Faculty, Staff and Student Publications
Publication Date
6-1-2023
Journal
Modern Pathology
DOI
10.1016/j.modpat.2023.100166
PMID
36990279
Abstract
The development of therapy-related myeloid neoplasms (t-MN) is a rare complication that can occur in myeloma patients treated primarily with novel therapies. To better understand t-MNs in this context, we reviewed 66 such patients and compared them with a control group of patients who developed t-MN after cytotoxic therapies for other malignancies. The study group included 50 men and 16 women, with a median age of 68 years (range, 48-86 years). Therapies included proteasome inhibitors, immunomodulatory agents, and high-dose melphalan-based autologous stem cell transplantation (HDM-ASCT) in 64 (97%), 65 (98.5%), and 64 (97%) patients, respectively; 29 (43.9%) patients were exposed to other cytotoxic drugs besides HDM. The latency interval from therapy to t-MN was 4.9 years (range, 0.6-21.9 years). Patients who received HDM-ASCT in addition to other cytotoxic therapies had a longer latency period to t-MN compared with patients who only received HDM-ASCT (6.1 vs 4.7 years, P = .009). Notably, 11 patients developed t-MN within 2 years. Therapy-related myelodysplastic syndrome was the most common type of neoplasm (n = 60), followed by therapy-related acute myeloid leukemia (n = 4) and myelodysplastic syndrome/myeloproliferative neoplasm (n = 2). The most common cytogenetic aberrations included complex karyotypes (48.5%), del7q/-7 (43.9%), and/or del5q/-5 (40.9%). The most frequent molecular alteration was TP53 mutation, in 43 (67.2%) patients and the sole mutation in 20 patients. Other mutations included DNMT3A, 26.6%; TET2, 14.1%; RUNX1, 10.9%; ASXL1, 7.8%; and U2AF1, 7.8%. Other mutations in less than 5% of cases included SRSF2, EZH2, STAG2, NRAS, SETBP, SF3B1, SF3A1, and ASXL2. After a median follow-up of 15.3 months, 18 patients were alive and 48 died. The median overall survival after the diagnosis of t-MN in the study group was 18.4 months. Although the overall features are comparable to the control group, the short interval to t-MN (< 2 years) underscores the unique vulnerable status of myeloma patients.
Keywords
Male, Humans, Female, Pregnancy, Middle Aged, Aged, Aged, 80 and over, Multiple Myeloma, Hematopoietic Stem Cell Transplantation, Transplantation, Autologous, Melphalan, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases
Published Open-Access
yes
Recommended Citation
Jelloul, Fatima Zahra; Quesada, Andres E; Yang, Richard K; et al., "Clinicopathologic Features of Therapy-Related Myeloid Neoplasms in Patients with Myeloma in the Era of Novel Therapies" (2023). Faculty, Staff and Student Publications. 4915.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4915
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