Treatment of Childhood Acute Myeloid Leukemia in Bulgaria.

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. Unified 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 M2 followed by M4. 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.

Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease Detection.

UNLABELLED: 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.

Childhood acute lymphoblastic leukemia presenting with osteoarticular syndrome--characteristics and prognosis.

UNLABELLED: Children with leukemia often present with osteoarticular syndrome as a first complaint thus mimicking juvenile idiopathic arthritis. The objective of the present study was to determine the frequency of osteoarticular syndrome at the onset of acute lymphoblastic leukemia in childhood, the clinical and laboratory specificity of such patients and the prognostic value of osteoarticular syndrome as an initial symptom. PATIENTS AND METHODS: We studied 60 children with acute lymphoblastic leukemia at a mean age of 5 +/- 0.5 years between February 2002 and October 2007. RESULTS: Osteoarticular syndrome was present as an initial symptom of leukemia in 18 (30.5%) patients. The oligoarticular involvement was prevalent--in 8 children (44%). Middle-sized joints were affected more commonly--in 10 patients (55.6%), followed by large joints and spine. Laboratory results in patients with osteoarticular syndrome show more often normal or slightly decreased platelet count, higher values of lactate dehydrogenase and rarely--leukocytosis (> 20 x 10(9)/l). Parablasts in the blood film were detected in 13 children (72.2%) with osteoarticular syndrome. Event-free survival in patients with osteoarticular syndrome is comparable to that of the remaining group of acute lymphoblastic leukemia patients. In conclusion we point out that there should be frequent blood tests in children with osteoarticular syndrome and timely bone marrow biopsy in cases with atypical signs of juvenile arthritis.

Pseudomembranous necrotizing tracheobronchitis caused by Aspergillus spp--contribution of one case with acute myeloid leukemia.

Acute tracheobronchitis is a rare clinical manifestation of respiratory tract invasive aspergillosis, sporadically reported in patients with hematological malignancies against the background of conventional chemotherapy. The authors report on a case of pseudomembranous necrotizing form of histologically proven tracheobronchitis, caused by Aspergillus spp in the time of induction chemotherapy in a patient with acute myeloid leukemia. The clinical evolution is gradual: from mild non-specific manifestations of acute tracheobronchitis against the background of a prolonged fever unaffected by antibiotic therapy to the onset of severe acute respiratory insufficiency and unilateral bronchial obstruction syndrome. Multiple spontaneous expectoration of a part of the bronchial wall was observed in which Aspergillus spp hyphae were histologically proven. Tracheobronchoscopy verified nearly complete obturation of the left main bronchus with thick mucous plugs. Lethal outcome from the infection occurred at the stage of hematological remission because of a massive hemoptysis. The diagnostic methods, therapeutic possibilities and differential diagnosis of this rare infectious complication in immunocompromised patients are discussed.