Myelodysplasia after Autologous Stem Cell Transplantation for Multiple Myeloma.

Autologous stem cell transplantation (ASCT) increases the overall survival of patients with newly diagnosed multiple myeloma (MM), and it has become standard of care in this setting. Long-term survivors of ASCT transplanted for lymphoma or Hodgkin’s disease are known to have a high risk of developing myelodysplasia (MDS), but the risk of MDS is not clear for patients transplanted for MM. From 1996 through 2005, 82 patients underwent ASCT for MM at our center, survived at least 6 months and have adequate documentation of follow-up for review. The group included 47 males and 35 females of median age 56 years (range, 37–74 yrs). Median time from diagnosis to ASCT was 8.2 mos (range, 2.6–86.1 mos). Prior to coming to transplantation, 28% had received melphalan (MEL), 98% received some form of chemotherapy, and 34% received radiation. This prior therapy included 1 or 2 regimens for 48% of the patients, and more than 2 regimens for 52% of patients. Mobilization was effected using CYC plus growth factor for 79% of the patients, CAD or VAD plus growth factor for 17%, and growth factor alone for 4%. The median mobilization rate was 28.7 × 10⁶ CD34/L blood processed (range, 2.0–250.1 × 10⁶ CD34/L blood processed). A single ASCT was provided for 68%, and 32% underwent ASCT more than once. High-dose MEL alone was used as the preparative regimen for 83%, and the remainder received at least one ASCT with a more intensive preparative regimen. The median CD34 dose for the first ASCT was 5.1 × 10⁶/kg (range, 0.4–113.0 × 10⁶/kg). Nine patients developed MDS. The 5-yr actuarial risk was 26% (95% CI, 8–43%). On multivariate analysis, there was a trend for an increased risk of developing MDS with a CD34 cell dose <3 × 10⁶/kg (HR 3.0, 95% CI 1.0–16.2, p=0.059), but there were otherwise no significant prognostic factors. Eight of the 9 patients with MDS had a PR or better as the best response to ASCT for MM. Five of the MDS patients had relapse of MM as well. Median survival after the diagnosis of MDS was 18.1 mos. Five patients with MDS have died, two from recurrent myeloma, two from AML, and one from sepsis and MDS. The median survival for all patients was 51.7 mos from ASCT and 69.1 mos from diagnosis, and there were no differences in survivals between those with or without MDS. We conclude that there is a relatively high risk of MDS after ASCT for MM, but development of MDS does not appear to worsen overall survival.