Cardiac functions by myocardial performance index and QT dispersion in survivors of childhood lymphoblastic leukaemia.

AIM: Childhood leukaemia treatment contains multiple chemotherapeutic agents in high doses that can cause severe toxic effects on heart and other vital organs. In this respect patients taking cancer chemotherapy are followed for these adverse effects. Echocardiographic myocardial performance index (MPI) was reported as a new method of combined systolic and diastolic function for both adults and children, calculated as isovolumic relaxation time plus isovolumic contraction time divided by ejection time. In addition, it has been postulated that increased inter-lead differences in QT interval (QT dispersion) may be associated with an increased risk of cardiac death. The aim of this study was to determine the probable immediate and late adverse effects of childhood leukaemia treatment containing moderate dose of anthracyclines on heart by MPI and corrected QT dispersion (QTcD). METHODS: MPI and QTcD in 55 children with leukaemia and 38 healthy controls matched for age and sex were evaluated. RESULTS: There was no statistically significant difference between MPI values of patients and controls (20.7+/-13.1 (1-59.4) and 16.1+/-13.5 (0.3-77.5), P: 0.1, respectively). Also, there was no significant difference in MPI and QTc values between patients taking active treatment and those who completed the therapy and between the patients given a cumulative dose of anthracycline lower and higher than 250 mg/m2. But QTcD values were found to be higher in patients than controls (0.08+/-0.03 and 0.03+/-0.01, P<0.01, respectively). CONCLUSIONS: There was no overt cardiotoxicity in our children with leukaemia treated with protocols of ALL BFM 95 and TRALL 2000 (Modified BFM in Turkey) containing moderate dose of anthracyclines. However, they can cause subclinical cardiotoxicity and further monitoring and evaluation with such sensitive and noninvasive methods over a longer period of time are needed.

Sinopulmonary aspergillosis in children with hematological malignancy.

Invasive pulmonary aspergillosis is a serious infectious complication in immunocompromised especially neutropenic patients. Despite improvements in early diagnosis and effective treatment, invasive pulmonary aspergillosis is still a devastating opportunistic infection. These infections also interfere with the anticancer treatment. We report our experience in the diagnosis and therapeutic management of sinopulmonary aspergillosis in 4 children with hematologic malignancy. All patients except the first were neutropenic when sinopulmonary aspergillosis was diagnosed. Clinical signs included fever, cough, respiratory distress, swallowing difficulty, headache, facial pain-edema and hard palate necrosis. Radiodiagnostic methods showed bilateral multiple nodular infiltrations, soft tissue densities filling all the paranasal sinuses, and bronchiectasis. Diagnosis of aspergillosis was established by bronchoalveolar lavage in one case, tissue biopsy, positive sputum and positive cytology, respectively, in the other 3 cases. One patient was treated with liposomal amphotericin B and other 3 cases were treated with liposomal amphotericin B + itraconozole. Outcome was favorable in all cases except the one who died due to respiratory failure. Early diagnosis, appropriate treatment and primary disease status are important factors on prognosis of Aspergillus infections in children with hematological malignancy.

Mutational analysis of beta-thalassemia cases from the Aegean region of Turkey using an allele-specific oligonucleotide hybridization technique.

The aim of the present study was to evaluate the point mutations of beta-thalassemia patients from the Aegean region of Turkey by using an allele-specific oligonucleotide hybridization technique. DNA isolated from peripheral blood samples of 75 children with beta-thalassemia major or intermedia was analyzed using a Bio-Rad mD(x)(TM)-Be Tha Gene 1 kit. We determined mutations in 56 (74.6%) patients. The allelic frequency of mutations in 150 chromosomes was as follows: IVS-I-110 (G-A) 44.1%, IVS-I-1 (G-A) 28.2%, IVS-I-6 (T-C) 13.3%, IVS-II-745 (C-G) 9.3%, IVS-II-1 (G-A) 2.7%, Cd 39 (C-T) 2.4%, -87 (C-G) 0% and Cd 6 (-A) 0%. The distribution of the mutation types was consistent with the findings of other research groups.

Serum immunoglobulins, IgG subclasses, isohemagglutinins and complement-3 levels in patients with thalassemia major.

Serum IgG, IgM, IgA, IgG subclasses (IgG1, G2, G3, G4), isohemagglutinins and complement-3 concentrations were measured in 23 beta-thalassemic patients suffering from recurrent infections. No significant abnormalities were found in these humoral immunity investigations, both in splenectomized and non-splenectomized patients. On the other hand, iron overload or repeated blood transfusions were not found to down-regulate the humoral immune system of thalassemic patients.

Plasma interleukin-3 (IL-3) and IL-7 concentrations in children with homozygous beta-thalassemia.

Plasma levels of IL-3 and IL-7 were studied in 23 patients with homozygous beta-thalassemia in order to determine whether these cytokines are involved in abnormalities in erythropoiesis and immune responses as observed in thalassemic patients. No significant difference was found in plasma IL-7 concentrations between thalassemic patients and healthy controls and it was suggested that IL-7 is not a cytokine involved in cellular immunological alterations in beta-thalassemia. However, the number of thalassemic patients with detectable IL-3 concentrations was significantly higher. It was concluded that IL-3 production has to be studied in detail in order to learn more about the involvement of this cytokine in erythropoiesis of thalassemic patients.

Recombinant human erythropoietin trial in thalassemia intermedia.

It has been shown that high doses of human recombinant erythropoietin (r epo) increase haemoglobin levels by augmentation of F-cells, and Hb-F production in animal models and in human trials. In this study, r epo was used in patients with beta thalassemia intermedia. Our purpose was to improve haemoglobin levels by at least 2 g and maintain an average level between 10 and 12 g/dl. Ten patients aged 6-29 years (mean 14 +/- 7.6 years) with thalassemia intermedia were treated with r epo. It was given subcutaneously in rising doses from 500 to 1000 U/kg three times weekly for 3 months. During r epo therapy eight cases (80 per cent) showed an increase in haemoglobin, haematocrit, and reticulocyte levels, and an increase of at least 2 g of haemoglobin was obtained. Blood transfusion was not needed during the study except in one case. Five cases (50 per cent) improved life quality with therapy. Hb levels of all patients returned to baseline values over 1 or 2 months after r epo was discontinued. There was no significant change in absolute Hb-F, F-cells, and ferritin levels during treatment. Generally, the drug was well tolerated. No patient had hypertension. Recombinant erythropoietin seems to be an effective treatment for anaemia of beta-thalassemia intermedia, but longer term randomized trials are needed especially in patients with beta thalassemia major.

alpha-Interferon-2b treatment for chronic hepatitis-B infection in children with cancer.

We have evaluated the efficacy of treatment with recombinant Interferon-2b (IFN-2b) in 12 children with cancer who developed chronic hepatitis-B infection. Seven of them had lymphoblastic leukaemia and others had solid tumours. Seven cases were male. Mean age was 10.5 years with a range of 5-16 years. Chronic Hepatitis B was diagnosed biochemically, serologically and histopathologically. They were HBsAg(+), HBV-DNA(+), and HCV(-), HIV(-). Seven cases were HBeAg(+) and two of them were anti-Delta IgG(+). Liver biopsy revealed chronic active hepatitis in six cases and persistent hepatitis in three cases. IFN was given at the dose of 5 MU/m2 three times a week, subcutaneously for 6 months. It was well tolerated. After IFN therapy, ALT levels returned to normal in seven cases. All cases were still HBsAg(+). Four of them seroconverted to anti-HBe antibody. Loss of serum HBV-DNA in three cases, but 11 cases showed a marked decrease after IFN. The control liver biopsies showed that histopathological activity index was diminished in five cases. Other 16 patients, serving as control, received no therapy. Five of them were leukaemia and others were solid tumours. Twelve cases were male. Mean age was 9.3 years with a range of 4-19 years. After 6 months, only one patient lost HBV-DNA and three of them seroconverted to anti-HBe with normalization of ALT values. In our study, IFN treatment favourably influenced the progress of chronic hepatitis B in children with cancer.

A patient with WT syndrome and Castleman disease.

WT syndrome, an autosomal dominant condition, combines hematological abnormalities with mild lib defects. Anemia, pancytopenia, leukemia and lymphoma can occur at varying ages from childhood to middle age. Limb defects include ulnar and radial defects, bifid or hypoplastic thumbs and cutaneous syndactyly. Castleman disease is characterized by tumorous masses of lymphoid tissue showing plasma cell or hyaline vascular type changes in histological specimens. A 13 year old boy, diagnosed as WT syndrome with ulnar and radial deviation and 5th finger clinodactyly also had neutropenia, cervical and mediastinal lymphadenopathy. Histology of the cervical lymph node showed angiofollicular hyperplasia of the hyaline-vascular type (Castleman disease). This interesting patient is reported because Castleman disease, together with WT syndrome has not been previously described.