High Readmission Rates Are Associated with a Significant Economic Burden and Poor Outcome in Patients with Grade 3/4 Acute GvHD
Authors: Dignan Fiona L , Potter Michael N , Ethell Mark E , Brennan Joy , McNamara Louise , Evans Stephen O , Dearden Claire E. , Davies Faith E , Morgan Gareth J , Shaw Bronwen E. 
Published: October 2019

Abstract
Abstract 2061
The impact of graft versus host disease (GvHD) on readmission rates following allogeneic stem cell transplantation (SCT) has not been reported. We hypothesised that patients with GvHD would have a higher readmission rate than patients without GvHD. To test this hypothesis a retrospective review was undertaken of 187 consecutive patients who underwent allogeneic SCT from 1/1/2006 to 30/4/2009 at the Royal Marsden Hospital, UK. Data were collected from the electronic patient record. The study was approved by the hospital audit committee.
Patient characteristics: male 113(60%), median age 47 yrs (17–70), diagnosis: acute leukaemia 123 (66%), chronic leukaemia 22 (12%), lymphoma 23 (12%), myeloma 12 (6%), other 7 (4%), donor: sibling 60 (32%), unrelated 115 (61.5%), cord 12 (6.5%), stem cell source: PBSC: 158 (84.5%), BM 17 (9%), cord 12 (6.5%); donor sex: M 111(59.5%), F 64 (34%), cord 12 (6.5%); match: full 130 (69.5%), mismatch 45 (24%), cord 12 (6.5%), conditioning intensity: full 73 (39%), reduced 114 (61%); use of alemtuzumab 113 (60%); GvHD prophylaxis: cyclosporine 116 (62%), mycophenolate 32 (17%), cyclosporine and methotrexate 26 (14%), other 13 (7%).
Median follow up was 3.8 (2.2–5.5) yrs from transplant. 118/187 (63%) of patients developed GvHD. There was no significant difference between patients with or without GvHD except for increased use of alemtuzumab in the non-GvHD group (71% v 54%, p=0.024). GvHD was diagnosed clinically at the transplant centre. Biopsies were undertaken if the diagnosis was unclear. Glucksberg criteria were used to stage acute GvHD (aGvHD). NIH criteria were used to diagnose chronic GvHD (cGvHD). 45/118 (38%) had biopsy-proven GvHD. 88/187 (47%) had aGvHD (grades: 1 – 17 (9%), 2 – 43 (23%), 3 – 15 (8%), 4 –13 (7%)). 58/187 (31%) of patients had cGvHD. 36/187 (19%) had both acute and chronic GvHD (52 (29%) had aGvHD alone, 22 (12%) had cGvHD alone). 8 developed GvHD following donor lymphocyte infusion. 104/118 (88%) required steroid treatment. 61/118 (52%) commenced steroids within 100 days of transplant. 61/118 (52%) were steroid refractory. 5 patients had received a second allogeneic transplant for relapse to induce GvHD and graft versus malignancy effect.
The median duration of initial transplant admission was 31 days (20–138) in GvHD group compared to 32 days (16–103) in non GvHD group (p=NS). 14 patients died during initial admission (5 in GvHD group, 9 in non-GvHD group) and were excluded from readmission analysis. The overall readmission rate was higher in GvHD patients (89% (101/113) v 41/60 (68%), p=0.001). In the first 100 days post transplant, 42/56 (75%) of patients who had started steroids were readmitted compared to 60/117 (51%) in patients who started steroids after day 100 or had no GvHD (p=0.003).Critical care unit admission was higher in the GvHD group (38/113 (34%) v 7/60 (12%),p=0.002). The mean total number of admission days was higher in the GvHD group (42 days v 18 days, p<0.001). 337/455 (74%) of readmission episodes and 231/305 (76%) of infection-related admissions were in the GvHD group. Patients with grade 3/4 GvHD had a higher readmission rate (96%) than grade 1/2 GvHD patients (88%) or patients with no aGvHD (74%). The mean total number of admission days was 57 days in grade 3/4 GvHD compared to 37 days in grade 1/2 GvHD. (p=0.054).
Costs were calculated based on the 2010 hospital tariff (€600/inpatient day and €2295/CCU day). The mean cost of readmission was higher in GvHD patients (€32217) than in non-GvHD patients (€15622) (p=0.003). Mean cost was higher in grade3/4 GvHD (€44535) than in grade 1/2 GvHD (€27001) (p=0.032). These figures do not include drug or procedural costs.
Overall survival was 42% at 2 years. Survival was higher in the GvHD group (48%) than in the non GvHD group (30%) (p=0.006). Survival was higher in those with grade 1/2 GvHD (55%) compared to those with grade 3 or 4 GvHD (14%) (p<0.001). There was no significant difference in survival in those with grade 1/2 GvHD (55%) and those with no GvHD (43%) (p=0.15).
In conclusion, patients with GvHD had significantly higher readmission rates and longer duration of admission than those without GvHD. Despite the high readmission rate, patients with grades 1/2 GvHD had improved survival. Patients with grade 3/4 GvHD had a very high level of readmission and poor outcome. Improving strategies for managing GvHD may help to reduce post transplant readmission rates and the associated burden on the healthcare system.

Disclosures:
Dignan: Therakos, a Johnson and Johnson company: Honoraria, Research Funding. Shaw:Therakos, a Johnson and Johnson company: Honoraria, Speakers Bureau.