Donor selection in allogeneic stem cell transplantation.

PURPOSE OF REVIEW: Recent progress in human leukocyte antigen (HLA) characterization, increased accrual of unrelated donors and cord blood units, and a new platform for haploidentical transplantation have resulted in the widespread availability of donors for allogeneic hematopoietic stem cell transplantation. RECENT FINDINGS: Advances in HLA typing have identified an increasing number of loci and alleles that are crucial for successful transplantation. Newer HLA A, B, C, DRB1, and DQB1 alleles, DPB1 mismatches, and HLA B leader sequence matching are incorporated into donor selection algorithms. Donor selection is highly relevant because of recently published conflicting studies using different donor types. These studies are largely retrospective and compare patients with different diseases and stages, conditioning regimens, graft versus host disease (GVHD) prophylaxis, and time periods. A broad consensus indicates that the best donor is an available matched sibling, followed by a matched unrelated donor, and then alternative donors such as haploidentical, mismatched unrelated, and cord blood units. This consensus is being challenged by other factors, such as donor age, patient condition, urgency of transplantation, and costs involved. SUMMARY: In this review, we will analyze the unique characteristics of each donor type, the HLA and non HLA factors that affect donor choices, and the outstanding comparative outcome studies of different donor usage in hematologic malignancies.

Long-term remission of infantile Takayasu arteritis associated with germline CBL syndrome after allogeneic hematopoietic stem cell transplantation: A case report and literature review.

Takayasu arteritis (TA) is a large-vessel vasculitis that rarely presents in infancy. Casitas B-lineage lymphoma (CBL) syndrome is a rare genetic disorder due to heterozygous CBL gene germline pathogenic variants that is characterized by a predisposition to develop juvenile myelomonocytic leukemia (JMML). Vasculitis, including TA, has been reported in several patients. Herein, we describe a patient with CBL syndrome, JMML, and TA, developing long-term remission of this vasculitis after allogeneic hematopoietic stem cell transplant (HSCT), and perform a literature review of CBL syndrome with vasculitis or vasculopathy. We report a female patient with growth delay, developmental issues, and congenital heart disease who was admitted at 14 months of age with massive splenomegaly, lymphadenopathy, fever, and hypertension. Body imaging studies revealed arterial stenosis and wall inflammation of the aorta and multiple thoracic and abdominal branches. Whole exome sequencing revealed a pathogenic variant in CBL with loss of heterozygosity in blood cells, diagnosing CBL syndrome, complicated by JMML and TA. Allogeneic HSCT induced remission of JMML and TA, permitting discontinuation of immunosuppression after 12 months. Six years later, her TA is in complete remission off therapy. A literature review identified 18 additional cases of CBL syndrome with vasculitis or vasculopathy. The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.

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.

5 years DKMS Chile: approach, results and impact of the first unrelated stem cell donor center in Chile.

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.

HLA allele and haplotype frequencies of registered stem cell donors in Chile.

Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed "non-Indigenous" (n=92,788) and "Mapuche" (n=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile's complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.

The viral nucleocapsid protein and the human RNA-binding protein Mex3A promote translation of the Andes orthohantavirus small mRNA.

The capped Small segment mRNA (SmRNA) of the Andes orthohantavirus (ANDV) lacks a poly(A) tail. In this study, we characterize the mechanism driving ANDV-SmRNA translation. Results show that the ANDV-nucleocapsid protein (ANDV-N) promotes in vitro translation from capped mRNAs without replacing eukaryotic initiation factor (eIF) 4G. Using an RNA affinity chromatography approach followed by mass spectrometry, we identify the human RNA chaperone Mex3A (hMex3A) as a SmRNA-3'UTR binding protein. Results show that hMex3A enhances SmRNA translation in a 3'UTR dependent manner, either alone or when co-expressed with the ANDV-N. The ANDV-N and hMex3A proteins do not interact in cells, but both proteins interact with eIF4G. The hMex3A-eIF4G interaction showed to be independent of ANDV-infection or ANDV-N expression. Together, our observations suggest that translation of the ANDV SmRNA is enhanced by a 5'-3' end interaction, mediated by both viral and cellular proteins.

Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda / Age does not affect the outcome of allogeneic hematopoietic precursor transplantation for acute myeloid leukemia

BACKGROUND: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. AIM: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. MATERIAL AND METHODS: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. RESULTS: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. Conclusions: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.

[Humoral immune response induced by influenza vaccine in children with acute lymphoblastic leukemia]. / Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda.

BACKGROUND: Patients with acute lymphoblastic leukemia (ALL) have high risk of severe influenza infection and vaccination is highly recommended. The immunogenicity and effectiveness of vaccination are lower than in healthy people. AIM: To evaluate the immune response induced by influenza vaccine in children with ALL and observe effectiveness. METHOD: Children with ALL in maintenance phase and healthy children were recruited. Blood samples were taken at vaccination day (D0) and at day 28 (D28). Humoral response was evaluated by hemaglutination inhibition test (HAI) against H1N1. Patients were followed up for one year, clinical data and influenza episodes were recorded. RESULTS: 34 children with ALL and 9 healthy children were included. Concerning HAI on D28, 12/34 patients and 5/8 healthy children had titers ≥ 1/40, with seroprotection rates of 35 and 63% respectively. Seroprotected children were older than non-seroprotected ones. During follow-up, only 3 patients non seroprotected, presented influenza infection, without oxygen supplementation or critical care support. DISCUSSION: Children with ALL had a lower seroprotection rate than healthy children. Nevertheless, none of the seroprotected children presented influenza infection, reinforcing the annual vaccination recommendation.

Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda / Humoral immune response induced by influenza vaccine in children with acute lymphoblastic leukemia

Resumen Introducción: Los pacientes con leucemia linfoblástica aguda (LLA) tienen alto riesgo de influenza grave y la vacunación es altamente recomendada. La inmunogenicidad y efectividad de la vacuna es menor comparada a los sujetos sanos. Objetivo: Evaluar la respuesta inmune inducida por vacuna anti-influenza en niños con LLA y observar su efectividad. Métodos: Se reclutaron niños con LLA en terapia de mantención y niños sanos. Se tomaron muestras de sangre el día de la vacuna (D0) y al día 28 (D28), y se realizó test de inhibición de hemaglutinación (IHA) contra H1N1. Los pacientes fueron seguidos por un año, registrando datos clínicos y episodios de influenza. Resultados: Se incluyeron 34 niños con LLA y 9 niños sanos. Respecto al IHA en D28, 12/34 pacientes y 5/8 niños sanos presentaron títulos ≥ 1/40, resultando una tasa de seroprotección de 35 y 63%, respectivamente. Los niños seroprotegidos eran significativamente mayores. Durante el seguimiento, sólo tres pacientes, no seroprotegidos, presentaron infección por influenza, ninguno requirió oxigeno o cuidados intensivos. Discusión: Los niños con LLA alcanzaron una tasa seroprotección más baja que la observada en niños sanos. Sin embargo, ninguno de los niños seroprotegidos presentó infección por influenza, reforzando la recomendación de vacunación anual.

Abstract Background: Patients with acute lymphoblastic leukemia (ALL) have high risk of severe influenza infection and vaccination is highly recommended. The immunogenicity and effectiveness of vaccination are lower than in healthy people. Aim: To evaluate the immune response induced by influenza vaccine in children with ALL and observe effectiveness. Method: Children with ALL in maintenance phase and healthy children were recruited. Blood samples were taken at vaccination day (D0) and at day 28 (D28). Humoral response was evaluated by hemaglutination inhibition test (HAI) against H1N1. Patients were followed up for one year, clinical data and influenza episodes were recorded. Results: 34 children with ALL and 9 healthy children were included. Concerning HAI on D28, 12/34 patients and 5/8 healthy children had titers ≥ 1/40, with seroprotection rates of 35 and 63% respectively. Seroprotected children were older than non-seroprotected ones. During follow-up, only 3 patients non seroprotected, presented influenza infection, without oxygen supplementation or critical care support. Discussion: Children with ALL had a lower seroprotection rate than healthy children. Nevertheless, none of the seroprotected children presented influenza infection, reinforcing the annual vaccination recommendation.

HLA-A, -B, -DRB1 allele and haplotype frequencies of 920 cord blood units from Central Chile.

We present human leukocyte antigen (HLA) haplotype and allele/antigenic group frequencies derived from a data set of 920 umbilical cord blood units collected in Central Chile. HLA-A and -B genotypes were typed using sequence specific oligonucleotide probe methods while HLA-DRB1 genotypes were obtained from sequencing-based typing. The most frequent haplotype is A*29~B*44~DRB1*07:01 with an estimated frequency of 2.1%.

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank]. / Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón.

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis.

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.

[Use of desmopressin in children with inherited platelet dysfunctions undergoing adenotonsillar procedures]. / Uso de desmopresina en niños con disfunción plaquetaria congénita sometidos a adeno y/o amigdalectomía.

INTRODUCTION AND GOALS: Adenotonsillar surgery represents a major haemostatic challenge in paediatric patients with mild inherited platelet dysfunction. While there are recommendations for perioperative haemostatic management, there are no reports of the outcomes with the different recommendations in these children when undergoing adenotonsillectomy. Our objective was to evaluate the management of perioperative bleeding with desmopressin in children with mild platelet dysfunctions who underwent adenotonsillar surgery in our hospital. METHODS: We performed a retrospective study aimed at determining the perioperative bleeding and complication rate in children with mild inherited platelet dysfunction in whom desmopressin was used while undergoing adenotonsillar procedures. RESULTS: Between 2004 and 2010, 27 children with mild inherited platelet dysfunction underwent adenotonsillar procedures in our hospital and were treated with desmopressin. One patient developed perioperative bleeding (3.7%) and there was 1 child (3.7%) who presented transitory hypotension as a side effect of desmopressin. CONCLUSIONS: The use of desmopressin allowed adequate perioperative bleeding prophylaxis management in children with mild inherited platelet dysfunction who underwent adenotonsillar procedures without presenting severe complications.

Hematopoietic stem cell transplantation: clinical use and perspectives.

Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone marrow environment, the biology of hematopoietic stem cells and histocompatibility. The development of this new discipline has allowed numerous groups working around the world to cure patients of diseases previously considered lethal. Together with the ever growing list of volunteer donors and umbilical cord blood banks, this has resulted in life saving therapy for thousands of patients yearly. We present an overview of the procedure from its cradle to the most novel applications, as well as the results of the HSC transplant program developed at our institution since 1989.

Hematopoietic stem cell transplantation: clinical use and perspectives

Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone marrow environment, the biology of hematopoietic stem cells and histocompatibility. The development of this new discipline has allowed numerous groups working around the world to cure patients of diseases previously considered lethal. Together with the ever growing list of volunteer donors and umbilical cord blood banks, this has resulted in life saving therapy for thousands of patients yearly. We present an overview of the procedure from its cradle to the most novel applications, as well as the results of the HSC transplant program developed at our institution since 1989.

Trombo tumoral en aurícula derecha en tumor de Wilms / Tumoral thrombus in right auricle in Wilms tumor

En el tumor de Wilms (TW) el trombo cavo atrial (TCA) es < 5 por ciento, siendo rareza el compromiso auricular derecho. Revisamos los abordajes quirúrgicos del TCA en el TW. Materiales y métodos: Paciente de 3 años y medio con tumor renal derecho de 10 cm, un cava inferior ocupada por trombo tumoral hasta la aurícula derecha. Además tumor en la vena renal izquierda y cava infra renal. Se utiliza quimioterapia preoperatoria previa biopsia por punción. Resultados: seis semanas de quimioterapia y un TAC demostró reducción 10 por ciento del tumor y menor TCA. Se realizó nefrectomía radical derecha con trombectomía cava abdominal y renal izquierda combinada con trombectomía cava toráxica y auricular, con paro cardiopulmonar, circulación extracorpórea e hipotermia. Evolucionó sin complicaciones, la biopsia no demostró tumor en el riñón o TCA. Se catalogó TW etapa III sin anaplasia y entró en un protocolo DD4A del NWTSG. A 1 mes de la cirugía el TAC mostró ausencia de tumor. Conclusiones: El compromiso tumoral de la cava y aurícula derecha es excepcional en TW. Los mejores resultados y menor morbilidad están asociados a quimioterapia preoperatoria y buena planificación de la vía de abordaje.

Introduction: In the tumor of Wilms (TW) the thrombus cava atrial (TCA) it is < 5%, being exceptional the atrial right involvement. We check the surgical routes of access of the TCA in the TW. Materials and methods: 3-year-old patient with renal right tumor of 10 cm, a inferior vena cava occupied by tumor thrombus up to the right auricle. Also tumor in the renal left vein and vena cava under the kidney. We use preoperative chemotherapy previous biopsy for puncture. Results: 6 weeks of chemotherapy and a TAC demonstrated reduction 10% of the tumor and decrease TCA. We realized radical right nephrectomy with thrombectomy abdominal cava and renal left combined with thrombectomy thorax cava and atrial right, with cardiopulmonar unemployment, extracorporeal circulation and hypothermia. She evolved without complications, the biopsy did not demonstrate tumor in the kidney or TCA. TW catalogued stage the IIIrd without anaplasia and she entered a protocol DD4A of the NWTSG. To 1 month of the surgery the TAC showed absence of tumor. Conclusions: The tumor commitment of the vena cava and right auricle is exceptional in TW. The best results and minor morbidity are associated with preoperative chemotherapy and good planning of the routes of access.

Heparina con vancomicina en la prevención de bacteremias asociadas a cateter venoso permanente en pacientes oncológicos: resultados preliminares de un estudio randomizado de doble ciego / Heparin plus vancomycin in prophylaxis of catheter associated bacteremias in oncological patients: preliminar results of a double blind, randomized study

Objetivos: probar si la adición de vancomicina en microdosis (25 mcg/ml) a la solución de heparinización de catéteres venosos centrales permanentes (CVP) previene la ocurrencia de bacteremias por gérmenes vancomicina sensibles en pacientes oncológicos. Métodos: 39 pacientes con patología oncológica portadores de CVP externo (Hickman-Broviac) participaron en un estudio prospectivo, randomizado de doble ciego y fueron asignados a recibir una solución de heparina sola (Hep) o de heparina-vancomicina (HepVan). Todos los episodios febriles fueron registrados, realizándose hemograma y hemocultivo central y periférico. Los episodios febriles fueron tratados con antibióticos según normas establecidas. Resultados: se observaron en 14 meses 6.519 días catéter. Hubo 70 episodios febriles y 16 episodios de bacteremia, de los cuales 9 fueron por gérmenes sensibles a la vancomicina, 6 en el grupo Hep y 3 en el grupo HepVan (p = 0,31). En los episodios no neutropénicos (recuento absoluto de neutrófilos > 500/cm3) hubo 4 bacteremias en el grupo Hep y 0 en el grupo HepVan (p = 0,057). Conclusiones: la adición de vancomicina a la solución de heparinización de CVP no previene bacteremia asociada a CVP. La menor incidencia de bacteremias por gérmenes sensibles a la vancomicina en pacientes no neutropénicos versus neutropénicos en el grupo HepVan apoya la hipótesis de que la colonización intraluminal del CVP es un factor importante en las bacteremias en pacientes no neutropénicos

Quimioterapia de los tumores malignos del sistema nervioso central: estado actual / Chemotherapy of central nervous system malignant tumors: present state

El manejo de los pacientes con tumores del SNC ha evolucionado gracias a la introducción de nuevas modalidades terapéuticas y, mas importante, a la integración de las diversas especialidades; cirugía, radioterapia, oncología médica, conformando una nueva disciplina, la neurooncología. La utilización de la quimioterapia en esquemas convencionales ha conseguido mejorar significativamente las posibilidades y la calidad de sobrevida de un grupo selecto de tumores. Esquemas de tratamiento con dosis altas de quimioterapia junto con técnicas de apoyo hematológico están abriendo un nuevo campo para tratar eficazmente a pacientes con un pronóstico antes inevitablemente sombrío