Transformed Waldenström macroglobulinaemia: clinical presentation and outcome. A multi-institutional retrospective study of 77 cases from the French Innovative Leukemia Organization (FILO)

Br J Haematol. 2017 Nov;179(3):439-448. doi: 10.1111/bjh.14881. Epub 2017 Aug 2.


Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose-positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans' algorithm harboured a non-germinal centre B-cell phenotype. First-line treatment for transformation consisted of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen in 85% of patients. The overall response rate after first-line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.

Keywords: Waldenström macroglobulinaemia; chemoimmunotherapy; diffuse large B-cell lymphoma; extranodal involvement; histological transformation.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood
  • Biopsy
  • Cell Transformation, Neoplastic / pathology*
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Lymphoma, Large B-Cell, Diffuse / diagnostic imaging
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Prednisone / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Survival Analysis
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vincristine / therapeutic use
  • Waldenstrom Macroglobulinemia / diagnostic imaging
  • Waldenstrom Macroglobulinemia / pathology*


  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • R-CHOP protocol
  • Fluorodeoxyglucose F18
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • L-Lactate Dehydrogenase
  • Prednisone