IL-6 and IL-8 levels in plasma during hematopoietic progenotor transplant

Background and objective: the relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. Design and methods: pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. Results: in spite of the great variability of plasma cytokine profiles between the different patients, we came to various conclusions. Patients' TNF-alpha and IL-1 concentrations correlated well over time. IL-6 and IL-8 profiles were similar and correlated well with febrile episodes. In some cases, an increase in IL-6 preceded hematologic recovery. In our study, increased levels of TNF-alpha, IL-6 and especially IL-8 correlated with hepatic or renal dysfunction as evaluated by increased bilirubin and creatinine in plasma, while pulmonary complications correlated only with increased IL-6 levels. Allogeneic transplant patients had a tendency to have higher TNF-alpha concentrations than autologous transplant patients, probably because an allogeneic transplant is associated with more transplant-related toxicity. Basal disease usually had no effect on cytokine profiles. Interpretation and conclusions: IL-6 and IL-8 were the only cytokines studied whose increase correlated with febrile episodes. High IL-8 values may be a useful predictor of renal dysfunction and pulmonary disease and seems to trigger off high IL-6 levels. Plasma TNF-alpha and IL-1 concentrations during the posttransplant period have not been shown to be predictive of the development of transplant-related complications, and none of the profiles was recognized to be specific for a particular complication in this study

Few and nonsevere adverse infusion events using an automated method for diluting and washing before unrelated single cord blood transplantation

Graft dilution and DMSO washing before cord blood (CB) administration using an automated system may offer low incidence of adverse infusion events (AIE), ensuring reproducible cell yields. Hence, we analyzed the incidences and significance of immediate AIE, cellular yield, and engraftment after single CB infusion. One hundred and fifty-seven patients (median age, 20 years; range, 1 to 60) received a single CB unit for treatment of hematologic and nonhematologic malignancies with myeloablative conditioning after graft dilution and washing. The median total nucleated cell (TNC) doses was 3.4× 10/kg (range, 2 to 26) and the median post-thaw recovery was 84% (range, 45 to 178). The cumulative incidence of neutrophil engraftment at 50 days was 84% (95% confidence interval [CI], 83 to 93). A total of 118 immediate AIE were observed in fifty-two (33%) patients. All reported AIE were transient, graded from 1 to 2 by Common Terminology Adverse Events version 4. The most frequent toxicity was cardiovascular but without any life-threatening reaction. Infused TNC, recipient's weight, and rate of infusion per kilogram were risk factors associated with cardiovascular AIE in multivariate analysis (odds ratio [OR], 1.2 (95% CI, 1.1 to 1.4); P <.001; OR,.94 (95% CI,.9 to.97); P <.001; and OR, 1.5 (95% CI, 1.2 to 1.8); P <.001; respectively). In summary, use of an automated method for graft washing before CB administration showed low incidence of AIE without compromising cell yields and engraftment. Infused TNC dose, recipient's weight, and rate of infusion per kilogram were risk factors associated with infusion reactions

ICO-ICS Praxis para el tratamiento de la leucemia linfática crónica

Tractament mèdic; Tractament amb irradiació; Leucèmia limfàtica crònicaMedical treatment; Irradiation treatment; Chronic lymphocytic leukemiaTratamiento médico; Tratamiento con irradiación; Leucemia linfática crónicaLa leucèmia limfàtica crònica (LLC) és una alteració hematopoètica monoclonal caracteritzada per una expansió progressiva de limfòcits de la línia B. Aquests limfòcits, madurs des del punt de vista morfològic, però menys madurs des del punt de vista immunològic, s’acumulen a la sang, la medul·la òssia, els nòduls limfàtics i la melsa. Els principals objectius d’aquesta ICO-ICSPraxi són: - Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de la leucèmia limfàticacrònica (LLC). - Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta xarxa. - Implementar els resultats de la terapèutica en els pacients amb LLC tractats d'acord amb lesrecomanacions d'aquesta guia

Combining Three Different Pretransplantation Scores Improves Predictive Value in Patients after Haploidentical Stem Cell Transplantation with Thiotepa, Busulfan, and Fludarabine Conditioning and Post-Transplantation Cyclophosphamide.

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

Outcome of Second Allogeneic Hematopoietic Cell Transplantation after Relapse of Myeloid Malignancies following Allogeneic Hematopoietic Cell Transplantation : A Retrospective Cohort on Behalf of the Grupo Español de Trasplante Hematopoyetico

Allogeneic stem cell transplantation (allo-HCT) represents the most effective immunotherapy for acute myeloid leukemia (AML) and myeloid malignancies. However, disease relapse remains the most common cause of treatment failure. By performing a second allo-HCT, durable remission can be achieved in some patients. However, a second allo-HCT is of no benefit for the majority of patients, so this approach requires further understanding. We present a retrospective cohort of 116 patients diagnosed with AML, myelodysplastic syndromes, and myeloproliferative disorders who consecutively underwent a second allo-HCT for disease relapse. The median age was 38 years (range, 4 to 69 years). Sixty-three patients were alive at last follow-up. The median follow-up of the whole cohort was 193 days (range, 2 to 6724 days) and the median follow-up of survivors was 1628 days (range, 52 to 5518 days). Overall survival (OS) at 5 years was 32% (SE ± 4.7%). Multivariate analysis identified active disease status (P <.001) and second allo-HCT < 430 days (the median of the time to second transplantation) after the first transplantation (P <.001) as factors for poor prognosis, whereas the use of an HLA-identical sibling donor for the second allo-HCT was identified as a good prognostic factor (P <.05) for OS. The use of myeloablative conditioning (P =.01), active disease (P =.02), and a donor other than an HLA-identical sibling (others versus HLA-identical siblings) (P =.009) were factors statistically significant for nonrelapse mortality in multivariate analysis. Time to second transplantation was statistically significant (P =.001) in the relapse multivariate analysis, whereas multivariate analysis identified active disease status (P <.001) and time to second transplantation (P <.001) as poor prognosis factors for disease-free survival. This study confirms active disease and early relapse as dismal prognostic factors for a second allo-HCT. Using a different donor at second allo-HCT did not appear to change outcome, but using an HLA-identical sibling donor for a second transplantation appears to be associated with better survival. Further studies are warranted