Measurable residual disease study through three different methods can anticipate relapse and guide early interventions in childhood acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Measurable residual disease (MRD, previously named minimal residual disease) study can guide therapy adjustments or preemptive interventions that might avoid hematological relapse. METHODS: Clinical decision making and patient outcome were evaluated in 80 real-life childhood ALL patients, according to the results observed in 544 bone marrow samples analyzed with three MRD methods: multiparametric flow cytometry (MFC), fluorescent in-situ hybridization (FISH) on B or T-purified lymphocytes and patient-specific nested reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Estimated 5 year overall survival and event-free survival were 94% and 84.1%, respectively. A total of 12 relapses in 7 patients were associated with positive MRD detection with at least one of the three methods: MFC (p < 0.00001), FISH (p < 0.00001) and RT-PCR (p = 0.013). MRD assessment allowed the anticipation of relapse and adapted early interventions with different approaches including chemotherapy intensification, blinatumomab, HSCT and targeted therapy to halt relapse in five patients, although two of them relapsed afterwards. CONCLUSION: MFC, FISH and RT-PCR are complementary methods for MRD monitoring in pediatric ALL. Although, our data clearly show that MDR positive detection is associated with relapse, continuation of standard treatment, intensification or other early interventions were able to halt relapse in patients with different risks and genetic background. More sensitive and specific methods are warranted to enhance this approach. However, whether early treatment of MRD can improve overall survival in patients with childhood ALL needs to be evaluated in adequately controlled clinical trials.

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia.

PURPOSE: Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. METHODS: In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). RESULTS: Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. CONCLUSIONS: MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.

Cross-sectional study of echocardiographic characteristics in healthy children living at high altitude.

Non-echocardiographic studies in healthy high altitude children have shown right ventricle predominance during infancy and childhood, associated to asymptomatic pulmonary hypertension and an increased pulmonary artery pressure. Systematic studies on echocardiography in such children have not been performed. In a cross-sectional study, we measured right and left heart morphologic and functional parameters, through M-mode, two-dimensional Doppler, and color Doppler echocardiographies, in a population of 321 healthy children ranging in age from 2 months to 19 years and living at high altitude (Tintaya, Peru, 4,100 m). Structured ad-hoc interviews were done to obtain information on medical history, patterns of exposure to high altitude of children and their parents and grandparents, place and altitude of pregnancy and birth, and housing conditions. A complete physical examination was performed before echocardiography. Hemoglobin concentration, pulse oximetry, and anthropometry were measured in all participating children. The right and left heart morphologic and functional echocardiographic measurements expressed by age and by body surface area were generally similar to sea-level reference populations. They were not consistently influenced by sex, nutritional status, chest dimensions, pulse oximetry, hemoglobin concentration, ethnicity, length of residence at high altitude, or parental history of exposure to high altitude. Most children had at least some degree of high-altitude ancestry as assessed by ethnicity and history of parental exposure to altitude. The cardiovascular development at high altitude in children with some degree of high-altitude ancestry seems to follow a pattern similar to sea-level children. The results can be used as reference values to interpret individual echocardiographic studies in comparable children living in similar settings.

Patología del hombre nativo de las grandes alturas : Investigación de las causas de muerte en 300 autopsias / Pathology of natives of high altitudes : Investigation of the causes of death in 300 autopsies

The authors give the results of autopsies on 300 persons native to our living in the city of Cerro de Pasco, Peru, which is situated at an altitude of 14,300 ft, and in adjacent villages

With the exception of infant diseases, the most frequent causes of death are diseases of the respiratory system. Of these, pneumonia and bronchopneumonia occupy the first place, and their incidence is higher than that observed at sea-level. Among infectious diseases, tuberculosis occupies the first place. The findings also show that at high altitudes intestinal obstruction by volvulus is more frequent in adults than at sea-level

Another significant finding was the frequency in adults of vascular lesions of the central nervous system, the rate of which was higher than that observed at sea-level. In addition, hemorrohagic complication of various types of lesions, especially of the respiratory and digestive systems, both in adults and in children, are more frequent at high altitudes than at sea-level(AU)