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Abstract Background The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Methods We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p

El trasplante de progenitores hemopoyéticos (TPH) es una terapia asociada a complicaciones que generan malestar y que son potencialmente mortales (toxicidad, enfermedad injerto contra huesped, infecciones, recaída de la enfermedad etc). Objetivo: Explorar las condiciones en las que mueren los pacientes trasplantados en nuestra institución. Metodología: Análisis descriptivo y retrospectivo. Sujetos de estudio: Adultos con TPH en el HGU Gregorio Marañón que murieron entre Octubre de 2000 y Septiembre de 2003. Resultados: 32 pacientes (60% hombres) fueron incluidos. Tipo de transplante: Auto en 13 (40%) y alo en 19 (60%). La Causa de muerte fue progresión de la enfermedad en el 50% y mortalidad relacionada con el procedimiento en el otro 50%. La mediana de supervivencia fue de 5 meses (rango 0,5-39,5). El 78% de los pacientes murió hospitalizado y el resto (22%) en casa. Seis (24%) de los pacientes que murieron en el hospital fueron ingresados para un manejo paliativo. Dolor, disnea y ansiedad fueron los síntomas mas frecuentes, y el 23,5% de los pacientes murió sin un control óptimo de la sintomatología. Comentarios sobre la sintomatología durante la última semana de vida aparecieron en 15 de 16 registros de Enfermería y en 6 de 16 registros médicos. Conclusiones: Una elevada proporción de nuestros pacientes murieron en el hospital pero ninguno en la Unidad de Cuidados Paliativos. En la mayoría de los casos, a pesar de que un adecuado tratamiento fue prescrito, los síntomas no fueron completamente controlados. Las referencias a la situación sintomática de los pacientes son recogidas esencialmente en los registros de Enfermería. Abstract Stem cell transplantation is a therapeutic procedure associated with potentially fatal complications (toxicity, graft versus host disease, infections, relapse/progression, etc). Aim: To explore the conditions in which patients transplanted in our institution die. Methods. Descriptive and retrospective analysis of the clinical chart and MED-A forms from adult patients who were transplanted in our hospital and died between October 2000 and September 2003. Results: 32 patients (60% males) were included. Type of transplant: Auto 13 (40%), allo 19 (60%). Cause of death: 50% progression, 50% transplant related mortality. Median of survival was 5 months (range 0,5-39,5). Regarding place of death, 78% of patients died within the hospital and other 22% died at home. Six (24%) of patients dying within the hospital were admitted for palliative management. Pain, disnea and anxiety were the most frequent symptoms and 23,5% of patients died with an insufficient symptom control. Comments regarding the symptomatology in the last week of life were recorded in 15 of 16 nursing charts and in 6 of 16 physician charts. Conclusions: A high proportion of our patients died within the hospital but none in the Palliative Care Unit. In most of cases, despite an appropriate treatment, symptoms were not completely controlled. Most of comments regarding symptomatology of patients were recorded in Nursing charts. Centro de Trabajo: 30th Annual Meeting of the European Group for Blood and Marrow Transplantation, 20th Meeting of the EBMT Nurses Group and 3rd Meeting of the EBMT Data Management Group. Barcelona. 28-31 Marzo 2004 Fecha del Trabajo: 01/05/2004 Palabra Clave: Trasplante de progenitores hemopoyéticos, muerte, cuidados paliativos, Enfermería Key Words: Stem Cell transplantation, death, palliative care, Nursing

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for patients with hematologic malignances. Haploidentical HSCT (Haplo-HSCT) is an alternative option for patients who do not have an HLA-matched donor. The use of post-transplantation high dose cyclophosphamide (PT-Cy) is commonly employed for graft-versus-host disease (GVHD) prophylaxis in haplo-HSCT. Cyclophosphamide (Cy) is an alkylating agent with antineoplastic and immunosuppressive activity, whose bioactivation requires the activity of polymorphic enzymes in the liver to produce phosphoramide mustard, which is a DNA alkylating agent. To identify polymorphisms in the genes of Cy metabolism and correlate them with post-HSCT complications [GVHD, sinusoidal obstruction syndrome (SOS), hemorrhagic cystitis (HC) and transplant-related mortality (TRM)], we designed a custom next-generation sequencing panel with Cy metabolism enzymes. We analyzed 182 patients treated with haplo-HSCT with PT-Cy from 2007 to 2019, detecting 40 variants in 11 Cy metabolism genes. Polymorphisms in CYP2B6, a major enzyme involved in Cy activation, were associated with decreased activity of this enzyme and a higher risk of Graf-versus-host disease (GVHD). Variants in other activation enzymes (CYP2A6, CYP2C8, CYP2C9, CYP2C19) lead to decreased enzyme activity and were associated with GVHD. Polymorphisms in detoxification genes such as glutathione S-transferases decreased the ability to detoxify cyclophosphamide metabolites due to lower enzyme activity, which leads to increased amounts of toxic metabolites and the development of III-IV acute GVHD. GSMT1*0 a single nucleotide polymorphism previously recognized as a risk factor for SOS was associated with a higher risk of SOS. We conclude that polymorphisms of genes involved in the metabolism of cyclophosphamide in our series are associated with severe grades of GVHD and toxicities (SOS and TRM) after haplo-HSCT and could be used to improve the clinical management of transplanted patients.

Abstract: The only curative treatment in patients with intermediate or high-risk myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), which usually results in a long-term, disease-free survival rate of between 30% and 50%, depending on the disease risk and the type of donor. In patients without an HLA-matched sibling donor, a family haploidentical donor is an alternative option. The present study reports the European Group for Blood and Marrow Transplantation activity for haploidentical transplantation in MDS patients. A total of 228 patients transplanted from a mismatched HLA-related donor between 2007 and 2014 were studied. The median age at transplant was 56 years. Eighty-four (37%) patients had MDS transformed into acute myeloid leukemia at the time of transplant. Ex vivo T-cell depletion was used in 34 patients. One hundred ninety-four patients received a T-cell replete transplant and 102 patients received posttransplant cyclophosphamide (PT-CY) as graft-versus-host disease (GVHD) prophylaxis. The cumulative incidences of acute and chronic GVHD in PT-CY vs other patients were 25% vs 37% and 37% vs 24%, respectively. The cumulative incidence of nonrelapse mortality was 55% in patients who did not receive PT-CY (no PT-CY) and 41% in patients who did receive PT-CY. Three-year overall survival was 28% in no PT-CY patients and 38% in PT-CY patients. In multivariable analysis, the main risk factors were the intensity of the conditioning regimen and the use of PT-CY. In conclusion, the outcomes of MDS patients who received an haploidentical transplant are close to the results other transplantations from HLA-mismatched donors with approximately one-third of patients alive and free of disease 3 years after transplant, and the use of PT-CY may improve their outcomes.

High-dose chemotherapy with autologous peripheral blood stem cell rescue has been reported as feasible and effective in HIV-associated lymphoma. Although a sufficient number of stem cells seems achievable in most patients, there are cases of stem cell harvest failure. The aim of this study was to describe the mobilization policies used in HIV-associated lymphoma, evaluate the failure rate and identify factors influencing mobilization results. We analyzed 155 patients who underwent attempted stem cell mobilization at 10 European centers from 2000–2012. One hundred and twenty patients had non-Hodgkin lymphoma and 35 Hodgkin lymphoma; 31% had complete remission, 57% chemosensitive disease, 10% refractory disease, 2% untested relapse. Patients were mobilized with chemotherapy + G-CSF (86%) or G-CSF alone (14%); 73% of patients collected >2 and 48% >5 × 106 CD34+ cells/kg. Low CD4+ count and refractory disease were associated with mobilization failure. Low CD4+ count, low platelet count and mobilization with G-CSF correlated with lower probability to achieve >5 × 106 CD34+ cells/kg, whereas cyclophosphamide ≥3 g/m2 + G-CSF predicted higher collections. Circulating CD34+ cells and CD34/WBC ratio were strongly associated with collection result. HIV infection alone should not preclude an attempt to obtain stem cells in candidates for autologous transplant as the results are comparable to the HIV-negative population.