Daniel Ernst

Admission of Hematopoietic Cell Transplantation Patients to the Intensive Care Unit at the Pontificia Universidad Católica de Chile Hospital

Patients undergoing hematopoietic cell transplantation (HCT) can have complications that require management in the intensive care unit (ICU). We conducted a retrospective study of patients undergoing HCT between 2007 and 2011 with admission to the ICU. We analyzed 97 patients, with an average age of 37 (range, 15 to 68). The main indications for HCT were hematologic malignancies (84%, n = 82). Ninety percent (n = 87) received myeloablative conditioning. Thirty-one percent were admitted (autologous transplant recipients 15%, allogeneic transplant recipients 34%, and umbilical cord blood [UCB] transplant recipients 48%) with an average length of stay of 19 days (range, 1 to 73 days). The average time between transplantation and transfer was 15 days. The main causes of admission were acute respiratory failure (63%) and septic shock (20%). ICU mortality was 20% for autologous transplantations and 64% for allogeneic transplantations (adult donor and UCB combined). On average, patients died 108 days after the transplantation (range, 4 to 320 days). One-year overall survival, comparing patients entering the ICU with those never admitted, was 16% versus 82% (P < .0001) for allogeneic transplantations (adult donor and UCB combined) and 80% versus 89% (P = not significant) for autologous transplantations. Acute graft-versus-host disease was significantly associated with death in ICU after UCB HCT. ICU support is satisfactory in about one half of patients admitted, characterized by a short and medium term prognosis not as unfavorable as has been previously reported.

Outcomes in relapsed Hodgkin's lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Católica de Chile

Introduction 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 incomplete 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 conditioned with busulfan-based regimens and 20% in allogeneic transplantations. Conclusions Hematopoietic cell transplantation for relapsed Hodgkins 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 Hodgkins lymphoma.

Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome

The interaction between acute myeloid leukemia cells (AML) with the bone marrow stroma cells (BMSCs) determines a protective environment that favors tumor development and resistance to conventional chemotherapy. We showed that BMSCs secrete soluble factors that protect AML cells from Ara-C induced cytotoxicity. This leukemia chemoresistance is associated with a decrease in the equilibrative nucleoside transporter (ENT1) activity by inducing removal of ENT1 from the cell surface. Reduction of cell proliferation was also observed with activation of AKT and mTOR-dependent cell survival pathways, which may also contribute to the tumor chemoprotection. Analysis of primary BMSC cultures has demonstrated that AML patients with stroma capable to confer Ara-C resistance in vitro compared to AML patients without this stroma capacity were associated with a worse prognosis. The two year overall survival rate was 0% versus 80% respectively (p=0.0001). This is the first report of a chemoprotection mechanism based on the removal of a drug transporter from the cell surface and most importantly the first time that a stroma phenotype has correlated with prognostic outcome in cancer.

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 identified. 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 transplants. 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 transplants, 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.

Excelente respuesta a tratamiento con ABVD en pacientes con Linfoma de Hodgkin localizado

BACKGROUND Recent trials show that > 90% of patients with early stage Hodgkin`s Lymphoma (ESHL) can be cured, especially when using the ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapeutic (CT) protocol. The use of radiotherapy (RT) is variable and can be selected according to the presence of specific risk factors, including PET-CT, as recently reported. AIM To report the experience in the treatment of ESHL. MATERIAL AND METHODS Retrospective and descriptive analysis of patients with ESHL treated at the Red de Salud UC-Christus between 2011-2015. RESULTS Twenty-two patients were treated. In 73%, the tumor was of nodular sclerosis histologic type. Most patients (95%) were in stage II, and 78% had a favorable prognosis according to the Deutsche Hodgkin Studiengruppe (GHSG) criteria. All patients were stratified using PET-CT and treated using the ABVD CT protocol, for 4-6 cycles. Only 5 patients received RT. There was no change of conduct after interim-PET-CT results. Ninety one percent of patients achieved complete response and there were two cases of refractory disease. Both cases underwent hematopoietic stem cell transplantation. After 17 months of median follow-up, 91% of patients are relapse-free, and only one patient died (5%). CONCLUSIONS ABVD offers excellent results for ESHL patients. The benefit of PET-CT should be evaluated with prospective protocols, aiming to select patients needing RT or to reduce the number of CT cycles.Background: Recent trials show that >90% of patients with early stage Hodgkin`s Lymphoma (ESHL) can be cured, especially when using the ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapeutic (CT) protocol. The use of radiotherapy (RT) is variable and can be selected according to the presence of specific risk factors, including PET-CT, as recently reported. Aim: To report the experience in the treatment of ESHL. Material and methods: Retrospective and descriptive analysis of patients with ESHL treated at the Red de Salud UC-Christus between 2011-2015. Results: Twenty patients were treated. In 73%, the tumor was of nodular sclerosis histologic type. Most patients (95%) were in stage II, and 78% had a favorable prognosis according to the Deutsche Hodgkin Studiengruppe (GHSG) criteria. All patients were stratified using PET-CT and treated using the ABVD CT protocol, for 4-6 cycles. Only 5 patients received RT. There was no change of conduct after interim-PET-CT results. Ninety one percent of patients achieved complete response and there were two cases of refractory disease. Both cases underwent hematopoietic stem cell transplantation. After 17 months of median follow-up, 91% of patients are relapse-free, and only one patient died (5%). Conclusions: ABVD offers excellent results for ESHL patients. The benefit of PET-CT should be evaluated with prospective protocols, aiming to select patients needing RT or to reduce the number of CT cycles.

Salud ósea en pacientes sometidos a trasplante de precursores hematopoyéticos: un nuevo problema a considerar

BACKGROUND Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of developing osteoporosis. AIM To determine the frequency and severity of Vitamin D deficiency, secondary hyperparathyroidism and low bone mass in patients undergoing HCT. PATIENTS AND METHODS Analysis of the database of patients undergoing HCT in our institution in the 2010-2015 period. We searched for patients with measurements of 25-OH vitamin D (25OHD), parathyroid hormone (PTH) and bone densitometry by double beam X ray absorptiometry (DXA) prior and up to one year after HCT. RESULTS Ninety patients were included, 53 were evaluated prior to HCT and 37 after HCT. They represent 73% of all patients undergoing HCT in the period. Median 25OHD was 12 ng/ml (range 4-41.4). Ninety seven percent of patients had levels considered insufficient and 85% compatible with deficiency. Median PTH was 60.5 pg/ml (range 21-186). Forty five percent of patients had secondary hyperparathyroidism. DXA was performed in 65 patients (prior to HCT in 54 and after HCT in 11). Of these, 11% had had a low bone mineral density. CONCLUSIONS Patients undergoing HCT have a high risk of vitamin D deficiency, secondary hyperparathyroidism and low bone mineral density.

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

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.

Fiebre de origen desconocido como forma de presentación atípica de mieloma múltiple: Caso clínico

Fever of unknown origin (FUO) can be caused by tumors, especially those arising from the hematopoietic system. Multiple myeloma can also cause fever but it is not a common cause of fever of unknown origin. We report a 53 year-old man presenting with fever lasting eight weeks. An extensive study for common causes of FUO was negative. The appearance of hypercalcemia and proteinuria during the evolution suggested the presence of a multiple myeloma, that was confirmed with a bone marrow biopsy. Thalidomide and dexametasone were prescribed with resolution of fever.