ALL BFM REZ

Managing a child with acute lymphoblastic leukemia (ALL) after relapse is arduous in low- and middle-income countries. A file review of children aged ≤15 years diagnosed with relapsed ALL from 2010 to 2019 was performed. Classification of relapse followed the Berlin-Frankfurt-Münster (BFM) scheme. The majority of patients were treated with a modified ALL-REZ-BFM protocol. Of 764 children treated for ALL in the study period, 163 (21.3%) relapsed. The median age at relapse was 101 months (range: 8-297)...

Children with other extramedullary relapse of acute lymphoblastic leukemia are currently poorly characterized. We aim to assess the prevalence and the clinical, therapeutic and prognostic features of extramedullary localizations other than central nervous system or testis in children with relapse of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) treated on a relapsed ALL protocol. PATIENTS AND METHODS: Patients with relapse of ALL and LBL, treated according to the multicentric ALL-REZ BFM trials between 1983 and 2015, were analyzed for other extramedullary relapse (OEMR) of the disease regarding clinical features, treatment and outcome...

AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses...

Activating mutations in the cytosolic 5´-nucleotidase II (NT5C2) are considered to drive relapse formation in acute lymphoblastic leukemia (ALL) by conferring purine analogue resistance. To examine the clinical effects of NT5C2 mutations in relapsed ALL, we analyzed NT5C2 in 455 relapsed B-cell precursor ALL patients treated within the ALL-REZ BFM 2002 relapse trial using sequencing and sensitive allele-specific real-time PCR. We detected 110 NT5C2 mutations in 75 (16.5%) of 455 B-cell precursor ALL relapses...

PURPOSE: Minimal residual disease (MRD) helps to accurately assess when children with late bone marrow relapses of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) will benefit from allogeneic hematopoietic stem-cell transplantation (allo-HSCT). More detailed dissection of MRD response heterogeneity and the specific genetic aberrations could improve current practice. PATIENTS AND METHODS: MRD was assessed after induction treatment and at different times during relapse treatment until allo-HSCT (indicated in poor responders to induction; MRD ≥ 10-3 ) for patients being treated for late BCP-ALL bone marrow relapses (n = 413; median follow-up, 9...

BACKGROUND: Acute lymphoblastic leukemia (ALL) represents the most common malignancy in children with an overall cure rate of 85%. Relapses occur in 20% of the cases. Commonly, extramedullary relapses (EMRs) involve central nervous system (CNS) or testes. Unusual EMRs in ALL are relatively rare reported. CASE PRESENTATION: The authors present a 24-year-old woman with ALL, who experienced three unusual EMRs. In 2007, she was diagnosed with B-cell precursor (BCP)-ALL - high-risk (HR) group, and she was treated according to ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002∕HR Protocol...

Aneuploidy is common in paediatric B-cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Using DNA index and centromere screening by multiplex ligation-dependent probe amplification, we investigated aneuploidy in 413 children treated for first relapse of B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol...

The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4...

Cytogenetic classification of acute lymphoblastic leukemia (ALL) is primarily based on numerical and structural chromosomal abnormalities. In T-cell ALL (T-ALL), chromosomal rearrangements are identified in up to 70% of the patients while the remaining patients show a normal karyotype. In the present study, a 16-year-old male was diagnosed with T-precursor cell ALL and a normal karyotype after standard GTG-banding, was studied retrospectively (>10 years after diagnosis) in frame of a research project by molecular approaches...

For most children who relapse with acute lymphoblastic leukemia (ALL), the prognosis is poor, and there is a need for novel therapies to improve outcome. We screened samples from children with B-lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (www.clinicaltrials.gov, #NCT00114348) for somatic mutations activating the Ras pathway (KRAS, NRAS, FLT3, and PTPN11) and showed mutation to be highly prevalent (76 from 206). Clinically, they were associated with high-risk features including early relapse, central nervous system (CNS) involvement, and specifically for NRAS/KRAS mutations, chemoresistance...

PURPOSE: In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy...

The BFM studies for relapsed childhood acute lymphoblastic leukemia (ALL) were started in 1983, at a time when cure rates for ALL were still lower and the number of children with ALL relapse equaled about the number of children with newly diagnosed neuroblastoma. Today, relapses have become relatively rare events in ALL although, because of the frequency of ALL, they are still a significant cause of death in children and adolescents. With currently used treatment modalities, cure rates of about 50% after relapse can be achieved, and, together with the improved results of front-line therapy, the survival rate of childhood ALL is now about 90%...

PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT). METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96...

INTRODUCTION: The majority of hyperglycaemic incidents in oncohaematological patients treated with glucocorticosteroids remain undiagnosed. The aim of our study was to work out a detailed protocol for the control of carbohydrate metabolism and to evaluate whether such a protocol can help in diagnosis of carbohydrate metabolism disturbances in oncohaematological paediatric patients. MATERIAL AND METHODS: A one hundred and twenty-eight children treated for proliferative diseases of the haematopoietic system and severe aplastic anaemia with therapeutic protocols including glucocorticosteroids were divided into two groups...

Despite risk-adapted treatment, survival of children with relapse of acute lymphoblastic leukemia (ALL) remains poor compared with that of patients with initial diagnosis of ALL. Leukemia-associated genetic alterations may provide novel prognostic factors to refine present relapse treatment strategies. Therefore, we investigated the clinical relevance of 13 recurrent genetic alterations in 204 children treated uniformly for relapsed B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol. The most common alterations were deletions of CDKN2A/2B, IKZF1, PAX5, ETV6, fusion of ETV6-RUNX1 and deletions and/or mutations of TP53...

BACKGROUND: In 2000, the Hong Kong Pediatric Hematology Oncology Study Group started a new relapsed acute lymphoblastic leukemia (ALL) treatment protocol based on modified ALL-REZ BFM 96 protocol aiming at improving the treatment outcome in Chinese children. PROCEDURE: All patients in Hong Kong with first relapse of childhood ALL were included. Patients were stratified into four risk groups (S1, S2, S3, and S4) and the treatment consisted of intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if indicated...

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Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < ...

BACKGROUND: Resistance to therapy and subsequent relapse remain major challenges in the clinical management of relapsed childhood acute lymphoblastic leukemia. As the bone marrow environment plays an important role in survival and chemotherapy resistance of leukemia cells by activating different signaling pathways, such as the VLA-4 and PI3K/Akt pathways, we studied the prognostic and biological impact of VLA-4 expression in leukemia cells from children with relapsed B-cell precursor acute lymphoblastic leukemia and its influence on the sensitivity of the leukemia cells to drugs...

PURPOSE: In the clinical management of children with relapsed acute lymphoblastic leukemia (ALL), treatment resistance remains a major challenge. Alterations of the TP53 gene are frequently associated with resistance to chemotherapy, but their significance in relapsed childhood ALL has remained controversial because of small studies. PATIENTS AND METHODS: Therefore, we systematically studied 265 first-relapse patients enrolled in the German Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Mü nster 2002 (ALL-REZ BFM 2002) trial for sequence and copy number alterations of the TP53 gene by using direct sequencing and multiplex ligation-dependent probe amplification...