Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (HR=2.76 [1.90-4.00]), overall survival (HR=2.36 [1.73-3.22]), and cumulative incidence of relapse (HR=3.65 [2.53-5.27]), but not non-relapse mortality (HR=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I(2)=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation

Identifikace prognostickych faktoru u nemocnych lecenych autologni transplantaci krvetvornych bunek pro non-Hodgkinsky lymform.

The analysis and the evolution of prognostic factors influencing survival of patients with non-Hodgkin's lymphoma treated with autologous stem cell transplantation during the period 1993 - 2000 was performed. 109 patients with NHL were evaluated: 47 (43,1%) DLCL, 38 (34,9%) FCL, 7 (6,4%) MCL, 1 (0,9%) lymphoplasmocytoid lymphoma, 2 (1,8%) lymphoblastic lymphomas, 1 (0,9%) MALT, 4 (3,7%) PTL, 2 (1,8%) ALCL and 7 (6,4%) B lymphomas unspecified. 36 (33%) patients were transplated in first (complete or partial) remission, 55 (50,5%) at chemosensitive relapse and before ASCT 18 (16,5%) patients were considered as chemoresistant. The median follow-up was 32 months, estimated PFS in 3 years was 39,5% (CI95%; 29-50%), median time to progression was 6,1 months. OS in 3 years was 54,8% (CI 95%; 44,4-65,2%), EFS in 3 years 37,5% (CI 95%; 27,3-47,7%). The factors significantly predictive in univariate analysis appeared: non-B phenotype (for OS, PFS, EFS), for PFS and EFS: presence of B symptomatology, number of lymphatic areas affected, dissemination of disease up and under diaphragma, clinical stage, and the presence of bulky disease for PFS. There was no evidence of any influence of evaluating factors on OS. We have not observed the significant influence on survival between the group of patients treated with escalated doses of etoposide (BEAM 400) and standard regimen BEAM 200. We have not proved the benefit of tandem transplantation for high risk patients(in our analysis 15 patients) in comparison with standard simple transplantation. However the factors significantly predictive in univariate analysis appeared: the disease status at transplantation, time to relapse (evaluated in patients with first relapse only) and also the best result of transplantation significantly affects the next prognosis of patients. We have not proved the significancd of CD 34+ selection as ex vivo purging method of graft decontamination. The important trend for better EFS (p=0,058) and PFS (p=0,058) in group of patients who reached PCR negativity after ASCT was observed. In comparison of survival analysis between DLCL and FCL we observed better trend for PFS in DLCL group (p=0,08), also the curve of PFS in this group reached the plateau. The factors significantly predictive in multivariate analysis for all patients appeared: presence of bulky disease, disease status at transplantation, performance status and presence of extranodal disease. For DLCL group was significant: the disease status at transplantation, presence of bulky disease, performance status, elevated LDH and B symptomatology. For FCL group was significant the presence of extranodal and bulky disease only. We conclude, that however ASCT have an important role in therapy of chemosensitive relapses, the further improvement of results is not probable. The potential future way is the use of new approach as immunomodulation or adoptive immunotherapy.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Traumatic Injuries Detected during Post-Mortem Slaughterhouse Inspection as Welfare Indicators in Poultry and Rabbits

The findings of traumatic injuries during post-mortem inspection in slaughterhouses reflect the level of pre-slaughter handling of animals at the farm and during transport to the slaughterhouse. The prevalence of traumatic injuries was monitored in poultry (1,089,406,687 broiler chickens, 20,030,744 laying hens, 1,181,598 turkeys, 37,690 geese, 28,579,765 ducks) and rabbits (1,876,929) originating from farms in the Czech Republic and slaughtered in slaughterhouses in the Czech Republic between 2010 and 2019. The greatest incidence of traumatic injuries was found in laying hens (2.80%) and rabbits (1.52%); while the overall incidence of trauma was less than 0.5% in other species and categories. The results show that the current rearing conditions and/or pre-slaughter handling of poultry and rabbits particularly affect the limbs; traumatic findings were significantly (p &lt; 0.01) more frequent on the limbs than on the trunk in all species studied. In poultry, traumatic findings on the trunk were orders of magnitude lower to negligible, so the focus should be on preventing injuries to the limbs. In rabbits, the difference was less pronounced, and many injuries were found on both limbs (0.83%) and trunk (0.69%). Our results emphasize the need to reconsider both housing and pre-slaughter handling methods to determine minimum standards for the protection of rabbits, which are still lacking in European legislation

Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease

Background: Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. Methods: This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. Results: A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. Conclusions: Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.)