title: Myeloid neoplasms secondary to plasma cell myeloma: an intrinsic predisposition or therapy-related phenomenon? A clinicopathologic study of 41 cases and correlation of cytogenetic features with treatment regimens.
abstract: We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.
authors.affiliation: Dept of Pathology, Department of Medicine, Duke University Medical Center,Durham, NC 27710, USA.
authors.forename: Deepti M
authors.initials: DM
authors.lastname: Reddi
authors.forename: Chuanyi M
authors.initials: CM
authors.lastname: Lu
authors.forename: George
authors.initials: G
authors.lastname: Fedoriw
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Liu
authors.forename: Frances F
authors.initials: FF
authors.lastname: Wang
authors.forename: Scott
authors.initials: S
authors.lastname: Ely
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Boswell
authors.forename: Abner
authors.initials: A
authors.lastname: Louissaint
authors.forename: Murat O
authors.initials: MO
authors.lastname: Arcasoy
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Goodman
authors.forename: Endi
authors.initials: E
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D022423:Myeloid Cells / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D008558:Melphalan