Risk Of Myelodysplastic Syndrome (MDS) After Hematopoietic Progenitor Cell Collection Using Plerixafor
Authors: Khan Rashid Z , Rosenbaum Eric R , Boota Mariam M , Usmani Saad Z , Barlogie Bart , Cottler-Fox Michele 
Published: October 2019

Introduction
Plerixafor has recently been reported to be associated with an increased risk for developing MDS in patients with hematologic malignancies (Deol A et al. 2013; Bone Marrow Transplant 48:1112-6). Our group has extensive experience with plerixafor and we sought to confirm this finding.

Patients and Methods
A total of 294 patients treated at our institution between 2003-2013 (MM: 252, NHL: 22, Hodgkin: 4, Waldenstrom macroglobulinemia: 4, Amyloidosis: 4, LCDD: 2, other: 6) were identified as having received plerixafor as part of their mobilization regimen (62% male/ 38% female, median age 63.2 years (range 26-85)). Metaphase karyotypes for all 294 patients were reviewed for cytogenetic abnormalities typical for MDS (MDS-Ca). Clinical MDS/AML was defined as the condition for which specific MDS/AML therapy was required and administered. Of these, 11 patients developed MDS-Ca or clinical MDS prior to plerixafor administration and were excluded from further evaluation. For statistical analyses we divided our group by age (<60 and >60) and looked at variables our group has found to correlate with development of MDS-Ca or clinical MDS, i.e. albumin, hemoglobin, and platelet count immediately prior to mobilization and inadequate HPC collection (defined as<2.5 x 106 CD34+ cells/kg).

Results
Of the 283 eligible patients, 20 patients demonstrated a relevant outcome for this study (MM: 19, NHL: 1). MDS-Ca developed in 18 patients (6.4%), of whom 8 went on to develop clinical MDS/AML. Clinical MDS developed in 1 patient without prior MDS-Ca and 1 patient developed AML without any preceding cytogenetic abnormality, thus clinical MDS/AML developed in 10 patients overall (3.5%). The average time from HPC collection and plerixafor exposure to either MDS-Ca or clinical MDS/AML was 21.2 months (range 94-2268 days). None of the laboratory variables examined significantly correlated with likelihood of developing MDS-Ca or clinical MDS/AML. Inadequate collection was not associated with an increased incidence of MDS-Ca or clinical MDS/AML. Of the 283 eligible patients who were collected, 208 went on to autologous HPC transplant. Of those who were transplanted, 11 patients developed MDS-Ca (of which 4 later developed clinical MDS), 1 patient developed clinical MDS and 1 developed AML without preceding cytogenetic abnormalities. The average time from infusion of HPC to development MDS-Ca or clinical MDS/AML post-transplant was 24.2 months (range 221-2253 days).

Conclusion
The numbers of patients in this study who received plerixafor and developed MDS-Ca or clinical MDS/AML are comparable to recently reported rates of secondary MDS-Ca (11%) and clinical MDS/AML (3%) in patients with MM treated in our institution on our TT2/TT3 protocols (Usmani SZ Blood;121:4753-7). Further analyses to include additional variables, including collection of HPC infused at transplant before first transplant or later is currently underway.

Disclosures:
Usmani: Celgene: Consultancy, Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Barlogie:Celgene: Consultancy, Honoraria, Research Funding; Myeloma Health, LLC: Patents & Royalties.