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. 2025 Dec 1;17(1):13.
doi: 10.1007/s12672-025-04142-2.

Extent of bone marrow infiltration predicts disease progression in asymptomatic Waldenström macroglobulinemia

Nicolò Danesin  1 , Giovanni Leone  1 , Mattia D'Antiga  1 , Greta Scapinello  1 , Marco Carraro  1 , Alessandro Cellini  1 , Francesco Angotzi  1 , Simone Zoletto  1 , Laura Bonaldi  2 , Fabrizio Vianello  1 , Sabrina Manni  1   3 , Marco Pizzi  4 , Andrea Visentin  1 , Livio Trentin  1 , Francesco Piazza  5   6
Affiliations

Extent of bone marrow infiltration predicts disease progression in asymptomatic Waldenström macroglobulinemia

Nicolò Danesin et al. Discov Oncol. .

Abstract

While data suggest that bone marrow (BM) disease burden in asymptomatic Waldenström Macroglobulinemia (WM) may be related to time to progression, no consensus has yet been reached regarding the optimal thresholds. A 25% BM infiltration threshold was used to stratify our cohort of 150 asymptomatic WM into high- and low-disease burden subgroups. The primary outcomes evaluated were time to progression (TTP) and overall survival (OS). We found that the high BM tumor burden subgroup exhibited distinct clinical and biological features, including lower hemoglobin levels, higher serum IgM concentrations, increased monoclonal component levels, and a lower prevalence of peripheral neuropathy. This subgroup also demonstrated significantly shorter median TTP compared with patients with lower BM involvement (64 months vs. 137 months, p = 0.01). Factors associated with shorter TTP included advanced age (hazard ratio [HR] 1.04), lower hemoglobin levels (HR 1.02), elevated serum monoclonal component (MC) (HR 1.06), increased IgM concentrations (HR 1.06), and the presence of cytogenetics aberrations (HR 2.5). In multivariate analysis, only elevated serum IgM (HR 1.09) remained an independent predictor of shorter TTP, whereas cytogenetic abnormalities showed only a trend toward significance (HR 2.4). In the OS analysis, no significant differences were observed between the two subgroups. Finally, a higher BM tumor burden at diagnosis is associated with shorter TTP in asymptomatic WM. Elevated serum IgM independently predicted inferior TTP. Our results are consistent with previously published series and the 5th WHO Lymphoid Neoplasm Classification, underscoring the prognostic significance of BM disease burden in WM.

Keywords: Bone marrow; Lymhoplasmacytic lymphoma; Non hodgkin lymphoma; Smoldering waldenström macroglobuliemia.; Waldenstrom macroglobulinemia.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the declaration of Helsinki. This study has been approved by the local ethical committee of the Azienda Ospedale Università Padova (approval number: protocol # 4089/AO/17). Authors declare that each patient has signed written informed consent to participate to this study. Consent for publication: The authors give the permission of the publication of the results reported in this manuscript. Competing interests: The authors declare no competing interests.

Figures

None
CONSORT diagram of the study
Fig. 1
Fig. 1
Kaplan Meier curves of time to progression (TTP) and overall survival (OS) considering low (<25%) vs high (≥25%) bone marrow tumor burden
See this image and copyright information in PMC

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