Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Leucemia agresiva de células natural killer en un paciente pediátrico / Agressive NK-cell leukemia in a pediatric patient

Resumen Introducción: Las neoplasias de células natural killer (NK) son poco frecuentes y representan <5% de todas las neoplasias linfoides. Comprometen diferentes entidades clínicas, como la leucemia de células NK, que es una neoplasia hematológica altamente agresiva con un pronóstico precario, que se presenta en hombres jóvenes y se observa con mayor frecuencia en ascendencia asiática. El virus de Epstein-Barr (VEB) parece estar relacionado con la patogenia de esta leucemia. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 1 año y 7 meses de edad, quien inició su padecimiento con síndrome anémico, febril, infiltrativo e hiperleucocitosis. En el aspirado de médula ósea se detectaron blastos de morfología L2 (96%), inmunofenotipo CD56 (80.87%) y desoxinucleotidil transferasa terminal (84.11%). En la biopsia de médula ósea se identificó CD2+ membranoso, CD3+ citoplásmico y CD56+ membranoso; la serología para VEB fue positiva. El paciente recibió dos esquemas diferentes de quimioterapia basados en metotrexato, ifosfamida, etopósido, dexametasona y L-asparaginasa, y se documentó remisión parcial. Actualmente, se encuentra vivo con la enfermedad. Conclusiones: La leucemia de células NK es rara en adultos jóvenes, pero aún más en pacientes en edad pediátrica. Además, es de muy difícil tratamiento, ya que solo se cuenta con algunos reportes de casos, la sobrevida es de semanas a meses y las oportunidades de tratamiento se limitan. Recientemente, se ha evidenciado la utilidad del trasplante de médula ósea alogénico o células de cordón umbilical, y se ha logrado una sobrevida a 2 años. Las posibilidades terapéuticas en estos pacientes se encuentran en estudio. Se espera lograr en un futuro cercano la remisión completa y sobrevida a 5 años.

Abstract Background: Natural killer (NK) cell neoplasms are rare and represent <5% of all lymphoid neoplasms. They involve different clinical entities, of which one is NK cell leukemia, a highly aggressive hematologic neoplasm with poor prognosis that presents in young men and is more frequently seen in Asian descent. Epstein-Barr virus (EBV) seems to be related to the pathogenesis. Case report: A male patient of 1 year and 7 months of age, who began his condition with anemic, febrile, infiltrative syndrome and hyperleukocytosis is described. Bone marrow aspirate showed L2 morphology blasts (96%), CD56 (80.87%) and terminal deoxynucleotidyl transferase (84.11%) immunophenotype. Bone marrow biopsy showed membranous CD2+, cytoplasmic CD3+ and membranous CD56+; serology positive to EBV. The patient received two different chemotherapy schemes based on methotrexate, ifosfamide, etoposide, dexamethasone and L-asparaginase, which resulted in partial remission. Currently, the patient lives with the disease. Conclusions: NK cells leukemia is rare in young adults, but even more in pediatric patients, for which it is very difficult to treat because only a few cases have been reported in the literature, the survival varies from weeks to months and the chances of treatment are limited. Recently, the usefulness of allogeneic bone marrow transplantation or umbilical cord cells has been demonstrated, achieving a 2-year survival. The therapeutic possibilities in these patients are under study. In the near future, we hope to achieve the complete remission of the disease and a 5-year survival.

Agressive NK-cell leukemia in a pediatric patient.

Background: Natural killer (NK) cell neoplasms are rare and represent <5% of all lymphoid neoplasms. They involve different clinical entities, of which one is NK cell leukemia, a highly aggressive hematologic neoplasm with poor prognosis that presents in young men and is more frequently seen in Asian descent. Epstein-Barr virus (EBV) seems to be related to the pathogenesis. Case report: A male patient of 1 year and 7 months of age, who began his condition with anemic, febrile, infiltrative syndrome and hyperleukocytosis is described. Bone marrow aspirate showed L2 morphology blasts (96%), CD56 (80.87%) and terminal deoxynucleotidyl transferase (84.11%) immunophenotype. Bone marrow biopsy showed membranous CD2+, cytoplasmic CD3+ and membranous CD56+; serology positive to EBV. The patient received two different chemotherapy schemes based on methotrexate, ifosfamide, etoposide, dexamethasone and L-asparaginase, which resulted in partial remission. Currently, the patient lives with the disease. Conclusions: NK cells leukemia is rare in young adults, but even more in pediatric patients, for which it is very difficult to treat because only a few cases have been reported in the literature, the survival varies from weeks to months and the chances of treatment are limited. Recently, the usefulness of allogeneic bone marrow transplantation or umbilical cord cells has been demonstrated, achieving a 2-year survival. The therapeutic possibilities in these patients are under study. In the near future, we hope to achieve the complete remission of the disease and a 5-year survival.

Introducción: Las neoplasias de células natural killer (NK) son poco frecuentes y representan <5% de todas las neoplasias linfoides. Comprometen diferentes entidades clínicas, como la leucemia de células NK, que es una neoplasia hematológica altamente agresiva con un pronóstico precario, que se presenta en hombres jóvenes y se observa con mayor frecuencia en ascendencia asiática. El virus de Epstein-Barr (VEB) parece estar relacionado con la patogenia de esta leucemia. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 1 año y 7 meses de edad, quien inició su padecimiento con síndrome anémico, febril, infiltrativo e hiperleucocitosis. En el aspirado de médula ósea se detectaron blastos de morfología L2 (96%), inmunofenotipo CD56 (80.87%) y desoxinucleotidil transferasa terminal (84.11%). En la biopsia de médula ósea se identificó CD2+ membranoso, CD3+ citoplásmico y CD56+ membranoso; la serología para VEB fue positiva. El paciente recibió dos esquemas diferentes de quimioterapia basados en metotrexato, ifosfamida, etopósido, dexametasona y L-asparaginasa, y se documentó remisión parcial. Actualmente, se encuentra vivo con la enfermedad. Conclusiones: La leucemia de células NK es rara en adultos jóvenes, pero aún más en pacientes en edad pediátrica. Además, es de muy difícil tratamiento, ya que solo se cuenta con algunos reportes de casos, la sobrevida es de semanas a meses y las oportunidades de tratamiento se limitan. Recientemente, se ha evidenciado la utilidad del trasplante de médula ósea alogénico o células de cordón umbilical, y se ha logrado una sobrevida a 2 años. Las posibilidades terapéuticas en estos pacientes se encuentran en estudio. Se espera lograr en un futuro cercano la remisión completa y sobrevida a 5 años.

Pediatric mature B-cell NHL, early referral and supportive care problems in a developing country.

OBJECTIVE: Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. An official report published by the Mexican National Center for the Control and Prevention of Cancer in the Pediatric and Adolescent Populations, reported a lymphoma OS of 71% (including all Hodgkin and NHL). The Mexican Association of Pediatric Oncology and Hematology conducted a retrospective study to analyze the clinical characteristics and outcomes of children with diagnosis of B-NHL in Mexico, in order to perceive the main areas of improvement in the health care. METHODS: From 1 January 2000 to 31 December 2016, 166 pediatric patients were diagnosed with B-cell NHL at the participant institutions. RESULTS: According to histology the outcomes were 5-year EFS 63%, for BL/BLL, and 80% DLBCL, (P = .051), 5-year PFS 81%, for BL/BLL, and 91% for DLBCL, (P = .126), and 5-year OS 71%, for BL/BLL, and 83% for DLBCL, (P = .095). DISCUSSION: 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.

Correlación de la composición corporal con parámetros antropométricos y bioquímicos en pacientes pediátricos con leucemia / Correlation between anthropometric and biochemical parameters whit body composition in children with leukemia

INTRODUCCIÓN: el estado nutricional del paciente pediátrico con cáncer es importante, ya que la desnutrición aumenta la morbilidad por la quimioterapia, así como el abandono del tratamiento, lo que disminuye la sobrevivencia. Obtener un diagnóstico acertado podría mejorar la atención nutricional e impactar en la calidad de vida y sobrevivencia del paciente; actualmente existen alternativas eficientes como la bioimpedancia eléctrica, para realizar diagnósticos eficientes; sin embargo, su uso es poco viable en algunas instituciones públicas. OBJETIVO: determinar la correlación de parámetros antropométricos (circunferencia media de brazo, IMC, puntaje Z de IMC y puntaje Z de talla para la edad) y bioquímicos (albúmina sérica) con la composición corporal en pacientes pediátricos con leucemia linfoblástica aguda. MÉTODOS: se evaluaron a 17 pacientes con diagnóstico reciente de leucemia linfoblástica aguda en un hospital pediátrico en México, las evaluaciones incluyeron parámetros antropométricos (peso, talla, circunferencia media de brazo, IMC, puntaje Z de IMC y puntaje Z de TE) bioquímicos (albúmina) y de composición corporal (proteína, masa grasa corporal, porcentaje de masa grasa y masa de musculo esquelético). RESULTADOS: Se encontró correlación de la circunferencia media de brazo con peso, talla, IMC, proteína corporal total, masa de músculo esquelético, masa grasa corporal y puntaje Z de IMC. El IMC presentó asociación con proteína corporal total, masa de músculo esquelético y masa grasa corporal. El puntaje Z de IMC presento correlación con el porcentaje de grasa corporal y con masa grasa corporal. No se halló correlación del puntaje Z para la talla y para concentración de albúmina. CONCLUSIONES: este estudio nos ayuda a establecer que la valoración nutricional de los pacientes con cáncer debe ampliarse a otros elementos que impliquen una evaluación profunda y que son de vital importancia en el pronóstico de morbi-mortalidad de estos pacientes

INTRODUCTION: the nutritional status of the pediatric cancer patient is important, since malnutrition increases morbidity due to chemotherapy, as well as abandonment of treatment, which decreases survival. Obtaining a correct diagnosis could improve nutritional care and impact the patient's quality of life and survival; currently there are efficient alternatives such as electrical bioimpedance, to perform efficient diagnoses; however, its use is not viable in some public institutions. OBJECTIVE: to determine the correlation of anthropometric parameters (mean arm circumference, BMI, BMI Z score and age-sized Z score) and biochemical (serum albumin) with body composition in pediatric patients with acute lymphoblastic leukemia. METHODS: 17 patients with a recent diagnosis of acute lymphoblastic leukemia were evaluated in a pediatric hospital in Mexico, evaluations included anthropometric parameters (weight, height, average arm circumference, BMI, BMI Z score and TE Z score) biochemical (albumin) and body composition (protein, body fat mass, percentage of fat mass and skeletal muscle mass). RESULTS: Correlation of the average arm circumference with weight, height, BMI, total body protein, skeletal muscle mass, body fat mass and BMI Z score was found. The BMI presented association with total body protein, skeletal muscle mass and body fat mass. The Z score of BMI showed a correlation with the percentage of body fat and body fat mass. There was no correlation of the Z score for height and albumin concentration CONCLUSIONS: This study helps us to establish that the nutritional assessment of cancer patients should be extended to other elements that imply a thorough evaluation and that are of vital importance in the prognosis of morbi-mortality of these patients

Treatment of acute myelogenous leukemia in a Mexican pediatric hospital.

Acute leukemia is the most common malignancy in children, and accounts for nearly 35% of all childhood cancers. Acute myelogenous leukemia (AML) constitutes about 20% of acute leukemias. Initially, treatment of AML involves the immediate management of emergencies associated as hyperleukocytosis, tumor lysis syndrome, hemorrhages and infections. Therefore we performed a retrospective, descriptive and transversal study to investigate the drugs used in patients with AML who were admitted at the Hospital del Niño DIF from 2007 to 2008. Data were collected from hospital. The data included demographic, clinical data and drug usage. A total of 13 patients (12 male and 1 female) were included (prevalence of 16.5% among all cancers in the hospital). The mean age of patients was 6.2 +/- 4.6 years. The mortality rate was 30.8%. Twelve different drugs were given to the patients (10 antineoplastic agents, ondansetron and folinic acid). The median number of drugs/inpatient was 5.4 (range 3-9). Four-hundred thirty-one doses of antineoplastic drugs were administered in 409 sessions. The most used were cytarabine (55.9 %), followed by doxorubicin (7.2 %) and vincristine (6.7 %). Three-hundred twenty-four doses of ondansetron were administered in 409 sessions. We conclude that AML is common in our hospital with a high mortality rate. Also, the antineoplastic agent most used was the pyrimidine analogue cytarabine.