Waldenstrom's Macroglobulinemia Associated Bone Disease the UAMS Experience
Authors: Papanikolaou Xenofon , Waheed Sarah , Barlogie Bart , Alapat Daisy V. , Yoon Donghoon , Kumar Manoj , Matin Aasiya , Zhu Hongyun , Harcourt Cerisse , Zangari Maurizio 
Published: October 2019

Abstract
Introduction: Bone disease in patients with paraproteinemias is typically associated to a diagnosis of of multiple myeloma (MM) and the presence of an IgM monoclonal gammopathy with associated lytic bone abnormalities always suggests the possibility of an IgM MM. Because Waldestrom’s Macroglobulinemia (WM) with lytic bone disease has also been reported in the literature we decided to retrospectively investigate the incidence of bone disease in patients carrying a diagnosis of WM and to evaluate the clinical relevant associations.
Methods: After receiving IRB approvalwe retrospectively interrogated the UAMS Multiple Myeloma Data Base for cases of WM. From 01/01/1997 to 01/01/2014 a total of 167 subjects were identified and subsequently all cases reviewed by faculty hemopathologist to confirm diagnosis of WM.Within this cohort at baseline visit a total of 100 (61%) patients underwent MRI T1 and STIR sequences of head spine, pelvis, shoulder and sternum and 44 (27%) individuals received PET-CT scanning.
Results: With a median age of 62 years (48-94), 61% of the subjects were male. Metaphase cytogenetic data were available in 146/164 (89%) of the cases at baseline, of which 38/146 (26%) were abnormal. Among the 100 patients who underwent baseline MRI examination 17(17%) had evidence of focal bone disease which was localized preferentially to the spine (11 cases) and the limbs (6 cases). Throughout the entire patient follow up PET-CT documented osteolytic lesions were described in 11 (24%) cases, 9 at baseline. Within the 109 patients with either MRI or PET-CT examination bone disease was reported in 23% of the subjects. With a median follow up of 10.9 years the median Overall Survival (OS) and Progression Free Survival (PFS) was 16.5 years and 15.9 years respectively. The presence of MRI bone focal lesions at baseline correlated with the presence of anemia (Hg<10g/dl, p=0.01) but did not affect either OS or PFS. PET-CT associated bony lesions carried no prognostic implications for OS or PFS, nor was related to any other clinical parameters. The same was also true when the combine results of PET-CT and MRI were taken into consideration
Conclusion: To our knowledge this is the first study of bone disease in Waldenstrom’s patients by MRI and PET-CT. While PET-CT defined bone disease was present in 24% of the tested cases we could not identify significant correlation with clinical parameters. MRI defined bone disease was evidentin 17% of the patients retained a positive correlation with the presence of anemia (Hg<10gr/dl, p=0.03) without significant impact in OS or PFS. TablePatient Characteristicsn/N (%)Age: median (minimum-maximum)62 (48-94)Male100/164 (61%)Abnormal Cytogenetics38/146 (28%)Hg<10gr/dL48/164 (29%)MRI positive for bone disease17/100 (17%)PET-CT positive for bone disease11/44(24%)

Disclosures
Barlogie: Celgene: Consultancy, Patents & Royalties, Research Funding; Millenium: Consultancy, Patents & Royalties, Research Funding. Zangari:Norvartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Research Funding; Millennium: Research Funding.