Association of CD38+ Immunophenotyping Biomarker With a Better Prognosis in Elderly Acute Myeloid Leukemia Patients.

BACKGROUND/AIM: The relevance of cytogenetic markers as prognostic risk factors has been demonstrated in a vast number of studies, with many prognostication tools utilizing these factors to determine treatment approaches. Patients aged above 60 years represent an important subgroup of acute myeloid leukemia (AML) patients, especially because they usually exhibit a poorer cytogenetic landscape and are less suitable for intensive treatments. The importance of evaluating prognostic parameters in AML, especially in low-income countries, prompted an investigation into CD38 expression and its effects. PATIENTS AND METHODS: Medical records of AML patients aged above 60 years from three hospitals in Brazil's northwest region were analyzed. A total of 67 patients were evaluated in terms of overall survival and factors predicting worse outcomes. The risk stratification was performed based on the European LeukemiaNet 2022 guidelines. The analysis of immunophenotyping markers was conducted using multi-parametric flow cytometry. RESULTS: The overall survival of CD38-positive AML patients was higher than that of patients with CD38-negative AML, with survival rates of 15.6 months versus 4 months, respectively (p-value=0.026). The impact of CD38 positivity was relevant also in multivariable Cox proportional hazards regression, demonstrating a positive effect on overall survival, with a hazard ratio of 0.33 (95%CI=0.13-0.79; p-value=0.014). CONCLUSION: Expression of CD38 in patients with AML was associated with better overall survival and serves as a relevant predictor of improved outcome in patients aged above 60 years.

Adoptive immunotherapy with double-bright (CD56bright /CD16bright ) expanded natural killer cells in patients with relapsed or refractory acute myeloid leukaemia: a proof-of-concept study.

Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56bright /CD16bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106 -107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.

Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study.

OBJECTIVE: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT). STUDY DESIGN: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units. RESULTS: From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P < .0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10-4) compared with a-HSCT recipients who did not receive antifungal prophylaxis. The main cause of IFI in children receiving prophylaxis was emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to the prophylactic agents. CONCLUSIONS: The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.

From the "missing self" hypothesis to adaptive NK cells: Insights of NK cell-mediated effector functions in immune surveillance.

The original discovery of NK cells approximately 40 yr ago was based on their unique capability to kill tumor cells without prior sensitization or priming, a process named natural cytotoxicity. Since then, several studies have documented that NK cells can kill hematopoietic and nonhematopoietic cancer cells. NK cells also recognize and kill cells that have undergone viral infections. Besides natural cytotoxicity, NK cells are also major effectors of antibody-dependent cell cytotoxicity (ADCC). Therefore, NK cells are well "armed" to recognize and mount immune responses against "insults" that result from cell transformation and viral infections. Because of these attributes, an essential role of NK cells in tumor surveillance was noted. Indeed, several studies have shown a correlation between impaired NK cell cytotoxicity and a higher risk of developing cancer. This evidence led to the idea that cancer initiation and progress is intimately related to an abnormal or misdirected immune response. Whereas all these ideas remain current, it is also true that NK cells represent a heterogeneous population with different abilities to secrete cytokines and to mediate cytotoxic functions. In addition, recent data has shown that NK cells are prone to suffer epigenetic modifications resulting in the acquisition of previously unrecognized attributes such as memory and long-term survival. Such NK cells, referred as "adaptive" or "memory-like," also display effector functions that are not necessarily equal to those observed in conventional NK cells. Given the new evidence available, it is essential to discuss the conceptual reasoning and misconceptions regarding the role of NK cells in immune surveillance and immunotherapy.

Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells.

Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (<2%), did not increase over time, and was only transiently affected by the use of NSG-S mice. Co-injection of mesenchymal stem cells did not enhance human myelodysplastic syndrome cell engraftment. Overall, we conclude that engraftment of acute myeloid leukemia samples is more robust compared to that of myelodysplastic syndrome samples and unlike those, acute myeloid leukemia cells respond positively to human cytokines, whereas myelodysplastic syndrome cells demonstrate a general unresponsiveness to them.

Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing

Abstract Introduction Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic-driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. Patients and methods Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D-index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (≥0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. Results Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p = 0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p = 0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p = 0.007) of high, intermediate, and low risk patients, respectively. All patients survived. Conclusion A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk.

Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing.

INTRODUCTION: Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic-driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. PATIENTS AND METHODS: Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D-index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (≥0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. RESULTS: Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p=0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p=0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p=0.007) of high, intermediate, and low risk patients, respectively. All patients survived. CONCLUSION: A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk.

Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts.

Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly × 3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.

Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals / Comparação do perfil bioquímico e imunológico de pacientes pediátricos com leucemia mieloide aguda e de indivíduos saudáveis

ABSTRACT OBJECTIVE: To compare the biochemical and immunological profiles of pediatric patients with acute myeloid leukemia (AML) with healthy children and adolescents. METHODS: This was a cross-sectional study in which 21 therapy-naïve patients with AML were compared with a group of 24 healthy individuals. The following data were analyzed: serum proteins, leucocytes and subgroups, erythrocytes, hematocrit, hemoglobin, platelets, cytokines in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, immunoglobulin A, and erythrocytic glutathione. Statistical analysis was performed using SPSS software, considering as significant p-values < 0.05. RESULTS: Serum albumin levels were higher (p < 0.0001) in the control group, as well as all the parameters related to red blood cells (p < 0.0001). For leucocytes and subgroups, no statistical difference was found between the AML and the control groups. For cytokines, the concentrations were significantly higher under spontaneous and BCG-stimulated conditions for TNF-a, IL-6, IL-10, and IFN-? in the control group. Under PHA-stimulated conditions, the concentration was higher (p = 0.002) only for IL-6. No difference was found between the two groups for the other cytokines and for IgA in the saliva. Erythrocytic glutathione was higher (p < 0.0001) in AML patients. CONCLUSIONS: It was possible to characterize the biochemical and immunological profile of pediatric patients with AML, as well as highlight some significant differences in these parameters when comparing with healthy children and adolescents.

RESUMO OBJETIVO: Comparar o perfil bioquímico e imunológico de pacientes pediátricos portadores de leucemia mieloide aguda (LMA) em relação a um grupo de crianças e adolescentes saudáveis. MÉTODOS Estudo transversal, em que foram avaliados 21 pacientes com LMA virgens de terapia e 24 indivíduos saudáveis. Foram analisados: proteínas séricas, leucócitos e subgrupos, eritrócitos, hematócrito, hemoglobina e plaquetas, citocinas em cultura de células mononucleares do sangue periférico sob condição espontânea e estimulada por BCG ou PHA, imunoglobulina A e glutationa eritrocitária. Análise estatística foi feita com o software SPSS considerando p < 0,05. RESULTADOS: Albumina sérica foi superior (p < 0,0001) no grupo de controle, bem como todos os parâmetros relacionados com os glóbulos vermelhos (p < 0,0001). Para os leucócitos e subgrupos não houve diferença estatística entre os pacientes com LMA e o grupo controle. As concentrações foram significativamente mais elevadas sob condições espontânea e estimulada por BCG para as citocinas TNF-a, IL-6, IL-10 e IFN-? no grupo controle. Sob condição estimulada com PHA a concentração foi superior (p = 0,002) apenas para a IL-6. Não houve diferença estatística para as demais citocinas e para IgA salivar entre os dois grupos. Glutationa eritrocitária foi superior (p < 0,0001) nos pacientes LMA. CONCLUSÕES: Diante do exposto, foi possível caracterizar o perfil bioquímico e imunológico de pacientes pediátricos com LMA, bem como evidenciar diferenças significativas em alguns desses parâmetros ao se compararem os indivíduos doentes e o grupo de crianças e adolescentes saudáveis.

Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals.

OBJECTIVE: To compare the biochemical and immunological profiles of pediatric patients with acute myeloid leukemia (AML) with healthy children and adolescents. METHODS: This was a cross-sectional study in which 21 therapy-naïve patients with AML were compared with a group of 24 healthy individuals. The following data were analyzed: serum proteins, leucocytes and subgroups, erythrocytes, hematocrit, hemoglobin, platelets, cytokines in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, immunoglobulin A, and erythrocytic glutathione. Statistical analysis was performed using SPSS software, considering as significant p-values<0.05. RESULTS: Serum albumin levels were higher (p<0.0001) in the control group, as well as all the parameters related to red blood cells (p<0.0001). For leucocytes and subgroups, no statistical difference was found between the AML and the control groups. For cytokines, the concentrations were significantly higher under spontaneous and BCG-stimulated conditions for TNF-α, IL-6, IL-10, and IFN-γ in the control group. Under PHA-stimulated conditions, the concentration was higher (p=0.002) only for IL-6. No difference was found between the two groups for the other cytokines and for IgA in the saliva. Erythrocytic glutathione was higher (p<0.0001) in AML patients. CONCLUSIONS: It was possible to characterize the biochemical and immunological profile of pediatric patients with AML, as well as highlight some significant differences in these parameters when comparing with healthy children and adolescents.

First proposed panels on acute leukemia for four-color immunophenotyping by flow cytometry from the Brazilian group of flow cytometry-GBCFLUX.

Multiparameter flow cytometry is a highly sensitive, fast, and specific diagnostic technology with a wide range of applicability in hematology. Although well-established eight-color immunophenotyping panels are already available, most Brazilian clinical laboratories are equipped with four-color flow cytometer facilities. Based on this fact, the Brazilian Group of Flow Cytometry (Grupo Brasileiro de Citometria de Fluxo, GBCFLUX) for standardization of clinical flow cytometry has proposed an antibody panel designed to allow precise diagnosis and characterization of acute leukemia (AL) within resource-restricted areas. Morphological analysis of bone marrow smears, together with the screening panel, is mandatory for the primary identification of AL. The disease-oriented panels proposed here are divided into three levels of recommendations (mandatory, recommendable, and optional) in order to provide an accurate final diagnosis, as well as allow some degree of flexibility based on available local resources and patient-specific needs. The proposed panels will be subsequently validated in an interlaboratory study to evaluate its effectiveness on the diagnosis and classification of AL. (Assoc editor comm. 2).

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations.

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

[Esophageal aspergillosis in a patient with acute myelogenous leukemia and febrile neutropenia]. / Aspergilosis esofágica en una paciente con leucemia mieloide aguda y neutropenia febril.

Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients.

Caracterización inmunofenotípica de pacientes con leucemia mieloide aguda / Immunophenotypic characterization of patients with acute myeloid leukemia

Introducción: la leucemia mieloide aguda incluye un grupo heterogéneo de neoplasias caracterizadas por una expansión clonal de mieloblastos, cuya clasificación involucra varios criterios, incluidos los inmunológicos. Objetivo: caracterizar el inmunofenotipo de los pacientes con leucemia mieloide aguda evaluados en el Instituto de Hematología e Inmunología. Métodos: se realizó un estudio descriptivo transversal de los pacientes diagnosticados con este tipo de leucemia, cuyas muestras de sangre fueron procesadas en el Departamento de Inmunología en el período 2008-2012. Se usó un ultramicrométodo inmunocitoquímico que utiliza un panel de anticuerpos monoclonales específicos de antígenos mieloides y linfoides. Las variables analizadas fueron: edad, sexo, subtipo de leucemia y expresión de marcadores inmunológicos, cuyas asociaciones fueron analizadas con los estadígrafos Chi-cuadrado y coeficiente de correlación de Spearman. Resultados: se estudiaron 58 pacientes, 28 del sexo femenino y 30 del masculino. El grupo de edad predominante fue de 0 a 9 años con una mediana de 26 años. El subtipo M4 resultó el más frecuente (30,4 por ciento). Los subtipos M4 y M7 predominaron en niños, mientras que el M0, predominó en adultos, con diferencias estadísticamente significativas (p d»0,05). La combinación de los antígenos panmieloides CD13 y CD33 se presentó en el 91 por ciento de los enfermos. Las combinaciones de CD13/CD33, CD14/CD15, CD33/CD14 y CD33/CD15 mostraron correlación significativa. En el 20,6 por ciento de los pacientes evaluados, fueron detectados, además, antígenos linfoides. No se encontraron diferencias significativas en cuanto al sexo y la edad. El antígeno CD7 fue el más expresado, seguido de los antígenos: CD3, CD20, CD22 y CD79, en igual proporción. Conclusiones: el inmunofenotipaje celular demostró ser un procedimiento útil para confirmar el diagnóstico morfológico y clínico de la leucemia mieloide aguda

Introduction: Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by clonal expansion of myeloblasts; its classification involves several criteria, including the immunological one. Objective: To characterize the immunophenotype of patients with acute myeloid leukemia who were evaluated at the Institute of Hematology and Immunology. Methods: A descriptive study of patients diagnosed with this kind of leukemia, whose blood samples were processed at the Department of Immunology during 2008-2012. An immunocytochemical ultramicromethod that uses a panel of monoclonal antibodies specific for myeloid and lymphoid antigens was applied. The variables analyzed were age, sex, subtype of leukemia and expression of immunological markers; their association was analyzed with the Chi-square test and Spearman's rank correlation coefficient. Results: The study covered 58 patients; 28 were males and 30 females. The predominant age group was 0 - 9 years with a median of 26 years. M4 subtype was the most common (30,4 percent). M4 and M7 subtypes predominated in children, while M0 predominated in adults with statistically significant differences (p d» 0,05). The combination of pan-myeloid antigens CD13 and CD33 was present in 91 percent of patients. Combinations of CD13/CD33, CD14/CD15, CD33/CD14 and CD33/CD15 showed significant correlation. In 20,6 percent of patients tested, lymphoid antigens were also detected. In this group, no significant differences by gender and age. CD7 antigen was the most expressed followed by antigens: CD3, CD20, CD22 and CD79, in equal proportion. Conclusions: Immunophenotyping of leukemia cells appeared as a useful tool to confirm the morphological and clinical diagnosis of acute myeloid leukemia

Evaluación del tratamiento de inducción y consolidación clásico en la leucemia aguda no linfoblástica de Novo / Evaluation of induction and consolidation classic treatment in de Novo acute non-lymphoblastic leukemia

Introducción: la validación de las alteraciones citogenéticas y moleculares presentes al diagnóstico constituyen los factores pronósticos más importantes de la leucemia aguda no linfoblástica y ha permitido establecer el riesgo individual, estratificar a los pacientes e individualizar su tratamiento. Objetivo: describir el comportamiento clínico y la evolución de pacientes con leucemia aguda no linfoblástica, no promielocítica, de novo, que recibieron tratamiento de inducción y consolidación clásico en el servicio de Hematología del Hospital Clínico Quirúrgico Hermanos Ameijeiras. Método: se realizó un estudio descriptivo, longitudinal y prospectivo que incluyó 23 pacientes ingresados entre mayo de 2008 y enero de 2011. Se estratificaron los pacientes en grupos de riesgo favorable, intermedio y desfavorable, teniendo en cuenta factores pronóstico clínicos, biológicos, citogenéticos y moleculares. Resultados: el 60,9 por ciento presentó recuento de leucocitos menor de 25 x 10(9)/L; el 47,8 por ciento tuvo la variante mielomonocítica, el 21,7 por ciento presentó cariotipo normal y el 10 por ciento la translocación (8;21). Las mutaciones del gen FLT3 y el gen NPM1 estuvieron presentes en 2 y 4 pacientes respectivamente. Con el tratamiento de inducción, el 84,2 por ciento alcanzó la remisión completa, predominaron los pacientes en el grupo de riesgo favorable sin diferencias significativas. En el grupo de riesgo molecular favorable el número de remisiones completas fue significativamente mayor (85,7 por ciento) (p = 0.05). El grupo de pacientes de riesgo favorable que se mantuvo en remisión completa con el tratamiento de consolidación representó el 54,5 por ciento, aunque no resultó significativo

Introduction: validation of cytogenetic and molecular abnormalities present at diagnosis is the most important prognostic factors of acute non-lymphoblastic leukemia. This has allowed us to establish the individual risk, stratify the patients and individualize their treatment. Objective: to describe the clinical behavior and outcome of patients with acute de novo non-lymphoblastic non-promyelocytic leukemia, receiving induction and classic consolidation therapy at the Department of Hematology of the Clinical Surgical Hospital Hermanos Ameijeiras. Methods: a descriptive, prospective longitudinal study was carried out with 23 patients admitted between May 2008 and January 2011. Patients were stratified into: favorable, intermediate, poor risk groups, according to biological, molecular and cytogenetics clinical prognostic factors. Results: 60.9 percent of patients had leukocyte counts less than 25 x 10(9)/L, 47.8 percent had myelomonocytic variant, 21.7 percent had normal karyotype and 10 percent had translocation (8; 21). Mutations of the genes FLT3 and NPM1 were present in 2 and 3 patients respectively. 84 percent of patients undergoing induction therapy achieved complete remission, predominantly the ones in the favorable risk group with no significant differences. In the favorable molecular risk group, the number of complete remissions was significantly higher (85.7 percent) (p=0.05). The group of favorable risk patients remaining in complete remission with the consolidation treatment had 54.5 percent, although it was not significant. Conclusions: the disease free survival was greater whereas overall survival rate was similar to the data reported in the international literature. Both were higher within the favorable risk group but without no significant difference, what is considered an important achievement of Cuban Healthcare System

Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil.

Invasive fusariosis (IF) is an infection with Fusarium spp. fungi that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. A cutaneous portal of entry is occasionally reported. We reviewed all cases of IF in Brazil during 2000-2010, divided into 2 periods: 2000-2005 (period 1) and 2006-2010 (period 2). We calculated incidence rates of IF and of superficial infections with Fusarium spp. fungi identified in patients at a dermatology outpatient unit. IF incidence for periods 1 and 2 was 0.86 cases versus 10.23 cases per 1,000 admissions (p<0.001), respectively; superficial fusarial infection incidence was 7.23 versus 16.26 positive cultures per 1,000 superficial cultures (p<0.001), respectively. Of 21 cases of IF, 14 showed a primary cutaneous portal of entry. Further studies are needed to identify reservoirs of these fungi in the community and to implement preventive measures for patients at risk.