[Hemophagocytic syndrome. Current concepts]. / Síndrome hemofagocítico. Conceptos actuales.

Hemophagocytic lymphohistiocytosis is a syndrome characterized by pathological immune activation that may occur as either a primary a familial disorder (associated with genetic mutations), or as a sporadic condition, associated to infections, malignancies or autoimmune diseases. The clinical picture is characterized by a disproportionate inflammation that causes fever, cytopenias, splenomegaly, bone marrow hemophagocytosis, hypertriglyceridemia and hypofibrinogenemia. Syndrome-related mortality is high, so it is important to maintain a high index of suspicion and start early treatment with immunochemotherapy and bone marrow transplantation in primary and refractory cases. In this article, we review the clinical manifestations, pathology, diagnosis and treatment of these patients.

A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMICs) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included the use of Escherichia coli asparaginase,6-mercaptopurine instead of thioguanine and the use of rituximab among patients with CD20+. A total of 95 patients with a median age of 23 (range, 14-49) years treated with this modified scheme were prospectively assessed at 5 centers in Mexico and 1 in Guatemala. Among these, 87.8% achieved a complete response after induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.81-10.10) and postinduction minimal residual disease (HR, 4.67; 95% CI, 1.75-12.44). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation, respectively), and the treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.

Comparison of Two Pediatric-Inspired Regimens to Hyper-CVAD in Hispanic Adolescents and Young Adults With Acute Lymphoblastic Leukemia.

BACKGROUND: Pediatric-inspired regimens (PIR) in adolescents and young adults with acute lymphoblastic leukemia have led to better long-term outcomes. In Latin America, the adolescent and young adult population has an increasing incidence of acute lymphoblastic leukemia with poor outcomes (5-year OS of approximately 20%) with traditional regimens. PATIENTS AND METHODS: A retrospective cohort study was performed of adolescent and young adult acute lymphoblastic leukemia patients treated with PIR in two reference centers in Mexico City between March 2016 and June 2019, in which the primary endpoint was OS, compared to a historic cohort of patients treated with hyper-CVAD treated between February 2009 and June 2015. RESULTS: We compared 73 patients treated with PIR (46 and 27 received modified versions of the ALL-BFM 90 and CALGB C10403 regimens, respectively) and 173 patients treated with hyper-CVAD. Patients treated with PIR experienced higher 4-week complete response rates (79.5% vs. 64.2%; P = .02) and lower relapse rates (44.1% vs. 60.0%; P = .04). OS was significantly higher with PIR than with hyper-CVAD (24 months: 41.5% vs. 28.1%; P = .012). The benefit on OS for PIR was only significant for CALGB (24-month OS: 61.1% vs. 28.0%; P = .01) but not for BFM. In the multivariate analysis, hyperleukocytosis (hazard ratio [HR] = 1.90; 95% confidence interval [CI], 1.11-3.22; P = .02), autologous stem-cell transplantation (HR = 0.38; 95% CI, 0.17-0.86; P = .02), and 4-week complete response (HR = 0.43; 95% CI, 0.26-0.70; P < .01) were independent prognostic factors. For the group of patients older than 20 years, only CALGB had an independent prognostic factor for OS (HR = 0.44; 95% CI, 0.20-0.97; P = .04). CONCLUSION: In terms of 4-week complete response, relapse rates, and OS, PIR provides benefits to Hispanic patients.

Central nervous system (CNS) involvement has an adverse impact on survival in newly diagnosed adult acute lymphoblastic leukemia (ALL) assessed by flow cytometry.

The role of CNS involvement detected by flow cytometry (FCM) in patients with acute lymphoblastic leukemia has been discussed previously; however, its impact on survival has not been described enough. We analyzed a retrospective cohort of newly diagnosed ALL adult patients who had a cerebrospinal fluid (CSF) analysis by FCM and conventional cytology. We evaluated 81 patients; 19 (23.4%) were only positive by FCM, five (6.3%) were double-positive (DP) and 57 (70.4%) were double-negative (DN). The detection of CNS involvement was increased from 6% to 24%, employing FCM; In our final analysis, patients with FCM + had a lower survival of 7.01 months [95% CI (5.90-8.24)], compared with 11.71 months [IC95% (9.49-13.94)] in the DN group (p = 0.03).

Portal Dissemination of Fusarium graminearum in a Patient with Acute Lymphoblastic Leukemia and Febrile Neutropenia.

We present the case of a man with acute lymphoblastic leukemia and prolonged profound neutropenia, who developed an invasive infection by Fusarium graminearum, acquired via non-cutaneous entry, with gastrointestinal symptoms, sigmoid perforation and liver abscesses due to portal dissemination. The etiologic agent was identified using the 18S-ITS1-5.8S-ITS2-28S rRNA sequence gene, from a liver biopsy. The infection was resolved with surgical drainage and antifungal treatment based on voriconazole. As far as we know, there are no previous reports in the literature of cases of human infection due to Fusarium graminearum.

Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.

PURPOSE: The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS: Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS: We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION: These results highlight the collateral damage of COVID-19 in oncology patients.

Acute Myeloid Leukemia in Mexico: The Specific Challenges of a Developing Country. Results From a Multicenter National Registry.

BACKGROUND: In the past decades, long-term survival outcomes for younger patients with acute myeloid leukemia (AML) have improved. Nonetheless, developing nations might be lagging behind, highlighting the need to assess real-world outcomes in such regions. METHODS: We performed a multicenter retrospective study, which included patients with AML diagnosed between January 2013 and December 2017 from 13 centers in Mexico. RESULTS: A total of 525 patients with AML met the inclusion criteria and were included in the study. Median age for the entire cohort was 47 years. The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6%, and unfavorable 28.4%. Most patients received intensive chemotherapy (80.2%), and among these 74.1% underwent a 7 + 3 induction regimen. A complete remission was achieved in 71.3% of patients. Induction-related mortality occurred in 17.8% and we identify the following as independent risk factors: >60 years (odds ratio [OR] 2.09 [1.09-4.02]), Eastern Cooperative Oncology Group >2 (OR 4.82 [2.46-9.43]), prior solid tumor (OR 3.8 [1.24-11.59]) and active infection (OR 1.82 [1.06-3.12]). Further, allogeneic hematopoietic stem-cell transplantation (AlloHSCT) was performed in 8.2% in CR1. The 3-year overall survival (OS) was 34.8%. In a multivariate analysis, several factors were independently associated with a worse OS, including secondary AML (hazard ratio [HR] 2.14 [1.15-4.01]) and unfavorable cytogenetic risk (HR 1.81 [1.16-2.82]), whereas maintenance therapy (HR 0.53 [0.32-0.86]) and AlloHSCT (HR 0.40 [0.17-0.94]) were associated with better OS. CONCLUSIONS: This is the first multicenter report analyzing AML survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed to improve outcomes.

Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA).

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia-positive was present in 16.7%. The most commonly used treatment regimen was hyper-CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3-year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

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Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.