Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate [see comments]

Abstract

Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse

“…Previous investigators have reported high early mortality rates in patients transplanted for advanced-phase CML (Apperley et al, 1988;Goldman et al, 1986Goldman et al, , 1988Martin et al, 1988;Thomas et al, 1986) as well as relapsed or refractory acute leukaemia (Doney et al, 1981;Marmont et al, 1991). The association of advanced leukaemia and the occurrence of severe GVHD has also been reported by Nash et al (1992). Cumulative effects of prior chemotherapy and reduced tolerance of the intensive conditioning regimens used at BMT (Biggs et al, 1992;Bortin et al, 1981;Clift et al, 1987Clift et al, , 1990Clift et al, , 1991Deeg et al, 1991;Nash et al, 1992) may account in part for the severe GVHD seen in patients transplanted for advanced leukaemia.…”

The use of novel Therakos™ Cellex® for extracorporeal photopheresis in treatment of graft‐versus‐host disease in paediatric patients

“…Graft-versus-host disease (GVHD) is the most common cause of non-relapse mortality post-haematopoietic progenitor cell transplant (HPCT) (Lee et al, 2003). Acute GVHD (aGVHD) develops in 80% of recipients of unrelated HPCT and 30% of recipients of matched sibling HPCT (Nash et al, 1992). On the other hand, chronic GVHD (cGVHD) affects 20-50% of paediatric recipients several months post-HPCT (Baird et al, 2010).…”

188Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

“…In addition, elderly people are more frequently diagnosed with high-risk AML as defined by recurring karyotypic abnomalities, including monosomies and complex aberrations, rendering them at an increased risk of relapse and treatment failure. Standard intensity conditioning at this age often leads to excessive organ toxicity as well as a high incidence of graft-versus-host disease (GvHD) (Nash et al, 1992). On the other hand, reduced-intensity conditioning results in an increased incidence of relapse especially in patients with residual marrow blasts (Alyea et al, 2006).…”