<p>Immunochemotherapy for Richter syndrome: current insights</p>

Abstract

Richter syndrome (RS) is recognized as the development of a secondary and aggressive lymphoma during the clinical course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most of such histological transformations are from RS to diffuse large B-cell lymphoma (DLBCL-RS, 90%) and Hodgkin’s lymphoma (HL-RS, 10%). Histopathological examination is a prerequisite for diagnosis. It is crucial to assess the relationship between the RS clone and the underlying CLL/SLL because clonally related DLBCL-RS has a poor outcome, while clonally unrelated cases have a prognosis similar to de novo DLBCL. An anti-CD20 antibody-based immunochemotherapy is hitherto the frontline treatment of choice for DLBCL-RS; nonetheless, the results are unsatisfactory. Allogeneic stem cell transplantation should be offered to younger and fit patients as a consolidative treatment; however, the majority of the patients may not be qualified for this procedure. The HL-RS transformation has better outcomes than those of DLBCL-RS and can effectively be treated by the adriamycin, bleomycin, vinblastine, and dacarbazine regimen. Although novel agents are currently being investigated for RS, immunochemotherapy nevertheless remains a standard treatment for DLBCL-RS.

Educational Case: Small Lymphocytic Lymphoma: Diagnostic Features and Prognosis

“…Typically, patients with symptomatic disease, disease with advanced stage, or otherwise high-risk disease are treated with chemoimmunotherapy with fludarabine, cyclophosphamide, and the anti-CD20 monoclonal antibody rituximab. More aggressive chemotherapy and immunotherapy (such as using an R-CHOP regimen: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) 3 is the standard of care in Richter’s transformation, followed by stem cell transplant in eligible patients (who are usually younger than 65 years and otherwise healthy); however, overall patient outcomes are dismal with median survival of less than a year. 4 In a study of 100 patients with CLL/SLL undergoing biopsy, usually for clinical suspicion of transformation, the median survival from time of biopsy for patients with CLL/SLL and with DLBCL were 76 and 4.3 months, respectively.…”

U-RT1 – A new model for Richter transformation

“…The RS-DLBCL cells are morphologically distinct from small monomorphic CLL cells, appearing as large blast-like neoplastic B cells with small nucleoli. RS-DLBCL shows a diffuse growth pattern and a highly proliferative potential [6] . Immunohistologically, most cases of RS-DLBCL no longer express CD5 and CD23, giving a different immunophenotype from the underlying CLL [7] .…”

“…Despite the multitude of tested combinations of chemotherapy and novel immunotherapies, the results are still unsatisfactory and the overall survival of patients with clonally related RS-DLBCL remains poor [6 , 21] . Traditionally, therapeutic regimens for RS resemble those of de novo DLBCL [10] with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), usually in combination with rituximab (R-CHOP) [22] , and autologous or allogeneic stem cell transplantation as postremission or salvage therapy for patients without limiting comorbidities [23] .…”

Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia

“…Patients characterized by p53 protein defects (short arm of chromosome 17 deletion [del(17p)] or TP53 gene mutation) are refractory or achieve only transient responses to anti-CD20 antibody based immunochemotherapy [10,11]. Furthermore, transformation to poor prognostically aggressive diffuse large B-cell lymphoma (DLBCL) also occurs in up to 10% of cases [12].…”