Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial.

PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].

Epidemiology of chronic lymphocytic leukemia in Chilean and Amerindian population in Chile.

The study aim was to analyze incidence and presentation features of chronic lymphocytic leukemia (CLL) in Chile, in Amerindian population and in non-Native. Between 2012 and 2019, 912 patients were diagnosed, and 13 (1.4%) were Amerindian. The estimated incidence in Chilean population was 1.17/100,000 person per year, while in Amerindian, 0.09/100,000 person per year. Median age was 73 years. At diagnosis, 48, 27, and 25%, had low (0), intermediate (I/II) and high-risk (III/IV) disease on Rai classification. Diagnostic immunophenotypic Matutes score was ≥4 in 90%. Median follow-up was 37 months (range 2-87). 5-year OS was 56%, with median overall survival (OS) not reached. It was worse in men, ≥65 years, high-risk and those with increased prolymphocytes (CLL/PL). This study shows low incidence and worse OS in Chilean CLL patients, compared to those from European countries, despite similar clinical features. It also demonstrates that CLL is very uncommon in Amerindian population.

An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report.

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19- and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.

[Cerebriform variant type of T cell prolymphocytic leukemia: Report of one case]. / Leucemia prolinfocítica T variante de células cerebriformes: Presentación de un caso y revisión de la literatura.

T cell Prolymphocytic Leukemia (T-PLL) is a rare and aggressive mature T cell Lymphocyte Leukemia. Twenty five percent of cases present as a small cell variant, and only 5% as a cerebriform variant. We report a 58 year-old man with rapidly progressive severe leukocytosis, skin lesions, lymphadenopathy, hepatosplenomegaly and pleural effusion. The lymphocytes had a cerebriform type. The diagnosis of T-PLL variant was made by morphology and immunophenotype study of peripheral blood. Karyotype was found to be complex. He was refractory to chemotherapy and died two months later.

Leucemia prolinfocítica T variante de células cerebriformes: presentación de un caso y revisión de la literatura / Cerebriform variant type of T cell prolymphocytic leukemia: report of one case

T cell Prolymphocytic Leukemia (T-PLL) is a rare and aggressive mature T cell Lymphocyte Leukemia. Twenty five percent of cases present as a small cell variant, and only 5% as a cerebriform variant. We report a 58 year-old man with rapidly progressive severe leukocytosis, skin lesions, lymphadenopathy, hepatosplenomegaly and pleural effusion. The lymphocytes had a cerebriform type. The diagnosis of T-PLL variant was made by morphology and immunophenotype study of peripheral blood. Karyotype was found to be complex. He was refractory to chemotherapy and died two months later.

[Chronic lymphoproliferative syndromes in Chile. A prospective study in 132 patients]. / Síndromes linfoproliferativos crónicos en Chile. Estudio prospectivo de 132 casos.

BACKGROUND: Chronic lymphoproliferative disorders include a variety of diseases which are often a diagnostic problem for clinical hematologists. AIM: To study prospectively the distribution and incidence of chronic lymphoproliferative disorders in Chile and compare them with those of other Western, Latin American and Oriental countries. PATIENTS AND METHODS: A group of 132 patients were studied in a 36 months period (1999-2001), with a panel of monoclonal antibodies. A score for chronic lymphocytic leukemia was employed to differentiate it from other B-cell disorders. RESULTS: The median age was 63 years old (range 32-94). Most patients had B-cell tumors (109) and the rest (23), T-cell tumors (82% vs 18%). Forty five percent of patients with B-cell tumors had a chronic lymphocytic leukemia (CLL), while the others were disseminated lymphomas. The incidence of T-cell tumors was slightly higher than that of other Western countries. Noteworthy is that the most common of these disorders was adult T cell leukemia/lymphoma (ATLL), in concordance with the high HTLV-1 seroprevalence in Chile. CONCLUSIONS: A morphologic, immunophenotypic and pathological study in a large number of patients with chronic lymphoproliferative disorders in Chile, shows a relatively low incidence of CLL when compared to other chronic B-cell tumors and a high representation of ATLL associated to HTLV-1 infection, compared with other Western countries. The lower incidence of CLL in our study might be due to patient's selection and/or underdiagnosis of this disease as a substantial proportion of CLL are asymptomatic.