ABSTRACT
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. Methods: We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. Results: We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Discussion: Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.
ABSTRACT
Hodgkin's Lymphoma has a very good prognosis. In the unusually refractory patients allogeneic transplantation offers a chance of cure. The so-called checkpoint inhibitors, such as Nivolumab can play a relevant role in this type of patients. Their side effects and usefulness after allogeneic transplantation are under investigation. Relapse after allogeneic transplantation has an extremely poor prognosis. We report two patients with refractory Hodgkin's lymphoma who relapsed after an allogeneic transplant and who were successfully treated with Nivolumab.
Subject(s)
Humans , Hodgkin Disease/pathology , Hodgkin Disease/drug therapy , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Nivolumab/therapeutic use , Neoplasm Recurrence, LocalABSTRACT
Hodgkin's Lymphoma has a very good prognosis. In the unusually refractory patients allogeneic transplantation offers a chance of cure. The so-called checkpoint inhibitors, such as Nivolumab can play a relevant role in this type of patients. Their side effects and usefulness after allogeneic transplantation are under investigation. Relapse after allogeneic transplantation has an extremely poor prognosis. We report two patients with refractory Hodgkin's lymphoma who relapsed after an allogeneic transplant and who were successfully treated with Nivolumab.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Neoplasm Recurrence, Local , Nivolumab/therapeutic use , Transplantation, HomologousABSTRACT
Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-ß1, atRA and RAPA. The resulting cells were characterized by the expression of FOXP3, activation, surface and homing markers. Methylation of the Conserved Non-coding Sequence 2 was also evaluated. Functional comparison of the different culture conditions was performed by suppression assays in vitro. Culturing naive human T cells with IL-2/TGFß1 resulted in the generation of 54.2% of Treg cells (CD4+CD25+FOXP3+) whereas the addition of 100 nM atRA increased the yield of Treg cells to 66% (p = 0.0088). The addition of RAPA did not increase the number of Treg cells in any of these settings. Treg cells generated in the presence of atRA had an increased expression of the ß7 integrin to nearly 100% of the generated Treg cells, while RAPA treated cells showed enhanced expression of CXCR4. The differential expression of homing molecules highlights the possibility of inducing Treg cells with differential organ-specific homing properties. Neither atRA nor RAPA had an effect on the highly methylated CNS2 sites, supporting reports that their contribution to the lineage stability of Treg cells is not mediated by methylation changes in this locus. Treg cells generated in the presence of RAPA show the most potent suppression effect on the proliferation of effector cells.
Subject(s)
Sirolimus/pharmacology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes/drug effects , Tretinoin/pharmacology , Adolescent , Adult , Antineoplastic Agents/pharmacology , Cells, Cultured , CpG Islands/genetics , DNA Methylation/drug effects , Drug Synergism , Flow Cytometry , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2/pharmacology , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-2 Receptor alpha Subunit/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta1/pharmacology , Young AdultABSTRACT
Introducción: Estudios recientes indican que el trasplante intracoronario de células mononucleares de médula ósea (BMCs) autólogas, mejoran la fracción de eyección (FEVI) y otros marcadores clínicos en pacientes con insuficiencia cardíaca (IC). Objetivo: Evaluar la seguridad y eficacia de la administración intracoronaria de BMCs autólogas, en pacientes con insuficiencia cardíaca (IC) en fase dilatada, de diferente etiología y en óptimas condiciones de tratamiento médico. Método: De 23 pacientes consecutivos que cumplieron con los criterios de inclusión, 12 fueron asignados a trasplante intracoronario de BMCs autólogas, recibiendo una dosis media de 8.19+/-4.43 x 10(6) células CD34+ (Grupo trasplantado). Los pacientes restantes sólo recibieron terapia estándar (Grupo control). Todos los pacientes fueron evaluados mediante Electrocardiograma, Ecocardiografía, Holter ECG, RMN Cardíaca, Test de esfuerzo, Potenciales Ventriculares Tardíos, Variabilidad de Frecuencia Cardíaca y evaluación clínica a los 0, 3, 6 y 12 meses. La capacidad funcional (CF) fue evaluada clínicamente y por cuestionarios de calidad de vida. Elanálisis estadístico fue realizado mediante Test Anova, y test de Bonferroni. Resultados: El grupo trasplantado presentó un aumento significativo de la FEVI a los 6 meses (26.75+/-4.85 vs 37.82+/-6.97 por ciento, p=0.001) mejoría que se mantuvo a los 12 meses (26.75+/-4.85 vs 37.27+/-7.51 por ciento, p=0.002). Hubo una mejora significativa de la CF en el grupo trasplantado a los 6 y 12 meses (p<0.001). No hubo cambios significativos en los volúmenes de ventrículo izquierdo, así como en las restantes variables estudiadas. En el grupo control no observamos cambios de estas variables. No hubo complicaciones en relación al trasplante de BMCs. Conclusión: En pacientes con IC severa y baja FEVI, el trasplante intracoronario de células BMCs au-tólogas, se asoció a una mejoría significativa de la FEVI y la CF, a los 6 y 12 meses. Adicionalmente, no observamos ...
Background: Recent studies indicate that intra-coronary delivery of autologous bone marrow mono-nuclear cells (BMCs) improves the ejection fraction (LVEF) and other clinical markers in patients with heart failure (HF). Aim: To evaluate the safety and efficacy of intraco-ronary delivery of autologous BMCs in patients with HF in dilated phase under optimal medical treatment. Method: Of 23 consecutive patients who met the inclusion criteria, 12 were assigned to autologous BMCs intracoronary transplantation, receiving a mean dose of 8.19+/-4.43 x 106 CD34+ cells (BMCs group). The remaining patients received only standard therapy (control group). All patients were evaluated by Electrocardiogram, Echocardiography, Holter Monitoring, Cardiac Magnetic Resonance Imaging, Stress Testing, Ventricular Late potetials, Heart Rate Variability, and regular clinical examination at baseline and at follow-up (3, 6 and 12 months). Repeated measures ANOVA and Bonferroni testing were used for statistic analysis. Results: The BMCs group presented a significant increase in EF at sixth months (26.75+/-4.85 vs. 37.82+/-6.97 per cent, p=0.001) and 12 months post-transplant (26.75+/-4.85 vs. 37.27+/-7.51 per cent, p=0.002). There was a significant improvement in functional (NYHA) in the transplanted group at 6 and 12 months (p<0.001). There were no significant changes concerning left ventricular volumes, heart rate variability and exercise stress testing. We observed no improvement of these variables in the control group. There were no complications related to the BMCs transplant. Conclusions: Intracoronary infusion of auto-logous BMCs, in addition to standard therapy, was associated with significant improvement of left ventricular function at 12 months in patients with HF. We observed no complications relative to the procedure.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Bone Marrow Transplantation , Heart Failure/therapy , Ventricular Function , Analysis of Variance , Cardiomyopathy, Dilated/physiopathology , Follow-Up Studies , Single-Blind MethodABSTRACT
BACKGROUND: Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident. METHODS: Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis. RESULTS: A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08). CONCLUSIONS: Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.
Subject(s)
Fever of Unknown Origin/complications , Neoplasms/complications , Neutropenia/complications , Sepsis/diagnosis , Sepsis/physiopathology , Adolescent , Age Factors , Biomarkers , Blood Glucose , Blood Urea Nitrogen , C-Reactive Protein/analysis , Calcitonin/blood , Calcitonin Gene-Related Peptide , Child , Child, Preschool , Chile , Female , Hospitalization , Humans , Interleukin-8/blood , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Prospective Studies , Protein Precursors/bloodABSTRACT
BACKGROUND: Early identification of children with cancer at risk for death during a febrile neutropenic (FN) episode may increase their possibility for survival. Our aim was to identify at the time of admission, clinical and laboratory variables differing significantly among children who survived or died during a FN episode. METHODS: In a prospective, multicenter study, children admitted with a high-risk FN episode were uniformly evaluated at enrollment and managed according to a national consensus protocol. Medical charts of children who died were evaluated to determine whether the death could be associated with an infection. Admission clinical and laboratory variables significantly associated with death were identified. RESULTS: A total of 393 (70%) of 561 FN episodes evaluated from June 2004 to December 2005 were classified as high risk for invasive bacterial infection, of which 14 (3.6%) resulted in an infectious-related death. Deaths occurred from 2 to 27 days after admission, and most dying children were admitted with relapse of acute lymphocytic leukemia (36%), hypotension (71%), and a diagnosis of sepsis (79%), compared with surviving children (16%, 20%, and 5% respectively, P < 0.001). Children who died were admitted with lower absolute neutrophil count (P < 0.001) and absolute monocytes count levels (P = 0.008), higher blood urinary nitrogen (P = 0.03) and C-reactive protein values (P < 0.001), and had more positive cultures (79% versus 32%, P = 0.008). CONCLUSIONS: We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death.
Subject(s)
Fever/complications , Neoplasms/complications , Neutropenia/complications , Neutropenia/mortality , Sepsis/complications , Sepsis/mortality , Adolescent , Age Factors , Child , Child, Preschool , Chile/epidemiology , Female , Humans , Infant , Male , Medical Records , Neoplasms/blood , Neoplasms/mortality , Neoplasms/urine , Neutropenia/blood , Neutropenia/urine , Recurrence , Risk Factors , Sepsis/microbiology , SurvivorsABSTRACT
BACKGROUND: In Chile, survival estimates for pediatric patients with cancer are comparable to those in the United States and Western Europe. Approximately 80% of these patients are treated at government-supported centers, and an estimated 65% are cured. We reasoned that cure rates could be further improved if transplantation with hematopoietic stem cells were available for patients with chemotherapy-resistant malignancy. PATIENTS AND METHODS: Physicians and nurses were selected to be trained in international centers, and a transplantation unit was developed at Luis Calvo Mackenna Hospital in Santiago. Between October 1999 and December 2003, 59 patients received transplants. Of these, 42 were from HLA-matched family members and 11 were autologous. RESULTS: The 3-year event-free survival estimate was 72 +/- 10% overall, and it was 81 +/- 10% for the subgroup treated with matched related transplants. Peritransplant mortality was 6.6%. The average cost for an allogeneic transplant in our unit was 50,000 US dollars. CONCLUSIONS: We are encouraged by this experience as well as by the overall survival rates and hope to expand the program. Our goal is to extend treatment to all children in the country for whom HSCT is indicated, including those who do not have HLA-identical family donors.