Overall, 18 patients died due to acute treatment toxicity, resulting in a cumulative incidence of toxic death of 10.84% and an early death rate of 7.23%, defined as <30 days after initial treatment. In conclusion, there is an urgent need to establish an academic collaboration to create strategies to improve pediatric cancer care according to our resources, especially in diseases with expected excellent prognosis as B-NHL. These strategies must include comprehensive supportive care, early referral, and the creation of easy communication between pediatric and adults centers as well as late-effects clinics.

No abstract

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 &lt;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 &lt;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 &lt;0.01% and 5 patients MRD ≥0.01%, from which 3 had MRD at day 15 &gt;1% and none registered an MRD result &lt;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.

To the Editor: Second neoplasms associated with retinoblastoma are common with a cumulative incidence of 3.7% at 10 years and 17.7% at 35 years [1]. Osteosarcoma and soft-tissue sarcomas are chief among them, but acute myeloid leukemia (AML) is rare.Our experience with such a patient is therefore of interest. He was a 10-year old boy who developed retinoblastoma of the right eye. Vincristine (52 mgm 2 cumulative dose), doxorubicin (420 mgm 2 ), and cyclophosphamide (13,860 mgm 2 ) were given. Six and a half years after having completed the treatment, he presented with epistaxis, ecchymoses, and pallor. Peripheral blood counts showed: hemoglobin 7.9 g/dl, 32,000/ml platelets, and 12,800 leukocytes/mm 3 with 30% blasts. Bone marrow aspiration reported M2 morphology AML, positive for CD11, CD15, and CD33 markers; bone marrow karyotype was normal 46xy. He received daunorubicin plus cytarabine alternating with etoposide plus cytarabine for seven cycles. Remission was achieved after the first cycle but the patient died of sepsis apparently free of AML 8 months after the diagnosis.Between 5-15% of patients with a primary neoplasm treated with chemotherapy develop AML as a second neoplasm. Alkylating agents, topoisomerase II inhibitors, and radiation have been considered as the main causative agents [2][3][4][5]. Two subgroups of patients can be identified: the first includes patients with alkylating agents exposure, with or without radiotherapy. They usually have a previous myelodysplastic phase with a M1, M2, M6, and M7 morphology according to the FAB classification, and alterations on chromosomes 5 and 7 [6,7]. The second group includes patients exposed to epipodophyllotoxins. They evolve in an acute manner without a previous myelodysplastic phase, with M4 and M5 morphology and with changes in chromosome 11q23 [8,9]. Due to the morphologic characteristics, and the absence of chromosomal anomalies, our patient might be included in the first group since an absence of cytogenetic alterations have been observed in up to 21% of cases of chemotherapyassociated leukemia [10]. The time span between the two neoplasms in our patient is within the average of 4-7 years cited in the article [11]. The cumulative chemotherapy dose has been related to the risk of developing a secondary leukemia. Our patient received a total dose of over 13 g of cyclophosphamide. Also, our patient's retinoblatoma was not of the hereditary type and the karyotype was always normal. We believe his leukemia to have been related to the cyclophosphamide he received.

No abstract