Myeloid Neoplasms Secondary to Plasma Cell Myeloma: An Intrinsic Predisposition or Therapy-Related Phenomenon?

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.

Extramedullary plasmacytoma of the larynx: Literature review and report of a case who subsequently developed acute myeloid leukemia

“…On the other hand, the occurrence of AML in this case maybe closely related to chemotherapy or radiotherapy, and so it is referred to as therapy-related AML (t-AML). At this time, it is unclear whether this represents an intrinsic predisposition or therapy-related phenomenon ( 75 ). Similarly, the pathologic procedure and pathogenesis for this case are unclear and must be elucidated.…”

Targeting NF-κB Signaling for Multiple Myeloma

“…In addition to treatment efficacy, the tendency to trigger secondary neoplasm development is another key factor to consider during development of novel anti-MM drugs. Early small cohort studies showed that DNA alkylating drugs might possess a higher tendency to induce secondary neoplasms [ 130 , 131 , 132 ]. However, more recent study using a 403-patient cohort suggested that the therapeutic mechanism exhibited an insignificant impact; instead, complex karyotypes are largely correlated to the risk of developing secondary neoplasms [ 133 ].…”

“…However, more recent study using a 403-patient cohort suggested that the therapeutic mechanism exhibited an insignificant impact; instead, complex karyotypes are largely correlated to the risk of developing secondary neoplasms [ 133 ]. Nevertheless, the skewed tendency of developing myelodysplastic syndrome (MDS) [ 130 ] warrants deeper investigation into therapy-related secondary neoplasms.…”

A case of simultaneous presentation of symptomatic PCM and MDS unrelated to prior chemotherapy

“…As chemotherapy for the treatment of plasma cell myeloma (PCM) includes alkylating agents, the incidence of therapy-related myeloid neoplasms such as acute myeloid leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasm due to prior PCM chemotherapy has increased. Several studies reported the mutagenic effect of some PCM treatment regimens on the development of MDS [ 1 2 3 ]. By contrast, cases with simultaneous presentation of PCM and MDS unrelated to prior chemotherapy are far less frequently observed than cases with MDS related to prior chemotherapy [ 4 5 6 ].…”