Invasive Fusariosis in the Voriconazole Era: Single-Center 13-Year Experience

Background. Invasive fusariosis remains an aggressive, albeit infrequent infection in immunocompromised patients. Methods. We identified all cases of invasive fusariosis between January 2002 and December 2014. We recorded patient characteristics including clinical presentation, treatment, and outcomes at 6 and 12 weeks after diagnosis, as well as species identification and antifungal drug susceptibilities. Results. Fifteen patients were diagnosed with proven (12, 80%) or probable (3, 20%) fusariosis. Median age was 60 years (range, 26–78), and 10 patients were male. Underlying conditions included hematological malignancies (13, 87%), juvenile idiopathic arthritis (1, 7%), and third-degree burns (1, 7%). Five patients underwent hematopoietic stem-cell transplantation before diagnosis. Six patients (40%) received systemic glucocorticoids, and 11 patients (73%) had prolonged neutropenia at the time of diagnosis. Clinical presentations included the following: skin/soft tissue infection (8, 53%), febrile neutropenia (4, 27%), respiratory tract infection (2, 13%), and septic arthritis (1, 7%). Twelve patients were treated with voriconazole: 6 (40%) with voriconazole alone, 4 (27%) with voriconazole and terbinafine, and 2 (13%) with voriconazole, terbinafine, and amphotericin. One patient (7%) was treated with terbinafine alone, and another with micafungin alone. Four patients underwent surgical debridement (4, 27%). Susceptibility testing was performed on 9 isolates; 8 demonstrated voriconazole minimum inhibitory concentrations ≥4 µg/mL. The cumulative probability of survival was 66.7% and 53.3% at 6 and 12 weeks after diagnosis. Conclusions. Mortality associated with invasive fusariosis remains high. Cumulative mortality at our center was lower than previous reports despite elevated voriconazole minimum inhibitory concentrations. Combination therapy should be studied systematically for fusariosis

Erdheim-Chester disease, moving away from the orphan diseases: A case report

With approximately 750 cases reported, Erdheim-Chester disease is an exceedingly rare histiocyte cell disorder. Affected sites typically include long bones, large vessels and central nervous system. However, cutaneous and pulmonary involvement can also occur. The diagnosis is ascertained by identification of foamy histiocytes positive for CD68, CD163, and factor XIIIa on immunoperoxidase staining. Recently published literature have described an association between Erdheim-Chester disease and BRAF V600E mutation. This finding prompted the investigation of therapeutic possibilities with BRAF inhibitors, successful agents against other BRAF mutation-positive diseases. Vemurafenib, a BRAF kinase inhibitor, has been shown to be effective in BRAF V600E mutation-positive malignancies, such as NSCLC and melanoma, as well as in several case reports of Erdheim-Chester disease. We report a case of Erdheim-Chester disease diagnosed at our institution, treated with vemurafenib

Granulomatous response to invasive pulmonary aspergillosis in an immunotherapy-naive host, a maladaptive response?

Pulmonary aspergillosis causes a wide spectrum of disease, ranging from asymptomatic airway colonization to severe invasive disease, contingent on the host's immune status and underlying pulmonary anatomy. The invasive form of aspergillosis is a rare occurrence in the immunocompetent population. Nevertheless, patients with a compromised innate immune response are at greatest risk. We present a case of a patient with known Crohn's disease who developed invasive pulmonary aspergillosis. His clinical picture was further complicated by an uncommon immune response characterized by the development of granulomas encasing the Aspergillus forms found on his lung biopsy, likely representing a maladaptive response, possibly related to the effects of his granulomatous disease in the lungs. He was successfully treated with antifungal therapy and video assisted thoracoscopic surgery with placement of thoracostomy tube drainage for a parapneumonic effusion. We will discuss the factors leading to his atypical presentation and clinical outcome

Birth characteristics and risk of meningioma in a population-based study in California

BackgroundWe evaluated the potential role of birth characteristics in the etiology of early-onset meningioma.MethodsLeveraging a population-based linkage of California birth records (from 1978 to 2015) and cancer registry data (from 1988 to 2015), we identified 362 nonmalignant meningioma cases aged 0-37 years and selected 18 100 controls matched on year of birth. Cases and controls were compared with regard to birth characteristics, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) estimated from unconditional multivariable logistic regression models. We also conducted stratified analyses by race/ethnicity and age.ResultsFemale sex (compared to male: OR = 1.43, 95% CI: 1.16 to 1.79; P < .01) and Black race (compared to White: OR = 1.46, 95% CI: 1.02 to 2.07; P = .04) were associated with higher risk of meningioma. Higher birth order (OR = 0.90, 95% CI: 0.81 to 0.99 per additional birth position; P = .04) was associated with a lower risk. No significant associations were observed between birthweight, gestational age, delivery mode, maternal age, or maternal education and meningioma risk. In the non-Latino White subgroup, higher birthweight was associated with a higher risk of meningioma (OR = 1.20, 95% CI: 1.02 to 1.41 per 500 grams; P = .03), but this was not recapitulated in the Latino subgroup. In age-stratified analyses, female sex was a risk factor for those diagnosed at the age of 20-37 years but not among younger individuals.ConclusionsIn this large population-based study less prone to selection and recall bias, higher birth order was associated with a reduced risk of early-onset meningioma, while female sex and Black race were linked to an increased risk. There were also indications of differential associations by race/ethnicity and age of diagnosis

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia

Abstract Background Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry‐ and claims‐based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. Methods We identified 4010 older adults (aged 66–99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population‐based cohort study using the Surveillance, Epidemiology, and End Results‐Medicare database with median follow‐up of 3.92 (interquartile range: 2.58–5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. Results 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all‐cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63–0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64–0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51–0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49–0.66, p < 0.01) as well as in PV and ET subgroups. Conclusions These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET

Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database

JPB and TK are co-first authors; RK and AMZ are co-senior authors Introduction: Efficacy of therapies used in HR-MDS pts has long been assessed using IWG 2006 MDS criteria, but important limitations in clinical utility and practical application of these criteria have become apparent. The revised IWG response criteria for HR-MDS were proposed in 2023 (Zeidan et al., Blood 2023) were proposed to address these gaps. IWG 2023 re-defined CR by lowering hemoglobin (Hb) threshold from 11 to 10 g/dL and bone marrow [BM] blasts from ≤5% to 3.5 (n=213 pts excluded). Pts were excluded (N=90) if age at diagnosis was 180 days after HMA initiation, except in cases of overt disease progression. Best responses were assessed based on IWG 2006 and 2023 criteria. Kaplan-Meier analysis estimated OS from HMA initiation, and the log-rank test was used to compare subgroups. Cox multivariable regression models identified predictors of OS. This study was supported by an independent research grant from AbbVie. Results: Of 1,223 pts in VALIDATE database, 629 were met eligibility. Median age was 68 years, 27.7% and 27.4% were red blood cell and platelet transfusion-dependent, respectively, 38.1% had TP53 mutations, and 45.3% underwent allogeneic transplantation (allo-HCT). Most pts (71.6%) received HMA monotherapy (51.7% azacitidine, 19.9% decitabine), while 28.4% received HMA-based combinations. Median duration of therapy was 4 cycles (Range: 1-94). Median OS of different subgroups pts are shown in Figure 1. Median OS for pts with IWG 2023-defined cCR (CR+CR-L+CRh+CRequ; N = 230) was 26.5 months (mo; 95% CI: 20.7 - 32.2 mo) vs 14.3 mo (95% CI: 12.5 - 16.9 mo) for pts who did not achieve cCR (p=0.002). Median OS for pts who achieved IWG 2023-defined CR (N = 90) was 29.8 (95% CI: 23.1 - 41.8) vs. 26.4 mo (95% CI: 22.0 - 41.3) for IWG 2006-defined CR (p=0.71). The 124 pts (19.7%) who achieved CR-L had a median OS of 26.4 mo (95% CI: 17.6 - 36.2 mo); of those 67 pts achieved CRbi and had a median OS of 29.1 mo (95% CI: 20.7 - not reached), while 57 pts achieved CRuni and had a median OS of 18.7 mo (95% CI: 15.5 - 54.4 mo), with no significant difference in OS between CRbi and CRuni (Hazard ratio: 1.24; 95% CI: 0.78-1.98, p=0.71). Given the hierarchical prioritization of CR-L designation over CRh in IWG 2023 if a pt meets both response definitions, only 6 pts achieved CRh which precluded a reliable estimate of their OS. Similarly, CRequ was achieved only in 10 pts limiting a reliable assessment of OS in these pts. In a multivariable Cox model that adjusted for sex, HMA type, age, allo-HCT, complex karyotype, TP53 mutation, and IPSS-M risk group, achieving a cCR per IWG 2023 criteria was statistically significantly associated with improved OS was associated with improved OS compared to those who did not achieve cCR (HR: 1.64; 95% CI: 1.30 - 2.08; p<0.001, Figure 2). Discussion: In this real-world analysis of HR-MDS pts treated with HMA-based therapy, cCR according to IWG 2023 were associated improved OS. In particular, CR and CRL (including CRbi and CR uni) were associated with improved OS, supporting their inclusion in the overall response rate in clinical trials. The number of pts who achieved CRh and CRequ was too small to reliably assess their specific association with OS. Additional pts are being added to the database and detailed analyses will be presented in the meeting

Impact of Type of Hypomethylating Agent (HMA) Used on Outcomes of Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) - a Large, Multicenter, Retrospective Analysis

JPB and TK Co-first; RK and AMZ are Co-senior authors Introduction HMAs remain the mainstay for frontline treatment of HR-MDS. Azacitidine (AZA) and decitabine (DEC; including oral cedazuridine/decitabine) are the only FDA-approved HMAs. However, AZA and DEC have not been compared directly in randomized trials. In this study, we aimed to assess the clinical outcomes of pts with HR-MDS treated with different HMA regimens, focusing on overall survival (OS) and treatment responses. Methods The VALIDATE database includes pts with HR-MDS treated with HMA-based therapies in the frontline setting from 14 specialized MDS centers. HR-MDS pts treated with HMA-based therapies in the frontline setting were included. HR-MDS was defined as having an IPSS ≥1.5 or IPSS-R >3.5 (n=213 pts excluded). Pts were excluded from the survival analysis if age at diagnosis was <18 years (n=1), bone marrow (BM) blasts ≥20% or unknown at HMA initiation (n=61), or if survival status, follow-up time, date of HMA initiation, or HMA type was unknown (n=28). To be included in the analysis of response based on IWG 2023 criteria (Zeidan A et al, Blood 2023), pts had to have a BM response assessment within 180 days after HMA initiation to allow determination of response (n=290 pts excluded). Time to event analyses were estimated using the Kaplan-Meier method and treatment groups (AZA vs DEC monotherapy) were compared by log-rank test and assessed from the time of HMA initiation. Multivariable Cox regression models were performed among pts treated with AZA and DEC monotherapy to identify predictors of response and OS. This study was supported by an independent research grant from AbbVie. Results 1,223 pts were screened of whom 919 were included in the survival analysis. Median age was 68 years (Range [R]: 19-95) with 66% males. Our cohort was enriched for pts with adverse genetic features including complex karyotype (38%) and TP53 mutations (36%). Overall, 76% of pts were treated with HMA monotherapy (56% AZA, 20% DEC) and 24% received HMA-based combination therapy (HMA/VEN: 15%, other HMA combinations: 9%). 38.2% underwent allogeneic hematopoietic cell transplant (allo-HCT). The median HMA duration was 5 cycles (R: 1 - 94). Due to the small number and the heterogeneity of pts receiving HMA combinations, as well the multiple partner drugs used in these pts ( Table), we compared OS and responses only between pts treated with AZA (n = 512 pts) or DEC monotherapy (n = 186 pts). In unadjusted analyses, median OS differed by treatment type (p = 0.002) and was 19.8 months (mo) with AZA (95% CI: 17.0 - 23.1 mo) and 14.3 mo with DEC (95% CI: 11.2 - 18.5 mo). Among 629 pts evaluable for response, rates of complete remission (CR) and overall response (ORR) were 14.8% and 48.6% for AZA monotherapy and 5.6% and 50.4% for DEC monotherapy, respectively. In a Cox multivariable regression model ( Figure) adjusted for age, sex, TP53 mutation status, complex karyotype, IPSS-M category (compared to very high risk), and receipt of allo-HCT, there was no difference in OS when comparing AZA and DEC monotherapy (Hazard ratio [HR]: 0.95, 95% CI: 0.72 - 1.26; p = 0.740). Variables associated with adverse OS were male sex (HR: 1.52; 95% CI: 1.16 - 2.00; p = 0.002) and presence of TP53 mutation (HR: 1.50, 95% CI: 1.05 - 2.14; p = 0.027). Conversely, receipt of allo-HCT (HR: 0.26, 95% CI: 0.19 - 0.37; p<0.001) and IPSS-M moderate-high (HR: 0.57, 95% CI: 0.37 - 0.87; p=0.009) and moderate-low (HR: 0.58, 95% CI: 0.36 - 0.95; p = 0.031; both compared to IPSS-M very high risk) were associated with improved OS. Similarly, there were no statistically significant differences in ORR between AZA and DEC (OR: 1.05, 95% CI: 0.66 - 1.68; p = 0.832) in a Cox multivariable regression model adjusted for age, sex, TP53 mutation, complex karyotype, IPSS-M category, and treatment type. Conclusions: Among pts included in the real-world VALIDATE database, there were no significant difference in OS or ORR (IWG 2023) between AZA- and DEC-treated pts in adjusted analyses. Other factors (e.g., TP53 mutations, complex karyotype) are substantially more relevant to outcomes than the specific HMA used. The small number of pts and heterogeneity of partner drugs in HMA-based combinations precluded robust analyses or conclusions regarding differences in efficacy. Additional analyses evaluating the impact of combinations and molecular subtypes on response and survival will be presented during the meeting as more pts are added to the database

Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Underwent Allogenic Stem Cell Transplantation (HSCT)

TK and JPB Co-first; RK and AMZ are Co-senior authors. Introduction MDS are genetically heterogenous neoplasms with diverse prognoses. While hypomethylating agents (HMA) can improve outcomes, HSCT remains the only potentially curative therapy. The IPSS-M incorporates clinical and molecular features to improve outcome prediction beyond traditional risk stratification tools. The IPSS-M has been validated in studies that either variably included pts who underwent HSCT, were limited by sample size, or were single-institution analyses. We aimed to validate the performance of the IPSS-M in predicting outcomes among pts with MDS who were treated with HMAs and subsequently underwent HSCT. Methods The VALIDATE database includes MDS pts treated with frontline HMA from 14 specialized centers. Only pts with available molecular data pre-HMA therapy and subsequently underwent HSCT were included. Time-to-event analyses used Kaplan-Meier estimator and the log-rank test. Overall survival (OS) was measured from time of HSCT. Multivariate-adjusted survival analysis used Cox proportional hazards. We compared the different scoring scores by Harrell's c-index. This study was supported by an independent research grant from AbbVie. Results A total of 350 pts met eligibility ( Panel A). Median age was 63 years (IQR: 58-68). MDS with excess blasts 1/2 (66%) was the most common type. Overall, 74% of pts received HMA monotherapy (27% decitabine; 73% azacitidine), while 26% received HMA in a combined therapy. The most prevalent mutations were TP53 (29%), ASXL1 (21%), RUNX1 (13%), STAG2 (12%), SRSF2 (12%), and DNMT3A (11%); 53% of pts had disease harboring >1 gene mutation. Only 44% had TP53 CN-LOH and 40% had MLL-PTD testing. The most common donor types were matched unrelated donors (MUD, 46%), haploidentical donors (21%), and matched related donors (MRD, 17%). Myeloablative, non-myeloablative, and reduced-intensity conditioning were used in 38%, 27%, and 27% of the pts, respectively. Only 14% of pts received post-HSCT maintenance therapy. Our cohort was enriched with very high risk (41%) and high risk (30%) IPSS-R groups at time of diagnosis, while very low (1%), low (9%), and intermediate (20%) IPSS-R risk groups accounted for remaining 29% of pts. According to the IPSS-M, pts were classified into very low (2%), low (10%), moderate low (13%), moderate high (14%), high (27%) and very high (34%) risk groups. The IPSS-M re-stratified 198 (57%) pts, of whom 77 (39%) pts were up-staged and 121 (61%) pts were down-staged. More specifically, 35% and 26% of pts with intermediate risk IPSS-R MDS, and 32% and 35% of pts with high risk IPSS-R MDS were up-staged and down-staged, respectively. Importantly, 45% of pts with very high risk IPSS-R MDS were down-staged. Median follow-up time was 20 (IQR:8-36) months (mo). The median OS for the entire cohort was 32 mo (IQR:10-Not reached [NR]). The IPSS-M groups showed significantly different OS (p-value= 0.001, Panel B)withmedian OS (mo, 95%CI) of: very low (NR, 11.5-NR), low (55, 22-NR), moderate low (48, 25-NR), moderate high (35, 22-NR), high (29, 23-NR), and very high (20, 13-28). The 5-year OS (%) were as following: very low (56%), low (47%), moderate low (37%), moderate high (40), high (43%), and very high (17%). IPSS-M risk (HR: 1.3, 95% CI:1.1-1.5) was significantly associated with OS in a multivariable model (HR, 95%CI) adjusted for age (1.01, 1.00-1.03), sex (1.2, 0.9-1.7), type of HMA used before HSCT (1.0, 0.9-1.1), number of HMA cycles (1.0, 0.9-1.05), donor type (1.0, 0.9-1.1), and conditioning regimen used (1.3, 1.1-1.5). For OS, the IPSS-M significantly stratified pts assigned to the very high risk IPSS-R subgroup (p=0.009). However, the IPSS-M showed comparable performance to IPSS-R with c-index (95%CI): 0.597 (0.555-0.640) vs. 0.599 (0.554-0.643), respectively, for OS. When IPSS-M/IPSS-R were analyzed as continuous scores, the c-index (95%CI) for OS were: 0.606 (0.561-0.651) vs. 0.611 (0.559-0.662). When focusing on the higher risk group defined as IPSS ≥.1.5, the IPSS-M (c-index: 0.584) still had performance comparable to the IPSS-R (c-index: 0.606). Conclusions To our knowledge, this is the largest reported cohort in which IPSS-M performance was evaluated among pts with HMA-treated MDS and subsequently underwent HSCT. While the IPSS-M subgroups showed significant OS differences, the IPSS-M did not seem to substantially improve prediction when compared to the IPSS-R

Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA)

TK and JPB Co-first; RK and AMZ are Co-senior authors. Introduction Recognition of the growing importance of genetic mutations in prognostication for pts with MDS prompted the development of IPSS-M to improve outcome prediction. Subsequent validation studies included a heterogenous groups of pts; treated & untreated pts with lower & higher risk (HR) disease, and thus the value of IPSS-M in predicting outcomes of pts with HR-MDS treated with HMA remains unclear. We aimed to evaluate the ability of IPSS-M to predict outcomes of pts with HR-MDS who were treated with HMA in a large multicenter cohort. Methods Using the multi-center VALIDATE database, we included pts with HR-MDS (Defined as IPSS score >1 or IPSS-R score > 3.5) who were treated with any HMA in the frontline setting and had available molecular data before HMA initiation. Time-to-event analysis used Kaplan-Meier estimator and the log-rank tests. Survival was measured from time of HMA initiation. We compared the different scoring systems by Harrell's c-index. Best response to HMA was assessed using the IWG 2023 response criteria in HR pts (n=480) who had a marrow evaluation within 180 days of HMA initiation. This study was supported by an independent research grant from AbbVie. Results A total of 925 pts were included in the analysis. Median age was 68 years (IQR: 62-75) and 66% of the pts were men. MDS excess blast 1/2 accounted for 65% of the diagnosis. Overall, 76% of pts were treated with HMA monotherapy (29% decitabine and 71% azacitidine), 24% received HMA combination therapy, and 39% of pts had HSCT. The most common mutations (MT) were TP53 (32%), ASXL1 (20%), TET2 (13%) and SRSF2 (12%); 36% of pts had MDS harboring >1 gene MT. As anticipated, the cohort was enriched with high risk (26%) and very high risk (46%) IPSS-R groups. According to pre-therapy IPSS-M, pts were classified into very low (2%), low (9%), moderate low (11%), moderate high (14%), high (29%) and very high (36%) risk groups. IPSS-M reclassified 54% of pts, of whom 184 (37%) were up-staged and 317 (63%) were down-staged. Specifically, 38%/21% of pts with intermediate risk IPSS-R MDS, and 30%/36% of pts with high risk IPSS-R MDS were up-staged/down-staged, respectively. In addition, 44% of pts with very high risk IPSS-R MDS were down-staged. The median follow-up time was 19 (IQR:10-35) months (mo). Median overall survival (OS) was 19 (95% CI: 17-22) mo. Overall, 35% of the pts progressed to AML during follow up. IPSS-M groups showed significant differences for both OS and LFS (p-value: <0.0001 for both). The median OS (mo, 95%CI) based on IPSS-M categories were: low (37, 25-62), moderate low (30, 23-47), moderate high (29, 22-35), high (17, 14-20), and very high (14, 12-15) (Panel A). The 3-year LFS (%) were: low (20%), moderate low (48%), moderate high (41), high (50%), and very high (59%). IPSS-M was significantly associated with OS in a multivariable model adjusted for age, sex, type of HMA, number of HMA cycles and receiving allogeneic HSCT (HR: 1.4, 95% CI:1.2-1.5). However, IPSS-M showed comparable performance when compared with the IPSS-R with c-index (95%CI): 0.599 (0.557-0.622) vs. 0.619 (0.560-0.641) for OS. In addition, IPSS-M showed similar performance for LFS: 0.583 (0.560-0.606) vs. 0.588 (0.565-0.610) (Panel B). When IPSS-M/IPSS-R were used as continuous scores, the c-indices (95%CI) for OS and LFS were: 0.617 (0.592-0.640) vs. 0.6400 (0.616-0.664) for OS and 0.598 (0.575-0.622) vs. 0.606 (0.581-0.632) for LFS. We then analyzed the performance of IPSS-R/IPSS-M in pts with HR MDS (IPSS ≥1.5). Both IPSS-R and IPSS-M had comparable performance for OS prediction (c-index:0.548 vs. 0.566) and LFS (0.551 vs. 0.538). Based on the proposed IWG 2023 response criteria, complete remission rate (CR)/ overall response rate (ORR) were 12/47%, 9/58%, 13/47%, and 17/57% of pts assigned to moderate low, moderate high, high, and very high IPSS-M risk groups. No significant association was observed between IPSS-M and ORR (OR: 1.1, p=0.475) or CR (1.1, p=0.286). Conclusions In our multi-center large cohort of pts with HR MDS treated with frontline HMA, IPSS-M significantly stratified pts for OS and LFS. However, when compared with IPSS-R, IPSS-M did not seem to substantially improve prediction of outcomes among HMA-treated pts. Our results emphasize the high predictive prognostic power of clinical features and cytogenetic alterations among HR-MDS pts treated with HMA