and higher NRM. Conclusion: The comorbidity scores do not predict survivals nor NRM in haploidentical Allo‐HSCT with PTCY, suggesting that pre‐transplant comorbidities should not be a contra‐indication to this procedure. [ABSTRACT FROM AUTHOR]

• Patients who undergo autologous stem cell transplantation (ASCT) for lymphoma and develop therapy-related myelodysplastic syndrome (t-MDS) have a short overall survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT). • The use of donors with mismatched HLA is associated with a higher nonrelapse mortality. • Despite advances in allo-HSCT, patients with t-MDS remain a critical population with few therapeutic alternatives. Therapy-related myelodysplastic syndrome (t-MDS) after autologous stem cell transplantation (ASCT) is a rare complication with no curative option. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for eligible patients and has been understudied in t-MDS. We report 47 consecutive patients with t-MDS after an ASCT who underwent allo-HSCT with a median age of 58 years (range, 30 to 71 years) at transplantation and a median follow-up of 22 months (range, 0.7 to 107). The median overall survival (OS) was 6.9 months (95% confidence interval [CI], 0 to 19 months). OS rates were 45% (29% to 60%) and 30% (15% to 45%) at 1 and 3 years after transplantation, respectively. On univariate analysis, prior therapy for t-MDS before allo-HSCT (P =.02) and mismatched donors (P =.004) were associated with poor OS. Three-year nonrelapse mortality (NRM) and relapse rates were 44% (25% to 63%) and 41% (22% to 61%), respectively. Mismatched donors (P <.001) were associated with higher NRM and a high-risk MDS (P =.008) with a higher relapse risk. On multivariate analysis, HLA mismatch was associated with higher NRM (hazard ratio, 6.21; 95% CI, 1.63 to 23.62; P =.007). In conclusion, our results suggest that one third of the patients who develop t-MDS after an ASCT for lymphoma are cured after an allo-HSCT. The use of mismatched donors with standard graft-versus-host disease prophylaxis should be avoided in such an indication for allo-HSCT. It will be worthwhile to see if the implementation of cyclophosphamide post-transplantation will improve the outcome with mismatched donors. [ABSTRACT FROM AUTHOR]

To analyze the influence of distinct combinations ofmolecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1mut) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein a gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS fromHSCTwas 81 ± 5% in NPM1mut/FLT3wt, 75 ± 3% in NPM1wt/FLT3wt, 66 ± 3% in NPM1mut/ FLT3-ITD, and 54 ± 7% in NPM1wt/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1wt/FLT3wt revealed excellent results both in patients with CEBPαmut and with atriple negative genotype(2-year OS:100%/77 ± 3%). In aCox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). [ABSTRACT FROM AUTHOR]

Abstract: We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n = 153) or HLA-matched unrelated (n = 89). Patients received blood (n = 90) or marrow (n = 152) grafts after either myeloablative (n = 109) or reduced-intensity (n = 133) conditioning. Three-year overall and event-free survival, nonrelapse mortality, relapse, and chronic graft-versus-host disease (GVHD) development were not significantly different between the 2 groups. In contrast, acute grade II to IV GVHD occurred more often in the no-ATG group (55% of the patients) than in the ATG group (27%, P < .0001). Similar results were observed with acute grade III to IV GVHD (28% and 14% in the no-ATG group and ATG group, respectively; P = .009). In multivariate analysis, after adjustment with propensity score, the absence of ATG was the strongest parameter associated with an increased risk of acute grade II to IV GVHD (hazard ratio, 2.13; 95% confidence interval, 1.35 to 3.37; P = .001]. ATG had no impact on overall and event-free survival or cumulative incidence of the relapse. In conclusion, the addition of ATG to allo-SCT conditioning did not increase the incidence of relapse of patients with progressive MDS. The incidence of acute GVHD was decreased without compromising outcomes. [Copyright &y& Elsevier]