Donor-Derived Myelodysplastic Syndrome and Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Incidence, Natural History and Treatment Response
Authors: Dietz Andrew C. , Jackson Scott , Hirsch Betsy A. , Brunstein Claudio , Wagner John E. 
Published: October 2019

Abstract

Abstract 1306
Donor-derived myelodysplastic syndrome (DD-MDS) and acute leukemia (DD-AL) are rare complications of allogeneic HSCT with approximately 40 cases identified in the literature. While the estimated incidence of DD-MDS/AL is between 0.12–5% for recipients of allogeneic HSCTs, more precise estimates by HSCT source have been impaired by differences in follow-up and changes in diagnostic tools over time. To this end, we evaluated all allogeneic transplants performed at the University of Minnesota between 1992 and 2009 in whom molecular assays for chimerism were performed. Patients transplanted for malignancy also had routine marrow examinations for evidence of recurrent disease. During this interval, there were 226 related donor transplants (47 marrow, 164 peripheral blood, 3 marrow and peripheral blood, 12 umbilical cord blood [UCB]), and 1254 unrelated donor transplants (436 marrow, 16 peripheral blood, 802 UCB). Of the entire cohort, 73% had a malignant and 27% had a non-malignant disease with 60% male, and 57% aged >18 years. The median follow-up among survivors was 3.5 years (range, 0.5 to 15.1). Eight cases of DD-MDS/AL were identified with the event diagnosed between 3 months and 15 years (median 33 months) after transplant. At 5 years, the incidence of DD-MDS/AL by donor type was 3.4% after matched sibling donor, 0% after unrelated marrow/peripheral blood donor and 0.4% after unrelated UCB donor transplant. Main characteristics of the 8 cases are described in Table 1. Four patients had CMV reactivation during their post-transplant course requiring antiviral therapy; three had poor hematopoietic recovery with prolonged courses of hematopoietic growth factor therapy. Five had monosomy 7, including all 4 UCB cases. Time to DD-MDS/AL varied by HSCT source: 22 months for UCB and 50 months for MSD cases. Underlying mechanisms are not yet known but have been postulated to include inherited or chemotherapy-induced marrow stroma and microenvironment abnormalities, bystander injury due to residual low-level chemotherapy and radiation damage, impaired tumor surveillance, chronic antigenic stimulation, premature aging of donor cells, transfer of oncogenic material from host to donor cells and the presence of preleukemic clones found rarely in UCB samples. Interestingly, one patient with DD-MDS had a sustained complete remission and loss of the cytogenetic clone by removing GCSF. The patient with DD-acute lymphocyte leukemia completed Children’s Cancer Group protocol 1961 and remains disease-free currently out 43 months from DD-AL occurrence. Two of the DD-acute myeloid leukemia cases were treated with high dose Ara-C containing regimens and one patient went on to a second HSCT. Two of the DD-MDS cases were treated with a second HSCT, while one was given decitabine. These 8 cases illustrate the rarity of the event and potentially provide more accurate estimates of the risk of this complication by HSCT source for counseling patients. Furthermore, therapeutic interventions are limited but removal of hematopoietic growth factor may alone be effective in some cases.

Disclosures:
No relevant conflicts of interest to declare.