scholarly journals The graft-versus-leukemia effect is mainly restricted to NIH-defined chronic graft-versus-host disease after reduced intensity conditioning before allogeneic stem cell transplantation

Leukemia ◽  
2010 ◽  
Vol 24 (11) ◽  
pp. 1852-1858 ◽  
Author(s):  
S Thepot ◽  
J Zhou ◽  
A Perrot ◽  
M Robin ◽  
A Xhaard ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Reduced Intensity ◽  
Graft Versus Leukemia Effect

Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4407-4411 ◽  
Author(s):  
Mohamad Mohty ◽  
Didier Blaise ◽  
Catherine Faucher ◽  
Norbert Vey ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Inflammatory Cytokines ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Reduced Intensity ◽  
Acute Graft

This study investigated the role of inflammatory cytokines in acute graft-versus-host disease (aGVHD) incidence and severity in 113 patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Among all tested cytokines in the first 3 months after allo-SCT, only interleukin-12 p70 (IL-12p70) levels in the first month were significantly associated with grades II to IV aGVHD development (P < .001). IL-12p70 levels were directly correlated with aGVHD severity grade (P < .001). Before aGVHD onset, blood monocytes, the main precursor pool of IL12p70-secreting dendritic cells, recovered more rapidly in patients with grades II to IV aGVHD (P = .005). Similarly, at the effector level, there was a more robust reconstitution of naive CD3+CD4+CD45RA+CD27+ T cells in patients developing grades II to IV aGVHD (P = .006). In multivariate analysis, IL-12p70 level measured in the first month was the strongest predictive factor for aGVHD development (P < .001). These findings, reconstituting a TH1 loop, support a model in which aGVHD reflects a type 1 alloreaction after RIC allo-SCT.

Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5264-5270 ◽  
Author(s):  
Nicolaus Kröger ◽  
Ernst Holler ◽  
Guido Kobbe ◽  
Martin Bornhäuser ◽  
Rainer Schwerdtfeger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Confidence Interval ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Reduced Intensity

Abstract From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m2)–based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen–mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.

scholarly journals Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3956-3959 ◽  
Author(s):  
John Koreth ◽  
Kristen E. Stevenson ◽  
Haesook T. Kim ◽  
Michael Garcia ◽  
Vincent T. Ho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Reduced Intensity

Abstract Graft-versus-host disease (GVHD) is a significant complication of allogeneic stem cell transplantation (alloSCT). The proteasome inhibitor bortezomib has immunomodulatory properties of potential benefit for GVHD control. We undertook a phase 1 trial of bortezomib, tacrolimus, and methotrexate for GVHD prophylaxis after reduced-intensity conditioning alloSCT using human leukocyte antigen–mismatched unrelated donors. Twenty-three patients were enrolled. Bortezomib dose levels of 1, 1.3, and 1.5 mg/m2 were evaluated with 5, 3, and 5 patients, respectively. Ten additional patients were accrued at the 1.3 mg/m2 bortezomib dose level. Bortezomib-related toxicity was minimal. With a 12-month median follow-up, grade II-IV acute GVHD occurred in 3 patients, a 180-day cumulative incidence of 13%. Chronic GVHD occurred in 9 patients, a 1-year cumulative incidence of 41%. At 1-year, the nonrelapse mortality was zero, cumulative incidence of relapse/progression was 29%, and overall, progression-free, and event-free survival were 75%, 64%, and 59%, respectively. Bortezomib is a promising novel immunomodulatory agent in allogeneic transplantation. This study was registered at http://www.clinicaltrials.gov as #NCT00369226.

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