Risk Factors for MDS and Acute Leukemia Following Total Therapy 2 and 3 for Multiple Myeloma

Saad Z. Usmani, Jeffrey Sawyer, Adam Rosenthal, Michele Cottler-Fox, Joshua Epstein, Shmuel Yaccoby, Rachael Sexton, Antje Hoering, Zeba Singh, Christoph J. Heuck, Sarah Waheed, Nabeel Chauhan, Donald Johann, Al-Ola Abdallah, Jameel Muzaffar, Nathan Petty, Clyde Bailey, John Crowley, Frits van Rhee and Bart Barlogie

Key points

  • MDS-associated cytogenetic abnormalities were observed in 11% of 1080 patients and often preceded clinical MDS/acute leukemia.

  • Risk factors for MDS-type cytogenetic abnormalities included IMiDs, older age, male gender, and low CD34 dose (< 5 million/kg).


Lenalidomide has been linked to MDS after auto-transplants for myeloma. Total Therapy trials, TT2 (-/+ thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide), offered the opportunity to examine these immune-modulatory agents' contribution to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%. Risk features of MDS-CA included TT3b, age >=65yr, male sex, B2M >5.5 mg/L and MM relapse. Clinical MDS/AL occurred less frequently on the control arm of TT2 and more often with TT3a and TT3b. Since MDS-CA often antedated clinical disease, periodic cytogenetic monitoring is recommended. Higher CD34 quantities should be collected upfront as the risk of MDS could be reduced by applying higher CD34 doses with transplant. Thus, treatment, host and myeloma features could be linked to MDS development after therapy for this malignancy. ( TT3A: NCT00081939, TT3B: NCT00572169)

  • Submitted November 9, 2012.
  • Accepted April 13, 2013.