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Qiuju Liu,1 Brittny Major,2 Jennifer Le-Rademacher,2 Aref A Al-Kali,3 Hassan Alkhateeb,3 Kebede Begna,3 Michelle A Elliott,3 Naseema Gangat,3 William J Hogan,3 C Christopher Hook,3 Scott H Kaufmann,3 Animesh Pardanani,3 Mrinal S Patnaik,3 Ayalew Tefferi,3 Alexandra P Wolanskyj-Spinner,3 Wei Wei,4 Mark R Litzow3 1Department of Cancer Center, Division of Hematology, Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA; 3Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA; 4Department of Urology, Second Division, Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Mark R LitzowDivision of Hematology, Mayo Clinic, 200 First St, Rochester, MN 55902, USATel +1 507-284-2511Email litzow.mark@mayo.eduIntroduction: Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients.Methods: We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification.Results: The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥ 60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03– 2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84– 15.98) p< 0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population.Discussion: In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.Keywords: acute lymphoblastic leukemia, obesity, overweight, B cell, T cell

Sarmad Said,1 Haider Alkhateeb,1 Chad J Cooper,1 Emmanuel Rodriguez,1 Remi Trien,1 German T Hernandez,1,2 Hasan S Salameh1,2 1Department of Internal Medicine, 2Department of Internal Medicine, Division of Nephrology and Hypertension, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, TX, USA Introduction: Idiopathic cluster of differentiation 4 (CD4+) T-cell lymphocytopenia (ICL) is a rare non human immunodeficiency virus (HIV)-related syndrome with unclear natural history and prognosis that was first reported and defined in 1992. ICL has been observed in patients after the onset of an opportunistic infection without known immunosuppression. Case presentation: A 20-year-old Hispanic male patient without significant past medical history presented with progressive shortness of breath and cough for 3 weeks. Chest computed tomography showed bilateral cavitary lesions in the upper lung lobes. The HIV rapid screening test as well as the sputum acid-fast bacilli test were both positive. The patient was started on antituberculosis therapy. The CD4 count was noticed to be low. However, the HIV Western blot test was negative, and the HIV viral load was within normal limit. Further radiologic studies, hemato-oncologic, and autoimmune workups were normal. The patient was discharged on the treatment for tuberculosis. Follow-up after 8 weeks revealed a persistent low CD4+ count, and the repeated HIV tests were negative. Conclusion: The clinical features of ICL range from an asymptomatic condition to life-threatening complications that imitate the clinical course of HIV-infected patients. The differential diagnosis in adults comprises primarily HIV infection and other diseases or drug side effects. ICL is very rare and should be considered in the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T-cells. Early detection and recognition of the disease allow purposeful and systemic treatment approach and screening for the affected patients. Keywords: CD4 count, immunodeficiency, lymphocytopenia, opportunistic infection

SETBP1 mutations (m) have been previously reported in myeloid neoplasms and are associated with poor prognostic co-mutations and cytogenetic abnormalities. We retrospectively analyzed the charts of 113 patients diagnosed with myeloid neoplasms with SETBP1m. The most common diagnosis was MDS (31%). Cytogenetics were abnormal in 51 cases (46.4%), with monosomy 7 being the most common (41.1%). The most frequent co-mutations were ASXL1 (71.7%), SRSF2 (46.9%), TET2 (20.4%). Higher SETBP1m VAF was associated with proliferative features ( p  < 0.05). Most SETBP1m (96.5%) were in one of three hotspots (Asp868, Gly870, Ile871), with Asp868m being most frequent (51.3%). Patients with Ile871m had higher number of co-mutations (median= 4) compared to Asp868m and Gly870m ( p  = 0.07). On multivariate analysis, age ≥ 70 years ( p  = 0.004) and higher peripheral blood blasts ( p  = 0.02) had worse OS. Patients with Ile871m had lower OS when compared with Asp868m and Gly870m (5.5 months vs. 17.4 and 17 months, respectively, p  = 0.1).

Introduction: Relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B- and T-ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L-VCR and VEN for patients with r/r B-or T-cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644)., Methods: In a 3+3 dose escalation design, r/r ALL subjects were given single-agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L-VCR at 2.25 mg/m 2 IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination., Results: Among the 18 patients in phase I, grade ≥ 3 treatment-related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose-limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty-two percent of evaluable patients ( N  = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD)., Conclusion: The combination of VEN and L-VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L-VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Abstract: Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified patients with CCUS by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs 44.8%, P = .002) but had higher median bone marrow blast percentages. After a median follow-up of 2.2 years, t-CCUS had significantly shorter progression-free survival (PFS, 1.8 vs 6.3 years; hazard ratio [HR], 2.1; P = .007) and median overall survival (OS; 3.6 years vs not reached; HR, 2.3; P = .007) compared with CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes., Methods: A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center., Results: Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates., Conclusions: This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts., Competing Interests: The authors declare no conflict of interest., (Copyright 2024, Fadah et al.)

Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non-ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A-mutated cases less likely (p < 0.01) to be affected. Treatment-emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition molecule C1q bound to a tetrameric assembly of proteases C1r and C1s. Enzymatically active C1s provides the catalytic basis for cleavage of the downstream CP components, C4 and C2, and is therefore an attractive target for therapeutic intervention in CP-driven diseases. Although an anti-C1s mAb has been Food and Drug Administration approved, identifying small-molecule C1s inhibitors remains a priority. In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a Kd of ∼9.8 μM and competitively inhibits its activity with an inhibition constant (Ki) of ∼5.8 μM. A 1.8-Å-resolution crystal structure revealed the physical basis for C1s inhibition by A1 and provided information on the structure-activity relationship of the A1 scaffold, which was supported by evaluating a panel of A1 analogs. Taken together, our work identifies A1 as a new class of small-molecule C1s inhibitor and lays the foundation for development of increasingly potent and selective A1 analogs for both research and therapeutic purposes., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Background: Pulmonary arterial hypertension (PAH) is a deadly cardiopulmonary disease with multi-organ involvement including impaired liver function. Liver dysfunction in PAH is poorly understood but significantly associated with morbidity and mortality. Hispanics have a significantly higher prevalence of non-alcoholic fatty liver disease (NAFLD) and evidence of more advanced disease in comparison to other ethnic groups. The clinical impact of NAFLD in Hispanic PAH patients is unknown. We aimed to investigate the impact of a validated scoring system, non-alcoholic fatty liver disease fibrosis score (NFS), to predict the degree of liver fibrosis in a Hispanic PAH population and its relationship to hemodynamics, functional class, and outcomes., Methods: A retrospective review of all treatment-naive Hispanic patients with group I World Health Organization (WHO) pulmonary hypertension (PH) at a single academic center between February 2016 and March 2021 was performed. Patients with history of substance or alcohol abuse, non-group I WHO PH, pre-existent liver disease, chronic kidney disease, atrial fibrillation, thyroid disease, and warfarin use were excluded from the study. The diagnosis of group I WHO PH was determined by cardiac catheterization after the exclusion of other etiologies. NFS was calculated for each patient and correlated with functional capacity, hemodynamics, N-terminal-pro-B-type natriuretic peptide (NT-proBNP), and survival., Results: A total of 96 Hispanic patients were included in our study. The median age of patients in our cohort was 49 years (interquartile range: 15) and 69% of our cohort were females. Higher NFSs indicating advanced hepatic fibrosis (F3-F4) were found to correlate with elevated right-sided cardiac filling pressures (r = 0.27, P = 0.03), elevated levels of NT-proBNP (r = 0.32, P = 0.01), lower 6-minute walk distance (6MWD) (r = -0.49, P = 0.001), lower functional capacity (World Health Organization functional class, WHO-FC, r = -0.35, P = 0.051), a higher prevalence of diabetes (21.1% versus 51.9%, P = 0.001), a higher prevalence of risk factors for metabolic syndrome (81.5% versus 65.0%, P = 0.035), and worse 5-year survival rates., Conclusion: In Hispanic patients with PAH, NFSs correlate with the degree of right-sided pressure overload. In addition, advanced NFSs were independently associated with lower 5-year survival rates and added prognostic information to other established risk parameters in PAH. This study suggests that screening for liver disease in this vulnerable patient population can aid in earlier detection leading to discussion of lifestyle modifications and possible escalation of PAH-targeted therapies, thus leading to potential improvement in survival rates., Competing Interests: None to declare., (Copyright 2023, Kalas et al.)

We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation., (© 2023. Springer Nature Limited.)

Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as "blast-phase MPN", is the most feared disease complication, with incidence estimates of 1-4% for essential thrombocythemia, 3-7% for polycythemia vera, and 9-13% for primary myelofibrosis. Diagnosis of MPN-BP requires the presence of ≥20% circulating or bone marrow blasts; a lower level of excess blasts (10-19%) constitutes "accelerated phase" disease (MPN-AP). Neither "intensive" nor "less intensive" chemotherapy, by itself, secures long-term survival in MPN-BP. Large-scale retrospective series have consistently shown a dismal prognosis in MPN-BP, with 1- and 3-year survival estimates of <20% and <5%, respectively. Allogeneic hematopoietic stem cell transplant (AHSCT) offers the possibility of a >30% 3-year survival rate and should be pursued, ideally, while the patient is still in chronic phase disease. The value of pre-transplant bridging chemotherapy is uncertain in MPN-AP while it is advised in MPN-BP; in this regard, we currently favor combination chemotherapy with venetoclax (Ven) and hypomethylating agent (HMA); response is more likely in the absence of complex/monosomal karyotype and presence of TET2 mutation. Furthermore, in the presence of an IDH mutation, the use of IDH inhibitors, either alone or in combination with Ven-HMA, can be considered. Pre-transplant clearance of excess blasts is desired but not mandated; in this regard, additional salvage chemotherapy is more likely to compromise transplant eligibility rather than improve post-transplant survival. Controlled studies are needed to determine the optimal pre- and post-transplant measures that target transplant-associated morbidity and post-transplant relapse., (© 2023. The Author(s).)

Large pericardial effusion (LPE) and tamponade are purported manifestations associated with atypical chronic graft-versus-host disease (cGVHD); however, their temporal association with GVHD, management, and impact on overall outcome are not well established. We report a retrospective analysis of 38 patients who developed LPE from a cohort of 1265 (3.00%) patients age ≥18 years who underwent allogeneic hematopoietic cell transplantation (alloHCT) at Mayo Clinic between March 1993 and August 2020. The median patient age at the time of LPE was 54 years (interquartile range [IQR], 44 to 58 years), and 8 of the 38 patients (21%) had previous cardiomyopathy. The median time from alloHCT to detection of LPE was 197 days (IQR, 40 to 378 days). Overall, the incidence of grade II (15 of 38; 40%) and grade III-IV (9 of 38; 24%) acute GVHD (aGVHD) was higher in patients who developed LPE compared with those who did not develop LPE (P = .005). The incidence rates of moderate (10 of 38; 26%) and severe (15 of 38; 40%) cGVHD according to the 2014 National Institutes of Health cGVHD criteria were also higher in the LPE cohort (P = .03). Twenty-nine patients (76%) presented with cardiac tamponade, 32 patients (84%) underwent urgent pericardiocentesis for symptomatic LPE, and 2 patients had a pericardial window placement. Four patients were medically managed with colchicine, steroids, diuresis, and immunosuppressive therapy (IST). On multivariable analysis, HCT Comorbidity Index (HCT-CI) group (hazard ratio [HR] 3.57; [95% confidence interval (CI), 1.29 to 9.85; P = .014] for HCT-CI 1 to 2; 4.06 [95% CI, 1.50 to 10.99; P = .006] for HCT-CI ≥3) and aGVHD (HR, 2.38 [95% CI, 1.11 to 5.12; P = .026] for grade II and 2.82 [95% CI, 1.07 to 7.44; P = .038] for grade III-IV) were significant risk factors for developing LPE. At a median follow-up of 40 months post-alloHCT, median disease-free survival (DFS) was 34.2 months (95% CI, 25.3 to 45.7 months) in patients who did not develop LPE and 32.2 months (95% CI, 13.2 to undefined upper limit) in those who developed LPE (P = .41). The median overall survival (OS) post-alloHCT was 50.9 months (95% CI, 41.8 to 64.8 months) in patients who did not develop LPE and was 32.9 months (95% CI, 19.5 to undefined upper limit) in patients who developed LPE (P = .003). In summary, LPE and tamponade can present at various time points post-alloHCT, and management includes pericardiocentesis, steroids, and intensification/initiation of IST if associated with serositis. LPE does not appear to result in permanent cardiac damage but results in inferior OS., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model., Methods: The antinociceptive effects of various lysionotin doses (50, 100, 150, and 200 μg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively., Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 μg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% at 200 μg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw licking test. Naloxone significantly reverses the effect of lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 μg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system., Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2023 The Authors.)

Before the advent of tyrosine kinase inhibitors (TKI) the outcome of Philadelphia chromosome positive (Ph + ) acute lymphoblastic leukemia (ALL) was dismal. The TKI combination with induction regimens has greatly improved the long-term outcome of Ph + ALL, specifically ponatinib a most potent TKI in combination with HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) chemotherapy has demonstrated 5 years overall survival up to 75%. Historically, allogeneic hematopoietic stem cell transplantation (allo-HSCT) used to be the only potential curative option, recent data suggest that patients who achieve complete molecular remission within 3 months of TKI based induction therapies can achieve comparable overall survival with or without allo-HSCT. Intensive cytotoxic chemotherapy may not be the desirable treatment option in elderly Ph + ALL patients due to anticipated tolerance, recently in a phase II study, "chemotherapy free" combinations such as blinatumomab (bispecific anti-CD3 and anti-CD19 monoclonal antibody) with ponatinib in treatment naïve Ph + ALL patients have shown a complete response rate of 95% and 2 years overall survival of 93%. In this review we have highlighted the evolving treatment landscape of Ph + ALL and what to look for in future., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a cardiovascular disease with high mortality rate. Current guidelines propose initiation and escalation of PAH-targeted treatment based on a goal-directed approach targeting hemodynamic, functional, and biochemical variables. This approach has been successfully validated in large Caucasian cohorts. However, given the low number of Hispanic patients enrolled in large PAH trials and registries, it is unknown if the same prognostic tools can be applied to this patient population. We analyzed a single-center outpatient cohort that consisted of 135 Hispanic patients diagnosed with PAH. Baseline characteristics were calculated based on COMPERA, COMPERA 2.0 and REVEAL 2.0 risk scores before the initiation of PAH-targeted therapies. The survival rate at 1 year after diagnosis was 88% for the entire cohort. The three established risk scores to predict PAH outcomes yielded similar results with reasonable discrimination of mortality in the different risk strata (all p  < 0.001). Hispanic patients with PAH have a high mortality rate. Our analysis suggests that guideline proposed risk assessment at baseline yields important prognostic information in this patient population., Competing Interests: Sandeep Sahay declare he is an advisor for Janssen, Bayer, United Therapeutics, Gossamer Bio, Altavant sciences, MERCK; Speaker United Therapeutics, Janssen; Steering committee member for Bayer and Liquidia technologies; Clinical Trial support from Bayer, Janssen, United Therapeutics, Gossamer Bio, Altavant Sciences, Keros; Received Research Grant from United Therapeutics. The remaining authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)