title: Waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portends a poorer prognosis.
abstract: BACKGROUND
  The prognostic importance of extramedullary involvement in patients with Waldenström macroglobulinemia (WM) at diagnosis and treatment options for these patients has not been well evaluated. In this study, we investigated the clinical manifestations, biological features, and effect of first-line therapy on the outcome of WM patients diagnosed with extramedullary involvement (EMWM) vs those with only bone marrow involvement (BMWM).
  
  
  METHODS
  We analyzed the clinical data of 312 WM patients diagnosed with EMWM (n = 106) and BMWM (n = 206) at The University of Texas MD Anderson Cancer Center from 1994 to 2014. EMWM was confirmed by biopsy, positron emission tomography-computed tomography, or magnetic resonance imaging, and clinical laboratory analyses.
  
  
  RESULTS
  Characteristics associated with EMWM were male sex (P = 0.027), age younger than 65 years (P = 0.048), presence of B symptoms (P < 0.001), high serum beta-2 macroglobulin (P < 0.001) level, low serum albumin level (P = 0.036), and cytogenetic abnormalities (P = 0.010). Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients. Chemotherapy combined with targeted therapy improved PFS for BMWM patients (P = 0.004) but not for EMWM patients. Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients. However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021).
  
  
  CONCLUSIONS
  We show that extramedullary involvement at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy with nucleoside analogs improved PFS for patients with EMWM. The study provides unique clinical and treatment observations in subtypes of WM patients.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. cathyjiangsu@163.com.|Department of Hematology, the Affiliated Hospital of Nantong University, Nantong, China. cathyjiangsu@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. qingye1998@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ROrlowski@mdanderson.org.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. XWang30@mdanderson.org.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. SLoghavi@mdanderson.org.
authors.forename: Sanam
authors.initials: S
authors.lastname: Loghavi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. tmfsjj@hotmail.com.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. SThomas@mdanderson.org.
authors.forename: Sheeba K
authors.initials: SK
authors.lastname: Thomas
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jshah@mdanderson.org.
authors.forename: Jatin
authors.initials: J
authors.lastname: Shan
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. SLi6@mdanderson.org.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mqazilba@mdanderson.org.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Qazilbash
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. cyin@mdanderson.org.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. dmweber@mdanderson.org.
authors.forename: Donna
authors.initials: D
authors.lastname: Weber
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. roberto.miranda@mdanderson.org.
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. ZXu3@mdanderson.org.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. ljmedeiros@mdanderson.org.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. khyoung@mdanderson.org.|The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA. khyoung@mdanderson.org.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D016019:Survival Analysis; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology