Cardiovascular risk and use of conicity index in patients submitted to autologous hematopoietic stem cell transplantation / Risco cardiovascular e uso do índice de conicidade em pacientes submetidos ao transplante autólogo de células-tronco hematopoiéticas

ABSTRACT Objective To analyze the prevalence of overweight and the use of conicity index for cardiovascular risk assessment in individuals submitted to autologous hematopoietic stem cell transplantation. Methods The sample comprised 91 patients of both sexes, who underwent autologous hematopoietic stem cell transplantation from September 2008 to December 2013, aged 18 years or over. To determine the nutritional profile, we collected anthropometric data on weight, height, waist circumference upon hospital admission. The body mass index and the conicity index were calculated. Results A total of 91 patients diagnosed with multiple myeloma, Hodgkin's lymphoma, non-Hodgkin's lymphoma and other conditions were evaluated. The mean age was 43.5 (14.2) years, 63.7% were male. We verified that according to the body mass index, 63.7% were overweight and, according to waist circumference, 74.7% had a higher risk for cardiovascular diseases. According to the calculation of the conicity index, 92.3% of patients presented increased cardiovascular risk. Patients with multiple myeloma had a higher conicity index when compared to other patients (p<0.01). Conclusion This study revealed a high prevalence of overweight and cardiovascular risk. It should be noted that the conicity index was a good method to evaluate cardiovascular risk and that new studies using this index should be performed.

RESUMO Objetivo Analisar a prevalência de excesso de peso e a utilização do índice de conicidade para a avaliação do risco cardiovascular em indivíduos submetidos ao transplante autólogo de células-tronco hematopoiéticas. Métodos A amostra foi composta por 91 pacientes, de ambos os sexos, submetidos ao transplante autólogo de células-tronco hematopoiéticas, de setembro de 2008 a dezembro de 2013, com idade igual ou superior a 18 anos. Para traçar o perfil nutricional, foram coletados dados antropométricos, como peso, altura e circunferência da cintura, na admissão hospitalar. Calcularam-se o índice de massa corporal e o índice de conicidade. Resultados Foram avaliados 91 pacientes, diagnosticados com mieloma múltiplo, linfoma de Hodgkin, linfoma não Hodgkin e outras patologias. A média de idade foi de 43,5 (14,2) anos, e 63,7% eram do sexo masculino. Verificou-se que, de acordo com o índice de massa corporal, 63,7% apresentavam excesso de peso e, segundo a circunferência da cintura, 74,7% possuíam maior risco para doenças cardiovasculares. De acordo com o cálculo do índice de conicidade, constatou-se que 92,3% dos pacientes apresentavam risco cardiovascular aumentado. Os pacientes com mieloma múltiplo apresentaram índice de conicidade mais elevado, se comparado aos outros pacientes (p<0,01). Conclusão Este estudo revelou alta prevalência de excesso de peso e de risco cardiovascular. Salienta-se que o índice de conicidade se mostrou um bom método para avaliação do risco cardiovascular e que novos estudos utilizando este índice devem ser realizados.

Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution

We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51 percent) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23 percent of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38 percent at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.

Second allogeneic peripheral blood stem cell transplants with reduced-intensity conditioning / Segundos trasplantes hematopoyéticos con esquemas de acondicionamiento de intensidad reducida

In two institutions in México, twelve patients were given a second allogeneic stem cell transplantation, using the "Mexican" non-myeloablative preparative regimen. Eight had a malignant condition (six acute leukemias, one myelofibrosis and one myelodysplasia), eleven individuals were allografted twice from the same donor and in one case, cells from two different umbilical cords were used. The median time to conduct the second allograft after the first one was 6 months (range 1-41). The five patients who failed to engraft after the first transplant failed also to engraft after the second one; all of them had been heavily transfused. Only three patients were successfully rescued with the second transplant, two with acute leukemia and one with aplastic anemia. Seven patients are alive 10-41 months (median 35) after the second transplant, but only three (25%) remain disease-free. The 52-month overall survival (SV) of the patients is 58%, whereas the median overall SV has not been reached, being above 52 months. Conducting a second allograft may be useful to rescue some individuals relapsing after a first hematopoietic allotransplant.

En dos instituciones en México se llevaron a cabo doce segundos trasplantes de células hematopoyéticas usando el "método mexicano" de acondicionamiento no mieloablativo. Ocho pacientes tenían una enfermedad maligna (seis leucemias agudas, una mielofibrosis y una mielodisplasia). Once sujetos se retrasplantaron del mismo donador y en un caso se emplearon células hematopoyéticas de dos diferentes cordones umbilicales. La mediana del tiempo transcurrido entre los dos trasplantes fue de seis meses (rango 1 a 41). Los cinco pacientes que no se injertaron con el primer trasplante tampoco se injertaron con el segundo; todos ellos habían sido multitransfundidos antes de los trasplantes. Sólo tres pacientes se pudieron rescatar con el segundo trasplante, dos con leucemia aguda y uno con anemia aplástica. Siete pacientes están vivos 10 a 41 meses (mediana 35) después del segundo trasplante, pero sólo tres (25%) se encuentran libres de enfermedad. La supervivencia (SV) global a 52 meses es de 58%, en tanto que la mediana de SV no se ha alcanzado y es mayor de 52 meses. Hacer un segundo trasplante hematopoyético puede rescatar a algunos pacientes quienes recaen después de un trasplante de médula ósea.

Trasplante de células hematopoyéticas en mieloma múltiple / Hematopoietic stem cell transplantation in multiple myeloma

Multiple myeloma (MM) is the second most common hematologic malignancy, affecting approximately 14,000 new patients per year in the United States. For over four decades, the standard treatment for MM has been a regimen of melphalan combined with prednisone. Using this treatment modality, complete responses are rare, and 50% of patients have had disease that was resistant to chemotherapy. Attempts have been made to improve the outcome of MM by administering combinations of I. V. polichemotherapy, but these treatments are equivalent in terms of overall survival. High-dose therapy with peripheral blood stem cell support can be applied safely in these patients and achieves significantly higher complete remission rates as well as better event-free survival and overall survival. However, neither tumor-cell purging, positive selection, intensification of conditioning with additional chemotherapeutic agents, nor total body irradiation have been shown to improve outcome. The role of tandem transplantation with high-dose melphalan seems to be a good selection of treatment in hospitals having all resources. Future research will include the combination of the best remission-induction regimen with tandem transplants and maintenance treatments (thalidomide, idiotype or dendritic cell vaccination) that will sustain complete remission. Development of non-myeloablative allogeneic transplantation in order to exploit the graft-versus myeloma effect provides an alternative for patients who have a compatible donor. Combining all of these modalities with the new drugs developed few years ago (thalidomide, bortezomib, revlimid), we hope that MM will become a manageable chronic disease and perhaps a curable disease at least for 30% to 40% of the patients.

El mieloma múltiple (MM) es la segunda patología oncohematológica más frecuente. En Estados Unidos son diagnosticados anualmente 14,000 casos nuevos. En las últimas cuatro décadas el tratamiento estándar ha sido la combinación de melfalán y prednisona. Con este régimen raramente se logran remisiones completas y 50% de los pacientes no responden a esta terapia. Se han hecho intentos de mejorar los resultados combinando poliquimioterapia, pero la sobrevida global ha sido la misma. Al aplicar quimioterapia a dosis altas y rescate con trasplante de células hematopoyéticas se logra un mayor porcentaje de remisiones completas, asimismo, una mayor sobrevida libre de enfermedad y sobrevida global. La purga de células hematopoyéticas, selección positiva, intensificación del régimen de acondicionamiento con otras drogas o irradiación corporal total, no han demostrado utilidad en términos de sobrevida global. El doble trasplante autólogo de células hematopoyéticas parece ser una opción útil para hospitales que cuentan con la infraestructura y los recursos necesarios para realizarlo. En un futuro, la investigación deberá incluir el uso del mejor régimen de inducción a la remisión más doble trasplante autólogo y terapia de mantenimiento (talidomida o vacunas con células dendríticas), con la finalidad de al menos prolongar la remisión completa. El uso del trasplante alogénico no mieloablativo para provocar el efecto injerto contra mieloma parece una buena alternativa para los pacientes que tengan donador. Al combinar todas estas modalidades de tratamiento con las nuevas drogas desarrolladas en los últimos años (talidomida, bortezomid, revlimid), se espera que en un futuro el MM se convierta en una enfermedad crónica y curable en al menos 30 a 40% de los enfermos.