Research Progress of Immune Heterogeneity in Leukemia Microenvironment--Review / 中国实验血液学杂志

Although the body has a strong immune system which can resists the invasion of leukemia cells, leukemia cells disseminate systemically and form an immunosuppressive microenvironment through a variety of mechanisms, including regulation of antigen presentation, utilization of immunosuppressive enzyme AXL, immune cell inhibitory checkpoint NKG2A and immunoregulatory gene VISTA, resulting in immune escape. Therefore, most types of leukemia are inevitable for the affliction of drug resistance or relapse, and the immune efficacy is not as significant as that of other hematological tumors and the prognosis is suboptimal. This article reviews the immune heterogeneity of leukemia microenvironment from many aspects, including anti-leukemia immunity and immune escape. In addition, it also reviews the latest progress and future prospects of immune checkpoint inhibition, adoptive cell therapy and vaccine therapy in leukemia, providing a theoretical basis for the development of personalized combination therapy strategies with less toxic side effects.

Disfunções orofaciais em pacientes infantojuvenis com leucemia aguda / Orofacial dysfunctions in infants and young children with acute leukemia

RESUMO Objetivo Identificar a ocorrência de disfunções orofaciais em pacientes infantojuvenis com leucemia aguda, submetidos à quimioterapia de remissão. Métodos Em um período de 16 meses, 40 pacientes com leucemias agudas, entre 3 e 18 anos de idade, foram admitidos em um hemocentro no estado do Amazonas. Destes, 23 foram incluídos neste estudo transversal e submetidos à avaliação das funções orofaciais, por meio do Nordic Orofacial Test-Screening (NOT-S), entre o trigésimo (D30) e o trigésimo terceiro dia (D33) da fase de indução da remissão. A presença de manifestações orais também foi avaliada por meio de exame clínico. Resultados Disfunção orofacial foi observada em, aproximadamente, metade dos casos avaliados (n=11). Destes pacientes, todos tiveram o domínio Secura de Boca (VI) alterado e 81,8% (n=9) apresentaram alteração no domínio Mastigação e Deglutição (IV). Mucosites em lábios, língua, soalho e orofaringe foram as lesões orais mais encontradas após a fase de indução. Houve associação entre a ocorrência de lesões orais nos pacientes avaliados e a presença de disfunção orofacial, segundo o NOT-S (IC 95%, p-valor = 0,027). Conclusão Sugere-se que a disfunção orofacial seja frequente na fase de indução da remissão em pacientes infantojuvenis com leucemias agudas. Estudos sobre as disfunções orofaciais nessa população, bem como sua relação com as lesões orais são necessários para melhor esclarecimento e compreensão dos impactos funcionais.

ABSTRACT Purpose To Identify the occurrence of orofacial dysfunctions in young children and adolescents with acute leukemia who are undergoing remission chemotherapy. Methods Over a period of 16 months, 40 three to eighteen year -old patients with acute leukemia were admitted to the Amazonas State Hemocenter. Of these, 23 were included in the cross-sectional study and submitted to the evaluation of orofacial functions using the Nordic Orofacial Test-Screening, between D30 and D33 of the remission induction phase. The presence of oral manifestations was also evaluated via clinical examination. Results Orofacial dysfunction was observed in approximately half of the evaluated cases (n=11). Of these patients, all had alterations in the Dryness of the Mouth (VI) domain and 81.8% (n=9) showed alterations in the Chewing and Swallowing (IV) domain. Mucosites on lips, tongue, floor of the mouth and the oropharynx were the most commonly found oral lesions after the remission induction phase. According to the NOT-S, there was an association between the occurrence of oral lesions in the evaluated patients and the presence of orofacial dysfunction (95% CI, p-value = 0.027). Conclusion It is suggested that orofacial dysfunction is frequent in the remission induction phase in children and adolescents with acute leukemia. Studies regarding these orofacial dysfunctions in this population, as well as their relationship with oral lesions, are needed in order to fully understand their functional impact.

Imunoterapia com células CAR-T como nova perspectiva de tratamento da leucemia linfoblástica aguda recidivada/refratária / Immunotherapy with CAR-T cells as a new treatment perspective for relapsed/refractory acute lymphoblastic leukemia

Introdução: O tratamento da leucemia linfoblástica aguda (LLA) atualmente baseia-se em quimioterapia e/ou transplante de células tronco hematopoiéticas; entretanto, uma nova terapia vem se tornando promissora: a imunoterapia com células T modificadas geneticamente que expressam um receptor de antígeno quimérico (CAR-T) visando antígenos específicos presente em blastos de LLA, gerando resultados promissores em crianças e adultos com doença recidivada e refratária (r/r). Objetivo: Discorrer sobre a LLA e descrever a imunoterapia com CAR-T, como inovação terapêutica no tratamento da LLA de linhagem B. Método: Foi realizada uma revisão bibliográfica por meio de publicações indexadas nas bases de dados Scielo e Pubmed, utilizando os descritores: leucemia linfoblástica aguda de células B; células CAR-T; receptores de antígeno quimérico, recidivados/refratários; imunoterapia. Resultados: As altas taxas de remissão completa (42% até 100%) e parcial (28,5%) da LLA (r/r) tratadas com CAR-T, possibilitam um aumento considerável da sobrevida geral comparado a outros tratamentos convencionais. Efeitos desfavoráveis, tais como síndrome da liberação de citocinas (CRS) (0 até 90%) e neurotoxicidade (NT) (0 até 29%) podem ser vistos, sendo manejáveis, não prejudicando o desfecho do tratamento. Conclusão: A LLA é uma doença grave, de difícil tratamento e prognóstico reservado. A imunoterapia vêm se mostrando promissora à essa enfermidade, principalmente em casos de doença r/r se mostrado uma ferramenta poderosa que permite o foco específico de células malignas por meio de engenharia de células T

Introduction: The treatment of acute lymphoblastic leukemia (ALL) is currently based on chemotherapy and/or hematopoietic stem cell transplantation; however, a new therapy is becoming promising: immunotherapy with genetically modified T cells that express a chimeric antigen receptor (CAR-T) targeting specific antigens present on ALL blasts, reaching promising results in children and adults with relapsed and refractory disease (r/r). Objective: To discuss ALL and describe immunotherapy with CAR-T as a therapeutic innovation in the treatment of B-lineage ALL. Method: A literature review was carried out through publications indexed in the Scielo and Pubmed databases, using the following descriptors: B-cell acute lymphoblastic leukemia; CAR-T cells; chimeric antigen receptors, relapsed/refractory; immunotherapy. Results: The high rates of complete (42% to 100%) and partial remission (28.5%) of ALL (r/r) treated with CAR-T allows a considerable increase in overall survival compared to other conventional treatments. Unfavorable effects such as cytokine release syndrome (CRS) (0 to 90%) and neurotoxicity (NT) (0 to 29%) can be seen, being manageable, not impairing the treatment outcome. Conclusion: ALL is a serious disease, with a difficult treatment and poor prognosis. Immunotherapy has shown benefits for this disease, especially in cases of r/r ALL, showing itself to be a powerful tool that allows the specific focus of malignant cells through T cell engineering.

Diagnóstico, clasificación y tratamiento de la leucemia aguda de linaje ambiguo / Diagnosis, classification and treatment of acute leukemia of ambiguous lineage

Introducción: Las leucemias agudas de linaje ambiguo constituyen un grupo heterogéneo de leucemias agudas que no muestran una evidencia clara de diferenciación a lo largo del linaje celular. El diagnóstico definitivo se realiza exclusivamente por las características inmunofenotípicas, con el uso de la citometría de flujo multiparamétrica. Objetivo: Actualizar los criterios diagnósticos, la clasificación, el manejo clínico y terapéutico de las leucemias agudas de linaje ambiguo. Métodos: Se realizó una búsqueda de información científica relacionada con el tema en libros de textos de Hematología Clínica y en artículos publicados a través de PUBMED en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las características morfológicas de las células leucémicas procedentes de los pacientes con leucemias agudas de linaje ambiguo no muestran uniformidad. Pueden encontrarse de forma simultánea blastos de diferentes tamaños y estados de maduración. Estos pueden presentar apariencia linfoide, mieloide, indiferenciada o mixta. Conclusión: Las leucemias agudas de linaje ambiguo constituyen un subgrupo de alto riesgo, con un pronóstico desfavorable y una pobre supervivencia global de los enfermos. Su reporte oportuno es indispensable para aunar los criterios de la toma de decisiones terapéuticas en este grupo de pacientes(AU)

Introduction: Acute leukemias of ambiguous lineage constitute a heterogeneous group of acute leukemias that do not show clear evidence of differentiation along cell lineage. The definitive diagnosis is made exclusively based on immunophenotypic characteristics, with the use of multiparametric flow cytometry. Objective: To update the diagnostic criteria, classification, as well as the clinical and therapeutic management of acute leukemias of ambiguous lineage. Methods: A search for scientific information related to the subject was carried out in clinical hematology textbooks and in articles published through PUBMED in the last ten years. An analysis and summary of the revised bibliography was carried out. Information analysis and synthesis: The morphological characteristics of the leukemic cells from patients with acute leukemia of ambiguous lineage do not show uniformity. Blasts of different sizes and stages of maturation can be found simultaneously. These may appear as lymphoid, myeloid, undifferentiated, or mixed. Conclusion: Acute leukemias of ambiguous lineage constitute a high-risk subgroup, with unfavorable prognosis and poor overall patient survival. Its timely report is essential to gather criteria for making therapeutic decisions in this group of patients(AU)

Efficacy analysis of unrelated cord blood transplantation in the treatment of refractory and relapsed adult acute leukemia / 中华血液学杂志

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.

Advances in the diagnosis and treatment of acute and chronic leukemia in Mexico / Avances en el diagnóstico y tratamiento de las leucemias agudas y crónicas en México

Abstract In the last 60 years, there have been substantial advances regarding the diagnosis and treatment of patients with acute and chronic leukemia in Mexico. Immunologic and molecular classifications of these diseases have improved both diagnosis and therapeutic capabilities. Although the pace of diagnostic and therapeutic advances has been slower compared with developed countries, Mexico is at the forefront among developing countries. Supporting research in these fields is expected to enhance the generation of new knowledge and improve the care of patients suffering from these diseases.

Resumen En los últimos 60 años ha habido avances notables en el diagnóstico y tratamiento de los pacientes con leucemia aguda y crónica en México. Las clasificaciones inmunológicas y moleculares de esta enfermedad han mejorado tanto la capacidad diagnóstica como las derivaciones terapéuticas. Si bien el ritmo de los avances diagnósticos y terapéuticos en México se ha visto retrasado cuando se compara con el de países desarrollados, se encuentra a la vanguardia entre los países en vías de desarrollo. El apoyo a las labores de investigación en estas áreas del conocimiento seguramente redundará en beneficio de la generación de nuevos conocimientos y de la atención de los pacientes que sufren estas enfermedades.

Infant leukemia

An eleven-month-old Bahraini infant girl, born full-term, vaccinated up-to-age, with normal milestone development; she was referred from King Hamad University Hospital [KHUH] with one-month history of high grade on and off fever associated with cough; her CBC showed anemia [7.4g/dl] and thrombocytopenia [30x109/L]. On examination, multiple bruises and small cervical lymph nodes were observed. CBC showed blasts [30%]. Bone marrow aspiration, flow cytometry and cytogenetic were sent for Mixed Lineage Leukemia [MLL] rearrangement. She was low risk; she received chemotherapy. This case was reported because of its rarity and up-to-date chemotherapy modalities which is linked to specific cytogenetic abnormality

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Incidence and Factors Influencing Oral Mucositis in Patients with Hematopoietic Stem Cell Transplantation

PURPOSE: This study was done to examine the incidence of oral mucositis in hematopoietic stem cell transplantation patients and to identify factors influencing oral mucositis and patient outcomes according to severity. METHODS: In this retrospective study, data were collected from electronic medical records of 222 patients who had received hematopoietic stem cell transplantation. Oral mucositis was evaluated using WHO's assessment scale. Data were analyzed using Chi-square test, Fisher exact test, Spearman's correlation, Ordinal logistic regression, ANOVA and Kruskal-Wallis test. RESULTS: A total of 69.8% of the patients evaluated developed oral mucositis (grade II and over). As a results of ordinal regression, factors influencing oral mucositis severity were found to be diagnosis, type of transplantation, oxygen inhalation and the number of antiemetics administration before transplantation. The severity of oral mucositis was found to increase the days of hospitalization, days of TPN administration, days of using antibiotics and the number and dosage of analgesics. CONCLUSION: The results would help predict severity of oral mucositis in hematopoietic stem cell transplantation patients and suggest that provision of appropriate nursing assessment and oral care would improve patient outcomes.

A massagem na criança com câncer: eficácia de um protocolo / Massage in children with cancer: effectiveness of a protocol

OBJETIVOS: a massagem é uma intervenção que pode contribuir para o alívio da dor, embora as evidências empíricas sejam escassas e contraditórias. O objetivo deste trabalho foi avaliar a eficácia de um protocolo de massagem no alívio da dor na criança internada, com patologia oncológica. MÉTODOS: através de um estudo randomizado e controlado com cegamento simples, foram estudadas 52 crianças, com idades compreendidas entre os 10 e os 18 anos, internadas num serviço de oncologia pediátrica. A intervenção consistiu na aplicação de um protocolo de massagem de três sessões com duração entre 20 a 30 minutos em dias alternados durante uma semana. A eficácia do protocolo foi medida através da avaliação da dor com a aplicação do Inventário Resumido de Dor e a eficácia de cada sessão de massagem pela Escala Visual Analógica (EVA). RESULTADOS: o protocolo de massagem apenas se revelou eficaz na diminuição da interferência da dor no andar (p < 0,05), apesar de ter contribuído para o alívio da dor e sua interferência nas atividades da criança. Após cada sessão de massagem a intensidade da dor sentida pela criança diminuiu (p < 0,001). CONCLUSÕES: apesar da reduzida dimensão da amostra, a massagem parece ser uma intervenção útil no alívio da dor da criança que sofre de patologia oncológica, embora permaneçam dúvidas quanto à eficácia deste protocolo de massagem. Todavia, os autores recomendam a sua utilização pela sua contribuição na promoção do bem-estar e qualidade de vida da criança.

OBJECTIVES: massage can help relieve pain, although empirical evidence is scarce and contradictory. This study aims to assess the effectiveness of a massage protocol in relieving pain in children hospitalized with cancer. METHODS: a randomized, controlled, and single-blind trial was performed in a sample of 52 children aged between 10 and 18 years who were hospitalized in a pediatric cancer ward. The intervention consisted of the implementation of a massage protocol with three sessions of 20 to 30 minutes on alternate days over a one-week period. The effectiveness of the protocol was evaluated by assessing pain using the Brief Pain Inventory (BPI), while the effectiveness of each massage session was measured using the Visual Analogue Scale (VAS). RESULTS: the massage protocol was only effective in reducing the interference of pain in walking (p < 0.05), although it also contributed to relieve pain and its impact on the children's activities. After each massage session, the intensity of the pain experienced by the child decreased (p < 0.001). CONCLUSIONS: despite the small sample size, massage therapy appears to be a useful intervention in reducing pain in children with cancer. However, there are still questions regarding the effectiveness of this massage protocol. The authors recommend its use due to its contribution to the promotion of the child's well-being and quality of life.

Experiência em cuidados paliativos à criança portadora de leucemia: a visão dos profissionais / Experience in palliative care for children with leukemia: the professionals' viewpoint

O cuidado paliativo desenvolve-se por meio de assistência multiprofissional com ações de suporte e conforto para a criança e sua família. O suporte se constitui do alívio do sofrimento pelo controle da dor e dos sintomas, bem como pelo apoio psicossocial e espiritual. Trata-se de um estudo de caso qualitativo que objetivou compreender a visão da equipe multidisciplinar perante a criança portadora de leucemia em cuidado paliativo, em uma instituição hospitalar de Belo Horizonte. Os sujeitos da pesquisa foram 17 profissionais de saúde da equipe de assistência direta à criança nesses cuidados. Os dados foram submetidos à técnica de análise de conteúdo. A experiência profissional em cuidado paliativo é intrínseca ao sucesso e à continuidade do tratamento do paciente. Verificou-se que os profissionais possuem pouca experiência nessa área e têm dificuldade em lidar com os sentimentos, se sentindo, às vezes, impossibilitados de agir mediante as angústias dos envolvidos e com a morte. Contudo, apesar de a área de atuação gerar sofrimento e angústia ao profissional, percebe-se que a equipe multiprofissional identifica-se e gosta da área o que é importante para a criança e sua família se sentirem seguros, respeitados e acolhidos pelos profissionais.

Palliative care is developed through multi-professional assistance with actions to provide support and comfort for the children and their families. The support involves the alleviation of suffering by controlling the pain and its symptoms, as well as ensuring psychosocial and spiritual support. This is a qualitative case study which sought to understand the multidisciplinary view of the team vis-à-vis a child with leukemia in palliative care, in a hospital in Belo Horizonte. The subjects of research were 17 health professionals of the direct assistance team to the child receiving such care and the data were analyzed using the content analysis technique. The professional experience in palliative care is intrinsic to the success and continuity of the patient's care. It was found that the professionals have little experience in this area and have difficulty dealing with their emotions, and sometimes become unable to act when faced with the anguish of those involved and with death. However, despite the fact that the area of activity causes suffering and anguish to the professional, the multi-professional team still identifies with and likes the area, which is important for the children and their families to feel safe, respected and well cared for by the professionals.

Endodoncia en pacientes oncohematológicos / Endodontic therapy in oncohematological patients

Los pacientes oncohematológicos y oncológicos en general pueden recibir una atención endodóntica normal, siempre y cuando tengamos en cuenta su patología sistémica. El objetivo del presente trabajo es exponer las principales pautas que se deben considerar para realizar un tratamiento de endodoncia adecuado en pacientes oncológicos sometidos a quimioterapia y/o radioterapia.

Implication of Early Lymphocyte Recovery after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Leukemia

PURPOSE: The repopulating lymphocytes after allogeneic hematopoietic stem cell transplantation have an important role not only on the prevention of serious infections in the early transplantation period, but also on the killing of residual leukemic cells by graft-versus-leukemia effect. The aim of this study was to analyze the impact of lymphocyte recovery after allogeneic stem cell transplantation in children with hematologic malignancies. MATERIALS AND METHODS: We evaluated 69 children transplanted for acute lymphoblastic leukemia (ALL) (n=34), acute myeloid leukemia (AML) (n=26), chronic leukemia (n=7) and juvenile myelomonocytic leukemia (n=2) between 1996 and 2008 at the Chonnam National University Hospital, Korea. The patients were grouped based on absolute lymphocyte counts (ALC) or =500/microL at D+21 and D+30 after transplant. RESULTS: Patients with a High ALC at D+21 and D+30 had a faster neutrophil and platelet engraftment. The High at D+30 group had a better 5 year overall survival (71% vs. 53%, p=0.043) and event-free survival (72% vs. 53%, p=0.065) than the Low at D+30 group. The incidence of grade II-IV acute and chronic graft-versus-host disease (GVHD), and relapse rate did not differ by the ALC counts. However, the Low at D+30 group had a significantly increased risk for transplant-related mortality (p=0.019). The univariate analysis showed that the factors associated with decreased survival were a Low ALC at D+30, patients with high risk ALL, and grade II-IV aGVHD in patients with ALL and AML. CONCLUSION: Early posttransplant serial lymphocyte measurement would be a simple but useful method for predicting transplant outcomes.

Análisis de la mortalidad por leucemia aguda pediátrica en el Instituto Nacional de Cancerología / Analysis of mortality in pediatric acute leukemia at the National Cancer Institute

Introducción. La mortalidad por leucemia aguda pediátrica es un indicador trazador del acceso y efectividad de la atención en salud; su análisis permite identificar los factores involucrados en el proceso de la enfermedad que pueden influir en la condición final de los niños. Objetivo. Describir la experiencia operativa y los resultados obtenidos en los comités de análisis institucional de la mortalidad por leucemia aguda pediátrica. Materiales y métodos. Se hizo un análisis descriptivo de las muertes por leucemia linfoide o mieloide aguda ocurridas en niños menores de 15 años en el Instituto Nacional de Cancerología, 2008-2010. Se llevó a cabo el análisis de “evitabilidad” (sic.) con el modelo de las tres demoras propuesto por Thaddeus y Maine. Resultados. Se analizaron 24 defunciones. El 87,5 % fueron a causa de leucemia linfoide aguda. La mediana de edad fue de 10,5 años. Se encontró que la demora 3 (obtener el tratamiento adecuado y oportuno) ocurrió en el 83 % de los casos analizados y que los traslados durante el tratamiento fue la limitación más común (66,7 %). El 83,3 % de las muertes se consideraron no evitables dadas las condiciones clínicas de la enfermedad. Conclusiones. Es la primera experiencia en el análisis de mortalidad por un evento crónico en la población pediátrica del Instituto Nacional de Cancerología y en el país. Aunque las demoras identificadas no condicionaron de forma directa la mortalidad, sí constituyen la base para establecer acciones de mejoría que influyan en la calidad de la atención de los niños con cáncer.

Introduction. Mortality rate for childhood acute leukemia is an indicator of access to and efficacy of health services. Analysis of this indicator allows the identification of factors contributing to the development of the illness and the final condition of affected children. Objective. The operative experience results were described from data obtained by committee of analysis of institutional mortality by childhood acute leukaemia. Materials and methods. Formal reports of deaths in children under 15 due to acute lymphoblastic or myeloid leukemia were provided to the National Cancer Institute of Colombia. A descriptive analysis of these reports from the period 2008-2010 was undertaken by the National Cancer Institute. Avoidability analysis was performed using the 1994 “three delays” model of Thaddeus and Maine. Results. Of 24 deaths analyzed, 21 were caused by acute lymphoblastic leukemia. The median age was 10.5 years. The delay 3 (get adequate and timely treatment) was identified in 83% of the cases and transfers during treatment were the most common limitation (66.7%). 83.3% of deaths were deemed unavoidable given the clinical conditions of the patients. Conclusions. Even though the delays identified did not affect mortality in a direct way, they did nonetheless constitute the basis for improvements to the quality of attention to children with cancer.

Cytomegalovirus Infection according to Cell Source after Hematopoietic Cell Transplantation in Pediatric Patients

PURPOSE: This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type. MATERIALS AND METHODS: We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009. RESULTS: In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2x10(5) leukocytes vs. RD 7/2x10(5) leukocytes vs. UD 19/2x10(5) leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia. CONCLUSION: This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients.

Cyclophosphamide plus total body irradiation compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: a systematic review and meta-analysis

Cyclophosphamide plus total body irradiation [CYTBI] and oral busulfan plus cyclophosphamide [BUCY] are commonly used conditioning regimens prior to allergenic hematopoietic stem cell transplantation [HSCT] in patients with leukemia. However, there is conflicting data on the superiority of one regimen over the other. Our aim was to critically appraise and synthesize available evidence regarding the efficacy and safety of CYTBI compared to BUCY as a conditioning regimen. Systematic review and meta-analysis of randomized, controlled trials [RCTs] comparing BUCY with CYTBI. We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival [OS] and disease-free survival [DFS]. Acute and late toxicity were secondary endpoints. Meta-analysis was attempted only on RCTs. A relative risk or risk ratio [RR] and 95% confidence interval [CI] was calculated for each outcome in the meta-analysis. Fifteen non-randomized comparative studies involving 6280 patients were included in a narrative review without attempting a pooled analysis, in view of the potential for significant bias. Outcome data from seven RCTs involving 730 patients randomly assigned to either CYTBI or BUCY was pooled using meta-analytic methods. CYTBI was associated with a modest but non-significant reduction in all cause mortality [RR=0.82, 95%CI: 0.64-1.05; P=.12] and relapse of leukemia [RR=0.89, 95%CI: 0.72-1.10; P=.28]. Transplant-related mortality [TRM] was significantly lesser with CYTBI compared to oral BUCY [RR-0.53, 95%CI: 0.31-0.90; P=.02]. The cumulative incidence of major complications was not significantly different between the two regimens, but specific complications varied according to the conditioning regimen. TBI-based regimens were associated with more severe late effects on growth and development in children. This analysis represents the largest comparative analyses of CYTBI with BUCY as a conditioning regimen prior to HSCT in the indexed medical literature. Conditioning regimen and disease [type and setting] can significantly affect outcomes. TRM is significantly lesser with CYTBI, but this does not translate into a significant survival benefit. There remain valid concerns regarding the late effects of TBI, particularly in children. Although not overly superior, the weight of evidence favors CYTBI over BUCY as a first choice-conditioning regimen in patients with leukemia

[Growth inhibitory and apoptotic effects of carbenoxolone in human leukemia K562 cell line]

Leukemia is a malignant and progressive disorder in which genetic defects in hematopoietic cells lead to uncontrolled proliferation of blood cells. Different drugs have been proposed for the treatment of leukemia but none of them resulted in complete remission. Recently, anti-cancer effects of carbenoxolone [CBX], that is a 3- hemisuccinate, have been reported in several cell lines. In the present study we evaluated the effects of CBX on K562 cell line as an experimental model of chronic myeloid leukemia [CML]. K562 cells were cultured and treated for various time intervals with different concentrations of CBX [50-300 micro M]. Trypan blue exclusion test and tetrazolium salt absorption test [MTT] were used to evaluate the growth inhibitory and apoptotic effects of the drug. Fluorescence microscopy and DNA fragmentation assay were used to study apoptosis. The results of this study showed that CBX induced growth inhibition of K562 cells in a dose- and time- dependent manner. For example, growth inhibition rates after 48 hours treatment with concentrations of 50 micro m, 100 micro m, 150 micro m, 200 micro m and 300 micro m were 11%, 41%, 59%, 79% and 92%, respectively. Furthermore results of fluorescence microscopy and DNA fragmentation assays indicated that apoptosis, is the cause of cell death induced by CBX. Considering the growth inhibitory and apoptotic effects of CBX on human myeloid leukemia K562 cells, the drug can be considered as a potential candidate for further studies on CML treatment

Proliferation inhibition, cell cycle arrest and apoptosis induced in HL-60 cells by a natural diterpene ester from Daphne mucronata

Gnidilatimonoein [Gn], a new diterpene ester from Daphne mucronata, possesses strong anti-metastasis and anti-tumor activities. In this study, its apoptosis and differentiation capabilities were evaluated by using the leukemia HL-60 cell line. Cell prolifaration inhibition was estimated by MTT assay. The occurrence of apoptosis was evaluated by EtBr/AO double staining technique, cell cycle analyses and detection of apoptotic cells by Annexin V-FITC and propodium iodide [PI]. Differentiation of the cells was determined by NBT reduction assay and the expression of specific cell surface markers such as CD 14 and CD1 Ib, were analyzed by flow cytometry. The drug decreased the growth of the cells dose- and time-dependently and the IC[50] was found to be 1.3 microM. Our data suggested that Gn induced both monocytic differentiation and apoptosis among HL-60 cells. In addition, cell cycle analyses showed an increase in Gl phase population by 24 hrs, which was gradually replaced by Sub-Gl cell population [apoptotic cells] by 72 hrs. Based on these data, the Gn-treated HL-60 cells displayed differentiation-dependent apoptosis. Thus, Gn might be a good candidate for differentiation therapy of leukemia, pending full biological evaluation of the compound among the wide array of leukemia cells