Introduction: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin–Frankfurt–Münster (BFM) protocols and compare our results with the original BFM reports. Methods: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997–2007 and 2008–2018 cohorts were analyzed separately. Results: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997–2007 period, respectively, 88% and 80% (BFM standard risk group—SRG), 75% and 67% (intermediate risk group—IRG), and 48% and 33% (high-risk group—HRG). The corresponding numbers for the 2008–2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. Conclusion: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.

The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0–20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09–2.50). ADM development IR decreased from 2.09–1.75–0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson–Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era.

Lymphomas related to HIV are generally aggressive and have a poor prognosis, despite the use of combined antiretroviral therapy (cART) and effective chemotherapy treatment. To determine survival and prognostic factors in children and adolescents living with HIV (CLWH) in Rio de Janeiro (RJ), Brazil, who developed lymphomas, we performed a retrospective and observational study of vertically infected CLWH aged from 0 to 20 incomplete years during1995 to 2018 at five reference centers for cancer and HIV/AIDS treatment. Of the 25 lymphomas, 19 were AIDS-defining malignancies (ADM) and 6 were non-AIDS-defining malignancies (NADM). The 5-year overall survival (OS) and 5-year event-free survival (EFS) probabilities were both 32.00% (95% CI = 13.72–50.23%), and the 5-year disease-free survival (DFS) probability was 53.30% (95% CI = 28.02–78.58%). In the multivariate Cox regression analysis, performance status 4 (PS 4) was considered a poor prognostic factor for OS (HR 4.85, 95% CI = 1.81–12.97, p = 0.002) and EFS (HR 4.95, 95% CI = 1.84–13.34, p = 0.002). For the DFS, higher CD4+ T-cell counts were considered a better prognostic factor (HR 0.86, 95% CI = 0.76–0.97, p = 0.017) in the multivariate Cox regression analysis. This study demonstrates, for the first time, survival and prognostic factors for CLWH who developed lymphomas in RJ, Brazil.

Prevention is the best way to avoid relapse after hematopoietic cell transplantation (HCT). Immunomodulation can enhance graft-versus-leukemia effect and, if graft-versus-host disease (GVHD) is absent, prophylactic donor lymphocyte infusion (DLI) may be indicated for high-risk patients. Maintenance strategies with blinatumomab, inotuzumab, tyrosine kinase inhibitors, hypomethylating agents or venetoclax can be effective in reducing relapse rates. However, maintenance therapy response depends on individual toxicity and physician’s experience in handle with dose adjustments, undesirable drug interactions and complications. Preemptive approach guided by minimal residual disease (MRD) or mixed chimerism is fundamental to prevent hematologic relapse. Target agent or immunotherapy followed by DLI can be used, and if no response, low-dose chemotherapy can be added to reach disease control. After relapse, antigen-directed therapies with blinatumumab for CD19 ALL and inotuzumab for CD22 ALL are good options to induce MRD negativity and bridge to second HCT. Emerging therapies like daratumumab, immune checkpoint or menin inhibitors are promising but require validation. CAR-T cell therapy can provide a better chance of long-term survival if low leukemia burden and absence of GVHD. It is also effective in extramedullary disease, mainly in central nervous system relapse. Patients with B-cell aplasia loss after CAR T-cell therapy are second transplant candidates, as well as those with acute myeloid leukemia who respond to salvage therapy. Second HCT outcomes are better if relapse occurred ≥ 12 months after the first HCT. Strategies for expanding access to immunotherapy and target agents are crucial to improve long-term survival in these children.

Background/Objectives: Pediatric myelodysplastic syndrome (pMDS) is a rare, heterogeneous, clonal hematopoietic stem cell disease with a risk of evolution to acute myeloid leukemia (AML). Clonal cytogenetic abnormalities are present in 30–60% of pMDS. However, unlike in adults, the prognostic significance of chromosomal alterations, particularly their role in predicting evolution to AML, remains limited in pMDS. To acknowledge this gap, we studied the cytogenetic abnormalities in pMDS and analyzed their associations with subtypes and evolution to AML. Furthermore, in the Discussion Section, we pointed out key genes involved in these chromosomal alterations. Methods: Cytogenetic analysis was performed on 193 pediatric patients using G-banding and fluorescence in situ hybridization. Results: Abnormal karyotypes were observed in 43.5% (84/193) of patients, mainly in the advanced subtype. The main chromosomal alterations were monosomy 7 (−7) in 14% of the cases (12/84), deletion of the long arm of chromosome 11 [del(11q)] in 12% (10/84) and both trisomy 8 (+8) and deletion of the long arm of chromosome 7 [del(7q)] in 8% (7/84). Evolution from MDS to AML was observed in 22% of the patients (42/193), and it was associated with complex karyotypes, del(11q), −7/del(7q), and +8. Conclusions: Our results suggest that specific chromosomal alterations, such as del(11q), del(7q), and +8, may predict evolution to AML and might be considered high-risk cytogenetic markers in pMDS.

Background/Objectives Acute lymphocytic leukemia (ALL) is the most common pediatric cancer, more incident in Hispanics. The Berlin-Frankfurt-Münster (BFM) protocol for ALL began to be used in hospitals from Rio de Janeiro in the 1980’s. The aim of this study was to determine survival probabilities and prognostic factors for children and adolescents with ALL in the state of Rio de Janeiro (RJ) and to compare these results with other BFM studies. Design/Methods We conducted a survival analysis study with a retrospective cohort of 695 patients aged from zero to 19 years treated with a modified BFM protocols between 1998 and 2018 in four reference hospitals in RJ. Prognostic factors included age, sex, leukocyte count, early response to treatment and cytogenetic risk. The cohort was divided into two periods. We calculated the five- and ten-years event-free survival (EFS), the overall survival (OS) and performed a multivariate analysis using Cox proportional hazards models. Results In the 1 ^st period the five-year EFS was 50.3% (±3.0) and the OS was 61.5 (±2.9). These rates for high-risk patients (HR) were 33.4% and 47.7%, respectively. In the 2 ^nd period, the five-year EFS was 61.6% (±2.8) and the OS was 70.5% (±10.6). These rates for HR patients were 57.9% and 63.8%. In the cohort, 51.2% of patients were HR based on BFM classification, 54.7% were HR based on the National Cancer Institute classification, 27.1% had a leukocyte count greater than 50,000 and 28.6% were aged less than one or greater than 10 years. Conclusions Our results led us to hypothesize that delays in treatment, overestimated risk classification on the 8 ^th day of treatment and/or unique genetic features of our population may be causing a higher leukocyte count at the time of diagnosis and an increased prevalence of HR classification compared to other BFM studies mainly composed by Caucasians.