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Annals of Hematology Jun 2024Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies....
Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.
PubMed: 38907072
DOI: 10.1007/s00277-024-05847-0 -
Indian Journal of Pathology &... Jun 2024Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct...
BACKGROUND
Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm.
MATERIALS AND METHODS
This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details.
RESULTS
These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate.
CONCLUSION
Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.
PubMed: 38904435
DOI: 10.4103/ijpm.ijpm_474_23 -
Haematologica Jun 2024The recent progress with ruxolitinib treatment might improve quality-of-life as well as overall survival in patients with primary myelofibrosis (PMF). Therefore, the...
The recent progress with ruxolitinib treatment might improve quality-of-life as well as overall survival in patients with primary myelofibrosis (PMF). Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) remains to be elucidated in the ruxolitinib era. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with PMF, and compared outcomes between immediate HCT and delayed HCT after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged < 60 and ≥ 60 separately in subgroup analyses. The expected life years was consistently longer in delayed HCT after ruxolitinib failure regardless of patient age. Regarding quality-adjusted life years (QALYs), a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 versus 2.26). In patients aged < 60, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 versus 2.31). On the other hand, in patients aged ≥ 60, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 versus 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for QALYs, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥ 60, and is also a promising strategy even in those aged < 60.
PubMed: 38899343
DOI: 10.3324/haematol.2024.285256 -
Journal of Clinical Medicine Jun 2024Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the...
Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.
Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. We translated the MPN-10 and tested its psychometric properties. We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss ( < 0.001), fatigue ( = 0.006), early satiety ( = 0.007), night sweats ( = 0.047), pruritus ( = 0.05), and TSS ( = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant ( < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.
PubMed: 38892995
DOI: 10.3390/jcm13113284 -
Virchows Archiv : An International... Jun 2024Herein is reported a series of five patients with myeloid neoplasms presenting hepatic complications in whose liver biopsy revealed obstruction of sinusoids by platelet...
Herein is reported a series of five patients with myeloid neoplasms presenting hepatic complications in whose liver biopsy revealed obstruction of sinusoids by platelet aggregates associated to liver extramedullary haematopoiesis. Indication of liver biopsies was jaundice, unexplained hepatomegaly or portal hypertension. Haematological disorders were classified according to the World Health Organisation. Molecular profile was established in all cases as well as grade of liver extramedullary haematopoiesis and myelofibrosis. The patients were four men and one woman aged from 50 to 82 years. Two patients had myeloproliferative neoplasm (triple negative primary myelofibrosis and JAK2-mutated essential thrombocytopenia), two patients had unclassifiable myelodysplastic/myeloproliferative neoplasm and one patient had chronic myelomonocytic leukaemia type 1. Liver biopsies revealed platelet aggregates occluding sinusoids in association with extramedullary haematopoiesis grade 1 in one patient, grade 2 in two patients and grade 3 in two patients. Two of these patients presented co-existing liver fibrosis due to chronic alcoholic consumption and ischemic heart failure. These five patients died from 2 to 23 months after liver biopsy due to acute myeloblastic leukaemia (three patients), portal hypertension (one patient) or other causes (acute heart failure). Intrahepatic sinusoidal microthromboses through platelet aggregates might cause portal hypertension or liver deficiency in patients with myeloid neoplasms, independently of JAK2 mutational status and grade of extramedullary haematopoiesis.
PubMed: 38877359
DOI: 10.1007/s00428-024-03844-2 -
Annals of Hematology Jun 2024We evaluated RDW in a single-center series of 61 consecutive patients with primary and secondary MF at diagnosis and during treatment with ruxolitinib (RUX) and examined...
We evaluated RDW in a single-center series of 61 consecutive patients with primary and secondary MF at diagnosis and during treatment with ruxolitinib (RUX) and examined any possible prognostic impact. Elevated RDW values were present in all but 4 patients at diagnosis with a median RDW of 18.9%. RDW was higher in subjects with palpable splenomegaly (p = 0.02), higher ferritin, as well as among those cases who did not receive any cytoreduction before RUX (p = 0.04). Interestingly, higher RDW at diagnosis also correlated with a shorter time from MF diagnosis to RUX start (-4.1 months per one RDW unit; p = 0.03). We observed a modest increase (< 1%) in RDW during the first 6 months of RUX treatment. In a multivariable random-intercept model that considered all time points and contained the covariates time and RUX dose, we also observed a clear decrease in RDW with increasing hemoglobin (Hb) during RUX (slope: -0.4% per g/dL of Hb; p < 0.001). The median RDW at diagnosis of 18.9% was used as a cut-off to identify two subgroups of patients [Group 1: RDW 19.0-25.7%; Group 2: RDW 13.1-18.7%], showing a difference in mortality [Group 1 vs. 2: crude HR 2.88; p = 0.01]. Using continuous RDW at diagnosis, the crude HR was 1.21 per RDW unit (p = 0.002). In a Cox model adjusted for gender, age and Hb at diagnosis, the HR was 1.13 per RDW unit (p = 0.07). RDW may have prognostic significance at MF diagnosis and during RUX, helping in the rapid detection of patients with poor prognosis.
PubMed: 38864904
DOI: 10.1007/s00277-024-05801-0 -
British Journal of Haematology Jun 2024Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are... (Review)
Review
Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are comprised of polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Historically, the majority of MPNs are diagnosed in adults older than 60 years of age; however, in recent years, there has been recognition of MPNs in the adolescent and young adult (AYA) population. AYAs with MPN, typically defined as between the ages of 15 and 39 years old, may comprise up to 20% of patients diagnosed with MPN. They demonstrate unique patterns of driver mutations and thrombotic events and remain at risk for progression to more aggressive disease states. Given the likely long length of time they will live with their disease, there is a significant unmet need in identifying well-tolerated and effective treatment options for these patients, particularly with the advent of disease modification. In this review, we provide a comprehensive overview of the clinical features, disease course and management of AYA patients with MPN and, in doing so, highlight key characteristics that distinguish them from their older counterparts.
PubMed: 38853641
DOI: 10.1111/bjh.19557 -
Bulletin Du Cancer Jun 2024
PubMed: 38839535
DOI: 10.1016/j.bulcan.2024.04.010 -
Leukemia & Lymphoma Jun 2024The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet...
The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 10/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population ( = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 ( = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.
PubMed: 38838026
DOI: 10.1080/10428194.2024.2346733 -
[Rinsho Ketsueki] the Japanese Journal... 2024Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and...
Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Some of these agents not only achieve hematologic complete response, reduce spleen size, and alleviate constitutional symptoms, but also induce molecular response, which means that they reduce the allele burden of driver gene mutations. These agents also prevent and alleviate fibrosis in bone marrow, which reduces the incidence of thrombotic events and disease progression and might improve prognosis. This article discusses the latest findings and promising treatments, including ongoing clinical trials, in PV, ET, and PMF.
Topics: Humans; Myeloproliferative Disorders; Mutation; Molecular Targeted Therapy
PubMed: 38825516
DOI: 10.11406/rinketsu.65.375