Clinicopathologic Features of Therapy-Related Myeloid Neoplasms in Patients with Myeloma in the Era of Novel Therapies.

Autor:	Jelloul FZ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: fjelloul@mdanderson.org., Quesada AE; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Yang RK; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Li S; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Wang W; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Xu J; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Tang G; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Yin CC; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Fang H; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., El Hussein S; Department of Pathology, University of Rochester Medical Center, Rochester, New York., Khoury J; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Bassett RL; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Manasanch EE; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Orlowski RZ; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Qazilbash MH; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Patel KP; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Medeiros LJ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Lin P; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: peilin@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2023 Jun; Vol. 36 (6), pp. 100166. Date of Electronic Publication: 2023 Mar 27.
DOI:	10.1016/j.modpat.2023.100166
Abstrakt:	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. (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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