Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

Abstract

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P ‫؍‬ .001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P ‫؍‬ .046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P < .001) and treatment failure (HR, 5.2; P < .001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome. (Blood. 2001;98:1695-1700)

Graft‐versus‐host disease (GVHD)‐specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation

“…Several reports have shown that the use of peripheral blood as a source of haematopoietic stem cells increased the incidence of chronic GVHD (Cutler et al, 2001;Przepiorka et al, 2001;Flowers et al, 2002). However, stem cell source did not influence GSS or the duration of systemic IST in our study.…”

“…There should be no other explanation for these abnormalities. Acute GVHD was classified according to the criteria of Przepiorka et al (1995) and chronic GVHD was graded as either limited (localized skin or single organ involvement) or extensive (generalized skin or multiple organ involvement) (Przepiorka et al, 2001). The mode of presentation was defined as progressive if chronic GVHD developed after acute GVHD without remission from acute GVHD, quiescent if chronic GVHD developed after remission from acute GVHD, or de novo if chronic GVHD developed without being preceded by acute GVHD (Shulman et al, 1980).…”

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

“…40,41 It is possible that our findings are not due to the effects of GM-CSF on the allograft per se, but rather that allografts mobilized following GM-CSF alone contain significantly fewer CD34 þ cells, resulting in a lower risk of acute GVHD, as previously suggested by another group. 42 However, the observation that higher CD34 þ cell doses are associated with a greater risk of acute GVHD has not been supported by other studies and a mechanistic basis for the observation remains elusive. 39,43 On multivariate analysis, we were unable to find any association between CD34 þ cell dose and the risk of acute GVHD.…”

“…While some studies have suggested that high doses of CD34 þ cells are associated with a greater likelihood of chronic GVHD, our data suggest that other factors may be more important since the risk of chronic GVHD was high within GM-CSF group despite the fact that they received a relatively modest median CD34 þ cell dose (3.1 Â 10 6 /kg). 10,38,39 Despite the fact that the cohort of donors receiving combination G/GM-CSF mobilized the greatest numbers of CD34 þ cells without significant additive toxicity, this did not translate into any clear clinical advantages to the recipients as the rate of hematopoietic engraftment, incidence of chronic GVHD, risk of relapse, and overall likelihood of survival did not differ significantly from the G-CSF alone group. In fact, the risk of acute GVHD was greatest in this combination group.…”

Dihydropyridine Receptors Are Selective Markers of Th2 Cells and Can Be Targeted to Prevent Th2-Dependent Immunopathological Disorders

“…cGVH disease that is thought to be Th2 mediated in humans occurs frequently in long term survivors of allogeneic hemopoietic stem cell transplantation (26). Clinical manifestations have been likened to those of systemic immune diseases such as progressive systemic sclerosis, systemic lupus erythematosus-like disease, or Sjögren's syndrome.…”