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4389 Incidence and Time to Diagnosis of Secondary Malignancies in Patients with Hairy Cell Leukemia: A Systematic Review and Meta-Analysis

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, Epidemiology, Clinical Research, Diseases, Lymphoid Malignancies, Adverse Events
Monday, December 9, 2024, 6:00 PM-8:00 PM

Manasawee Tanariyakul1*, Sakditad Saowapa, MD2, Akihiro Miyashita, MD1*, Chalothorn Wannaphut, MD1, Panisara Fangsaard, MD3* and Kensuke Takaoka, M.D., MSc, PhD1*

1Department of Internal Medicine, University of Hawaii John A.Burns School of Medicine, Honolulu, HI
2Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX
3Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY

Introduction: Hairy cell leukemia (HCL) is a rare, indolent, chronic lymphoid neoplasm that represents approximately two percent of all leukemias. Due to their high response rate, purine analogs are the preferred initial treatment for most symptomatic patients. However, the risk of secondary neoplasms remains a significant concern among patients treated with purine analogs. Although some studies suggest an increased risk of developing a second cancer, the rarity of HCL and the lack of randomized trials comparing purine-based and non-purine-based chemotherapies have led to uncertainty regarding the risk of secondary malignancies. In this meta-analysis, we investigated the incidence and the time from the diagnosis of HCL to the development of secondary malignancies, focusing on the impact of different frontline therapies (purine vs non-purine).

Methods: The articles included in this systematic review and meta-analysis were retrieved through an extensive search of Google Scholar, PubMed, and Cochrane CENTRAL databases. Additional articles were identified by skimming the reference lists of similar systematic reviews and meta-analyses. The search included relevant articles from inception to July 2024 using a detailed search via MeSH (medical subject heading) terms and keywords. The review adheres to the Cochrane methodology and follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A Comprehensive Meta-Analysis (CMA) version 3 was utilized for all statistical analyses.

Results: Data from 16 studies were pooled to evaluate the incidence of secondary malignancies in HCL patients. A subgroup analysis compared incidence rates based on therapeutic interventions: non-purine analogs, purine analogs, and a combination of both. Additionally, the time from HCL diagnosis to the development of secondary malignancies was analyzed. The cumulative incidence of secondary malignancies among HCL patients was 12.1% (95% CI: 9.5 – 15.3). Subgroup analysis revealed a higher incidence in patients treated with purine analogs (13.7%) than those treated with non-purine analogs (4.8%). Patients receiving a combination of both therapies had an incidence of 11.9%. The differences were statistically significant (p<0.0001), with a z-score of -14.138. Of the 16 studies, 9 reported the time duration from HCL diagnosis to secondary malignancy development, with a pooled mean time of 111.66 months (95% CI: 88.82 – 134.49). The mean time varied across treatment groups: 85.25 months for non-purine analogs, 114.97 months for combination therapies, and 120.01 months for purine analogs, but these differences were not statistically significant (p = 0.106).

Conclusions: The incidence of secondary malignancies in HCL patients is significantly influenced by the type of frontline treatment, with purine analogs being associated with a higher risk compared to non-purine analogs. These findings highlight the importance of long-term surveillance and careful consideration of treatment options to mitigate the risk of secondary malignancies. Further research is necessary to understand the mechanisms driving these associations and to develop strategies for reducing secondary malignancy risk in HCL patients.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH