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ABSTRACT Background The emergence of JAK2‐mutated myeloproliferative neoplasms (MPNs) after remission from acute myeloid leukaemia (AML) is exceedingly rare. Case Description This case series describes two patients who developed JAK2‐mutated MPNs years after achieving AML remission, each retaining persistent TET2 and SRSF2 mutations while losing AML‐defining mutations. Pathogenetic Insight Findings support clonal persistence from a shared haematopoietic progenitor with divergent progression into distinct myeloid neoplasms. A two‐pathway model is proposed to explain this trajectory. Implications These observations highlight the biological relevance of CHIP‐associated mutations and underscore the value of post‐remission molecular surveillance to detect emerging secondary neoplasms in AML survivors. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

INTRODUCTION Myeloproliferative neoplasms (MPNs) are a group of rare clonal disorders of hematopoietic progenitor cells that are associated with morbidity from disease-related symptoms, thrombotic events, and risk of transformation to acute myeloid leukemia (AML) [ 1]. Investigations for other malignancies including multiple myeloma were normal. 18Fluorodeoxyglucose positron emission tomography (PET) scan confirmed the right femur lesion with increased metabolic activity, but found no other abnormalities. TABLE 1 Clinical cases reports for osteolytic lesion in myeloproliferative neoplasm (MPN) Articles Patient age, gender, and diagnosis History and presentation Site of osteolytic lesion Diagnostic work-up Treatment Response Outcomes Licht et al., 1973 [ 6] 40F CML to MF In 1966, incidental finding of leukocytosis and thrombocytosis, no symptoms, no splenomegaly Bone marrow biopsy confirmed CML In April 1971 developed severe bone pain, found to have left shift and leukopenia Femur, ribs, pelvis, and skull Repeat bone marrow confirmed myelofibrosis Prednisone and 6-mecaptopurine Patient admitted as condition continue to decline N/A Death: 1 month from initial finding of lytic lesion (May 1971) Rudders & Kilcoyne 1974 [ 7] 73F MPN to MF In December 1966, found to have leukocytosis and thrombocytosis Bone marrow biopsy suggestive of MPN In July 1971, presented with chest pain, anemia, and weakness, Ribs, pelvis, femur, and skull Repeat marrow showed myelofibrosis No treatment interventions N/A Death: 17 months from initial finding of osteolytic lesion (Dec 1972) Leimert et al., 1978 [ 8] 49M Post PV MF Diagnosed in 1971 with PV, treated with phlebotomies In September 1976 developed persistent knee pain and constitutional symptoms Fibula, tibias, pelvis, and lumbar spine Bone marrow biopsy revealed fibrosis in marrow Radiation therapy to knees No improvement Death: 4 months from initial finding of osteolytic lesion (Jan 1977) Kosmidis et al., 1980 [ 9] 52 F Post PV-MF In 1959 initially diagnosed with PV based on elevated blood counts In January 1976 disease progressed to MF, with symptomatic splenomegaly, anemia In February 1978 severe acute chest pain Ribs and long bone Bone biopsy of osteolytic lesion (no further details provided) confirmed extensive fibrosis Analgesics and transfusion support N/A Death: 5 months from initial finding of osteolytic lesion (July 1978) Gruber & Osby, 1987 [ 10] 64F PMF Diagnosed with PMF in November 1974 In 1979 developed back pain that progressively worsened over the years Skull, scapulae, humeri and vertebrae Bone biopsy (site not specified) confirmed hematopoietic cells Myeloma work-up negative Analgesics, busulphan, and transfusion support Temporary relief Death: 9 years 11 months from initial finding of osteolytic lesion (October 1984) Clutterback et al., 1995 [ 11] 59M PMF 33-year history of MF, stable disease Patient presented with pneumonia, weakness, and paresthesia in his left leg with flaccid paralysis of the left foot Left femur Bone biopsy of left femur revealed hematopoietic cells, no evidence of other malignancy Intramedullary nailing of the femur Recovered from the surgery and discharged Death due to septicemia after 6 months Sadoun et al., 1997 [ 12] 30M Hyper-eosinophilic syndrome transform to MF In 1989, diagnosed with hypereosinophilic syndrome, confirmed by bone marrow aspirate In July 1992 admitted with severe hypercalcemia (3.7 mmol/l), anemia, bone pain Pelvis Repeat bone marrow biopsy confirmed transformation to MF cytogenetics remained normal Oct 1992 underwent bone marrow transplant 12-month post-transplant repeat pelvic x-ray showed resolution of osteolytic lesion Alive at last follow-up Sideris et al., 2006 [ 13] 72M Post PV MF Presented to hospital with low back pain and anemia Rib, sternum, vertebra, pelvis and calcaneus Bone biopsy (vertebrae) most aligned with MPN, N/A N/A Death: 11 months after progression to AML Jurisic et al., 2008 [ 14] 49F PMF to AML In 1991 presented with abdominal pain, splenomegaly, anemia, and general malaise Bone marrow biopsy confirmed diagnosis of PMF Condition continued to deteriorate and developed bone pain. Pelvis and long bones Multiple myeloma work-up negative Bone marrow biopsy showed 72% blast indicating transformation to AML Cytosine-arabinoside, did not achieve remission Subsequently treated with hydroxyurea did not achieve remission Did not achieve remission Alive at last follow-up Transfusion support Merry & Aronowitz. 2010 [ 15] 83M PMF 7-year history of MF diagnosis, managed with transfusion support and thalidomide Worsening fatigue and weakness, leading to fall at home Left wrist, hand, and forearm N/A Cast to left arm and wrist Transfusion support N/A Death: 1 month after admission (cause unclear) Sacre et al, 2010 [ 16] 44F PMF Longstanding history of systemic lupus erythematosus In 2002, low hemoglobin and platelets.

The impact of driver and other somatic mutations on pregnancy outcomes is unknown. The purpose of this study was to report the management and outcome of pregnancies in a cohort of myeloproliferative neoplasms (MPN) patients, particularly to evaluate the impact of somatic mutations. The cohort included consecutive patients with MPN who had a least one confirmed pregnancy. The primary outcome was live births. Secondary outcomes were thrombotic and major bleeding events. Between 2010 and 2021, 29 pregnancies occurred in 24 individuals with MPN. Aspirin was used in 24 cases (83%) and interferon alfa in five (17%). There were 24 live births (83%). There were three thrombotic events, two antepartum and one postpartum. Miscarriages and thrombotic events occurred in JAK2‐mutated and triple negative, but not CALR‐mutated, MPN. Additional somatic mutations were rare, and there were no apparent associations with pregnancy loss or complications. While JAK2 V617F is associated with an increased risk of thrombosis, its impact on pregnancy outcome has been inconsistently reported. The association between triple negative MPN and adverse pregnancy outcome has not previously been reported. While limited by small numbers, this study underscores the importance of describing driver and other mutations to direct optimal antenatal care in individuals with MPN.

No new drugs have been approved for essential thrombocythemia (ET) treatment since the anagrelide approval in 1997. Ropeginterferon alfa-2b-njft (ropeg) is approved for polycythemia vera, providing a rationale for its use in ET. Its current dosing schema requires dose up-titrations with 50 mcg every 2 weeks and takes approximately 20 weeks to reach a plateau. The goal of this study is to assess the efficacy and safety of ropeg in ET using a higher initial dose and accelerated titration (HDAC) regimen. This is a single-arm, multicenter study in the US and Canada. Patients with ET receive ropeg at 250 mcg on Day 0, 350 mcg at Week 2, and 500 mcg from Week 4 onward with flexibility of dose adjustment. The primary endpoint is: platelets ≤400×10 9 /L, white blood cells <10×10 9 /L, improvement or non-progression of spleen size or major symptoms, and absence of hemorrhagic or thrombotic events, at months 10 and 13. Secondary endpoints include molecular response, safety and tolerability. A total of 91 patients were enrolled with 77 (84.6%) patients in the US and 14 (15.4%) in Canada. The last patient was enrolled on March 28, 2024. JAK2 V617F was found in 52 (57.1%) patients while CALR and MPL mutations in 34 (37.4%) and 5 (5.5%), respectively. As of November 12, 2024, the discontinuation rate was 8.8%. The study results will be available in mid-2025. This study will provide efficacy, tolerability and safety, molecular response and quality of life data that will be critical in assessing ropeg for ET treatment.

PEG‐asparaginase is used as a treatment for Philadelphia‐negative acute lymphoblastic leukemia. In pediatric studies, triglycerides (TGs) were affected more by PEG‐asparaginase than by native L‐asparaginase (10.0% vs. 5.5%). We conducted a retrospective study to determine the safety of re‐challenging adult patients with PEG‐asparaginase after experiencing an episode of severe hypertriglyceridemia (>1000 mg/dl or 11.4 mmol/L). The incidence of hypertriglyceridemia associated with PEG‐asparaginase in adult patients was high (67.5%). Therefore, checking TGs at baseline and monitoring levels while receiving PEG‐asparaginase need to be considered and studied in prospective studies. However, in patients with hypertriglyceridemia not complicated by acute pancreatitis, re‐challenging is safe once TG levels normalize.

Congenital neutropenias due to mutations in ELANE, SBDS or HAX1 or in the setting of glycogen storage disease (GSD) which is caused by SLC37A4 mutation, often require prolonged granulocyte colony stimulating factor (G‐CSF) therapy to prevent recurrent infections and hospital admission. There has been emerging evidence that prolonged exposure to G‐CSF in cases with congenital neutropenia other than GSD is associated with transformation to myelodysplastic syndrome/acute myeloid leukemia.

Current therapies for acute myeloid leukemia (AML), failing induction, are rarely effective. We report our experience in 4 patients with AML who received 16 Gy TBI prior to allogeneic hematopoietic cell transplantation (alloHCT), between June 2010 and May 2011. Patients were 20 to 55 years of age, 2 with relapsed disease and 2 with AML failing induction. An HLA-matched graft from related or unrelated donor was infused on day 0. All but one, who received a CD34+-selected graft, received methotrexate and tacrolimus +/− antithymocyte globulin, as GVHD prophylaxis. The other patient received tacrolimus alone. Neutrophil and platelet engraftment occurred at a median of 18 and 14 days, respectively. Patients were discharged at a median of 28 days. There were no unexpected toxicities in the first 30 days. One patient had cytomegalovirus (CMV) viremia and anorexia, at two months. One patient had grade 2 acute GVHD of the skin. One patient developed chronic GVHD of the eyes, mouth, skin, joints, and lung at 4 months. Two patients died from relapse of their leukemia at days 65 and 125. Two patients remain in remission beyond day 1500. 16 Gy TBI followed by an alloHCT for AML, failing induction, is feasible and tolerable.

Abstract Background and aims Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. Methods In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). Results We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13–27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06–0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. Conclusions In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. Trial registration NCT03186404. Graphical Abstract Graphical Abstract Summary of study enrollment, assessments, and outcomes. Randomized patients had cardiovascular magnetic resonance imaging (CMR) pre- and 72 (63–122) days post-anthracycline initiation / 22 (13–27) days post last dose of anthracycline. The stethoscopes and blood tubes reflect repeated clinical and biomarker assessment after every anthracycline cycle.