Clinical Outcomes and Prognostic Factors in Patients with Richter’s Syndrome Treated with Chemotherapy and/or Immunotherapy with or without Stem Cell Transplantation.
Authors: Tsimberidou Apostolia-Maria , O’Brien Susan , Khouri Issa , Giles Francis J. , Kantarjian Hagop M. , Wen Sijin , Smith Susan C. , Lerner Susan , Freireich Emil J. , Keating Michael J. 
Published: October 2019

Abstract
Introduction: Richter’s syndrome (RS) is a rare complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The clinical outcome is generally poor. The purpose of this study was to assess the presenting characteristics, treatment outcomes, and prognostic factors in patients with RS.
Methods: An electronic database search of patients with CLL/SLL or RS who presented at U. T. M. D. Anderson Cancer Center between 1/75 and 6/05 was performed.
Results: Among 3,986 patients with CLL/SLL, 204 patients (5.1%) had possible RS and 148 patients (3.7%) had biopsy- or fine-needle aspiration-proven RS. The median age was 61 years (range, 29–83 years); and 70% were men. Among 148 patients with RS, 53% were ≥ 60 years, 79% had Zubrod performance status 0–1, 47% had lactate dehydrogenase (LDH) levels ≥ 1.5 x the upper limit of normal, 57% had platelets ≥ 100 x 109/L, 57% had β 2-microglobulin ≥ 6 mg/dL (3 x the upper limit of normal), and 45% had tumor size >5 cm. Treatment included chemoimmunotherapy, such as rituximab with fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (R-hyper-CVAD) or cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and chemotherapy. A total of 135 patients were treated and 130 patients were evaluable. The overall response rate was 39% (chemoimmunotherapy, 47%; chemotherapy, 34%, p=0.2). In multivariate analysis (MVA), factors predicting response were platelet counts ≥ 100,000 (p=0.02), hemoglobin levels ≥ 11g/dL (p=0.036), performance status (PS) 0 or 1 (p=0.037), and β 2-microglobulin <6 mg/dL (p=0.05). Factors predicting prolonged survival were PS 0–1 (p=0.006), LDH ≤ 1.5 x upper limit of normal (p=0.003), platelet counts ≥ 100,000 (p=0.01), tumor size ≤ 5 cm (p=0.02), and <2 prior therapies (p=0.02). Factors predicting prolonged FFS were PS 0–1 (p=0.006), LDH ≤ 1.5 x upper limit of normal (p=0.019), tumor size ≤ 5 cm (p=0.021), age <60 years (p=0.025), <2 prior therapies (p=0.041), and platelet counts ≥ 100,000 (p=0.045). A total of 20 patients underwent stem cell transplantation (SCT). Seven patients underwent allogeneic SCT as postremission therapy, and 13 patients underwent allogeneic SCT (n=10) or autologous SCT (n=3) as salvage therapy. Patients who underwent allogeneic SCT as postremission therapy appeared to have longer survival than patients who achieved remission and received no further therapy (n=35) or patients who underwent allogeneic or autologous SCT as salvage therapy (p=0.019).
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Conclusions: Our results suggest that chemoimmunotherapy, such as R-Hyper-CVAD or R-CHOP, followed by allogeneic SCT results in longer survival compared to other therapies. Until curative therapies are developed, patients with available donors should be considered for allogeneic SCT as postremission therapy.