In a mixed medical-surgical ICU, older women have a higher mortality rate than men. This difference is not apparent for patients staying longer in the ICU.

Introduction: Acute lymphoblastic leukemia (ALL) represents approximately 50% of all childhood cancers in Latin America. Mexico is not the exception. The impact of ALL survival on overall childhood cancer survival is significant. According to government data, five-year survival is about 52%. Mexico in Alliance with St. Jude (MAS) is a multi-site, intersectoral collaboration. The collaborative network has explored and reported on factors associated with this suboptimal outcome and have identified challenges with ALL risk group classification as a leading cause. For example, as many as 82% of children diagnosed with ALL in Mexico receive high-risk treatment and the tendency for higher-risk group assignment often occurs in response to limited access to cytogenetic testing and minimal residual disease (MRD) testing. This leads to higher intensity treatment and may explain the high rate of treatment-related death (TRD) (12%) documented during the induction but also subsequently. In our previous case series, only 75% of patients were alive at the end of the first year of treatment. These findings, led MAS to develop a consensus-derived standardized diagnosis and treatment schema (MAS-ALL18), which takes into account clinical, cytogenetic, and MRD results. Diagnostic testing is performed in a centralized laboratory. Although centred on delivery of standard of care, this experience represents is the first prospective multi-site cooperative group effort in Mexico. We report on early treatment (first 90 days) clinical and implementation outcomes utilizing the MAS-ALL18 adapted management guideline (AMG) in four member hospitals of the MAS collaboration network. Results: From June 2019 to June 2020, 137 patients received treatment utilizing the MAS-ALL18 AMG in four publicly funded hospitals in Mexico. B-cell ALL represented 91.9% of the cases, 20.4% of patients were older than 9 years of age, 25.5% had a white blood cell count greater than 50,000 at diagnosis and 58.3% were male. Complete remission at the end of the induction was achieved in 90.6% of patients. TRD during the induction phase was 8%. MRD at Day 15 in 123 patients with B-cell ALL, 84.5% of them had MRD <1% and 7.3% had MRD ≥5%. MRD at Day 29 was assessed for the 10 patients diagnosed with T-cell ALL, 4 patients had MRD <0.01%, 2 had 0.02%, and 4 died during the induction phase. MRD was also assessed during consolidation (at Day 84) in 99 patients, 94.9% had MRD <0.01% and 5 patients MRD ≥0.01%, from which 3 had MRD at day 15 >1% and none registered an MRD result <0.5%. Utilizing the MAS-ALL18 risk group stratification, 50% of patients were assigned to a favorable risk group at the end of the consolidation. In 34 patients, the risk group was reclassified following the standardized algorithm; 30 reclassification events happened at the end of the induction and four at the end of the consolidation. Only two events were reassigned to a lower risk group, while the rest of the reclassifications were conducted to assign patients to a higher risk group due to unfavorable cytogenetics or an inadequate early response to treatment. High-risk treatment was ultimately assigned to 30% of patients using the MAS-ALL18 risk classification schema. Conclusion: It is feasible to implement a standardized multi-site adapted management guideline for ALL risk group stratification and treatment allocation in Mexico in the context of a collaborative network. TRD remains high during the induction phase, nevertheless, this number shows an improvement (8%) compared to the 2015 data report (12%). The ALL risk group classification is transitioning from a rigid scheme that placed 80% of patients in a high-risk group to a dynamic classification system that considers cytogenetic testing and MRD conducted in a centralized and externally validated laboratory that serves as reference for all the participating hospitals. The standardized MAS-ALL18 approach allowed us to classify 50% of patients in a favorable risk group during and at the end of the induction phase, which implies receiving a lower intensity treatment with a high probability of cure and a lower risk of TRD. The implementation of MAS-ALL18 risk classification scheme reduced the number of children requiring high-risk treatment in the participating hospitals. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Cancer is the second leading cause of death in Mexico among children 5-14 years. In 2017, Mexico in Alliance with St. Jude (MAS), a multi-site intersectoral collaboration, explored reasons for suboptimal outcomes for children with acute lymphoblastic leukemia (ALL). Results showed 82% of patients to be classified as high-risk and 30% of patients be missing standard molecular or minimal residual disease (MRD) studies needed to inform risk- group stratification. Making sense of the molecular characteristics was challenging in the context of variable access and lack of common denominators. These findings led to the development of the "Bridge Project"; a prospective quality improvement demonstration project aiming to bridge this access and quality gap through multi-site collaboration, centralization, and standardization. Methods: Six MAS collaborating hospitals, located in six different states (Mérida, Guadalajara, Sinaloa, Baja California, Chiapas, and Veracruz), have sent diagnostic samples for children 0-18 years old with suspected ALL to Hospital Infantil Teletón de Oncología (HITO), in Queretaro, which serves as the centralized laboratory for the MAS cooperative group. Access to the diagnostic panel is secured upfront through dedicated funding obtained from a local foundation. The first sample was shipped in July 2019. The consensus-derived diagnostic panel includes morphology, immunophenotype, karyotype, fluorescent in situ hybridization (FISH), molecular biology (RT-PCR) and flow cytometry (FC) MRD at two time points. Protocols vary by institution and MRD evaluation is only done if the institutional protocol incorporates MRD-evaluation into the risk-group stratification. Hospitals send several empty boxes prior to shipping patient samples to assess their regional shipping vendors and timelines. The also standardize data collection processes and use PDSA cycles to monitor sample quality and address issues with sample quality. HITO produces FC results (for diagnosis or MRD evaluation) and FISH/cytogenetic results within 3 to 21 days of sample arrival. Results: As of July 2021, the centralized lab has received samples from 217 patients with suspected ALL through this project and 93% of these samples have arrived within the 48hr target. Of these, 176 (81.1%) had confirmed ALL and 14 (6.4%) had acute myeloid leukemia (AML), 2 (0.9%) cases had other malignant conditions, and in 25 (11.5%) of the cases leukemia was ruled out. Among the 176 cases of confirmed ALL, 162 (92%) had B-cell lineage and 14 (8%) had T-cell lineage. FISH was reported for 172 (97.7%) patients and positive in 126 (73.2%) cases; 46 (26.7%) cases had reported gains, 34 (19.7%) detected t(12;21), 18 (10.4%) detected iAMP cr21, 8 (4.7%) detected breaks of the MLL gene t(4;11), 7 (4%) detected t(1;19), and 6 (3.4%) detected t(9;22). Four T-cell ALL cases had breaks CDKN2A del(9)(p21) and three cases had TRA/D rearrangement (14) (q11.2). Karyotype alterations were detected in 90 (52.3%) of the samples, of which 41 (23.8%) showed hyperdiploidy and 13 (7%) showed complex karyotype. One case of hypodiploid was identified. Day 15 MRD was assessed in 131 (80%) patients with B-cell lineage, Day 84 MRD was assessed in 99 (61.1%) patients with B-cell lineage, and Day 29 MRD in 8 (57.1%) patients with T-cell lineage whose treatment schema utilizes MRD-based stratification. Among B-lineage patients, 84% had MRD <1% at Day 15 and 94.9% MRD <0.01% at Day 84. Among T-cell lineage patients, 75% had MRD <0.01% at Day 29 and 80% MRD <0.01% at Day 84, but numbers for T-cell lineage were small. Conclusions: Given proper structural and financial supports, patients with suspected childhood ALL in Mexico can access a comprehensive diagnostic panel following a centralized laboratory approach. Preliminary results from the Bridge Project allow characterizing childhood ALL to a degree that has not been previously possible in Mexico. In this cohort, favorable characteristics such a t(12;21), gains, and hyperdiploidy are observed in frequencies similar to those reported in Hispanic cohorts in high-income countries. MRD results are for B-cell lineage are also consistent with the literature. Continued engagement in this project from hospitals in diverse geographic settings and with diverse patient populations will allow the MAS cooperative group to continue to improve the characterization of childhood ALL in Mexico. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

By the end of August 2020, the pandemic caused by the new SARS-CoV-2 coronavirus has killed 826 743 people worldwide. All countries have been hit by the infection and have failed to prevent the progression of the infection in their populations. Ecuador, which already had serious social and economic difficulties before the pandemic, now faces very serious funding problems. The rate of diagnostic tests per 1 000 inhabitants is one of the lowest in the region, while the lethality of COVID-19 is one of the highest in the world. The trend has been to have cities paralyzed by fear, hospitals unable to receive more patients, people wandering the streets risking their lives to raising some money to support themselves and their families. Among the dead are friends, colleagues, parents, and grandparents, in addition to the excess mortality recorded in all cities of the country that account for indirect deaths from the pandemic. The health personnel have been the most sacrificed and continues to provide its contingent despite the limitations of supplies and medicines from hospitals.