Prognostic factors of chronic graft‐versus‐host disease after allogeneic blood stem‐cell transplantation

Abstract

Allogeneic hematopoietic stem cells in peripheral blood transplantation (alloPBSCT) or bone marrow transplantation (alloBMT) have different biological characteristics which may affect differently prognostic factors for incidence and severity of chronic graft-versus-host disease (cGVHD). To determine the prognostic factors of cGVHD in patients receiving alloPBSCT, data on 87 patients who survived at least 100 days after matched related donor myeloablative transplantation were analyzed. Factors significantly associated with higher incidence of cGVHD after alloPBSCT included CMV-positive donor, acute skin GVHD, and diagnoses other than lymphoma. Factors predictive for poor survival following cGVHD diagnosis included platelet count < 100,000/mm 3 and history of acute liver GVHD. Acute liver GVHD and etoposide in the preparative regimen significantly increased risk of death due to cGVHD after alloPBSCT. All alloPBSCT multivariate models were fit to an independent cohort of comparable matched related donor alloBMT patients (n = 75). After alloBMT, only acute skin GVHD and diagnoses other than lymphoma retained prognostic significance for predicting cGVHD. Low platelet count was the only variable predictive for poor survival in cGVHD patients after alloBMT. Acute liver GVHD was the only factor that retained prognostic significance for risk of death due to cGVHD after alloBMT. These data suggest there are some cGVHD prognostic factors that may be unique to recipients of alloPBSCT. More studies are needed to determine whether cGVHD prognostic systems should be used interchangeably in patient populations receiving different stem-cell products. Am.

The global severity of chronic graft-versus-host disease, determined by National Institutes of Health consensus criteria, is associated with overall survival and non-relapse mortality

“…However, our analysis did not support previously reported risk factors for mortality in chronic GVHD, such as bilirubin levels, [12][13][14] Karnofsky performance status, 2,[15][16][17] female donor/male recipient pairing, 12,13 HLA mismatch, 13,16 older donor age, 13 and prior acute GVHD. 12,13,16 Additionally, insufficient data did not permit analysis of previously reported risk factors including response of chronic GVHD to therapy, 18,19 and steroid dose. 13 While overlap and late acute GVHD were associated with inferior outcome in univariable analysis, multivariable analysis did not support an independent association of chronic GVHD classification with overall survival or nonrelapse mortality.…”

Long-term oral complications of allogeneic haematopoietic SCT

“…[10][11][12] The risk factors specific for the development of oral cGVHD are less well established; however, recent studies have described an association between oral GVHD and stem cell source, with an increased risk of oral GVHD in PBSCT (70%) relative to BMT (53%). 13 This association was also evident in our study, with a non-statistically significant trend suggesting that patients undergoing PBSCT had a higher prevalence of oral cGVHD (44%) relative to BMT (29%) and umbilical cord transplantation (25%). However, due to the very small study numbers of patients who underwent umbilical cord transplantation (n ¼ 4), this is unlikely to be a true representation of this group's risk for developing oral cGVHD.…”

Thrombocytopenia and hemostatic disorders in chronic graft versus host disease

“…14 The authors concluded that observed low platelet count may be a marker for a more severe form of cGVHD. 14 Pavletic et al 2 found platelets below 100 000/ml in cGVHD patients more frequently after alloBMT (41%) than after alloPSCT (27%), but the difference was not statistically significant. Similarly, Flowers et al 22 also did not find a statistically significant difference in prevalence of thrombocytopenia in cGVHD patients after alloBMT or alloPSCT.…”

“…1 It is a systemic disorder characterized by immune deregulation, immunodeficiency, impaired organ function, development of signs and symptoms of various autoimmune or immunologic disorders, and is associated with decreased survival. [1][2][3][4] A low platelet count in cGVHD patients is among the most consistent and strongest negative survival predictors across cGVHD studies in both allogeneic bone marrow transplantation (alloBMT) and allogeneic peripheral stem cell transplantation (alloPSCT). 2,3,[5][6][7][8][9][10][11] Patients with cGVHD and persistent thrombocytopenia show poorer responses to therapy, experience higher mortality rates from infection or, less often, from hemorrhage.…”

“…5,12 Low platelet counts were also reported as a marker for a group of patients with severe cGVHD who have increased incidence of transplantrelated complications and a higher mortality rate. 2,3,5,8,[12][13][14][15] The thrombocytopenia of cGVHD is not usually associated with disease relapse or graft rejection, but significantly correlates with increased non-relapse mortality, 6 indicating the existence of additional poorly understood pathophysiological mechanisms that could generate the association of thrombocytopenia and negative outcome of cGVHD. Patients with cGVHD may develop several other acquired hemostatic disorders, [16][17][18][19][20] including also an increased risk for venous thrombosis in spite of higher bleeding risk.…”