Diagnostic and clinical value of biomarkers and ferritinemia in Gaucher disease

Gaucher disease is a progressive, multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase (GBA), arising from autosomal recessive mutations in the GBA1 gene (1q21). There are several biomarkers used in Gaucher disease (i.e., chitotriosidase, CCL18/PARC, tartrate resistant acid phosphatase, angiotensin-converting enzyme), however, all of them have some disadvantages. It is believed that none of these biomarkers has a significant correlation with the clinical severity of Gaucher disease. A high proportion of patients with type 1 Gaucher disease present with hyperferritinemia, however, the pathophysiology of the high ferritin serum levels in Gaucher disease has not yet been elucidated and different mechanisms are possible. This review presents a current knowledge on biomarkers useful for diagnostic and monitoring of Gaucher disease with a focus on ferritinemia

Marketing mix conception (4P, 5P, 7P)

The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool

Długotrwała pancytopenia po chemioterapii jako objaw demaskujący chorobę Gauchera u pacjentki z rakiem płuca

The diagnosis of congenital metabolic disease can be very difficult and often extends in time. This applies particularly to metabolic diseases of milder phenotype, such as an adult form (type 1) of Gaucher disease caused by the inherited (autosomal recessive) deficiency of the lysosomal enzyme glucocerebrosidase.In this work, we present a case of 48-year-old Polish patient (living in Sweden) with lung cancer, who developed a prolonged pancytopenia complicated by sepsis after each cycle of chemotherapy. These symptoms led to initiation of hematological diagnostic work-up and the assumption that the complications are caused by Gaucher disease. Definitive diagnosis of Gaucher disease was confirmed by results of enzymatic analyses, which revealed reduced activity of glucocerebrosidase in peripheral blood lymphocytes to 0.44μkat/kg protein (ref.: 2.1–3.8), increased activity of plasma chitotriosidase to 1241nkat/L (ref.: G (N370S), confirming diagnosis of type 1 Gaucher disease in the patient. The presence of the mutation c.604C>T has never been previously reported in a Polish patient with Gaucher disease. Administration of enzyme replacement therapy with imiglucerase (Cerezyme™) led to a rapid improvement of peripheral blood counts and enabled further continuation of intensive chemotherapy for lung cancer.In conclusion, the authors would like to emphasize that knowledge of the symptoms and the principles of diagnosis of Gaucher disease among hematologists is very important for efficient diagnostics of patients affected by this rare disease

"Randomized phase II study of azacitidine +/- lenalidomide in higher-risk myelodysplastic syndromes and acute myeloid leukemia with a karyotype including Del(5q)"

Non peer reviewe

Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation

The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool

Recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 Gaucher disease

Background. The clinical presentation of Gaucher disease (GD), an inherited lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase, is highly variable, and three clinical types are distinguished based upon the presence of neurologic symptoms. Thrombocytopenia, anemia, hepatosplenomegaly, and bone manifestations are the most typical signs of GD type 1 (GD1). Case presentation. We present the case of an unsplenectomized man suffering from heterozygous GD1 with mutations of c.1226A>G (N370S) and RecNci I (L444P, A456P, and V460V) in the GBA1 gene, who developed recurrent pulmonary aspergillosis caused by Aspergillus fumigatus and a mycobacterial infection caused by Mycobacterium avium. Despite long-lasting therapy of both aspergillosis (including antifungal drugs and surgery), and the mycobacterial infection (triple therapy with rifampicin, ethambutol, and clarithromycin), recurrent positivity for M. avium and A. fumigatus was detected. Conclusions. Symptomatic lung involvement and an increased susceptibility to pulmonary infections are uncommon inGDand, if present, are often associated with more severe disease manifestations. To our knowledge, this is the first published report on the association of GD and pulmonary aspergillosis and mycobacterial infection. It illustrates the increased susceptibility of untreated GD patients to opportunistic pulmonary infections and ineffective eradication of these infections despite adequate therapy

The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting

In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .0015]; NPM1mut: female, 36%; male, 27% [P = .0001]), and more males were double negative (female, 53%; male, 64%; P < .0001). Patients with FLT3ITD were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1mut (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3ITD indicated poor survival in younger patients (<60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1mut indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3ITD/NPM1mut patients, the survival was less dependent on age than in the other molecular subsets. These findings are likely to have clinical relevance for risk grouping, study design, and choice of therapy

Acute myeloid leukemia in very old patients

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