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Resumen Fundamento y objetivo La enfermedad del injerto contra el receptor (EICR) y las infecciones son complicaciones del trasplante alogenico de progenitores hematopoyeticos (alo-TPH). La globulina antitimocitica (ATG) es una estrategia empleada para la profilaxis de la EICR. Este estudio analiza los resultados y la frecuencia de infecciones en funcion del uso de ATG, despues de un alo-TPH de donante no emparentado (DNE) en pacientes con leucemia aguda y sindrome mielodisplasico. Pacientes y metodo Estudio retrospectivo de pacientes que recibieron un alo-TPH de DNE entre diciembre de 2007 y abril de 2019. Se compararon los principales resultados en funcion del uso de ATG. Resultados Se incluyo a 66 pacientes. No se encontraron diferencias significativas en el grupo ATG (n = 50) frente al no ATG (n = 16) en supervivencia global, incidencia acumulada de recaida, mortalidad no debida a recaida o incidencia acumulada de EICR aguda o cronica. Hubo mayor frecuencia de infecciones en el grupo ATG (60 frente a 19%; p = 0,004). Conclusiones En este estudio no se demostro diferencia en los principales resultados del alo-TPH en funcion del uso de ATG, pero hubo mas infecciones en el grupo que recibio ATG.

Background and purpose Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome. Patients and methods Retrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG. Results Sixty-six patients were included. No significant differences were found between the ATG group (n = 50) vs. no-ATG group (n = 16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60% vs. 19%, p = .004). Conclusions In this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group.

Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.

One hundred and sixty-one patients underwent haploidentical stem cell transplantation (haploSCT) with thiotepa, busulfan, and fludarabine conditioning followed by post-transplantation cyclophosphamide (PTCy) (on days +3 and +4) and tacrolimus as graft-versus-host disease prophylaxis. Forty-two percent of patients had a high or very high revised Disease Risk Index (rDRI), 55% had an European Society for Blood and Marrow Transplantation risk score (EBMT-RS) ≥4, and 36% had an age-adjusted Hematopoietic Cell Transplant Comorbidity Index (HCT-CI-age) score ≥3. Each of these was considered an unfavorable score. Using the pretransplantation unfavorable scores that had an independent impact on each transplantation outcome studied in multivariate analysis allowed for better stratification of patient outcomes. Thus, the 3-year overall survival (OS) in patients with 0, 1, 2, and 3 unfavorable scores was 86%, 56%, 36%, and 24%, respectively. Nonrelapse mortality (NRM) was negatively impacted by the EBMT-RS and the HCT-CI-age score (3-year NRM in patients with 0, 1, and 2 unfavorable scores was 12%, 33%, and 43%, respectively), whereas the EBMT-RS and the rDRI had an impact on the 3-year relapse incidence (8%, 18%, and 41% in patients with 0, 1, and 2 unfavorable scores, respectively). In conclusion, our study shows that combining 2 or 3 of these well-defined pretransplantation scores improves the ability to predict transplantation outcomes in the setting of haploSCT with PTCy.

Patients with hematological neoplasms transferred to an Intensive Care Unit (ICU) for a life-threatening complication have a poor outcome. In these patients, it is crucial to identify clinical and biologic parameters with potential prognostic significance. This study prospectively evaluated the usefulness of serum procalcitonin (PCT) levels as a predictor of complications (infectious or not) and outcome in these patients.One hundred patients with hematological malignancy were admitted to the ICU from October 2004 until August 2009. In 59 of them serum PCT levels were daily measured from the ICU admission until a maximum period of 10 consecutive days.Hematological diseases were acute leukemia (n=30), lymphoma and other lymphoproliferative disorders (n=18), multiple myeloma (n=7) and other (n=4). Twenty-five patients (42%) had received hematopoietic stem cell transplantation. Thirty-seven patients (63%) presented neutropenia. Those patients who could not be discharged alive from the ICU presented higher PCT levels on days 1, 2 and 3. PCT levels were significantly higher in those patients with neutropenia or septic shock or other causes of hemodynamic instability. The presence of a microbiologically documented infection, respiratory failure or the need of mechanical ventilation support did not significantly affect PCT levels in this study.Early serum PCT levels measurement might be useful for predicting mortality in patients with hematological malignancy requiring advanced life support.

Severe acute graft versus host disease (GVHD) and extensive chronic GVHD not responding to steroids have poor prognosis. Infliximab has reported to be effective in some of these patients. The efficacy of infliximab for the treatment of patients with steroid-resistant GVHD was evaluated.Retrospective analysis to evaluate the activity and toxicity of infliximab in 9 patients with acute or chronic steroid resistant GVHD.Six patients had acute GVHD and 3 chronic GVHD. The source of progenitors was peripheral blood in all patients except one. Six received matched-related SCT and 3 unrelated SCT. Patients received between 2 and 7 doses of infliximab, and 5 achieved a partial response. All patients presented infections: 4 developed Pseudomonas aeruginosa septicemia and 5 probable or confirmed infection by Aspergillus fumigatus.Infliximab provides transient response in steroid-resistant GVHD. However, it is associated with a high rate of infections. Earlier administration of infliximab should be explored to reduce the frequency of infections.

There is scarce information on the influence of stem cell transplantation (SCT) on the prognosis of patients with hematological malignancies admitted to an intensive care unit (ICU).The mortality during ICU admission, long-term survival and the prognostic factors for survival were analyzed and compared in transplanted vs. non-transplanted patients.116 critically-ill patients with a hematological malignancy transferred to the ICU in a single institution were analyzed. Thirty patients had received SCT prior to ICU admission. Transplanted and non-transplanted patients were comparable for demographic variables (except age and disease status) and reasons for ICU admission. No differences were found in overall survival or survival after discharge from ICU between transplanted and non-transplanted patients. Thirty-nine out of 85 non-transplanted patients (46%) and 11 out of 31 transplanted patients (35%) could be discharged from the ICU. The prognostic factors for survival in non-transplanted patients were need of mechanical ventilation or cardiovascular vasoactive drugs. However, only the liver function impairment predicted the outcome in the transplanted patients through the multivariate analysis.A significant proportion of patients admitted to ICU were discharged despite previous SCT. These patients did not have a worse prognosis than those transferred to the ICU with a hematologic malignancy, although the prognostic factors for survival were different in the 2 groups of patients.

The frequency and cause of neurologic complications (NC) following hematopoietic stem cell transplantation (HSCT) have changed over time. We have analyzed the NC in 185 consecutive patients who underwent HSCT in a period of 5 years in a single HSCT Unit.185 consecutive patients underwent HSCT (44 allogeneic) between February 2000 and March 2005 to treat hematologic malignancies. Most frequent diagnoses were multiple myeloma (41 patients) and acute myeloblastic leukemia (n = 35). Demographic and clinical data, HSCT characteristics and procedure-related events with special attention to neurological findings were recorded. Imaging studies (magnetic resonance imaging and/or computerized tomography scan), cerebro-spinal fluid analyses and microbiological studies were performed in all patients developing NC.After a median follow-up of 27 months, 14 patients (7.5%) developed NC, 6 of them after an allogeneic HSCT. The most common conditioning regimen in these patients was BEAM (5/14); 6 patients submitted to allogenic-HSCT received methotrexate and cyclosporin as graft-versus-host disease prophylaxis, and intrathecal prophylaxis of relapse was administered to 3 patients. The median time to the appearance of a NC was 13 days from HSCT (range: -4 to + 135 days). Seizures (8 cases) and encephalopathy (n = 2) were the most frequent clinical manifestations. In 12 cases the cause of the NC was related to drugs, there was one case of viral encephalitis and in the remaining case was caused by hemorrhage. Two patients died, one due to thrombotic thrombocytopenic purpura attributed to cyclosporin and the other due to viral encephalitis.In our series drug toxicity was the main cause of NC (particularly seizures) following HSCT. Our results contrast with previous studies in which infections, especially of fungal origin, were the main cause of NC. These changes over time should be taken into account during diagnostic procedures.

Abstract 293 The effectiveness of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) followed by rituximab maintenance in the treatment of CLL has been investigated in a phase II clinical trial that includes two treatment parts. First, patients were given induction therapy with R-FCM up to 6 cycles, achieving an overall response (OR) rate of 93% and a CR rate of 82% (46% MRD-negative CR) (Bosch et al. J Clin Oncol 27:4578–4584, 2009). Patients achieving CR or PR with the initial part of the treatment received rituximab maintenance. Here we present the final results of the treatment maintenance part, initiated three months after concluding R-FCM, and consisting of rituximab 375 mg/m2 every three months for two years (up to 8 cycles). Sixty-four patients (median age 60 years, 70% male) receiving > 4 cycles of maintenance therapy were evaluated for response, including bone marrow (BM) examination and MRD assessment by four-color flow cytometry of peripheral blood and BM. Patients in whom rituximab maintenance was prematurely interrupted (≤ 4 cycles) due to toxicity were considered as failures. Median number of cycles of maintenance administered was 8 (range, 1 to 8) and 76% of patients completed the entire planned treatment. Treatment was delayed due to insufficient hematological recovery in 9 cycles (2%) and to non-hematological toxicity in 4 cycles (0.8%). Neutropenia was observed in 31.3% of cycles (grade 3&4 in 8.5%), thrombocytopenia in 4.6%, and anemia in 1.2%. At the end of the maintenance therapy, 45% of patients had low IgA serum levels, 37% low IgG, and 66% low IgM. Sixteen patients experienced grade 3&4 infectious episodes, including 9 pneumonia, 2 febrile neutropenia, 1 appendicitis, 1 myositis, 1 herpes zoster, and 1 cerebral abscess. Two patients died, one due to multifocal leukoencephalopathy and the other due to hemophagocytic syndrome. Infectious episodes grade 3&4 were observed in 19.5% of cycles with neutropenia 3&4, but in only 3% of cycles with neutropenia inferior to grade 3 (p Disclosures: Bosch: Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia.