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

• Published in: British journal of haematology Vol. 179; no. 3; pp. 439 - 448
• Main Authors: Durot, Eric, Tomowiak, Cécile, Michallet, Anne‐Sophie, Dupuis, Jehan, Hivert, Bénédicte, Leprêtre, Stéphane, Toussaint, Elise, Godet, Sophie, Merabet, Fatiha, Van Den Neste, Eric, Ivanoff, Sarah, Roussel, Xavier, Zini, Jean‐Marc, Regny, Caroline, Lemal, Richard, Sutton, Laurent, Perrot, Aurore, Le Dû, Katell, Kanagaratnam, Lukshe, Morel, Pierre, Leblond, Véronique, Delmer, Alain
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2017; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; Biomarkers, Tumor - blood; Biopsy; Cell Transformation, Neoplastic - pathology; Central nervous system; chemoimmunotherapy; Cyclophosphamide; Cyclophosphamide - therapeutic use; diffuse large B‐cell lymphoma; Doxorubicin; Doxorubicin - therapeutic use; Emission analysis; extranodal involvement; Female; Fluorodeoxyglucose F18; Genetic transformation; Hematology; histological transformation; Human health and pathology; Humans; L-Lactate Dehydrogenase - blood; Leukemia; Life Sciences; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnostic imaging; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Monoclonal antibodies; Positron emission tomography; Positron-Emission Tomography - methods; Prednisone; Prednisone - therapeutic use; Prognosis; Retrospective Studies; Risk Factors; Rituximab; Survival Analysis; Targeted cancer therapy; Tomography, X-Ray Computed; Treatment Outcome; Vincristine; Vincristine - therapeutic use; Waldenstrom Macroglobulinemia - diagnostic imaging; Waldenstrom Macroglobulinemia - pathology; Waldenström macroglobulinaemia; chemoimmunotherapy; extranodal involvement; diffuse large B-cell lymphoma; Waldenström macroglobulinaemia; histological transformation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.14881

Summary 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.