Lymphoplasmacytic lymphoma (LPL) is usually associated with a serum IgM paraprotein, corresponding to Waldenström's Macroglobulinemia (WM). Cases presenting with IgG or IgA, or without a monoclonal protein are extremely rare. We analyzed clinical characteristics, frontline treatment, and the outcome of 45 patients with non-IgM LPL, and compared them with a control group of WM patients. The median age was similar, with significantly higher prevalence of females in non-IgM LPL, than in WM patients (60% vs 39%, P =.016). Patients with non-IgM LPL more frequently presented with lymphadenopathies (53% vs 15%, P <.001), splenomegaly (22% vs 8%, P =.015) or extranodal involvement (20% vs 8%, P =.05). In non-IgM LPL a serum monoclonal protein and bone marrow infiltration were less common than in WM patients (69% and 84% of cases respectively, P <.001 for both comparisons). The MYD88 (L265P) mutation was found in 8/19 patients using allele-specific polymerase chain reaction. A CXCR4 mutation was found in 4/17 cases using Sanger. In 16 patients we performed targeted next-generation sequencing of genes MYD88, CXCR4, ARID1-A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3. Seven patients (44%) had a MYD88 mutation (S219C in one), four (25%) a CXCR4 mutation, three (19%) a KMT2D mutation, one (6%) a TP53 mutation and one (6%) a TRAF3 mutation. With a median follow-up of 55.7 months, 36 non-IgM LPL patients (80%) were treated. Non-IgM LPL patients received more frequently anthracycline-containing regimens, as compared with WM patients, who mainly received alkylating-based therapies. Five-year overall survival (OS) was 84%, similar to that of WM patients.

Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: A multicentric study of the Rete Ematologica Lombarda (REL) network / M. Varettoni, E. Boveri, S. Zibellini, A. Tedeschi, C. Candido, V.V. Ferretti, E. Rizzo, E. Doni, M. Merli, L. Farina, M. Goldaniga, A. Gallì, S. Rattotti, A.M. Frustaci, M. Deodato, L. Bandiera, G. Isimbaldi, S. Uccella, A.D. Cabras, U. Gianelli, L. Baldini, M. Paulli, L. Arcaini. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - 94:11(2019 Nov), pp. 1193-1199. [10.1002/ajh.25600]

Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: A multicentric study of the Rete Ematologica Lombarda (REL) network

A.D. Cabras;U. Gianelli;L. Baldini;
2019

Abstract

Lymphoplasmacytic lymphoma (LPL) is usually associated with a serum IgM paraprotein, corresponding to Waldenström's Macroglobulinemia (WM). Cases presenting with IgG or IgA, or without a monoclonal protein are extremely rare. We analyzed clinical characteristics, frontline treatment, and the outcome of 45 patients with non-IgM LPL, and compared them with a control group of WM patients. The median age was similar, with significantly higher prevalence of females in non-IgM LPL, than in WM patients (60% vs 39%, P =.016). Patients with non-IgM LPL more frequently presented with lymphadenopathies (53% vs 15%, P <.001), splenomegaly (22% vs 8%, P =.015) or extranodal involvement (20% vs 8%, P =.05). In non-IgM LPL a serum monoclonal protein and bone marrow infiltration were less common than in WM patients (69% and 84% of cases respectively, P <.001 for both comparisons). The MYD88 (L265P) mutation was found in 8/19 patients using allele-specific polymerase chain reaction. A CXCR4 mutation was found in 4/17 cases using Sanger. In 16 patients we performed targeted next-generation sequencing of genes MYD88, CXCR4, ARID1-A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3. Seven patients (44%) had a MYD88 mutation (S219C in one), four (25%) a CXCR4 mutation, three (19%) a KMT2D mutation, one (6%) a TP53 mutation and one (6%) a TRAF3 mutation. With a median follow-up of 55.7 months, 36 non-IgM LPL patients (80%) were treated. Non-IgM LPL patients received more frequently anthracycline-containing regimens, as compared with WM patients, who mainly received alkylating-based therapies. Five-year overall survival (OS) was 84%, similar to that of WM patients.
Settore MED/15 - Malattie del Sangue
Settore MED/08 - Anatomia Patologica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Varettoni_et_al-2019-American_Journal_of_Hematology.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.15 MB
Formato Adobe PDF
1.15 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Varettoni_et_al-2019-American_Journal_of_Hematology.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.15 MB
Formato Adobe PDF
1.15 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/677707
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 9
social impact