Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile / Acute myeloid leukemia. Analysis of 114 patients

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. Aim: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). Results: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

A real life use of ruxolitinib in patients with acute and chronic graft versus host disease refractory to corticosteroid treatment in Latin American patients

Abstract Introduction: Graft-versus-host disease (GVHD) is a serious complication in allogeneic transplantation. The first-line treatment is high doses of corticosteroids. In the absence of response to corticosteroids, several immunosuppressive drugs can be used, but they entail an elevated risk of severe infections. Added to this, there are patients who do not improve on any immunosuppressive treatment, with subsequent deteriorated quality of life and high mortality. Ruxolitinib has been shown to induce responses in refractory patients. In this study we have presented our real-life experience. Methods: A retrospective analysis was performed on patients with severe GVHD refractory to corticosteroids. Demographic, previous treatment, response and mortality data were collected. Results: Since 2014, seventeen patients with GVHD were treated with ruxolitinib due to refractoriness to corticosteroids and immunosuppressants and a few to extracorporeal photopheresis, 8 with acute GVHD (1 pulmonary, 4 cutaneous grade IV and 3 digestive grade IV) and 9 with chronic GHVD (5 cutaneous sclerodermiform, 2 pulmonary and 1 multisystemic). The overall response to ruxolitinib treatment for acute GVHD was 80%, 40% with partial response and 40% with complete remission. Global response in chronic GVHD was 79%. The GVHD mortality was only seen in acute disease and was 40%. Causes of mortality in those patients were severe viral pneumonia, post-transplantation hemophagocytic syndrome and meningeal GVHD refractory to ruxolitinib. Conclusions: In our series, the use of ruxolitinib as a rescue strategy in acute or chronic GVHD was satisfactory. Ruxolitinib treatment in patients with a very poor prognosis showed encouraging results. However, the GVHD mortality remains high in refractory patients, showing that better therapeutic strategies are needed.

Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda

Background: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. Aim: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. Material and Methods: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. Results: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. Conclusions: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.

Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Haploidentical transplantation outcomes are comparable with those obtained with identical human leukocyte antigen allogeneic transplantation in Chilean patients with benign and malignant hemopathies

Abstract Introduction Patients with benign or malignant blood disorders, who require allogeneic stem cell transplantation and lack an identical human leukocyte antigen HLA identicalHL sibling donor, could be transplanted with hematopoietic stem cells from unrelated adult or umbilical cord donors. However, in our country, both approaches are costly and time-consuming options. Methods Over the last few years, haploidentical modalities have been investigated as an alternative donor source, showing similar results to those obtained with identical HLA donors. We started using T-cell-replete haploidentical with post-transplant cyclophosphamide in 2012 and we presented our experience with patients undergoing haploidentical ransplantation compared to SIB. Results Since January 2012 to date, 91 allogeneic transplants have been performed, of which 49 were haploidentical and 42 were HLA identical. The mean age of the patients was 35 years (range: 17-62). The mean CD34/kg × 106 infused per group was 5.93 and 5.89, respectively. Time to granulocyte and platelet engraftment was 11 and 15 days, respectively, for haploidentical, and 12 and 14 days, respectively, for HLA identical (p = 0.10). The 100-day cumulative incidence of global acute GVHD was 34% for haploidentical and 29% for SIHLA identical (p = 0.9). The 2-year overall global graft-versus-host disease was 43% for haploidentical and 41% for HLA identical (p = 0.8). Overall survival, relapse, and transplant and relapse-related mortality were similar between both groups. Conclusion Our experience showed that haploidentical has similar outcomes to those obtained with HLA idential and can be performed in our country safely.

Cardiotoxicidad inducida por tratamientos oncológicos: fundamentos para la implementación de equipos de Cardio-Oncología / Cardiotoxicity of anticancer therapies: towards the implementation of cardio-oncology units

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Clostridium difficile infection in chilean patients submitted to hematopoietic stem cell transplantation

Introduction: Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identi- fied. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. Methods: A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. Results: Two hundred and fifty patients were studied (mean age: 39 years; range: 17-69), with 147 (59%) receiving allogeneic transplants and 103 (41%) receiving autologous trans- plants. One hundred and ninety-two (77%) patients had diarrhea, with 25 (10%) cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic trans- plants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia). In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value = 0.56). Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value = 0.008). In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p-value = 0.71). In the allogeneic transplant group, the median time to acute graft-versus- host disease was similar between the two groups (p-value = 0.08), as was the incidence of grades 1-4 acute graft-versus-host disease (40% vs. 48%; p-value >0.05). Conclusion: The incidence of C. difficile infection after hematopoietic stem cell transplantation was low, with a significant number of cases occurring shortly after transplantation. Allogeneic transplants had a three-time higher risk of infection compared to autologous transplants, but this was not associated with increased mortality, decreased overall survival or higher risk of acute graft-versus-host disease.

Fotoféresis en el tratamiento de Síndrome de Sézary: Caso clínico / Sézary syndrome treated with extracorporeal photopheresis: Report of one case

Sézary syndrome (SS) is an unusually aggressive T- cell lymphoma characterized by the triad of erythroderma, the presence of more than 1,000 Sézary cells in peripheral blood and lymphadenopathies. It is accompanied by generalized pruritus and poor quality of life. The management of SS depends on its stage, patient comorbidities, and treatment availability. Extracorporeal photopheresis (ECP) is the first line of treatment for patients with T-cell lymphomas in stage IVA1, IVA2 or SS. This treatment comprises three phases: leukapheresis, photoactivation and subsequent reinfusion of lymphocytes. As it is an immunomodulatory therapy it does not produce generalized immunosuppression. We report a 76 year-old male with SS stage IIIb initially treated with 12 sessions of ultraviolet phototherapy without response. After 10 well-tolerated sessions of ECP, itching and skin lesions eventually disappeared.

Resultados en el tratamiento de pacientes con leucemia mieloide aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica entre los años 2010-2014 / Results of acute myeloid leukemia treatment. Analysis of 63 patients between 2010-2014

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, emphasizing its high recurrence rate despite hematopoietic cell transplantation (HCT). Aim: To report the results of AML treatment at the Catholic University of Chile Clinical Hospital. Patients and Methods: Review of medical records of patients with AML. Results: 63 patients, median age 55.4 years (range:16-89), treated between 2010 and 2014. Admission laboratory values showed (median values): leukocytes 45.989/mm³, hemoglobin 9.1 g/dl, platelets 75.548/mm³, peripheral blood blasts 38% and bone marrow blasts 74%. According to cytogenetic risk classification we observed the following groups: favorable 8% (n = 5), intermediate 51% (n = 32), unfavorable 13% (n = 8) and unknown 28% (n = 17). Seventy five percent of patients received induction chemotherapy and 25% palliative care. Median survival of treated and palliative care patients was 27.3 and 1 month respectively. Induction chemotherapy (IC) mortality (ICM) was 4.2%. Seventy percent (n = 33) of patients who received IC had complete response (CR) with a 3-year relapse free survival (RFS) of 25% and overall survival (OS) of 31%. Multivariate analysis demonstrated that achievement of CR, cytogenetic risk group and receiving consolidation chemotherapy were significantly associated with better RFS and OS. Conclusions: AML treatment with standard chemotherapy in our center achieves similar results to what has been described in international series regarding induction rates and ICM, however RFS and OS are still very low, especially in intermediate and high cytogenetic risk groups.

Outcomes in relapsed Hodgkins lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidade Católica

Hodgkins lymphoma is a highly curable disease. Autologous and reduced intensity allogeneic hematopoietic cell transplantations are alternatives to treat relapsed patients. Here, we report on the results of one service using these procedures. Methods: All patients who underwent transplantations in our institution between 1996 and 2014 were retrospectively studied and demographics, toxicities and survival rate were analyzed. Results: This study evaluated 24 autologous and five reduced intensity allogeneic transplantations: the median ages of the patients were 29 and 32 years, respectively. At the time of autologous transplantation, ten patients were in complete remission, nine had chemosensitive disease but were not in complete remission, three had refractory disease and the status of two is unknown. In the allogeneic group, two were in complete remission and three had chemosensitive disease. The 5-year overall survival after autologous transplantation was 42% (66% patients were in complete remission, 37% had chemosensitive disease with incom- plete remission and 0% had refractory disease) and 1-year overall survival after allogeneic transplantation was 80%. Transplant-related mortality was 0% in patients conditioned with the ifosfamide/carboplatin/etoposide (ICE), carmustine/etoposide/cyclophosphamide (BEC) and carmustine/etoposide/cytarabine/melphalan (BEAM) regimens, 37% in patients condi- tioned with busulfan-based regimens and 20% in allogeneic transplantations. Conclusions: Hematopoietic cell transplantation for relapsed Hodgkin's lymphoma is a potentially curative procedure especially in patients in complete remission at the time of autologous transplantations, and possibly after allogeneic transplantations. Further studies are necessary to clarify the role of allogeneic transplantations in the treatment of relapsed Hodgkin's lymphoma.

Experiencia de 22 años de trasplante autólogo de células hematopoyéticas en pacientes con mieloma múltiple o amiloidosis sistémica. 1992-2014 / Autologous hematopoietic cell transplantation in patients with multiple myeloma. Experience in 53 patients

Background: Autologous hematopoietic cell transplantation (THA) in patients with multiple myeloma and amyloidosis is the standard of care to promote disease free survival and quality of life. Aim: To report our experience with THA in patients with multiple myeloma. Material and Methods: Retrospective review of the hematopoietic cell transplantation database of a hospital of a Medical School. Forty seven patients with multiple myeloma and six with amyloid light chain amyloidosis were identified. Clinical and demographic data were obtained from the records. Results: The overall five year survival of patients was 55%. Transplant-related or non-relapse mortality occurred in 7%. We found no differences in outcomes among patients younger or older than 50 years. Conclusions: Our data supports that THA can be done in our country with similar results to those obtained in international transplantation centers. Chronological age should not be a limitation to offer this therapy to patients with multiple myeloma and amyloidosis.

Leucemia de células velludas en el embarazo: Caso clínico / Hairy cell leukemia during pregnancy: Report of one case

Hairy cell leukemia (HCL) is a rare chronic B cell lymphoproliferative disorder that affects mostly men. It usually presents with pancytopenia, splenomegaly and bone marrow infiltration, without lymphadenopathy. Diagnosis is based on the presence of mononuclear cells with cytoplasmic projections in a blood smear, the typical bone marrow infiltration pattern and the immunophenotypic profile. HCL occurs seldom in young women and even more exceptionally during pregnancy. We report a 31-year-old woman in whom a splenomegaly was detected during routine prenatal care. Pancytopenia with 25 percent of hairy cells was found in her blood count. The patient was subjected to an open splenectomy and had an uneventful pregnancy. After two years of follow up, she has a normal blood count and has not required chemotherapy.

Complicaciones de la nutrición enteral / Complications of enteral nutrition

Se estudió prospectivamente a 35 pacientes que recibieron Nutrición Enteral (NE) durante su hospitalización, registrándose diariamente los aportes nutricionales, las complicaciones y sus causas. La edad promedio fue de 63,4 años. Recibieron NE por un total de 452 días (promedio 12,9 días/paciente), siendo el accidente vascular encefálico y el deterioro psicoorgánico las patologías más frecuentes, y el compromiso de conciencia y la desnutrición, los principales motivos de indicación. En todos se comprobó radiológicamente la posición de la sonda enteral. Los aportes promedios totales diarios fueron de 1.370 Calorías y de 50,1 g de proteínas. Ocho pacientes (23%) no presentaron complicaciones, y el (17%) tuvieron 3 o más de ellas. Las complicaciones más frecuentes fueron las digestivas, representando el 10% de los días totales; la diarrea fue la más frecuente de este grupo. No hubo casos de aspiración bronquial. Las complicaciones metabólicas e hidroelectrolíticas se presentaron en el 3% de los días de observación