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.
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.
Barlogie
Bart
B
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham, Little Rock, AR 72205, USA. barlogiebart@uams.edu
Tricot
Guido
G
Haessler
Jeff
J
van Rhee
Frits
F
Cottler-Fox
Michele
M
Anaissie
Elias
E
Waldron
James
J
Pineda-Roman
Mauricio
M
Thertulien
Raymond
R
Zangari
Maurizio
M
Hollmig
Klaus
K
Mohiuddin
Abid
A
Alsayed
Yazan
Y
Hoering
Antje
A
Crowley
John
J
Sawyer
Jeffrey
J
D017677:Age Distribution; D001131:Arkansas / Q000453:epidemiology; D002869:Chromosome Aberrations; D016208:Databases, Factual; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics / Q000401:mortality; D008558:Melphalan / Q000009:adverse effects*; D008677:Metaphase; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000009:adverse effects*; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014182:Transplantation, Autologous / Q000009:adverse effects* / Q000379:methods
D019653:Myeloablative Agonists; D008558:Melphalan