Early clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis.Aim: To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD-positive samples of children with B-cell precursor ALL and the possible implications for MRD detection.Patients and methods: Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes.Results: IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed.Conclusions: Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed.

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Background: During the last four decades the prognosis of childhood acute myeloid leukemia (AML) has been substantially improved due to an increase in complete remission (CR) rates, event-free survival (EFS) and reduced early mortality. The relapsed AML still remains a therapeutic challenge. Aim: To report the AML treatment results of the Bulgarian pediatric oncohematological centers. Materials and methods: Retrospective analysis of the treatment results of children and adolescents (age from 0 to 20 years) with primary AML. Unifi ed AML BFM-backbone type treatment protocol is used. Results: This study included 97 newly diagnosed patients (44 girls and 53 boys) with AML in Bulgaria between 2003 and 2016. The median age at diagnosis was 10.2 years. The most frequent FAB-morphologic subtype was М2 followed by М4. First complete remission (CR1) was achieved in 83 patients (85.6%). The 13-year EFS was 49%, while the overall survival (OS) was 54.6%. Twenty seven (27.8%) patients relapsed, with only 5 of them being still alive towards the end of the study period. Conclusion: The EFS and OS for the children with AML in Bulgaria are comparable with those reported by other European groups. The prognosis of relapsed AML remains still unfavorable for the past 13 years. BACKGROUND

Mucormycosis, caused by the widespread molds of the Mucorales order, is an insidious infection that manifests in different clinical forms. Even the most benign form, the cutaneous mucormycosis, can present with severe complications and a fatal outcome in patients with a suppressed immune system and underlining comorbidities. We present a rare case of a proven primary multifocal cutaneous mucormycosis in a child with newly diagnosed acute leukemia without multiorgan dissemination. Various laboratory techniques (histopathological, cultural and molecular-genetic) were used to detect and confirm the diagnosis. Etiological therapy (liposomal amphotericin B, 5 mg/kg) combined with surgical intervention were used to manage the infection. The case shows that a rapid and complex diagnostic approach is of crucial importance for the timely initiation of adequate therapy, as well as for the successful management of this life-threatening fungal infection.