Risk Of Myelodysplastic Syndrome (MDS) After Hematopoietic Progenitor Cell Collection Using Plerixafor

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.

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).

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).

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.

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