Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile / Treatment of Hodgkin lymphoma: analysis of 915 patients

Background: Hodgkin lymphoma has a high rate of curability, even in advanced stages. Aim: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. Material and Methods: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. Results: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. Conclusions: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

Resultados de pacientes con linfoma del manto: impacto de terapias basadas en citarabina y trasplante hematopoyético / Cytarabine and hematopoietic cell transplantation for mantle cell lymphoma: analysis of 20 patients

Background: Mantle cell lymphoma (MCL) has high relapse and mortality rates. There is a survival benefit when treatment is intensified with cytarabine (AraC), hematopoietic cell transplantation (HCT) and maintenance with rituximab. Aim: To assess the outcomes of patients with MCL treated in a university hospital. Material and Methods: Review of an oncology center database and medical records identifying patients with MCL treated between 2006 and 2017. Death dates were obtained from the death certificate database of the National Identification Service. We analyzed the response rate, overall survival (OS) and progression-free survival (PFS). As a secondary objective, the survival impact of AraC, HCT and maintenance with rituximab, was also analyzed. Results: Information on 20 patients aged 62 ± 11 years, followed for a median of 45 months was retrieved. Eighty-five percent were diagnosed at an advanced stage. The most used first-line regime was R-CHOP in 11 patients, followed by R-HyperCVAD in five. Only 47% achieved complete response. 4-year PFS and OS were of 30 and 77% respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) significantly predicted PFS and OS. Maintenance with rituximab or HCT was associated with better PFS (48 vs 21 months, p < 0.01). The exposure to AraC or HCT, in refractory or relapsed disease, was associated with an increase in PFS from 9 to 28 months (p = 0,02) and 4-year OS from 40 to 100% (p = 0.05). OS increased even more, from 25 to 100% in those with high-risk MIPI (p = 0.04). Conclusions: The incorporation of AraC, HCT and maintenance with rituximab in the therapeutic backbone of MCL, especially for high-risk cases, was associated with improved survival.

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.

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center / Resultados do transplante alogênico de células-tronco em doentes com leucemia mieloide aguda com doença ativa: experiência de um único Centro Oncológico Europeu

Summary Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). Conclusion: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

Resumo Introdução: o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo) representa uma abordagem potencialmente curativa para pacientes com leucemia mieloide aguda (LMA) recorrente ou refratária. Nosso trabalho apresenta o resultado de pacientes com recaída ou doença refratária tratados com TCTH-alo. Método: coorte retrospectiva incluindo 61 pacientes de 1994 a 2013 com diagnóstico de recidiva/LMA refratária. Os desfechos de interesse foram mortalidade relacionada ao transplante (MRT), incidência da doença aguda e crônica do enxerto contra hospedeiro (DECH), incidência de recaídas, sobrevida livre de progressão (PFS - progression-free survival) e sobrevida global (SG). A significância estatística foi considerada para p<0,05. Resultados: a média de idade foi de 61 anos (variação de 1 a 65). A incidência cumulativa de 90 dias, 1 ano e 3 anos de MRT foram de 60%, 26,7% e 13,3%, respectivamente (p<0,001). A incidência de recaída foi de 21,7% em 1 ano, 13% em 3 anos e 8,7% em 5 anos. A SG mediana foi estimada em 8 meses (IC 95% 3,266-12,734) e a mediana de PFS, em 3 meses (IC 95% 1,835-4,165). Conclusão: em nossa coorte, MRT no primeiro ano após o transplante permanece considerável, mas TCTH-alo nesse cenário parece ser uma boa opção para pacientes com LMA ativa. No entanto, novas abordagens são necessárias para reduzir MRT e recaída nesse conjunto de pacientes.

Utilização de células-tronco derivadas da medula óssea: terapia viável para doenças pulmonares obstrutivas crônicas? / Use of bone marrow stem cells: feasible therapy for chronic obstructive pulmonary disease?

Doenças pulmonares obstrutivas crônicas acarretam em redução na qualidade de vida dos portadores e altos gastos ao sistema público de saúde. Na maioria dos casos, o tratamento destas enfermidades envolve apenas medidas paliativas, o que as tornam grandes alvos de pesquisa com terapia celular. As células-tronco têm capacidade de se diferenciar em todos os tecidos que compõem o organismo devido à plasticidade, e sua ação na regeneração tecidual é comprovada apesar do mecanismo não estar totalmente elucidado. Células-tronco foram, em princípio, pesquisadas como panacéias para doenças neurológicas, cardiovasculares e diabetes. Os resultados favoráveis à utilização dessa terapia nestes sistemas impulsionaram pesquisas em doenças pulmonares obstrutivas crônicas, como enfisema, fibrose cística e fibrose pulmonar idiopática.

Chronic obstructive pulmonary disease have been targets of cell therapy research, because they decrease life quality, cost a lot to the public health system and can only be treated with palliative protocols. The stem cells are capable of differentiating into all body tissues, according to their plasticity, and its action in tissue regeneration is established, although the mechanism is not fully elucidated. Stem cells were initially investigated as panaceas for diabetes as well as for neurological and cardiovascular diseases. The positive results obtained with stem cell therapy in these systems stimulated research about its use for treatment of chronic obstructive pulmonary diseases, such as emphysema, cystic fibrosis and idiopathic pulmonary fibrosis.

Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: the experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.

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.

Trasplante de células hematopoyéticas de sangre periférica utilizando quimioterapia inmunosupresora sin destrucción de la médula ósea: "minitrasplante" / Peripheral blood hematopoietic cell transplant using immunosuppressive chemotherapy without bone marrow destruction: minitransplant

Using a nonmyeloablative, immunosuppressive, fludarabine (FLU)-base conditioning regimen, we have performed allogeneic peripheral blood stem cell transplants in 17 patients (six with chronic granulocytic leukemia, four with acute myelogenous leukemia, five with acute lymphoblastic leukemia, one with myelodysplasia and one, with thalassemia major). Conditioning regimen consisted of FLU/busulfan/cyclophosphamide or FLU melphalan. To avoid graft vs. host disease (GVHD), cyclosporine and methotrexate were used. Median granulocyte recovery time to 0.5 x 10(9) was 11 days, whereas median platelet recovery time to 20 x 10(9) was 12 days. Seven patients did not need red blood cell transfusions and four did not need platelet transfusions. In thirteen individuals (76), the procedure could be completed fully on an outpatient basis. Follow-up times range between 1 and 14 months. Five of 17 patients developed acute GVHD whereas 4/10 developed chronic GVHD. The 14-month survival (SV) is 70 and median SV is not reached. Five patients (29) have died, three due to relapse of the disease and two due to GVHD. The transplant-related mortality was 5.8. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and may represent another approach in management of patients requiring allogeneic stem cell transplant.

Transplante hematopoyetico alogenico con celulas progenitoras extraidas de la sangre periferica / Allogenic hematopoietic transplantation with peripheral blood progenitor cells

Cinquenta y tres pacientes (ptes) recibieron transplante alogénico con células progenitoras extraídas de la sangre periférica (PSP); 25 ptes eran mujeres y 28 varones. La edad media del grupo fue de 20 años, (rango 2-550. Los diagnósticos fueron leucemia mieloide aguda (LMA) en 16 ptes, leucemia linfoblástica aguda (LLA) en 15, leucemia mieloide crónica (LMC) en primera fase crónica en 12, aplasia medular en 4, síndrome mielodisplásico en 3 y Enfermedad de Hodgkin en recaída luego de trasplante autólogo, talasemia mayor y síndrome de Hunter en 1 caso, respectivamente. Los acondicionamientos fueron en 38 ptes radioterapia corporal total 1200 cGy y ciclofosfamida 120 mg/kg EV; en 10 ptes busulfán 16 mg/kg y ciclosfosfamida 120 mg/kg EV, 3 ptes radioterapia linfoide total (RLT) y ciclosfosfamida, 2 ptes con otros agentes quimioterápicos. Los PSP se infundieron a través de un catéter sin ningún tipo de manipulación. La profilaxis de injerto vs huésped (EICH) se realizó con ciclosporina y metotrexato. Los donantes fueron familiares con HLA compatibles 6/6 y un caso 5/6 de los antígenos. Previo a la extración de PSP, recibieron G-DSF (filgrastim) 10 mug/kg/día sc. Cuatro días. El quinto día se realizó la féresis, en los primeros treinta casos se hizo la extracción adicional de médula ósea. Las medias de CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg de peso) 4.12; 4.59; 2.57; 1.9; 0.55 y 0.68 respectivamente. La mediana de recuperación de nuetrófilos > 500 se obtuvo el día = 11 y de plaquetas > 20000, + 13. El tiempo de internación fue de 26 días (18-39) y la media de días con antibióticos parenterales fue de 12.2 días (5-45). La mortalidad relacionada al trasplante fue del 15 por ciento. EICH aguda se observó en el 43.4 por ciento de los ptes, con sólo 5 ptes con EICH aguda grado III o IV. En 43 ptes se pudo evaluar la aparición de EICH crónica con un tiempo medio de seguimiento de 18 meses (4-39). En la presente experiencia el trasplante de PSP alogénicos mantuvo una aceptable incidencia de EICH crónica; dados los recientes informes de aumento de esta complicación, parece lógico desaconsejar el uso de PSP en patología no maligna en la que no importaría la potencia del efecto injerto versus leucemia.