Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation

Abstract

Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia- free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.

The allogeneic graft‐versus‐cancer effect

“…In a study of 2000 patients with early leukaemia, those with ALL showed a correlation between acute GVHD and anti‐leukaemic activity (Horowitz et al , 1990). In patients with AML and CML the association was stronger with chronic GVHD, and severe acute GVHD resulted in superior GVL effects compared to mild‐moderate acute GVHD (Gratwohl et al , 1995). However, severe acute GVHD increases transplant‐related mortality (TRM), and, therefore, the highest leukaemia‐free survival (LFS) was seen in patients with grade I acute GVHD (Gratwohl et al , 1995; Ringden et al , 1996b).…”

“…In patients with AML and CML the association was stronger with chronic GVHD, and severe acute GVHD resulted in superior GVL effects compared to mild‐moderate acute GVHD (Gratwohl et al , 1995). However, severe acute GVHD increases transplant‐related mortality (TRM), and, therefore, the highest leukaemia‐free survival (LFS) was seen in patients with grade I acute GVHD (Gratwohl et al , 1995; Ringden et al , 1996b). Moreover, since chronic GVHD has a better anti‐leukaemic effect than acute GVHD, the highest LFS was reported in patients with mild acute and mild chronic GVHD (Ringden & Horowitz, 1989).…”

The gut microbiota and graft-versus-host disease

“…GvHD remains an important cause of death after allogeneic HCT, causing morbidity in 30% to 70% of allogeneic HCT recipients (3)(4)(5). Even when GvHD does not contribute to mortality, it can have a pernicious effect on quality of life, with some patients debilitated by diarrhea, abdominal pain, nausea, vomiting, wasting, oral ulcers, sclerosis of the skin, and other noxious manifestations (6,7). GvHD is characterized by damage to host tissues and organs mediated by the donor immune cells, particularly donor T cells that recognize host major and minor histocompatibility alloantigens presented by antigen-presenting cells (8)(9)(10).…”

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

“…Primary outcomes analyzed were overall survival (OS), disease-free survival (DFS; survival without evidence of active malignancy after transplantation), relapse/progression of malignancy, and NRM. Acute GVHD was classified as clinically significant (grades II to IV) or severe (grades III to IV) [24]. Chronic GVHD was classified as mild, moderate, or severe by National Institutes of Health consensus criteria [25].…”