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Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53–32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.

Background: Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for hematological disease however can be complicated by relapse or graft failure (GF), for which second-HCT and donor lymphocyte infusions (DLI) are performed. This study aimed to compare outcomes following the two interventions. Methods: We retrospectively investigated 89 patients with relapse or GF after first-HCT, 50 (56%) underwent second HCT and 39 (44%) received (DLI), from June 2011 to September 2020. Results: Median age at intervention was 55 years (19-72). Second-HCT was performed for relapse in 19 patients and for GF in 31 patients (primary GF in 11 and secondary in 20 patients), same donor was used in 25 (50%) patients. DLI was performed for relapse in 20 and for secondary GF in 19 patients. Median number of DLI administered was 2 (range 1-11). Univariate analysis demonstrated 2-year overall survival (OS) for second-HCT was superior when performed for relapse (65%) compared to GF (44%) (p=0.03). For DLI patients, 2-year OS was 49% for GF and 45% for relapse patients (p=0.49). For relapse as an indication, second-HCT demonstrated borderline superiority compared to DLI (p=0.07). Multivariable analysis demonstrated for OS for the entire cohort demonstrated donor mismatch (HR 0.50, 95%CI 0.26-0.94%, p=0.03), KPS at time of intervention (HR 2.10, 95%CI 1.14-3.85%, p=0.02) and time from first-HCT to intervention (HR 0.51, 95%CI 0.28-0.93%, p=0.03) as significant variables. Conclusion: Second-HCT may improve outcomes when performed for relapse post-transplant if patients achieve remission again, while DLI may be reserved for patients with active disease.

Increasing survival of patients with multiple myeloma (MM) has resulted in an increased recognition of therapy-related hematological malignancies (t-MDS/AML, t-ALL, and t-CMML). There are limited data on the role of allogeneic hematopoietic stem cell transplantation (HCT) in this patient population.We retrospectively reviewed patients who underwent HCT for t-MDS/AML, t-ALL, and t-CMML developing after receiving treatment for MM at our center. Patients were analyzed for myeloma characteristics and therapy, time to diagnosis of therapy-related hematological neoplasms, clinical, laboratory characteristics, transplant details, relapse-free survival (RFS), and overall survival (OS).Twenty patients underwent HCT for therapy-related hematological malignancies after MM (t-MDS/AML = 13, t-ALL = 6, t-CMML = 1). Median(range) age at time of transplant was 62.5 (49-73) years and 70% (n = 14) were male. The most common cytogenetic abnormality was complex/monosomal karyotype in 30% (n = 6) followed by monosomy/deletion of chromosome 5 or 7 in 15% (n = 3) of patients each. Donors were human leukocyte antigen matched (10/10 or 6/6) siblings in 30% (n = 6), unrelated in 60% (n = 12) and haploidentical in 10% (n = 2) patients. Estimated 2-year OS and RFS for the whole cohort were 53.1% and 47.2% respectively. There was a trend toward better survival in patients with t-ALL when compared to t-MDS/AML; however, the difference was not statistically significant. We did not find any pre-transplant or post-transplant factors that were predictive of survival outcomes after multivariate analysis.Allogeneic HCT provides substantial long-term disease-free survival in a proportion of patients with MM-associated therapy-related hematological malignancies. Multicenter studies with more patients and longer follow-up may provide additional information about factors affecting outcomes.

Background We evaluated feasibility, safety, and total resource use of subcutaneous immunoglobulin (SCIG) in a pilot study of patients who underwent allogeneic hematopoietic cell transplant (HCT) over a 6-month period. Methods A total of 20 eligible patients were treated with SCIG at 0.1 g/kg/week for up to 6 months. Patients were matched to 20 concurrent intravenous immunoglobulin (IVIG) controls. Clinical outcomes measured included adverse reactions, healthcare resource use, patient satisfaction, and quality of life (QOL). (ClinicalTrials.gov Identifier: NCT03401268.) Results Groups were comparable in terms of age, weight, sex, transplant indication, donor type, and conditioning intensity. All 20 IVIG patients completed 6 consecutive months of therapy compared with 13/20 (65%) SCIG patients. There were no adverse reactions in IVIG patients, compared with six (30%) SCIG patients. All adverse reactions in SCIG patients were grade I, transient, and required no medical intervention. Median overall cost per patient was lower with SCIG than with IVIG ($9,756 vs. $13,780, p = .046). Among patients who completed 6 months of SCIG, median preference and satisfaction scores were 100%. Over the 6-month period, QOL scores remained stable in SCIG patients. Conclusions In a subgroup of patients, SCIG was associated with high patient satisfaction and a reduction in total healthcare costs compared with IVIG in a cohort of HCT patients.

Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.

During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.

Refereed/Peer-reviewed Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML.

Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a provisional disease entity in the 2016 WHO classification, while its genetic profile of Ph+ AML remains poorly defined. In addition, the differentiating features of Ph+ AML and chronic myeloid leukemia in myeloid blast crisis (CML-MBC) remain controversial.We conducted a retrospective study of 15 Ph+ AML patients to compare their clinical and laboratory profiles with 27 CML-MBC patients.Compared to CML-MBC, Ph+ AML patients presented with significantly higher peripheral WBC count and bone marrow blast percentage. The immunophenotypic profiles were largely similar between Ph+ AML and CML-MBC, except for CD4 expression, which was significantly enriched in CML-MBC. Ph+ AML patients less frequently harboured co-occurring additional cytogenetic abnormalities (ACA) compared to CML-MBC, and trisomy 19 (23%) and IDH1/2 (46%) were the most common ACA and mutated genes in Ph+ AML, respectively. Overall survival (OS) did not significantly differ between Ph+ AML and CML-MBC. Ph+ AML without CML-like features appeared to have a better outcome compared to Ph+ AML with CML-like features; ACA in Ph+ AML may confer an even worse prognosis.Our results indicate that patients with Ph+ AML share similar genetic profiles and clinical outcomes with those with CML-MBC, thus should be classified as a high-risk entity.

Treatment-free remission is achievable in approximately half of patients with chronic myeloid leukemia who attain a sustained, deep molecular response with tyrosine-kinase inhibitor (TKI) therapy. We aimed to identify potential predictors of future achievement of stable MR4.5, defined as a sustained 4.5-log reduction in BCR-ABL1 transcripts for a minimum of 2 years, in 593 patients treated with imatinib as first-line TKI therapy. In multivariable analyses of patient and disease variables including baseline blood counts, disease phase, additional cytogenetic abnormalities, prior therapy, depth and rapidity of molecular response, the only predictor for future achievement of stable MR4.5 was molecular response at 6 months. In this study, patients failing to attain a molecular response of BCR-ABL1≤ 0.16%IS after 6 months of imatinib therapy were unlikely to subsequently achieve stable MR4.5 with imatinib. Our data suggest that achievement of BCR-ABL1≤ 0.16%IS at 6 months is predictive of future stable MR4.5.

Allogeneic hematopoeitic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF). We evaluate the impact of various factors on survival outcomes post-transplant in MF. Data of 89 consecutive MF patients (primary 47%) who underwent allo-HCT between 2005 and 2018 was evaluated. Fifty-four percent patients had received JAK1/2 inhibitors (JAKi) pre-HCT. The median CD34 count was 7.1x106 cells/kg. Graft failure was seen in 10% of the patients. Grade 3-4 acute GVHD (aGVHD) and moderate/severe chronic graft versus host disease (cGVHD) occurred in 24% and 40% patients, respectively. Two-year overall survival (OS) and relapse free survival (RFS) were 51% and 43%, respectively. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years were 11% and 46%, respectively. Higher CD34 cell dose (≤5 × 106 cells/kg vs 5-9 or ≥9 × 106 cells/kg) and lower pre-HCT ferritin (

While ruxolitinib is emerging as the treatment of choice for steroid refractory/dependent chronic graft vs host disease (cGVHD) based on randomized control trial data, there is relatively little real world data published on ruxolitninb for this indication.to evaluate the real world efficacy and safety of ruxolitinib in cGVHD patients who have failed any previous systemic therapy for cGVHD STUDY DESIGN: We retrospectively evaluated the efficacy of ruxolitinib in 115 heavily pre-treated patients with steroid-refractory or dependent chronic GVHD across 5 transplant centres.The majority of the study population had severe chronic GVHD (60%) and received ruxolitinib at the 4Overall, this study demonstrates the therapeutic efficacy of ruxolitinib for cGVHD in a heavily pretreated real-world population.

INTRODUCTION Allogeneic hematopoietic cell transplantation (HCT) can be curative for acute myeloid leukemia (AML). Novel therapies may render patients' bone marrow hypocellularity and lead to prolonged post-therapy pancytopenia. Patients' bone marrow cellularity (BMC) at pretransplant assessment and post-treatment pancytopenia (classification CR-incomplete [CRi]) may manifest AML persistence. METHODOLOGY We retrospectively examined the impact of BMC and ELN response (ELNr) on a single-center cohort of 337 patients who underwent allogeneic HCT for AML in CR1. RESULTS Median follow-up was 33 months. Overall survival (OS) for the whole cohort was 55.8% at 2 years, while cumulative incidence of relapse (CIR) was 20.8%, and non-relapse mortality was 27.5%. OS and CIR were not significantly different between BMC groups; and neither was ELNr. ELNr CRi was associated with BMC aplastic and hypocellular marrow states (P

Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

Objective/Background: Unsuccessful cytogenetic (US) analysis at baseline has been reported to be a poor prognostic feature in patients with acute myeloid leukemia (AML). We conducted this study to examine the prognostic impact of UC/inconclusive cytogenetic analysis on outcomes in patients with AML undergoing allogeneic hematopoietic stem cell transplantation (Allo HSCT). Methods: We retrospectively analyzed all adults undergoing Allo HSCT for AML from January 2011 to August 2019. Patients with any documented cytogenetic abnormalities were excluded. Baseline characteristics and transplant outcomes were compared between patients with normal cytogenetics and those with UC. Results: Overall, 243 AML patients (median age, 55 years; 55.1% female) were included. UC were reported in 79 patients, whereas 164 patients had a normal karyotype. The two groups were similar to each other in terms of baseline demographics, treatment received, and transplant related variables. There was no difference between patients with UC and normal cytogenetics in terms of relapse-free survival (66 months vs. 42 months, p = .53) or overall survival (OS; 77 months vs. 76 months, p = .72). Survival parameters remained similar even in subgroup analysis based on NPM1 and FLT3 mutation status. Significant predictors of OS after Allo HSCT in AML patients with UC were increased age at time of Allo HSCT (hazard ratio [HR] = –1.049; 95% confidence interval [CI], 1.005–1.095), favorable (NPM1Mut/FLT3wt) mutation profile (HR = 0.11; 95% CI, 0.01–0.84), neutrophil engraftment

Although total duration of tyrosine kinase inhibitor (TKI) therapy and of molecular response at 4 log reduction or deeper (MR4) correlates with treatment-free remission (TFR) success after TKI discontinuation, the optimal cut-off values of the duration remain unresolved. Thus, 131 patients were enrolled into the Canadian TKI discontinuation study. The molecular relapse-free survival (mRFS) was defined from imatinib discontinuation till molecular recurrence, that is, major molecular response (MMR) loss and/or MR4 loss. We evaluated mRFS at 12 months after imatinib discontinuation, analyzed it according to the imatinib treatment duration and MR4 duration, and calculated P value, positive (PPV) and negative predictive value (NPV) in the yearly cut-off period of time. The shortest cut-off was sought that met the joint criteria of a P value ≤ 0·05, PPV ≥ 60% and NPV ≥ 60%. We propose six years as the shortest imatinib duration cut-off with a P value 0·01, PPV 68% and NPV 62%: The patients treated with imatinib duration ≥ 6 years showed a superior mRFS rate (61·8%) compared to those with less treatment (36·0%). Also, 4·5 years MR4 duration as the shortest cut-off with a P value 0·003, PPV 63% and NPV 61%: those with MR4 duration ≥ 4·5 years showed a higher mRFS rate (64·2%) than those with a shorter MR4 duration (41·9%).

BCR-ABL1 plays a key role in the pathogenesis of chronic myeloid leukemia (CML), and it has been investigated as a druggable target of tyrosine kinase inhibitors (TKIs) over two decades. Since imatinib, the first TKI for anti-cancer therapy, was successfully applied in CML therapy, further generation TKIs and a novel allosteric inhibitor targeting the myristate binding site have been developed as alternative options for CML management. However, significant concerns regarding toxicity profiles, especially in long-term treatment, have emerged from TKI clinical data. Efforts to reduce adverse events and serious complications are warranted not only for survival, but also quality of life in CML patients. A better understanding of the mechanism of action will help to identify on- and off-target effects of TKIs, and guide personalized TKI drug selection in each individual CML patient. Herein, this review summarizes the biologic mechanism of BCR-ABL1 inhibition and differential target spectra, and related off-target effects of each TKI.

The impact of adverse risk genetic profiles on outcomes in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HCT) has not been fully elucidated. Accordingly, we have profiled somatic mutations at diagnosis using next-generation sequencing (NGS) in 178 AML patients who received allogeneic HCT. NGS revealed 598 somatic mutations in 165/178 patients (92.7%). Frequently mutated genes include DNMT3A, TET2, NPM1, RUNX1, IDH2, and FLT3. Commonly detected cytogenetic profiles include normal karyotype, trisomy 8, monosomal karyotype (MK), deletion 5, complex karyotype (CK), and monosomy 7. In univariate analyses, TP53 mutation, MK, CK, and monosomy 7 were associated with decreased overall survival (OS), relapse-free survival (RFS), and a higher relapse incidence (RI). We defined adverse molecular-genetic profile as harboring at least one of the molecular/genetic abnormalities of TP53 mutation, MK, CK, monosomy 7, and deletion 5. The patients harboring adverse molecular-genetic profile (n = 30) showed a lower 2-year OS (24.9% vs. 57.9%; p = 0.003), RFS (23.7% vs. 57.9%; p = 0.002), and higher RI (47.2% and 17.2%; p = 0.001) after HCT when compared to patients without those lesions. Multivariate analysis confirmed adverse molecular-genetic profile as an independent prognostic factor, associated with decreased OS (HR 2.19), RFS (HR 2.23), and higher RI (HR 2.94).

Avascular necrosis (AVN) is a debilitating complication of allogeneic hematopoietic cell transplantation (HCT). A retrospective review of 845 patients who underwent HCT was conducted. Cumulative incidence of AVN was 6.3% at 4 years. The following risk factors were significantly associated with AVN risk on univariate analysis: age < 45 (p=0.004), moderate to severe chronic GvHD (p

Background:Although cardiac catheterisation (cath) is the diagnostic test for pulmonary hypertension, it is an invasive procedure. Echocardiography (echo) is commonly used for the non-invasive diagnosis of pulmonary hypertension but maybe limited by lack of adequate signals. Therefore, emphasis has been placed on biomarkers as a potential diagnostic tool. No prior paediatric studies have simultaneously compared N-terminal pro-B-type-natriuretic peptide (NTproBNP) with cath/echo as a potential diagnostic tool. The aim of this study was to determine if NTproBNP was a reliable diagnostic tool for pulmonary hypertension in this population.Methods:Patients were divided into Study (echo evidence/established diagnosis of pulmonary hypertension undergoing cath) and Control (cath for small atrial septal defect/patent ductus arteriosus and endomyocardial biopsy post cardiac transplant) groups. NTproBNP, cath/echo data were obtained.Results:Thirty-one patients met inclusion criteria (10 Study, 21 Control). Median NTproBNP was significantly higher in the Study group. Echo parameters including transannular plane systolic excursion z scores, pulmonary artery acceleration time and right ventricular fractional area change were lower in the Study group and correlated negatively with NTproBNP. Receiver operation characteristic curve analysis demonstrated NTproBNP > 389 pg/ml was 87% specific for the diagnosis of pulmonary hypertension with the addition of pulmonary artery acceleration time improving the specificity.Conclusions:NTproBNP may be a valuable adjunctive diagnostic tool for pulmonary hypertension in the paediatric population. Echo measures of transannular plane systolic excursion z score, pulmonary artery acceleration time and right ventricular fractional area change had negative correlations with NTproBNP. The utility of NTproBNP as a screening tool for pulmonary hypertension requires validation in a population with unknown pulmonary hypertension status.

OBJECTIVES Hepatic grading systems for categorizing severity in chronic graft-versus-host disease (cGvHD) were determined arbitrarily, leading us to initiate the present study to provide objective evidence for the determination of optimal cutoff values and devise a hepatic grading system to predict prognosis. METHODS Of 842 patients who received allogeneic hematopoietic stem transplant (HCT), 336 patients diagnosed with cGvHD were evaluated for overall survival (OS) and non-relapse mortality (NRM) after cGVHD development. Multiple statistical parameters were evaluated to define optimal cutoff values of liver profile, including negative predictive value (NPV), positive predictive value (PPV), accuracy, and p-values as measures of risk stratification power. RESULTS We found that alkaline phosphatase (ALP) ≥ 146 IU/L (NPV: 83.4%; PPV: 32.8%; accuracy: 52.7%) and bilirubin ≥ 14 µmol/L (NPV: 81.8%; PPV: 39.4%; accuracy 68.1%) significantly correlated with OS. We developed a refined hepatic cGvHD grading score (RHS), stratifying patients into a low-RHS group with RHS score 0, OS at 3 years (n = 162) to 80.5%, compared to high-RHS group with score 1-2 (n = 172) 62.7%. Regarding NRM, score 0 segregated NRM at 3 years to 11.9%, compared with score 1-2 19.6%, P = .1. CONCLUSIONS Refined hepatic score is promising for stratifying patients with cGVHD and liver involvement according to long-term outcomes.

We evaluated standard-of-care (SOC) treatment with or without midostaurin to prevent relapse following allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML) harboring internal tandem duplication (ITD) in FLT3. Adults (aged 18–70 years) who received alloHSCT in first complete remission, had achieved hematologic recovery, and were transfusion independent were randomized to receive SOC with or without midostaurin (50 mg twice daily) continuously in twelve 4-week cycles. The primary endpoint was relapse-free survival (RFS) 18 months post-alloHSCT. Sixty patients were randomized (30/arm); 30 completed all 12 cycles (midostaurin + SOC, n = 16; SOC, n = 14). The estimated 18-month RFS (95% CI) was 89% (69–96%) in the midostaurin arm and 76% (54–88%) in the SOC arm (hazard ratio, 0.46 [95% CI, 0.12–1.86]; P = 0.27); estimated relapse rates were 11% and 24%, respectively. Inhibition of FLT3 phosphorylation to FLT3-ITD AML. (ClinicalTrials.gov identifier: NCT01883362).

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.

Objectives The aim of this study was to demonstrate the safety and functionality of the Alterra Adaptive Prestent and SAPIEN 3 transcatheter heart valve (THV) in patients with dysfunctional, dilated right ventricular outflow tract (RVOT) greater or equal to moderate pulmonary regurgitation (PR). Background Significant variations in the size and morphology of the RVOT affect the placement of transcatheter pulmonary valves. The Alterra Prestent internally reduces and reconfigures the RVOT, providing a stable landing zone for the 29-mm SAPIEN 3 THV. Methods Eligible patients had moderate or greater PR, weighed >20 kg, and had RVOT diameter 27 to 38 mm and length >35 mm. The primary endpoint was device success, a 5-item composite: 1 Alterra Prestent deployed in the desired location, 1 SAPIEN 3 THV implanted in the desired location within the Prestent, right ventricular–to–pulmonary artery peak-to-peak gradient Results Enrolled patients (N = 15) had a median age and weight of 20 years and 61.7 kg, respectively; 93.3% were in New York Heart Association functional class I or II. Device success was 100%. No staged procedures were necessary. No THV dysfunction was reported to 6 months. No serious safety signals were reported. Conclusions This early feasibility study demonstrated the safety and functionality of the Alterra Adaptive Prestent in patients with congenital RVOT dysfunction and moderate or greater PR. Durability and long-term outcome data are needed.

INTRODUCTION The polypeptide prolactin (PRL) is a peptide hormone and a cytokine mostly secreted from the anterior pituitary gland. PRL is also synthesized in extra pituitary tissues including thymocytes and T lymphocytes. Considering the need for chronic GVHD (cGVHD) biomarkers, we explored the relationship between hyperprolactinemia and active cGVHD in a cohort of long-term post-alloHCT survivors. METHODS Three-hundred sixteen adults underwent alloHCT between 2010 and 2016, survived more than 1 year and were included. All patients underwent a regular annual assessment that includes a hormone profile with serum PRL levels. RESULTS Overall, 236 (74.7%) patients had cGVHD, and in 199 (63%), the grade was moderate or severe. Sixty-five (21%) recipients had active cGVHD at the time of the annual evaluation, and hyperprolactinemia was documented in 63 (19.9%) patients. Hyperprolactinemia correlated with cGVHD activity (Odds Ratio 6.9 (95% CI; 3.6-13.1); P

Recent advances in allogeneic hematopoietic stem cell transplant (HSCT) have allowed us to offer HSCT to older, advanced disease patients with more co-morbidities. Cardiovascular toxicity post-transplant is a major concern due to the increased risk of mortality. Few studies have examined the prevalence of CV events including CAD (MI, angina, PCI, CABG, CHF, arrhythmias), HTN, stroke/TIA, and death in the first 100 days post-transplant.We assessed the impact of pretransplant MUGA results in predicting postallogeneic HSCT CV events and overall survival in the first 100 days, and whether or not transient anthracycline-induced cardiomyopathy or cumulative anthracycline dose affected overall survival. This retrospective, cohort study included 665 patients with a median age of 52 years who underwent HSCT from 2009 to 2015.The most frequent CV event in the first 100 days post-HSCT was arrhythmia seen in 2.9% of patients followed up by CHF (12.3%), MI (9%), and angina (8%). Two patients had PCI, and both survived the first 100 days. Cardiovascular risk factors predict for a poor MUGA scan but not survival. Higher dose anthracycline pretransplant predicted for a poor outcome.A history of CV disease, MI, or CAD was the most important predictive of CV events, P-value = .00002. 88.6% survived the first 100 days. Patients with an EF 50% had a significant likelihood of having a CV event compared to patients with an EF 60% (OR = 5.3, 95% CI [1.6-18.1], P = .0219). Cumulative anthracycline dose did not have a significant impact on overall survival.