Possible Role of Engraftment Syndrome in Myelodysplastic Syndrome after Autologous Transplants.
Authors: Keung Yi Kong , Beaty Michael W , Pettenati Mark , Levitan Denise , Molnar Istvan , Thakuri Mohan C. , Cruz Julia , Hurd David Duane 
Published: April 2020

Abstract
BACKGROUND: Autologous graft versus host disease (GVHD) and engraftment syndrome (ES) probably result from host immune dysfunction during the recovery from high dose chemotherapy and radiation. Since impaired immunity has been associated with myelodysplastic syndrome, we explore the risk factors of post-transplant myelodysplastic syndrome/acute myeloid leukemia (MDS), specifically, in relation to the GVHD and ES.
PATIENTS AND METHODS: Consecutive patients with lymphoma undergoing autologous transplantation in our institution from 1991 to 2006.
RESULTS: There is total of 452 lymphoma patients undergoing autologous transplants in this period; 274 males and 178 females, median age of 50 years (range 16–76). There are 85 patients with Hodgkin’s lymphoma (HL) and 367 non-Hodgkin’s lymphoma (NHL), of which, 291 are B-cell, 47 T-cell and 29 unknown. Total of 277 received TBI-based and 175 chemotherapy-alone conditioning regimens; 98 patients received transplantation of the bone marrow (BM), 343 peripheral blood stem cells (PBSC) and 11 both. Eleven patients had second autologous transplantation for progressive lymphoma and another four patients have second allogeneic transplant for MDS. Thirty-two patients (7%) died of regimen-related toxicity within 100 days of transplant. Eleven patients developed severe engraftment syndrome (high fever, skin rash ± pulmonary infiltrate requiring systemic steroid); 27 patients had skin and 2 patients had gastrointestinal biopsies consistent with GVHD. The median follow-up of the patients was 6.2 years and median overall survival 5.3 years. Univariate analysis using Kaplan-Meier plots and logrank tests, younger age, HL, B-phenotype, source of stem cells (BM vs PBSC), chemo-sensitivity, less prior chemotherapy are better prognostic indicators. Conditioning regimens (TBI-based vs non-TBI) do not affect the overall survival. Twenty-four patients (5.3%) developed MDS with median time of onset of 4.2 years (range 8 months-7.5 years). Additional 5 patients developed clonal karyotypic abnormalities in the bone marrow without clinical MDS. Actuarial probabilities of developing MDS 5 and 8 years after transplant are 5% and 15% respectively. The incidences of MDS are similar in HL and NHL. Significant risk factors of developing MDS include older age, advanced stage, onset of ES or GVHD, and longer intervals between the initial diagnoses to transplant.
CONCLUSION: Although overall incidence of MDS is only 5.3%, the actuarial risk at 8 years is up to 15% and may be higher in selected patients such as older age, and prolonged interval from initial diagnosis to transplant (a surrogate for prior chemotherapy). The association of engraftment syndrome and GVHD to MDS is intriguing. It is conceivable that perturbation to the host immunity caused by either prior chemotherapy, conditioning regimens in the elderly may play a role in the development of MDS after autologous transplant.