Serious Acute or Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplantation: A Comparison of Myeloablative and Non-Myeloablative Conditioning Regimens.
Authors: Sala-Torra Olga , Martin Paul J. , Storer Barry , Sorror Mohamed , Storb Rainer F. , Sandmaier Brenda M. , Flowers Mary E.D. 
Published: April 2020

Abstract
We have previously described serious graft-versus-host disease (GVHD) as a highly undesirable outcome after allogeneic hematopoietic cell transplantation (HCT). Serious GVHD encompasses death, lengthy hospitalization, major disability, or recurrent major infections related to either acute or chronic GVHD. In a previous study, we found a 25% incidence of serious GVHD among 171 consecutive patients who had HCT after non-myeloablative (NMA) conditioning between January 1998 and May 2002. To put this observation into perspective, we applied the same criteria for serious GVHD in a cohort of 264 consecutive patients who had HCT after myeloablative (MA) conditioning during the same period of time and compared results with those of the previous study. The overall incidence of serious GVHD was 17% (44/264) in the MA group, compared to 25% (43/171) in the NMA group. There were no statistically significant differences in the incidence of grades III–IV GVHD, extensive chronic GVHD or nonrelapse mortality between the two groups (Table). Patients in the NMA group were older and had higher comorbidity scores than those in the MA group. In the univariate analysis, the hazard ratio (HR) of serious GVHD for the NMA group compared to the MA group was 1.71 (95% C.I., 1.1–2.6) (p = 0.01). After adjusting for patient age, patient and donor gender, donor type, HLA-mismatch, aggressive versus indolent malignancy at HCT, remission versus relapse at HCT, myeloid versus non–myeloid malignancy, HCT co–morbidity index, and prior donor lymphocyte infusion, the HR of serious GVHD was 1.50 (95% C.I., 0.8–2.7) (p = 0.17). After censoring for recurrent or progressive malignancy after HCT, the cumulative incidence of serious GVHD at 3 years was 21% for the NMA group and 14% for the MA group, and the HR was 1.33 (95% C.I., 0.7–2.6) (p = 0.40). Reasons for categorization of GVHD as serious (i.e., death, lengthy hospitalization, major disability, or recurrent major infections) were similar between the MA and NMA cohorts. Among the 44 patients with serious GVHD in the MA group, 19 (43%) had serious acute GVHD, and 25 (57%) had serious chronic GVHD. Among the 43 patients with serious GVHD in the NMA group, 20 (46%) had serious acute GVHD, and 30 (70%) had serious chronic GVHD. Among the 264 MA patients, 28 (11%) had grade III–IV acute GVHD and 147 (56%) had extensive chronic GVHD that did not meet the criteria for serious GVHD, compared to 7 (4%) and 84 (49%) of the 171 NMA patients, respectively. We conclude that the type of pretransplant conditioning regimen does not have a large effect on the incidence of serious GVHD after HCT. Assessment of serious GVHD provides additional useful information to acute GVHD grades and the classification of limited and extensive chronic GVHD in describing overall GVHD-related outcomes after HCT.
MA NMA Outcome, n (%) n = 264 n = 171 Serious GVHD 44 (17) 43 (25) Grades III–IV acute GVHD 54 (20) 27 (16) Extensive chronic GVHD 174 (66) 114 (68) 2-year nonrelapse mortality 66 (25) 43 (25)