Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3,000 patients treated since 1989

Abstract

Myelodysplastic syndrome (MDS) is a well-recognized complication of chemotherapy for multiple myeloma (MM). Serial bone marrow metaphase examinations were performed for MM restaging in 3,077 patients undergoing high-dose therapy (HDT). MDS-associated cytogenetic abnormalities (MDS-CAs) were observed in 105 of 2,418 patients in whom cytogenetic data were available after HDT. MDS-CAs occurred transiently in 72 patients and on 3 successive occasions (persistent MDS-CAs) in 33 patients, for 10-year estimates of 4% and 2%, respectively; only 21 patients developed overt clinical MDS and 5, acute myeloblastic leukemia (AML). MDS-CA development was linked to lower CD34 yield at collection, longer time interval from MM diagnosis to HDT, older age, and lower platelet recovery after HDT; persistent MDS-CAs were predicted by CD34 yield of less than 3 x 10(6)/kg and need for more than 2 apheresis procedures. Applying a tertile frequency distribution over time to all 105 patients with MDS-CAs, its detection early after HDT was associated with longer time interval from diagnosis and low pre-HDT platelet count (likely resulting from pre-HDT damage), whereas late-onset MDS-CAs were noted among patients treated with Total Therapy 2 and Total Therapy 3 that applied post-HDT consolidation chemotherapy (suggesting possible post-HDT damage). While the risk of MDS-CAs was low and clinical MDS occurred infrequently, monitoring after post-HDT consolidation chemotherapy appears warranted.

Figure 1

Cumulative incidence of MDS-CAs. Denoted are the times from first transplantation to any MDS-CA (blue), to the detection of transient MDS-CAs (red), and to the observation of the first among 3 successive MDS-CA examinations (persistent MDS-CAs [green]).

Figure 2

Cumulative incidence of MDS-CAs according to number of risk factors. (A) Transient and persistent MDS-CAs. (B) Persistent MDS-CAs.

Figure 3

Cumulative incidence of MDS-CAs. (A) By calendar year of therapy. (B) According to protocol. (C) According to protocol among patients treated from 1989 to 1998. (D) According to protocol among patients treated from 1999 to 2006. (E) Among patients enrolled in TT2 protocol according to whether consolidation consisted of chemotherapy or dexamethasone.

Figure 4

Survival of patients with and without MDS-CAs matched on age, HDT date, months from diagnosis to first HDT, and CD34 quantity.