Syngeneic Donor Hematopoietic Stem Cell Transplantation Is Associated with High Rates of Engraftment Syndrome
Authors: Koreth John , Biernacki Melinda , Aldridge Julie , Kim Haesook T , Alyea Edwin P , Armand Philippe , Cutler Corey , Ho Vincent T. , Wu Catherine J , Antin Joseph H. , Soiffer Robert J 
Published: October 2019

Abstract
Abstract 1323
Engraftment syndrome (ES), typically characterized by non-infectious fever, rash and/or non-cardiogenic pulmonary edema, is a complication of autologous and allogeneic hematopoietic stem cell transplantation (HSCT). There is no data on ES after syngeneic HSCT.
We retrospectively analyzed syngeneic HSCT outcomes and determined ES incidence, risk factors, and prognostic impact. 32 adult patients with a median age of 46 years (range, 22–60) underwent syngeneic HSCT at our institution between July 1986-April 2009, primarily for hematologic malignancies (31% myeloid, 66 % lymphoid-including 16% plasma cell). Syngeneic donor typing methods varied over the time-period of this report and included: serologic HLA Class I and II typing; confirmatory SSP molecular HLA Class I typing; molecular PCR-RFLP and SSP HLA Class II typing; and STR genotyping using ABI Profile Plus Kit Human Identity markers.
Patient characteristics: 15 (47%) were male; 28 (88%) had high-risk disease; 18 (56%) received total-body irradiation (TBI) as a component of myeloablative conditioning; 16 (50%) received donor peripheral blood stem cell infusion; and 14 (41%), 10 (31%) and 9 (28%) had low-, intermediate- and high-risk HCT-comorbidity index score respectively. No graft-versus-host-disease prophylaxis, T-cell depletion, or pre-emptive or prophylactic donor lymphocyte infusion was utilized. The median duration of follow-up was 6.1 years (range, 3.7 months-18.1 years). 5-year progression-free and overall survival (PFS, OS) was 52% and 67% respectively. 5-year overall cumulative incidence of relapse and non-relapse mortality (NRM) was 37.6% and 10.2% respectively.
15 patients (47%) met diagnostic criteria for ES, 10 (67%) of whom received a brief course of systemic steroids with prompt clinical response in all except one patient (who died of respiratory failure). Patient age ≥50 years was a risk factor for developing ES (p=0.05). Median time to engraftment was 12 days in patients with ES vs. 11.5 days in those without ES. 5-year PFS was 47% in patients with ES vs. 56% in those without (p=0.37). 5-year OS was 63% with ES vs. 71% without (p=0.8). 5-year cumulative incidence of relapse was 32% with ES and 44% without (p=0.68). 5-year cumulative incidence of NRM was 21% with ES vs. 0% without (p=0.06). In multivariable Cox-models only myeloid diagnosis (vs. lymphoid) impaired PFS and OS (HR 4.83, 95% CI 1.33–17.53, p=0.02; HR 8.47, 95% CI 1.73–41.58, p<0.01 respectively).
In summary, we document a high incidence of ES after syngeneic HSCT. While syngeneic ES did not impact HSCT survival outcomes, the trend of increased NRM with ES is concerning and needs re-evaluation in a larger cohort.Figure:Cumulative Incidence of Relapse and NRM as Competing Risks-by ES cohortFigure:. Cumulative Incidence of Relapse and NRM as Competing Risks-by ES cohort

Disclosures:
No relevant conflicts of interest to declare.