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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

Purpose/objective(s): The COVID-19 pandemic has direct and indirect impact on patients with cancer. Low- and middle-income regions, especially sub-Saharan Africa, are especially vulnerable to a negative impact on cancer resources and outcomes. We report the initial indirect impact of COVID-19 on cancer care in the sub-Saharan Africa region approximately 14 months into the pandemic.Materials/methods: At the start of the pandemic, we created a consortium of African and North American cancer centers and NGOs for the distribution of factual and timely information and data on COVID-19 and cancer care. A survey was distributed to consortium members and other colleagues from the sub-Saharan Africa region to understand the impact of COVID-19 in cancer care resources. Survey respondents represent cancer experts from 8 centers in Ghana, Nigeria, Kenya, Ethiopia, South Africa, Rwanda, and Zimbabwe.Results: All sites report SARS-COv-2 transmission amongst cancer patients and staff. A total of 48 staff developed COVID-19 infection with one site reporting a single death. Additionally, 62.5% of sites report loss of oncology physician or nursing staff due to redeployment for COVID-19 care resulting in minimal (20%), moderate (60%), or other (20%) impact on cancer care. All 8 sites report a government mandated lockdown with a median duration of 2.3 months (IQR .9-4.2 months). Impact of the lockdown on cancer care was reported as none (12.5%), minimal (12.5%), moderate (50%) and severe (25%). Additionally, we surveyed the impact of COVID-19 on resources in radiation, medical and surgical oncology services. A total of 25% of responders reported decreases in radiation resources while 37.5% reported changes in medical and surgical oncology resources. For radiation oncology, the most common impact was access to CT imaging for 3D-conformal planning (25%), access to brachytherapy (12.5%), and medical physics support (12.5%). For medical oncology, the most frequent impact was access to chemotherapy (37.5%) and blood products (12.5%), and loss of oncology ward space (12.5%). The most frequent impact for surgical oncology was access to operating rooms (37.5%), ventilators (12.5%), anesthesia (25%), blood products (25%), and other supply chain issues (25%). Of centers who reported impact on cancer care, severity of impact was none (50%) and moderate (50%) for radiation oncology; mild (25%) and moderate (75%) for medical oncology; and moderate (75%) and severe (25%) for surgical oncology.Conclusion: Our survey identified diffuse impact of COVID-19 on all facets of cancer care across sub-Saharan Africa. Based on physician assessment of impact, the discipline of surgical oncology may be impacted the greatest. Additional studies measuring the impact of COVID-19 on cancer outcomes are ongoing. [ABSTRACT FROM AUTHOR]

Two-hundred pregnancies involving 100 women with essential thrombocythemia (ET) were accessed from Mayo Clinic databases (1990-2023). Median platelet count displayed a decline during pregnancy, nadiring at 48% of baseline, in the third trimester: 704-369 × 10 9 /L. Live birth rate was 72%. Of 53 (27%) unintentional pregnancy losses, 48 (24%) occurred in the first trimester. Other fetal complications included preterm birth 3%, intrauterine growth retardation 3%, and stillbirth 1%. Maternal complications included major hemorrhage (7%), preeclampsia (6%), thrombosis (1%), and placental abruption (0.5%). Antepartum management included no specific therapy in 52 (26%), aspirin alone in 112 (56%), aspirin combined with cytoreductive drugs or systemic anticoagulants in 23 (12%), and other permutations in the remaining. Postpartum systemic anticoagulation was documented in 29 (15%) pregnancies. Unintentional first-trimester loss was predicted by prior fetal loss (43% vs. 18%; p < .01), diabetes mellitus (DM; 67% vs. 23%; p = .02), and absence of aspirin therapy (45% vs. 14%; p < .01); the salutary effect of aspirin therapy was independent of the other two risk factors and apparent in both high (presence of ≥1 risk factor; 33% vs. 61%; p = .07) and low (absence of both risk factors; 10% vs. 34%; p < .01) risk scenarios. The benefit of aspirin therapy, in preventing first-trimester loss, was significant in both JAK2-mutated (18% vs. 50%; p < .01) and CALR-mutated (8% vs. 43%; p < .01) cases. Aspirin use was also associated with a lower risk of venous thrombosis (0% vs. 3%; p = .03). By contrast, the use of systemic anticoagulation, antepartum or postpartum, did not influence fetal or maternal complication rates. CALR mutation and DM predicted maternal hemorrhage (13% vs. 4%; p = .05) and preeclampsia (33% vs. 5%; p = .03), respectively. The current study demonstrates the protective role of aspirin in preventing first-trimester loss in ET, independent of driver mutation status or other risk factors., (© 2024 Wiley Periodicals LLC.)

The BCL6-corepressor (BCOR) is a tumor-suppressor gene located on the short arm of chromosome X. Data are limited regarding factors predicting survival in BCOR-mutated (mBCOR) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We evaluated 138 patients with mBCOR myeloid disorders, of which 36 (26.1%) had AML and 63 (45.6%) had MDS. Sixty-six (47.8%) patients had a normal karyotype while 18 (13%) patients had complex karyotype. BCOR-mutated MDS/AML were highly associated with RUNX1 and U2AF1 co-mutations. In contrast, TP53 mutation was infrequently seen with mBCOR MDS. Patients with an isolated BCOR mutation had similar survival compared to those with high-risk co-mutations by European LeukemiaNet (ELN) 2022 criteria (median OS 1.16 vs. 1.27 years, P=0.46). Complex karyotype adversely impacted survival among mBCOR AML/MDS (HR 4.12, P<0.001), while allogeneic stem cell transplant (alloSCT) improved survival (HR 0.38, P=0.04). However, RUNX1 co-mutation was associated with an increased risk of post-alloSCT relapse (HR 88.0, P=0.02), whereas melphalan-based conditioning was associated with a decreased relapse risk (HR 0.02, P=0.01). We conclude that mBCOR is a high-risk feature across MDS/AML, and that alloSCT improves survival in this population.

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.)

The World Health Organization (WHO) classification system categorizes advanced systemic mastocytosis (SM-Adv) into aggressive SM (ASM), mast cell leukemia (MCL), and SM with associated hematological neoplasm (SM-AHN). By contrast, the International Consensus Classification (ICC) requires "immature" MC cytomorphology for the diagnosis of MCL and limits SM-AHN to myeloid neoplasms (SM-AMN). The current study includes 329 patients with SM-Adv (median age 65 years, range 18-88; males 58%): WHO subcategories SM-AHN (N = 212; 64%), ASM (N = 99; 30%), and MCL (N = 18; 6%); ICC subcategories SM-AMN (N = 190; 64%), ASM (N = 99; 33%), and MCL (N = 9; 3%); WHO-defined MCL with "mature" MC cytomorphology and SM-AHN associated with lymphoid neoplasms were operationally labeled as "MCL-mature" (N = 9) and SM-ALN (N = 22), respectively, and distinguished from ICC-defined MCL and SM-AMN. Multivariable analysis that included the Mayo alliance risk factors for survival in SM (age >60 years, anemia, thrombocytopenia, increased alkaline phosphatase) revealed more accurate survival prediction with the ICC versus WHO classification order: (i) survival was significantly worse with MCL-immature versus MCL-mature (hazard ratio [HR] 15; p < .01), (ii) prognostic distinction between MCL and SM-AHN/AMN was confirmed in the context of ICC (HR 9.3; p < .01) but not WHO classification order (p = .99), (iii) survival was similar between MCL-mature and SM-AMN (p = .18), and (iv) SM-AMN (HR 1.7; p < .01) but not SM-ALN (p = .37) was prognostically distinct from ASM. The current study provides evidence for the independent prognostic contribution of both the ICC system for SM-Adv and the Mayo alliance risk factors for survival in SM., (© 2023 Wiley Periodicals LLC.)

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by somatic mutations in UBA1 (UBA1mut) and characterized by heterogenous systemic autoinflammation and progressive hematologic manifestations, meeting criteria for myelodysplastic syndrome (MDS) and plasma cell dyscrasias. The landscape of myeloid-related gene mutations leading to typical clonal hematopoiesis (CH) in these patients is unknown. Retrospectively, we screened 80 patients with VEXAS for CH in their peripheral blood (PB) and correlated the findings with clinical outcomes in 77 of them. UBA1mut were most common at hot spot p.M41 (median variant allele frequency [VAF] = 75%). Typical CH mutations cooccurred with UBA1mut in 60% of patients, mostly in DNMT3A and TET2, and were not associated with inflammatory or hematologic manifestations. In prospective single-cell proteogenomic sequencing (scDNA), UBA1mut was the dominant clone, present mostly in branched clonal trajectories. Based on integrated bulk and scDNA analyses, clonality in VEXAS followed 2 major patterns: with either typical CH preceding UBA1mut selection in a clone (pattern 1) or occurring as an UBA1mut subclone or in independent clones (pattern 2). VAF in the PB differed markedly between DNMT3A and TET2 clones (median VAF of 25% vs 1%). DNMT3A and TET2 clones associated with hierarchies representing patterns 1 and 2, respectively. Overall survival for all patients was 60% at 10 years. Transfusion-dependent anemia, moderate thrombocytopenia, and typical CH mutations, each correlated with poor outcome. In VEXAS, UBA1mut cells are the primary cause of systemic inflammation and marrow failure, being a new molecularly defined somatic entity associated with MDS. VEXAS-associated MDS is distinct from classical MDS in its presentation and clinical course.

Acute myeloid leukemia (AML) is a challenging cancer in terms of achieving and maintaining long-duration remissions. Many novel therapies have been added to the standard regimen (combining cytarabine and anthracycline "7 + 3") to achieve such goals. Nilotinib is an oral multikinase inhibitor that is active against KIT tyrosine kinase, an important stem cell target. In this trial, we combined nilotinib with 7 + 3 induction (daunorubicin 60 mg/m2), high-dose cytarabine consolidation, and subsequently, if the patient was a candidate, for 2 years' maintenance therapy in patients with AML and KIT (CD117) expression. Patients were allowed to proceed to allogeneic hematopoietic cell transplantation (HCT) if deemed necessary. Our primary goal was increased complete remission rate with this combination. Thirty-four patients (with a median age 58.5 years) were enrolled on a single-arm phase II bi-institutional study; 21 (62%) patients achieved remission. The complete remission rate was 78% in evaluable patients. Thirteen of 34 (38%) patients had allogeneic HCT, all thirteen of which are still alive (100%). Common (>20%) grade 3 non-hematological toxicities included febrile neutropenia, hypophosphatemia, elevated liver enzymes, and hypertension. Only one patient (3%) died in induction due to liver failure, which was thought secondary to daunorubicin. Our current study reveals good outcomes in patients who received HCT and may warrant a larger study to confirm our findings in that specific population., (© 2023 Wiley Periodicals LLC.)