Histological transformation to diffuse large B‐cell lymphoma in patients with Waldenström macroglobulinemia

Abstract

Histological transformation to diffuse large B-cell lymphoma (DLBCL) rarely occurs in patients with Waldenström Macroglobulinemia (WM). We identified 20 patients out of a cohort of 1,466 WM patients who experienced histologic transformation. The 5, 10, and 15-year cumulative incidence rates were 1, 2.4, and 3.8%, respectively. Approximately half of the patients were naive to nucleoside analogues, and a quarter were previously untreated for WM at the time of transformation. More than 80% of patients presented with extranodal involvement, 65% with high IPI scores. DLBCL cells did not express CD10 but expressed BCL6 and BCL2. All patients were treated with chemoimmunotherapy. The median survival from histological transformation was 2.7 years. The median overall survival was shorter for transformed patients versus those who did not transform (estimated 9 vs. 16 years; P = 0.09). Histological transformation to DLBCL is rare, and is associated with inferior survival in WM. Am. J. Hematol. 91:1032-1035, 2016. © 2016 Wiley Periodicals, Inc.

Impact of MYD88L265P mutation status on histological transformation of Waldenström Macroglobulinemia

“…7,23,24 Our study demonstrated a transformation rate of 4.4% in a large cohort of patients with WM. A slightly higher rate of 10-year cumulative incidence of histological transformation in our study compared to another study (4.7% vs 2.4%) 25 may be in part attributable to greater exposure to prior therapies (median two vs one lines) in our cohort. 25 To account for the long timeframe of the study, we compared the cumulative probability of transformation in patients diagnosed between 1996-2005 and 2006-2015, and it was found to be similar.…”

Genetic analysis of Diffuse Large B‐cell Lymphoma occurring in cases with antecedent Waldenström Macroglobulinaemia reveals different patterns of clonal evolution

“…Patients 1, 2 and 4 were also carried a heterozygous MYD88 L265P mutation at time of transformation (see Figure S1). Occasional cases of MYD88 L265P mutation occurring in transformed samples have been reported previously (Castillo et al , ). Patients 2 and 3 had the same IGHV sequence as the initial WM sample, consistent with clonal evolution from the initial WM (Table ).…”

“…Diffuse large B‐cell lymphoma (DLBCL) is known to occur in 2–10% of cases with antecedent WM (Lin et al , ; Leleu et al , ; Castillo et al , ). It can result either from histological transformation of the WM clone or arise as a de novo lymphoma, with the latter presumably carrying a better prognosis.…”

“…Higher rates of transformation to high-grade lymphoma have been reported after use of purine analogues, probably because of their mutagenic effects on haemopoietic cells (Leleu et al, 2009). While some studies have reported no transformation events in untreated WM (Leleu et al, 2009), other case series report that 20-25% of post-WM DLBCL cases occurs in treatment-na€ ıve patients (Castillo et al, 2016b;Durot et al, 2017), which argues against these agents working as mutagenic factors.…”

Composite cutaneous lymphoma of diffuse large B‐cell lymphoma‐leg type and subcutaneous panniculitis‐like T‐cell lymphoma

“…Clinically he only presented cutaneous lesions without lymphadenopathy, he did not have elevated serum LDH (lactate dehydrogenase) or altered ECOG PS (Eastern Cooperative Oncology Group Performance status) and was in complete remission after six cycles of R‐miniCHOP. Histological transformation to DLBCL rarely occurs in patients with WM and the 15‐cumulative incidence is 3.8% . Patients with transformed WM usually had altered ECOG PS (≥2), elevated serum LDH level, advanced Ann Arbor stage III or IV disease, B symptoms and had median OS (overall survival) of 16 months after transformation .…”