BACKGROUND: Hypogammaglobulinemia is common in Waldenström's macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the 'uninvolved' immunoglobulin production DESIGN AND METHODS: We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with Waldenström's macroglobulinemia and investigated the associated clinicopathological findings and impact of therapy. We also sequenced eight genes (AICDA, BTK, CD40, CD154, NEMO, TACI, SH2D1A, UNG) implicated in immunoglobulin deficiency in 19 Waldenström's macroglobulinemia patients with IgA and/or IgG hypogammaglobulinemia. RESULTS: At baseline 63.3%, 58.0% and 49.3% of the 207 patients had abnormally low serum levels of IgA, IgG, or both. No association between IgA and IgG hypogammaglobulinemia and disease burden, serum IgM levels, beta(2)-microglobulin, International Prognostic Scoring System score, or incidence of recurrent infections was observed, although the presence of adenopathy and/or splenomegaly was associated with a lower incidence of hypogammaglobulinemia. Lower IgA and IgG levels were associated with disease progression in patients managed with a 'watch and wait' strategy. IgA and/or IgG levels remained abnormally low despite response to treatment, including complete remissions. A missense mutation in the highly conserved catalytic site of UNG was observed in a patient with hypogammaglobulinemia, warranting further study of this pathway in Waldenström's macroglobulinemia. CONCLUSIONS: IgA and IgG hypogammaglobulinemia is common in Waldenström's macroglobulinemia and persists despite therapeutic intervention and response. IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström's macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström's macroglobulinemia patients being managed with a 'watch and wait' strategy.
BACKGROUND:Hypogammaglobulinemia is common in Waldenström's macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the 'uninvolved' immunoglobulin production DESIGN AND METHODS: We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with Waldenström's macroglobulinemia and investigated the associated clinicopathological findings and impact of therapy. We also sequenced eight genes (AICDA, BTK, CD40, CD154, NEMO, TACI, SH2D1A, UNG) implicated in immunoglobulin deficiency in 19 Waldenström's macroglobulinemiapatients with IgA and/or IgG hypogammaglobulinemia. RESULTS: At baseline 63.3%, 58.0% and 49.3% of the 207 patients had abnormally low serum levels of IgA, IgG, or both. No association between IgA and IgG hypogammaglobulinemia and disease burden, serum IgM levels, beta(2)-microglobulin, International Prognostic Scoring System score, or incidence of recurrent infections was observed, although the presence of adenopathy and/or splenomegaly was associated with a lower incidence of hypogammaglobulinemia. Lower IgA and IgG levels were associated with disease progression in patients managed with a 'watch and wait' strategy. IgA and/or IgG levels remained abnormally low despite response to treatment, including complete remissions. A missense mutation in the highly conserved catalytic site of UNG was observed in a patient with hypogammaglobulinemia, warranting further study of this pathway in Waldenström's macroglobulinemia. CONCLUSIONS: IgA and IgG hypogammaglobulinemia is common in Waldenström's macroglobulinemia and persists despite therapeutic intervention and response. IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström's macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström's macroglobulinemiapatients being managed with a 'watch and wait' strategy.
Authors: Roger G Owen; Steven P Treon; Ayad Al-Katib; Rafael Fonseca; Philip R Greipp; Mary L McMaster; Enrica Morra; Gerassimos A Pangalis; Jesus F San Miguel; Andrew R Branagan; Meletios A Dimopoulos Journal: Semin Oncol Date: 2003-04 Impact factor: 4.929
Authors: Pierre Morel; Alain Duhamel; Paolo Gobbi; Meletios A Dimopoulos; Madhav V Dhodapkar; Jason McCoy; John Crowley; Enrique M Ocio; Ramon Garcia-Sanz; Steven P Treon; Veronique Leblond; Robert A Kyle; Bart Barlogie; Giampaolo Merlini Journal: Blood Date: 2009-02-05 Impact factor: 22.113
Authors: N L Harris; E S Jaffe; J Diebold; G Flandrin; H K Muller-Hermelink; J Vardiman; T A Lister; C D Bloomfield Journal: Ann Oncol Date: 1999-12 Impact factor: 32.976
Authors: Robert J Biggar; Michael Christiansen; Klaus Rostgaard; Karin Ekström Smedby; Hans-Olov Adami; Bengt Glimelius; Henrik Hjalgrim; Mads Melbye Journal: Int J Cancer Date: 2009-06-01 Impact factor: 7.396
Authors: Robert A Kyle; Joanne Benson; Dirk Larson; Terry Therneau; Angela Dispenzieri; L Joseph Melton Iii; S Vincent Rajkumar Journal: Clin Lymphoma Myeloma Date: 2009-03
Authors: Mary Ellen Conley; A Kerry Dobbs; Dana M Farmer; Sebnem Kilic; Kenneth Paris; Sofia Grigoriadou; Elaine Coustan-Smith; Vanessa Howard; Dario Campana Journal: Annu Rev Immunol Date: 2009 Impact factor: 28.527
Authors: Steven P Treon; Zachary R Hunter; Jeffrey Matous; Robin M Joyce; Brian Mannion; Ranjana Advani; David Cook; Joseph Songer; John Hill; Bruce R Kaden; David Sharon; Ronald Steiss; Xavier Leleu; Andrew R Branagan; Ashraf Badros Journal: Clin Cancer Res Date: 2007-06-01 Impact factor: 12.531
Authors: Sigurdur Y Kristinsson; Min Tang; Ruth M Pfeiffer; Magnus Björkholm; Lynn R Goldin; Cecilie Blimark; Ulf-Henrik Mellqvist; Anders Wahlin; Ingemar Turesson; Ola Landgren Journal: Haematologica Date: 2011-12-16 Impact factor: 9.941
Authors: David F Moreno; Arturo Pereira; Natalia Tovar; María Teresa Cibeira; Laura Magnano; María Rozman; Mónica López-Guerra; Dolors Colomer; Beatriz Martín-Antonio; Raquel Jiménez-Segura; Ignacio Isola; Luis Gerardo Rodríguez-Lobato; Aina Oliver-Caldés; Mari Pau Mena; Laura Rosiñol; Joan Bladé; Carlos Fernández de Larrea Journal: Cancers (Basel) Date: 2021-04-23 Impact factor: 6.639
Authors: Hans-Hartmut Peter; Hans D Ochs; Charlotte Cunningham-Rundles; Donald C Vinh; Peter Kiessling; Bernhard Greve; Stephen Jolles Journal: J Allergy Clin Immunol Date: 2020-09 Impact factor: 10.793