Outcome of Transformed Diffuse Large B-Cell Lymphoma

Summary and Comment |
November 13, 2006

Outcome of Transformed Diffuse Large B-Cell Lymphoma

  1. Michael E. Williams, MD

Patients presenting with concomitant indolent and aggressive lymphoma had lower complete remission rates following induction chemotherapy, but their 5-year overall survival was equivalent to patients with de novo diffuse large B-cell lymphoma.

  1. Michael E. Williams, MD

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of non-Hodgkin lymphoma (NHL) cases. Although most cases arise de novo, an important subset appears to arise from previously occult indolent lymphomas; these cases usually manifest as aggressive lymphoma with evidence of a clonal small B-cell component in the marrow or within the nodal tissue. Whether the outcome of these transformed DLBCLs differs from that of de novo cases was the focus of this retrospective French study.

Sixty of the 782 large-cell lymphoma cases reviewed in this single-institution database fulfilled the inclusion criteria — namely, diagnosis of DLBCL with a coexisting small B-cell clonal population. Patients with histories of indolent lymphoma were excluded. DLBCL was found to have transformed from underlying marginal-zone lymphoma (32 cases), follicular lymphoma (22 cases), or small lymphocytic lymphoma (6 cases). Almost all patients were in stage III–IV, and half had more than one site of extranodal involvement, including 12% with central nervous system involvement. Forty-eight percent of patients had small B-cells in their marrow. Patients received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) as induction chemotherapy; 38% underwent stem-cell transplantation. For analysis, each transformed case was matched with three de novo DLBCL cases.

In the case-matched analysis, complete response (CR) was achieved in 79% of de novo versus 60% of transformed-DLBCL patients (P=0.004). Five-year freedom from progression (FFP) was 57% versus 33%, respectively (P=0.003), although 5-year overall survival was not significantly different (62% vs. 57%). Twenty-nine of the 60 transformed-DLBCL patients relapsed, 17 with aggressive lymphoma (median time to relapse, 8 months) and 12 with indolent lymphoma (median, 27 months).


Transformed lymphoma represents a challenge in diagnosis and management. Although aggressive histologic transformation more commonly occurs as a late event during follow-up of patients with indolent NHL, a subset of patients present with transformation at the time of diagnosis. Despite the lower CR rates with transformed lymphoma, no clear evidence shows that such patients should be managed with protocols different from standard aggressive lymphoma-induction regimens. This study predated current chemoimmunotherapy regimens. Consequently, the effect of concomitant monoclonal-antibody therapy such as rituximab-CHOP on CR and FFP rates is unknown, but it would be anticipated to increase these responses, based on existing data from both de novo DLBCL and indolent lymphoma cases.


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