Microcosting analysis of haematopoietic stem cell transplantation and chemotherapy with intermediate doses of cytarabine in the treatment of acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and effectiveness do not differ between consolidation therapy with intermediate-dose cytarabine or auto-HSCT, and so the cost can help physicians and health managers in their choice. METHOD: The cost of the second consolidation was compared in 18 to 60-year-old patients with de novo AML who were included in the International Consortium of Acute Myeloid Leukaemia (ICAML) protocol. Patients treated with auto-HSCT or intermediate doses of cytarabine (IDAC) were analysed during four years using the microcosting methodology. RESULTS: The mean costs for auto-HSCT and IDAC were BRL$ 34,900.95 (range: 23,611.36-41,229.59) and 15,231.64 (range: 6,546.36-23,253.53), respectively. The mean duration of in-hospital stay was 88.4 (93-133) and 94 (50-153) days, respectively. The mean cost of the four cycles of treatment was BRL$ 114.212,78 for auto-HSCT and BRL$ 121.980,93 for the chemotherapy group. Regardless of the type of treatment, the input that had the greatest economic impact was hospital admission, mainly due to infections. CONCLUSION: Auto-HSCT had a lower average cost per patient and hospitalization rate than chemotherapy.

Long-Term Cardiorespiratory, Endocrine, Ophthalmic, and Functional Outcomes in Adult Patients with Mucopolysaccharidosis Type I (Hurler Syndrome) Post Haematopoietic Stem Cell Transplantation: The Irish Experience

Abstract Mucopolysaccharidosis type IH (MPS IH) is caused by homozygous IDUA gene pathogenic variants. This results in deficiency of the enzyme α-L-iduronidase (IDUA), which is necessary for the degradation of glycosaminoglycans (GAGs). This study outlines the long-term outcomes in adult Irish patients affected with MPS IH, who were followed up for mean 28 years post Haematopoietic Stem Cell Transplantation. Nineteen adult MPS IH patients underwent HSCT in childhood. The participant cohort represents 6 families. Among the 13 patients with Irish Traveller ethnicity, 6 patients were either siblings or first cousins. All these related patients were homozygous for p. Trp402Ter (W402X). Mean age at the first transplantation was 8 months (range 3-21). Five patients had undergone a second transplantation (n=5, 26%) in childhood, due to graft failure. None of the patients had a cardiac valve surgery at the time of the study. 14/19 patients had mild to moderate aortic or mitral valve insufficiency or stenosis. 3/19 patients used non-invasive ventilation at night. Two patients had tracheostomy in situ. Both sensorineural as well as conductive hearing defects. No corneal clouding post corneal transplantation (n=8) was observed. Six patients attended regular secondary school. Multidisciplinary follow-up is needed to address the disease specific complications in adulthood.

Evaluation of Dengue, Zika virus, and Chikungunya virus transmission by blood components in recipients of haematopoietic stem cell transplantation.

BACKGROUND: Brazil has a high prevalence of arboviruses, especially Dengue (DENV), Zika (ZKV), and Chikungunya (CHKV). OBJECTIVES: To study the risk of DENV, ZKV, and CHKV transmission by blood components in the haematopoietic stem cell transplantation (HSCT) population. METHODS: Prospective cohort of HSCT recipients and donors performed at the Hospital das Clinicas da FMUSP, São Paulo-Brazil. Patients were evaluated by serology and RT-PCR for DENV, ZKV, and CHKV pre-transplantation and once a week until neutrophil grafting. In positive cases (positive RT-PCR and/or serology conversion), an investigation was carried out on the blood components that the patient received to evaluate the possibility of it being transfusion transmitted. RESULTS: A total of 93 patients were included during the study period. The mean age was 52 years with a predominance of males (56.9%). We considered five (5.3%) DENV cases positive by seroconversion in our study. One patient had IgM seroconversion and the other four presented IgG seroconversion to DENV. In the investigation of the blood components, 145 individual samples were analysed. None of the investigated blood components showed a positive RT-PCR. CONCLUSION: We observed a low prevalence of DENV, ZKV, and CHKV in HSCT donors and recipients by serology and RT-PCR, and no case of blood transfusion transmission by RT-PCR.

Stem-cell transplantation for children with primary immune deficiencies: A retrospective study of 19 patients from one centre in Mexico.

INTRODUCTION: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors.

Evidence of Treatment Benefits in Patients with Mucopolysaccharidosis Type I-Hurler in Long-term Follow-up Using a New Magnetic Resonance Imaging Scoring System.

We developed a brain and spine magnetic resonance scoring system based on a magnetic resonance assessment of 9 patients with mucopolysaccharidosis type I-Hurler who underwent hematopoietic stem-cell transplantation. The score is reliable and correlates with long-term clinical and cognitive outcome in patients with mucopolysaccharidosis type I-Hurler.

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing.

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml-1. Demographic and clinical data were retrieved from the patients' charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

Implicaciones clínicas de las quimiocinas y sus receptores en la medicina transfusional y el trasplante / Clinical implications of chemokines and their receptors in transfusion medicine and transplantation

Introducción: Las quimiocinas son proteínas secretadas con tamaño en el rango de 8-10 kDa, con numerosas funciones en la fisiología normal y patológica. El término deriva de las palabras citocinas quimiotácticas, que refleja su importante participación en la quimioatracción de leucocitos. Sin embargo, las evidencias muestran que las quimiocinas tienen muchas otras funciones como la comunicación intercelular, la activación celular y la regulación del ciclo celular. Objetivo: Analizar los conocimientos actuales sobre las quimiocinas y sus receptores, y la significación clínica de estas en la medicina transfusional y el trasplante. Métodos: Se realizó revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se efectuó análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: La transcripción de la mayoría de los genes de quimiocinas es inducible y se produce en respuesta a estímulos celulares específicos. Las quimiocinas son importantes en la movilización de células progenitoras hematopoyéticas para el trasplante y localización de células progenitoras hematopoyéticas trasplantadas. En los modelos de incompatibilidad ABO, las quimiocinas CXC y CC se producen en niveles elevados. Conclusiones: Muchas son las oportunidades de futuras investigaciones sobre las quimiocinas en la medicina transfusional por la considerable redundancia y superposición en la función biológica de estas moléculas y sus receptores. Son solo una parte de un proceso mucho más grande y complejo dentro de la red de citoquinas y otras moléculas del sistema inmune(AU)

Introduction: Chemokines are secreted proteins with size in the range of 8-10 kDa, with numerous functions in normal and pathological physiology. The term derives from the words chemotactic cytokines, reflecting its important role in the chemoattraction of leukocytes. However, the evidence shows that chemokines have many other functions such as intercellular communication, cell activation and cell cycle regulation. Objetive: To present current knowledge about chemokines and their receptors, and the clinical significance of these in transfusion medicine and transplantation. Method: A review of the literature was made, in English and Spanish, through the PubMed website and the Google academic search engine of articles published in the last 10 years. An analysis and summary of the revised bibliography was made. Developing: The transcription of most of the chemokine genes is inducible and occurs in response to specific cellular stimuli. Chemokines play an important role in the mobilization of hematopoietic progenitor cells for the transplantation and localization of transplanted hematopoietic progenitor cells. In the ABO incompatibility models, the CXC and CC chemokines are produced at high levels. Conclusions: There are many opportunities for future research on chemokines in transfusion medicine due to their considerable redundancy and superposition in the biological function of these molecules and their receptors. They are just one part of a much larger and more complex process within the network of cytokines and other molecules of the immune system(AU)

Immunological profile of periapical endodontic infection in patients undergoing haematopoietic transplantation.

OBJECTIVES: To evaluate the mRNA expression levels of cytokines interferon-γ, tumour necrosis factor-α, interleukin IL-1ß, IL-10, and the chemokine CCL2/MCP-1, CCL4, and CXCR4 in the periapical interstitial fluid from root canal infections before and after bacterial load reduction in patients undergoing haematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: The case group was composed of 10 patients undergoing HSCT, and our control group included 10 healthy patients. Clinical samples were taken from teeth with pulp necrosis. Three paper points were placed in the RCS and maintained for 2 min for microbial evaluation before cleaning and shaping procedures. After cleaning and drying the canal, three paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 min. Samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize gene expression using real-time PCR. RESULTS: The results showed significantly reduction in the microbial load on day 7. An increased expression level of TNF-α and IFN-γ on day 7 in control and case groups was observed (p < 0.05). The mRNA levels of IL-1ß and IL-10 in the pre-HSCT group increased in the samples from day 7 (p < 0.05). The chemokine CCL-2/MCP-1 was not detected in pre-HSCT group. Chemokine receptor CXCR4 levels increased in samples obtained from the day 7 in the control group (p < 0.05). CONCLUSIONS: Individuals undergoing HSTC presented similar cytokine and chemokine mRNA expression compared with healthy individuals. However, it was observed the total absence of mRNA MCP-1/CCL2 expression in those individuals undergoing HSCT. CLINICAL RELEVANCE: Patients undergoing HSCT are at higher risk of infection. No study has analysed the periapical immune responses to root canal infections in HSCT individuals.

Nursing interventions in autologous stem cell transplantation for autoimmune diseases.

AIMS: To identify clinical symptoms and nursing interventions for stem cell therapy in autoimmune diseases. DESIGN: This is a retrospective, cross-sectional study. METHODS: This study was undertaken with patients diagnosed with type 1 diabetes or multiple sclerosis, undergoing autologous haematopoietic stem cell transplantation from January 2004 - December 2018. Data were registered in a questionnaire, taken during the conditioning regimen comprising cyclophosphamide and rabbit anti-thymocyte globulin. Descriptive statistics and Fisher's exact test were used for data analysis. RESULTS: There were 68 and 23 patients in the multiple sclerosis and type 1 diabetes groups respectively. Skin rash, nausea, vomiting and fever were more frequent and diverse in the type 1 diabetes group. Steroids were used as prophylaxis for anti-thymocyte globulin-associated allergic reactions in 97% of multiple sclerosis patients. Most of the identified symptoms and nursing interventions were more associated with one or other disease group (p < .05) and were more frequent in the type 1 diabetes group. CONCLUSION: Patients with autoimmune diseases who underwent stem cell therapy present differences in their repertoire of adverse events and require disease-specific nursing actions. IMPACT: Our results may enable nurses to establish transplant and disease-specific guidelines to improve prevention and management of adverse events and therefore optimize patient care and therapeutic success.

Prophylactic photobiomodulation therapy using 660 nm diode laser for oral mucositis in paediatric patients under chemotherapy: 5-year experience from a Brazilian referral service.

The use of photobiomodulation therapy (PBMT) in the prevention of oral mucositis (OM) in paediatric care has increased. In this article, we report data of paediatric oncology/haematopoietic stem cell transplantation (HSCT) patients treated with PBMT to prevent chemotherapy-induced OM. A retrospective study was conducted at a Brazilian referral service. Prophylactic PBMT was used in children and adolescents (≤ 17 years) following the protocol: InGaAIP, 660 nm, 100 mW, 2 J, 3.33 W/cm2, and 20 s per point. Demographic data and OM severity scores were assessed. A regression model tested the association between OM with prophylactic PBMT and antineoplastic therapy. A total of 148 individuals who had undergone 358 chemotherapy cycles were analysed. A higher occurrence of OM was observed in HSCT and osteosarcoma (OS) patients. Except for HSCT, OM was associated with methotrexate (MTX) use in all disease groups. PBMT significantly reduced OM severity in acute lymphoblastic leukaemia (ALL) and OS patients. OM grade was 3.16 and 5.45 times higher among individuals with ALL and OS, who had not undergone prophylactic PBMT compared with those who had undergone prophylactic PBMT (p < 0.001). PBMT prevented chemotherapy-induced OM. Individuals who used MTX and did not undergo prophylactic PBMT were at increased risk of OM.

Clinical outcomes in allogeneic haematopoietic stem cell transplantation: A comparison between young and elderly patients. Observational study.

OBJECTIVES: To analyse clinical outcomes comparing two age groups of patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to identify risk factors associated with older patients' mortality. METHODS: In this retrospective study, the medical charts of all consecutive patients admitted in one hospital for allo-HSCT were reviewed. Overall survival (OS) and other outcomes were compared between patients aged up to 55 years (YG) and older than 55 (EG). RESULTS: From January 2007 to August 2014, 111 adult patients were admitted for allo-HSCT and were included 75 in the YG and 36 in the EG group. The OS rate at D+ 100 was 84% for YG individuals in contrast to 75% in the EG (p = 0.01), and 71% vs. 50% at one year after HSCT (p = 0.01) respectively. Therapy-related mortality (TRM) rates for the YG and EG were, respectively, 14% vs. 17% (p = 0.04) at D+ 100 and 17% vs. 32% (p = 0.04) at one year. Haploidentical donor type and active disease status significantly increased mortality risk in the EG (hazard ratio 2.42; p = 0.018; and 2.04; p = 0.033). CONCLUSION: YG and EG have similar TRM rates early after allo-HSCT, but the elderly had higher TRM during the critical period from 100 days to one year.

Trasplante autólogo de células madre hematopoyéticas en pacientes con diagnóstico de mieloma múltiple, experiencia en 9 años / Autologous stem cell transplant in patients with multiple myeloma, experience of 9 years

Resumen Objetivo: El mieloma múltiple representa la primera causa de trasplante autólogo de células madre hematopoyéticas (TCMH). El objetivo del presente trabajo es describir los resultados del TCMH en pacientes con diagnóstico de mieloma múltiple en la Fundación Valle del Lili. Materiales y métodos: Se realizó un estudio observacional, descriptivo de una cohorte retrospectiva, se incluyeron pacientes mayores de 18 años con TCMH autólogo tratados entre 2008 y 2016. Los desenlaces fueron: supervivencia global, supervivencia libre de progresión y la respuesta de la enfermedad postrasplante. Se realizó un análisis estadístico descriptivo y el análisis de supervivencia se hizo con el método Kaplan-Meier. Resultados: Durante el periodo de estudio se trasplantaron 103 pacientes. La mediana de la edad fue 57 años. El subtipo de inmunoglobulina secretada fue: 75% de IgG, 18% de IgA, 5% no secretor y 2% oligosecretor. El estadio Durie Salmon en la mayoría fue IIIA (43,7%). Previo al trasplante la mayoría de los pacientes estaba en muy buena respuesta parcial (31%), seguido por respuesta completa (25,2%) y respuesta parcial (19,4%). La supervivencia global y libre de progresión a 5 años fue de 71% y de 40%, respectivamente. Posterior al trasplante: el 33% de los pacientes estaba en muy buena respuesta parcial, el 25% en respuesta completa estricta, el 22% en respuesta completa, el 12% en respuesta parcial y el 8% en enfermedad progresiva o recaída. Conclusión: El TCMH autólogo es una estrategia que se asocia a buenas tasas de supervivencia, baja toxicidad y adecuada respuesta de la enfermedad postrasplante.

Abstract Objective: Multiple myeloma in Colombia is the one of the main reasons for autologous hematopoietic stem cell transplantation (HSCT). The aim of this study is to describe the results of the HSCT in adult patients diagnosed with multiple myeloma in the Fundación Valle del Lili. Materials and methods: An observational, descriptive study of a retrospective cohort was carried out. Patients older than 18 years with a diagnosis of multiple myeloma with autologous HSCT between 2008 and 2016 were included. The outcomes were overall survival, progression-free survival, and post-transplant disease response. A descriptive statistical analysis was carried out for all the variables considered in the analysis. The survival analysis was performed using the Kaplan-Meier method. Results: During the study period, transplants were performed on 103 patients with a diagnosis of multiple myeloma. The median age was 57 years. The subtype of secreted immunoglobulin was 75% IgG, 18% IgA, 5% non-secretor, and 2% oligo-secretor. The majority of patients were in Durie Salmon stage was IIIA (43.7%). Prior to transplantation 31% had a very good partial response, 25.2% complete response, 19.4% partial response, 10.7% progressive disease, 6.8% stable disease, 2.9% complete strict response, and in 3.9% of the patients the report of the disease status was not found. The 5-year overall survival was 71% (95% CI: 53-83) and progression-free survival was 40% (95% CI 25-54). After transplantation 33% of the patients were in very good partial response, 25% in strict complete response, 22% in complete response, 12% partial response, and 8% progressive disease or relapse. Conclusion: Autologous HSCT is a strategy that is associated with good survival rates, low toxicity, and an adequate post-transplant disease response.

Trasplante de células madre hematopoyéticas en pacientes pediátricos con diagnóstico de neoplasias mieloides, experiencia en 15 años / Haematopoietic stem cell transplantation in paediatric patients with myeloid malignancies; 15 years of experience

Resumen Objetivo: Describir la experiencia en términos de supervivencia y complicaciones de los pacientes llevados a trasplante de células madre hematopoyéticos (TCMH) en los últimos 15 años. Materiales y métodos: Se realizó un estudio descriptivo, tipo cohorte retrospectiva en el que se incluyeron pacientes menores de 18 años con diagnóstico de leucemia mieloide aguda (LMA), leucemia mieloide crónica (LMC) y síndrome mielodisplásico (SMD) llevados a TCMH entre enero de 2001 y diciembre de 2015. Los desenlaces fueron supervivencia global, supervivencia libre de evento y las complicaciones relacionadas con el trasplante. Resultados: Durante el periodo de estudio se trasplantaron: 43 pacientes con diagnóstico de neoplasias mieloides; 31 con LMA (72%); 4 con LMC (9%) y 8 con SMD (19%). Se realizaron 11 trasplantes de donante idéntico, 11 haploidénticos, 11 autólogos y 10 de sangre de cordón umbilical. De los pacientes con LMA (31 casos), el 58% fueron sometidos a trasplante en primera remisión completa y el 39% en segunda o subsecuente remisión completa. La supervivencia global y libre de evento a 5 años fue 56% y 38% respectivamente. La mortalidad relacionada al trasplante en el día 100 fue del 15%, la incidencia acumulada de enfermedad injerto contra huésped 59%, la infección por citomegalovirus 39%, las infecciones bacterianas 54% y la cistitis hemorrágica 14%. Conclusión: La baja tasa de mortalidad y complicaciones relacionadas al trasplante sugiere que el trasplante de células madre hematopoyéticas es una alternativa factible como tratamiento para pacientes con neoplasias mieloides en nuestro medio.

Abstract Objective: To describe the experience, in terms of survival and complications, with patients that received a haematopoietic stem cell transplantation (HSCT) in the last 15 years. Materials and methods: A descriptive, retrospective, cohort study was conducted on patients less than 18 years-old with a diagnosis of acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), and myelodysplastic syndrome (MDS) and received HSCT between January 2001 and December 2015. The outcomes were, overall survival, event-free survival, and complications associated with the transplant. Results: During the study period, a total of 43 patients with myeloid neoplasms received a transplant, of which 31 (72%) had AML, 4 (9%) with CML, and 8 (19%) with MDS. A total of 11 identical donor transplants were performed, as well as 11 haploidentical, 11 autologous, and 10 with umbilical cord blood. Of the patients with AML (31 cases), 58% were subjected to a transplant in the first full remission, and 39% in the second or subsequent full remission. The overall and event-free survival at 5 years was 56% and 38%, respectively. The transplant-related mortality at day 100 was 15%, with an accumulated incidence of graft versus host disease of 59%, cytomegalovirus infection of 39%, with 54% bacterial infections, and 14% haemorrhagic cystitis. Conclusion: The low mortality and complications rate associated with the transplant suggests that haematopoietic stem cell transplantation is a viable alternative as a treatment for patients with myeloid neoplasms in our country.

Trasplante autológo de células madre hematopoyéticas en pacientes con diagnóstico de neuroblastoma de alto riesgo en la Fundación Valle del Lili, Cali - Colombia / Autologous Haematopoietic Stem-cell Transplantation in Patients with High Risk Neuroblastoma in the Valle del Lili Foundation Hospital, Cali, Colombia

Resumen Objetivo: Describir la experiencia en el manejo de los pacientes con diagnóstico de neuroblastoma de alto riesgo manejados con trasplante autólogo de células madre hematopoyéticas en la Fundación Valle de Lili. Pacientes y métodos: Estudio descriptivo, tipo serie de casos de pacientes con diagnóstico de neuroblastoma de alto riesgo que recibieron trasplante autólogo de células madre hematopoyéticas entre 2001 y 2015. Los desenlaces de este estudio fueron: supervivencia global; supervivencia libre de evento; tiempo de injerto de plaquetas y neutrófilos, e incidencia acumulada de enfermedad veno oclusiva. Se realizó un análisis estadístico descriptivo para todas las variables consideradas en el análisis y para subgrupos seleccionados. El análisis de supervivencia se hizo con el método Kaplan-Meier. Resultados: Entre 2001 y 2015 quince pacientes con diagnóstico de neuroblastoma recibieron trasplante autólogo de células madre hematopoyéticas. La supervivencia globala3y5anos fue del 55% y la supervivencia libre de evento fue del 47%, donde 14 pacientes injertaron neutrófi los entre el día8y19 postrasplante e injerto de plaquetas entre los 9 y 91 días y 2 pacientes desarrollaron enfermedad venooclusiva hepatica como toxicidad a los fármacos quimioterapéuticos de acondicionamiento. Al momento del último seguimiento 10 pacientes permanecen vivos, de los cuales 8 no presentan evidencia clínica y/o paraclínica de la enfermedad. De los 5 pacientes que fallecieron, 2 fue por toxicidad al trasplante en los primeros 100 díasy3por progresión de la enfermedad. Conclusión: El trasplante autólogo de células madre hematopoyéticas es una alternativa facti ble como tratamiento en nuestro medio para pacientes con diagnóstico de neuroblastoma de alto riesgo, el cual ha contribuido a mejorar la supervivencia en este grupo de pacientes.

Abstract Objective: Describe the experience in the management of patients diagnosed with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation at the Valle de Lili Foundation Hospital. Patients and Methods: A series of cases of patients with a diagnosis of high-risk neuroblastoma who received an autologous haematopoietic stem cell transplantation between 2001 and 2015. The endpoints of this study were: overall survival, event-free survival, platelet and neutrophil graft time and the cumulative incidence of venous-occlusive disease. A descriptive statistical analysis was performed for all the variables considered in the analysis and for the selected subgroups. Survival analysis was performed using the Kaplan-Meier method. Results: A total of 15 patients diagnosed with high risk neuroblastoma received an autologous haematopoietic stem cell transplantation between 2001 and 2015. Overall survival at 3 and 5 years was 55%, and the event-free survival was 47%. 14/15 patients grafted Neutrophils grafted between day 8 and 19 post-transplant in 14/15 patients, with platelet graft between days 9 and 91 days. Hepatic venous-occlusive disease was observed in 2/15 patients as toxicity to conditioning chemotherapeutic drugs. At the time of the last follow-up, 10/15 patients remained alive, 8 of whom had no clinical and/or para-clinical evidence of the disease. Of the 5/15 patients that died, 2 were due to transplant toxicity in the first 100 days, and 3 due to disease progression. Conclusion: We conclude that autologous haematopoietic stem cell transplantation is a viable alternative as a treatment in our setting for patients with high-risk neuroblastoma, and has contributed to improve survival in this group of patients.

Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.

Quality of life related to oral mucositis of patients undergoing haematopoietic stem cell transplantation and receiving specialised oral care with low-level laser therapy: a prospective observational study.

Oral mucositis is a painful condition that occurs in 80% of patients who undergo haematopoietic stem cell transplantation (HSCT). Our objective was to determine the impact of mucositis on quality of life (QoL) of patients subjected to HSCT treated with low-level laser therapy (LLLT). Patients were evaluated: (1) on the first day of treatment; (2) 5 days after autologous or 8 days after allogeneic transplantation; (3) once bone marrow had integrated; and (4) 30 days after discharge. Clinical evaluation was performed using the World Health Organization criteria; oral health QoL was measured using the Oral Health Impact Profile (OHIP-14); and mucositis symptoms with the Patient-Reported Oral Mucositis Symptom (PROMS) scale. The higher the score, the lower the patient's QoL. The OHIP-14 responses showed that at D + 5/D + 8, all domains had the highest scores, while at times 1 and 4, the scores were lower. In the PROMS scale, all domains scored worst at time 2, and the differences between the scores at the four times were statistically significant. The study has shown that QoL improves over time in patients undergoing LLLT therapy for mucositis prevention.

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.

Detección precoz de infección por citomegalovirus en pacientes sometidos a trasplante alogéneico de precursores hematopoyéticos por reacción de polimerasa en cadena cuantitativa en tiempo real / Early detection of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant patients by real time-quantitative PCR

Introduction: CMV pp65-antigenemia (antigenemia) has been used for monitoring CMV viremia in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Recently, real time quantitative PCR (RT-qPCR ) has been used as a better approach than antigenemia for CMV diagnosis. The objective of this study was to assess the correlation of CMV viremia between RT-qPCR and antigenemia in aHSCT patients. Material and Methods: Observational prospective study of all aHSCT patients during 10 months in our center. CMV RT-qPCR in whole blood was performed weekly from day +7 to +100 after aHSCT. Simultaneous antigenemia was performed from engrafment to day +100. Concordance between both assays was evaluated. Results: Eighteen patients were included. In 120 simultaneous samples, 96 were concordant by both methods (80%). Kappa coefficient was 0.583. In 42% of cases without concordant results, patients were on antiviral therapy. Thirteen patients (72%) developed CMV infection (20 episodes). In 17 episodes, both the antigenemia and CMV RT-qPCR were positive. CMV RT-qPCR was detectable 1-2 weeks before antigenemia in 45% of the episodes. Conclusion: Both methods had a moderate concordance and CMV RT-qPCR detects CMV reactivations earlier than antigenemia, especially in neutropenic patients.

Introducción: La antigenemia pp65 (antigenemia) ha sido utilizada para monitorizar viremia de citomegalovirus (CMV) en pacientes sometidos a trasplantes alogeneicos de precursores hematopoiéticos (TPHa). Recientemente, la reacción de polimerasa en cadena cuantitativa en tiempo real (en inglés RT-qPCR) se ha usado como una mejor aproximación al diagnóstico de infección por CMV. El objetivo de este estudio fue evaluar la correlación de viremia por CMV a través de RT-qPCR con antigenemia, en pacientes que han recibido TPHa. Material y Métodos: Estudio prospectivo, observacional, de los pacientes sometidos a TPHa durante 10 meses. Se realizó RT-qPCR de CMV en sangre total semanalmente desde el día +7 al+100 después del trasplante y antigenemia en forma simultánea desde el prendimiento hasta el día +100. Se evaluó la concordancia entre ambos ensayos. Resultados: Dieciocho pacientes fueron incluidos. En 120 muestras simultáneas, 96 fueron concordantes por ambos métodos (80%). El coeficiente Kappa fue 0,583. En los casos no concordantes, el 42% se encontraba en terapia antiviral. Trece pacientes (72%) desarrollaron infección por CMV (20 episodios). En 17 episodios, ambos ensayos fueron positivos. La carga viral fue detectable 1-2 semanas antes que la antigenemia en 45% de los episodios. Conclusión: Existe una buena correlación entre ambas técnicas y la RT-qPCR detecta más precozmente que la antigenemia las reactivaciones de CMV, especialmente en pacientes neutropénicos.

Indicações em transplante de células-tronco hematopoéticas em pacientes adultos com leucemia linfoide aguda / Indications for hematopoietic stem cell transplantation in adults in acute lymphoblastic leukemia

Na leucemia linfoide aguda (LLA), a proliferação, acúmulo e infiltração de células imaturas caracterizam uma entidade heterogênea, apresentando ampla diversidade de aspectos clínicos e biológicos. Na LLA do adulto, a concentração de fatores prognósticos de alto risco, como o imunofenótipo B, alterações cromossômicas e, principalmente, a presença do cromossomo Ph positivo. Considerações a respeito da alta morbidade e mortalidade relacionadas ao transplante de células-tronco hematopoéticas (TCTH) têm gerado controvérsias quanto à indicação desta modalidade terapêutica, nos pacientes adultos com LLA em primeira remissão (1ª RC). Os resultados da terapia convencional com quimioterapia, diante dos diferentes grupos de risco em pacientes com LLA, têm sido utilizados para a indicação de TCTH. Apresentamos o algoritmo de indicações do transplante de células-tronco hematopoéticas em pacientes adultos com LLA.

In acute lymphoblastic leukemia, accumulation and proliferation of immature cells infiltration characterise a heterogeneous entity, featuring a wide variety of clinical and biological aspects. In the adult LLA concentration of high-risk prognosis factors such as age, B-cell, chromosomic changes, and chiefly the presence of chromosome positive Ph. Considerations of high morbidity and mortality rates related to haematopoietic stem cell transplantation (TCTH) have generated controversy about this therapeutic modality in adult patients with LLA in first remission (1st RC). The results of conventional therapy with chemotherapy in contrast with different risk groups of patients with LLA, has been used for the indication of TCTH. Thus we present the algorithm indications of haematopoietic stem cell transplantation in adult patients with LLA.