Clonal Myeloproliferative Disorders in Patients with Down Syndrome-Treatment and Outcome Results from an Institution in Argentina.

Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL). Patients with DS-AML were treated according to four BFM-based protocols. Classical ML-DS vs. non-DS-AMKL were compared and the outcome of ML-DS was analyzed according to treatment intensity. Only four patients with TAM required cytoreduction with a 5-year Event-Free Survival probability (EFSp) of 74.4 (±9.1)%. DS-AML treatment-related deaths were due to infections, with a 5-year EFSp of 60.6 (±8.2)%. Megakaryoblastic immunophenotype was the strongest good-prognostic factor in univariate and multivariate analysis (p = 0.000). When compared ML-DS with non-DS-AMKL, a better outcome was associated with a lower relapse rate (p = 0.0002). Analysis of administered treatment was done on 32/33 ML-DS patients who achieved CR according to receiving or not high-dose ARA-C block (HDARA-C), and no difference in 5-year EFSp was observed (p = 0.172). TAM rarely required treatment and when severe manifestations occurred, early intervention was effective. DS-AML good outcome was associated with AMKL with a low relapse-rate. Even if treatment-related mortality is still high, our data do not support the omission of HDARA-C in ML-DS since we observed a trend to detect a higher relapse rate in the arm without HDARA-C.

Colorectal carcinoma in children and adolescents. / Carcinoma colorrectal en niños y adolescentes.

Although colorectal carcinoma (CRC) is the third most common type of cancer in adults, only 1-4 % of cases are reported in individuals younger than 25-30 years. Its presentation is usually confused with other diseases, leading to significant delays in diagnosis. Given its low incidence, few pediatricians will see a case throughout their practice. However, multiple hereditary syndromes during childhood predispose to CRC. The objective of this review is to provide an update on syndromes predisposing to CRC. Screening indications will be reviewed because an early diagnosis during localized stages is the main prognostic factor. In addition, patient and family genetic counseling tools will be enhanced. In turn, the clinical and histological manifestations and prognostic factors typical of CRC in the pediatric population will be discussed. Although treatment guidelines are extrapolated from the adult experience, therapy guidelines will be summarized here.

Si bien el carcinoma colorrectal (CCR) es la tercera enfermedad oncológica más frecuente en adultos, solo el 1-4 % ocurre en menores de 25-30 años. Su presentación suele confundirse con otras patologías, lo cual lleva a significativas demoras diagnósticas. Dada su baja incidencia, pocos pediatras se enfrentarán con algún caso a lo largo de su carrera. Sin embargo, existen en la niñez múltiples síndromes hereditarios que predisponen al CCR. El objetivo de esta revisión es brindar una actualización sobre los síndromes predisponentes al CCR. Se revisarán las indicaciones de tamizaje, dado que el diagnóstico precoz en estadios localizados es el principal factor pronóstico. Además, se fortalecerán las herramientas de consejería genética para el paciente y su familia. A su vez, se discutirán las manifestaciones clínicas e histológicas y los factores pronósticos propios del CCR en la población pediátrica. Si bien las guías de tratamiento se extrapolan de la experiencia en adultos, se resumirán los lineamientos terapéuticos.

Carcinoma colorrectal en niños y adolescentes / Colorectal carcinoma in children and adolescent

Si bien el carcinoma colorrectal (CCR) es la tercera enfermedad oncológica más frecuente en adultos, solo el 1-4 % ocurre en menores de 25-30 años. Su presentación suele confundirse con otras patologías, lo cual lleva a significativas demoras diagnósticas. Dada su baja incidencia, pocos pediatras se enfrentarán con algún caso a lo largo de su carrera. Sin embargo, existen en la niñez múltiples síndromes hereditarios que predisponen al CCR. El objetivo de esta revisión es brindar una actualización sobre los síndromes predisponentes al CCR. Se revisarán las indicaciones de tamizaje, dado que el diagnóstico precoz en estadios localizados es el principal factor pronóstico. Además, se fortalecerán las herramientas de consejería genética para el paciente y su familia. A su vez, se discutirán las manifestaciones clínicas e histológicas y los factores pronósticos propios del CCR en la población pediátrica. Si bien las guías de tratamiento se extrapolan de la experiencia en adultos, se resumirán los lineamientos terapéuticos.

Although colorectal carcinoma (CRC) is the third most common type of cancer in adults, only 1-4 % of cases are reported in individuals younger than 25-30 years. Its presentation is usually confused with other diseases, leading to significant delays in diagnosis. Given its low incidence, few pediatricians will see a case throughout their practice. However, multiple hereditary syndromes during childhood predispose to CRC.The objective of this review is to provide an update on syndromes predisposing to CRC. Screening indications will be reviewed because an early diagnosis during localized stages is the main prognostic factor. In addition, patient and family genetic counseling tools will be enhanced. In turn, the clinical and histological manifestations and prognostic factors typical of CRC in the pediatric population will be discussed. Although treatment guidelines are extrapolated from the adult experience, therapy guidelines will be summarized here.

No benefit of Interfant protocols compared to BFM-based protocols for infants with acute lymphoblastic leukemia. Results from an institution in Argentina.

BACKGROUND: Infant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM-based protocols. PROCEDURE: This is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM-based protocols. RESULTS: During the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL-BFM'90 (n = 16), 1-ALL96-BFM/HPG (n = 7), Interfant-99 (n = 39), Interfant-06 (n = 35), and ALLIC-BFM'2009 (n = 19). The 5-year event-free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant-06 criteria (P = .0029). KMT2A-rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)-negative versus 11.5 months for those with MRD-positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149). CONCLUSIONS: Interfant protocols and BFM-based protocols presented comparable results. The risk group stratification proposed by Interfant-06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse.

Leucemia linfoblástica aguda en niños con síndrome de Down: análisis comparativo con pacientes sin síndrome de Down / Acute lymphoblastic leukemia in children with Down syndrome: Comparative analysis versus patients without Down syndrome

Introducción: Los niños con síndrome de Down (SD) tienen mayor frecuencia de leucemia linfoblástica aguda (LLA) y menor supervivencia que pacientes sin síndrome de Down (NSD). Analizamos las características clínicas, demográficas-biológicas y respuestas al tratamiento en SD-LLA versus NSD-LLA. Pacientes y métodos: Pacientes (0-19 años) con LLA desde enero de 1990 a noviembre de 2016. Se compararon características demográficas biológicas y respuestas al tratamiento con chi cuadrado y Wilcoxon rank sum. La supervivencia global y el intervalo libre de eventos (ILE) se analizaron con Kaplan-Meier y el test log-rank. Resultados: Se incluyeron 1795 pacientes, 54 con SD. Los SD-LLA presentaron edad mayor (p= 0,0189). T odos inmuno fenotipo precursor-B, con menor incidencia de anomalías recurrentes (p < 0,0001). Demostraron mejor tasa de respuesta a prednisona (p= 0,09) y mayor mortalidad en inducción y remisión completa (p < 0,0001). Todas las muertes de los SD-LLA fueron relacionadas con el tratamiento. La sobrevida libre de eventos en niños SD-LLA vs.NSD-LLA fue 47 (± 8)% vs. 73 (± 1)% (p= 0,006) y el ILE de los SD-LLA vs. NSD-LLA fue 54 (± 9)% vs. 75 (± 1)% (p= 0,0297). La tasa de recaídas fue similar en ambos grupos (p= 0,6894). El ILE de los SD-LLA fue menor en el grupo de 6-9 años: 39 (± 19)% (p= 0,7885). Conclusiones: Los niños de 6-9 años con SD-LLA años presentó menor sobrevida. Aunque estos niños presentaron una mejor respuesta temprana, la sobrevida libre de eventos e ILE fueron menores debido a la mortalidad relacionada con el tratamiento.

Introduction. Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests. Results. 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885). Conclusions. A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality.

Acute lymphoblastic leukemia in children with Down syndrome: Comparative analysis versus patients without Down syndrome. / Leucemia linfoblástica aguda en niños con síndrome de Down: análisis comparativo con pacientes sin síndrome de Down.

INTRODUCTION: Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests. RESULTS: 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885). CONCLUSIONS: A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality.

Introducción: Los niños con síndrome de Down (SD) tienen mayor frecuencia de leucemia linfoblástica aguda (LLA) y menor supervivencia que pacientes sin síndrome de Down (NSD). Analizamos las características clínicas, demográficas-biológicas y respuestas al tratamiento en SD-LLA versus NSD-LLA. Pacientes y métodos: Pacientes (0-19 años) con LLA desde enero de 1990 a noviembre de 2016. Se compararon características demográficas biológicas y respuestas al tratamiento con chi cuadrado y Wilcoxon rank sum. La supervivencia global y el intervalo libre de eventos (ILE) se analizaron con Kaplan-Meier y el test log-rank. Resultados: Se incluyeron 1795 pacientes, 54 con SD. Los SD-LLA presentaron edad mayor (p= 0,0189). Todos inmuno fenotipo precursor-B, con menor incidencia de anomalías recurrentes (p < 0,0001). Demostraron mejor tasa de respuesta a prednisona (p= 0,09) y mayor mortalidad en inducción y remisión completa (p < 0,0001). Todas las muertes de los SD-LLA fueron relacionadas con el tratamiento. La sobrevida libre de eventos en niños SD-LLA vs.NSD-LLA fue 47 (± 8)% vs. 73 (± 1)% (p= 0,006) y el ILE de los SD-LLA vs. NSD-LLA fue 54 (± 9)% vs. 75 (± 1)% (p= 0,0297). La tasa de recaídas fue similar en ambos grupos (p= 0,6894). El ILE de los SD-LLA fue menor en el grupo de 6-9 años: 39 (± 19)% (p= 0,7885). Conclusiones: Los niños de 6-9 años con SD-LLA años presentó menor sobrevida. Aunque estos niños presentaron una mejor respuesta temprana, la sobrevida libre de eventos e ILE fueron menores debido a la mortalidad relacionada con el tratamiento.