Duration of Initial Admission and Subsequent Readmission in the First 100 Days Following Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation.
Authors: Dungarwalla Moez , Brennan Joy , Kulkarni Samar , Saso Radovan , Shaw Bronwen , Jennifer Treleaven G. , Claire Dearden E. , Gareth Morgan J. , Mark Ethell E. , Mike Potter N. 
Published: April 2020

Abstract
Allogeneic stem cell transplantation (allo-SCT) after a reduced intensity conditioning (RIC) protocol is associated with decreased transplant related organ toxicity and mortality. Some authors have suggested that RIC allo-SCT be performed entirely in the outpatient setting. As a challenge to this hypothesis we examined the short term toxicity following RIC allo-SCT particularly focusing on duration of initial admissions and subsequent readmissions in the first 100 days post transplant. We analysed 104 consecutive RIC allo-SCT (median age: 52, range 19–67 yr; M: 69%, F:31%) performed at our institution between February 2003 and May 2007. All patients had a high risk haematological malignancy (27% Acute Myeloid Leukaemia, 20% Multiple myeloma, 20% Chronic Lymphocytic Leukaemia, 12% Lymphoma, 6% Myelodysplastic syndrome, 6% Acute Lymphoblastic Leukaemia, 6% Chronic Myeloid Leukaemia, 2% other). Conditioning was with fludarabine plus either melphalan, busulphan, cyclophosphamide or low dose TBI (2Gy). T cell depletion in vivo with alemtuzumab was utilised in 64%. Donor was matched related (39%) or unrelated (61%). Source of stem cells was PBSC (80%) or marrow (20%). GVH prophylaxis was CyA either alone or in combination with short term methotrexate. Patients were hospitalised from the beginning of the conditioning regimen until haematological and non-haematological toxicities had resolved. Eleven patients (10%) died before discharge. The median time required for achievement of neutrophil engraftment was 15 days (range 0–56). Four patients died prior to engraftment. Median duration of initial hospital admission was 31 days (range 17–192). In univariate analysis patients with Multiple myeloma were discharged earlier (p=0.001). Patients conditioned with Flu TBI were also discharged earlier (p&lt;0.0001). Unrelated donor RIC allo-SCT were discharged later (p&lt;0.001). Patients receiving alemtuzumab were also discharged later (p&lt;0.001). Readmissions within 100 days of transplant were documented in 50/104 (48%). The most common reasons were non CMV infections (30%), GVHD (22%), CMV reactivation (22%) and progressive disease (9%). Patient diagnosis, stem cell source, donor type, conditioning regimen, T cell depletion and age had no significant bearing on the incidence of readmission in the first 100 days post transplant by multivariate analysis. Transplant related complications (Infections, CMV reactivation, GVHD, TTP) were seen in 73/104 (70%) within 100 days of transplant. Transplant related mortality (TRM) at 100 days was 15%. Patients who required readmission in the first 100 days post transplant had lower OS at 1 year (45% v 73%) than those who did not require readmission (p&lt;0.001). The mean duration of readmissions in the first 100 days post transplant was 15.5 days. This had major financial implications with average bed costs of £7750 per readmission. In summary, although RIC regimens have undoubtedly widened the potential application of allo-SCT they are not without short term toxicity. Although early discharge following RIC allo-SCT has been advocated, our analysis demonstrates that the risk of readmission in the first 100 days post transplant is significant and is associated with increased costs and mortality. A full health economic analysis will be presented including a comparison with full intensity conditioning allo-SCT performed over the same period.