Therapy-related clonal cytopenia as a precursor to therapy-related myeloid neoplasms

Mithun Vinod Shah, Abhishek A. Mangaonkar, Kebede H. Begna, Hassan B. Alkhateeb, Patricia Greipp, Ahmad Nanaa, Michelle A. Elliott, William J. Hogan, Mark R. Litzow, Kristen McCullough, Ayalew Tefferi, Naseema Gangat, Mrinal M. Patnaik, Aref Al-Kali, Rong He, Dong Chen

Research output: Contribution to journalArticlepeer-review


Therapy-related myeloid neoplasms (t-MN) are aggressive leukemia that develops as a complication of prior exposure to DNA-damaging agents. Clonal cytopenia of undetermined significance (CCUS) is a precursor of de novo myeloid neoplasms. Characteristics of CCUS that develop following cytotoxic therapies (therapy-related clonal cytopenia, t-CC) and outcomes following t-CC have not been described. We identified 33 patients with t-CC and compared to a cohort of the WHO-defined t-MN (n = 309). t-CC had a distinct genetic and cytogenetic profile: pathogenic variants (PV) in TET2 and SRSF2 were enriched in t-CC, whereas TP53 PV was more common in t-MN. Ten (30%) t-CC patients developed a subsequent t-MN, with a cumulative incidence of 13%, 23%, and 50% at 6 months, 1, and 5 years, respectively. At t-MN progression, 44% of evaluable patients had identifiable clonal evolution. The median survival following t-CC was significantly superior compared all t-MN phenotype including t-MDS with <5% bone marrow blasts (124.5 vs. 16.3 months, P < 0.001) respectively. The presence of cytogenetic abnormality and the absence of variants in DNMT3A, TET2, or ASXL1 (DTA-genes) were associated with a higher likelihood of developing a subsequent t-MN and an inferior survival. We describe a putative precursor entity of t-MN with distinct features and outcomes.

Original languageEnglish (US)
Article number106
JournalBlood cancer journal
Issue number7
StatePublished - Jul 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology


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