Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.

Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.

Systemic Mastocytosis in a Patient with BCR-ABL1-Positive Chronic Myeloid Leukemia in the Remission Phase.

Systemic mastocytosis (SM) comprises a group of rare disorders resulting from tissue infiltration by pathological mast cells. In a percentage ranging from 5 to 40% in various patient series, SM appears to be associated with an accompanying hematologic neoplasm (SM-AHN). The coexistence of SM with chronic myelogenous leukemia (CML) is extremely rare with only 3 cases in the literature. The natural course of CML has changed dramatically over the past 2 decades with the use of tyrosine kinase inhibitors (TKIs). We report a case of diagnosing SM in a patient in complete molecular remission of CML after stopping TKI treatment.

Generalized Bullous Fixed Drug Eruption to Fluconazole with Positive Patch Testing and Confirmed Tolerance to Itraconazole.

Generalized bullous fixed drug eruption (GBFDE) is a specific variant of fixed drug eruption that belongs to severe cutaneous adverse reactions (SCARs) and its diagnosis is based mainly on clinical course and especially on the reoccurrence of typical bullous lesions in previous and new sites after re-administration of the offending drug. We present a well-documented case of fluconazole-induced GBFDE, with a positive patch test to fluconazole (30% weight/volume preparation) and clinical tolerance to itraconazole proven by negative oral provocation. Even in SCARs, patch testing represents a useful diagnostic tool, while oral provocation remains the gold standard in cases that an alternative but the chemically relevant drug must be administered.

The effect of laparoscopic sleeve gastrectomy on quality of life: A prospective cohort study with 5-years follow-up.

BACKGROUND: Obesity has a negative effect on quality of life (QoL). Bariatric surgery results in significant weight loss with improvement of QoL. Very few studies have evaluated QoL after sleeve gastrectomy (SG), especially with a long-term follow-up. OBJECTIVES: To assess long-term longitudinal changes of QoL of a laparoscopic SG cohort, with the obesity specific Moorehead-Ardelt II questionnaire (MAII) and to identify parameters associated with QoL outcome. SETTING: Bariatric Unit, University Hospital of Heraklion, Greece. METHODS: Morbidly obese patients admitted for laparoscopic SG over a 30-month period were prospectively studied. QoL was assessed using the Greek version of the MAII questionnaire and a visual analog scale preoperatively and at 6, 12, 24, and 60 months postoperatively. Anthropometric data and obesity-related co-morbidities were recorded. RESULTS: A total of 95 patients with mean age of 37.4 ± 9.2 years and body mass index of 48.3 ± 7.1 kg/m2 completed the 5-year follow-up. Percentage excess body mass index loss was 51.7 ± 14.2, 64.8 ± 16.9, 67.4 ± 17.7, and 55.8 ± 25.5 at 6, 12, 24, and 60 months, respectively. All obesity-related co-morbidities improved significantly. MAII score increased from -.38 ± 1.3 preoperatively to 1.77 ± .8, 2.08 ± 0.8, 2.12 ± .7, and 1.67 ± 1.1 at the above time points, respectively (trend P < .001), and visual analog scale increased from 3.05 ± 1.6 to 9.11 ± 1.0, 9.2 ± 1.1, 9.03 ± 1.3, and 7.85 ± 2.4 (P < .001). Overall QoL scores at 6 and 24 months (P < .001), as well as patients' female sex, correlated significantly with higher QoL at the end of the study. CONCLUSIONS: Laparoscopic SG is an effective bariatric operation, resulting in significant weight loss and improvements in QoL. Female sex and higher MAII score at 6 and 24 months predict better long-term QoL outcome.

Zellweger syndrome and secondary mitochondrial myopathy.

Defects in peroxisomes such as those associated with Zellweger syndrome (ZS) can influence diverse intracellular metabolic pathways, including mitochondrial functioning. We report on an 8-month-old female infant and a 6-month-old female infant with typical clinical, radiological and laboratory features of Zellweger syndrome; light microscopic and ultrastructural evidence of mitochondrial pathology in their muscle biopsies; and homozygous pathogenic mutations of the PEX16 gene (c.460 + 5G > A) and the PEX 12 gene (c.888_889 del p.Leu297Thrfs*12), respectively. Additionally, mitochondrial respiratory chain enzymology analysis in the first girl showed a mildly low activity in complexes II-III and IV. We also review five children previously reported in the literature with a presumptive diagnosis of ZS and additional mitochondrial findings in their muscle biopsies. In conclusion, this is the first study of patients with a molecularly confirmed peroxisomal disorder with features of a concomitant mitochondrial myopathy and underscores the role of secondary mitochondrial dysfunction in Zellweger syndrome, potentially contributing to the clinical phenotype.