Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial.

In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment.

Risk of Falls in Patients Aged Over 65 in the Context of the Treatment Facility.

This study assessed the risk of falls, the incidence of frailty, cognition, and nutritional status in people aged over 65 in the context of the treatment facility. To this end, we compared a group of 99 non-hospitalized patients treated in primary healthcare facilities with a group of 100 patients hospitalized in a geriatric ward. It was a survey-type study based on the following questionnaires: Mini-Mental State Examination, Tilburg Frailty Indicator, Mini Nutritional Assessment, and the Tinetti Balance and Gait Assessment. We found significant differences between non-hospitalized and hospitalized patients to the advantage of the former. A risk of falls was 56.6% vs. 85% (p < 0.001), the incidence of frailty was 51% vs. 71% (p = 0.005), and cognitive decline was 35% vs. 61% (p = 0.120), respectively. Additionally, nutritional detriment also was less expressed in outpatients. A distinctly worse overall health performance, with increased risk of falls, was confirmed in multifactorial regression analysis in hospitalized patients. We conclude that geriatric hospital setting is an independent risk factor aggravating the risk of falls, frailty, and cognitive weakness in senior persons.

[A rare case of plasmocytoma of uvulae and carcinoma of larynx]. / Rzadki przypadek szpiczaka plazmocytowego jezyczka i raka krtani.

Plasmocytoma solitare is a rare disease of lymphoprolipherative origin. It is usually diagnosed occasionally on ORL departaments because of its close relation to head and neck localisation. Surgical treatment and/or radiotherapy is a treatment of choice. It becomes disseminated after years usually. Carcinoma of larynx is a squamos cell carcinoma of well known ethiology strongly corralated with alcohol and nicotin abuse. There is described a case of patient in this paper, who in a short time of few months developed two neoplasms of different histological origin, but localised in the same region of head and neck: Plasmocytoma solitary of uvulae and carcinoma of larynx. Due to early diagnoses the radical treatment (combined surgery and radiotherapy) was performed. However the extremly short time of follow up do not allow to make the observation of the DFS and OS of the patient.

A de novo splice donor mutation in the thrombopoietin gene causes hereditary thrombocythemia in a Polish family.

BACKGROUND: Hereditary thrombocythemia is an autosomal dominant disorder with clinical features resembling sporadic essential thrombocythemia. Germline mutations in families with hereditary thrombocythemia have been identified in the gene for thrombopoietin (TPHO) and its receptor, MPL. DESIGN AND METHODS: Here we characterized a THPO mutation in a hereditary thrombocythemia pedigree with 11 affected family members. RESULTS: Affected family members carry a G --> C transversion in the splice donor of intron 3 of THPO that co-segregated with thrombocytosis within the pedigree. We previously described the identical mutation in a Dutch family with hereditary thrombocythemia. Haplotype analysis using single nucleotide polymorphisms surrounding the mutation indicated that the mutations arose independently in the two families. MPL protein levels, but not mRNA levels, were low in platelets from affected family members. Bone marrow histology showed features compatible with those of essential thrombocythemia, but the megakaryocytes were unusually compact, as assessed by planimetric analysis. Impaired microcirculation resulting in brief episodes of fainting and dizziness that responded well to aspirin were the predominant clinical features in a total of 23 affected family members studied. Disease onset is earlier in patients with hereditary thrombocythemia than in those with essential thrombocythemia, but the frequencies of thrombotic, vascular and hemorrhagic events are similar in the two groups. CONCLUSIONS: A mutation in THPO occurred de novo in the same position as in a previously described family with hereditary thrombocythemia. Patients with this mutation have elevated serum levels of thrombopoietin and a phenotype that responds to aspirin and does not require cytoreductive treatment.

The gain-of-function JAK2 V617F mutation shifts the phenotype of essential thrombocythemia and chronic idiopathic myelofibrosis to more "erythremic" and less "thrombocythemic": a molecular, histologic, and clinical study.

We investigated the prevalence of the JAK2 V617F gain-of-function mutation in patients with Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph- MPD) and explored the links between JAK2 mutational status and the clinicopathologic picture of essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV). Allele-specific polymerase chain reaction results for 59 ET, 18 CIMF, and 9 PV cases were compared with values for clinical variables at presentation and last follow-up and with the diagnostic trephine bone marrow biopsy pictures. JAK2 V617F was found in 38 (64%) of ET cases, 7 (39%) of CIMF cases, and 9 (100%) of PV cases. The ET patients with the mutant JAK2 showed significantly higher (although not overtly polycythemic) red blood cell parameter values, lower platelet counts, and higher white blood cell counts. Similar trends were found in CIMF. Megakaryocyte clustering was much less pronounced in the CIMF cases with mutant JAK2, with an analogous trend occurring in the ET cases. Bone marrow cellularity values and the numbers of CD34+ and CD117+ blasts in the ET and CIMF groups did not differ. Fibrosis was slightly less marked in the ET cases with mutant JAK2. The mutation did not significantly influence the clinical course during the follow-up in either disease in the short term (median follow-up, 22 months). The JAK2 V617F mutation is prevalent in all Ph- MPD and may skew their presenting phenotype, including bone marrow histology, toward a more "erythremic" and less "thrombocythemic" phenotype.

[Malignant lymphomas as a diagnostic problem in otolaryngology]. / Chloniaki zlosliwe jako problem diagnostyczny w otolaryngologii.

The authors presented the problems of etiology, pathophysiology and diagnosis of malignant lymphomas within head and neck due to own clinical material.