Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience.

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.

[Ovarian reserve and premature ovarian failure in girls and adolescents after hematopoietic stem cell transplantation]. / Reserva ovárica y falla ovárica prematura en niñas y adolescentes postrasplante de progenitores hematopoyéticos.

INTRODUCTION: The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have. OBJECTIVE: to measure ovarian function and reserve after SCT. PATIENTS AND METHOD: A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05. RESULTS: 41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF). CONCLUSIONS: All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.

Directed sibling donor cord blood donation in the Chilean Public Health System. / Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile.

INTRODUCTION: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. PATIENTS AND METHOD: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. RESULTS: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. CONCLUSION: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile / Directed sibling donor cord blood donation in the Chilean Public Health System

Resumen: Introducción: La sangre de cordón umbilical (SCU) como fuente para trasplante de células proge- nitoras hematopoyéticas (TPH) está bien establecida. Internacionalmente, menos del 10% de los TPH de SCU corresponde a donantes hermanos compatibles. Dentro de la red del Programa Infantil Nacional de Drogas Antineoplásicas (PINDA), existe desde enero 2004 un programa de donación dirigida de SCU para TPH. Pacientes y Método: Se diseñó un estudio observacional, retrospectivo, descriptivo, se revisaron el número y características de las unidades de SCU recolectadas en el PINDA y el número, características y evolución de los pacientes trasplantados con esas unidades entre enero de 2004 y octubre de 2018. Resultados: Sesenta unidades de SCU han sido recolectadas, de ellas 55 con registro completo. La mediana de volumen de las unidades almacenadas fue 74,8 ml (30,0-170,8), la mediana de células nucleadas totales 7,6 x 10e8 (2,0-21,1), mediana de células CD34+ 1,6 x 10e6 (0,2-11,6). Cuatro pacientes con leucemias de alto riesgo fueron trasplantados; mediana de segui miento es de 8 años. Todos desarrollaron complicaciones severas post TPH, uno de ellos falleció de recaída y los tres actualmente vivos presentan un Karnofsky/Lansky 100%. Conclusión: El programa ha permitido el trasplante de 4 pacientes que de otro modo no habrían tenido acceso a un donante. Este programa de donación dirigida puede ser considerado una primera etapa para el desarrollo de un banco público de sangre de cordón umbilical en Chile.

Abstract: Introduction: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. Patients and Method: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. Results: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. Conclusion: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Haploidentical stem cell transplantation for children with high-risk leukemia.

BACKGROUND: The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. PROCEDURE: To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced-intensity conditioning regimen for high-risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. RESULTS: Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell-depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10(6)/kg (range, 4.00-20.20 × 10(6)/kg); CD3+: 0.88 × 10(5)/kg (0.11-1.35 × 10(5)/kg); and CD56+: 71.30 × 10(6)/kg (31.50-131.80 × 10(6)/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13-50 months post-HSCT. Three patients died after bone marrow relapse, while only one died of transplant-related causes. Virus reactivation was the main post-transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD. CONCLUSIONS: HI-HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high-risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries.