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Chemotherapy and/or Immunotherapy With Stem Cell Transplantation Effective in Patients With Richter's Syndrome: Presented at ICML

By Chris Berrie

LUGANO, SWITZERLAND -- June 14, 2005 -- The use of chemoimmunotherapy (CI/T) followed by allogenic stem cell transplantation (allo-SCT) offers the best response, failure-free survival, and overall survival rates for patients with Richter's syndrome (RS), according to a study reported here at the 9^th International Conference on Malignant Lymphoma (ICML).

Richter's syndrome is a rare complication of chronic lymphocytic lymphoma (CLL) that occurs in 2% to 8% of these patients. While overall response rates to various therapeutic strategies can vary between 5% and 43%, median survival for RS patients with cytotoxic therapy is 5 to 8 months.

Coprincipal investigator Apostolia-Maria Tsimberidou, MD, PhD, assistant professor of medicine, department of leukaemia, MD Anderson Cancer Centre, University of Texas, Houston, Texas, United States, presented the findings on June 9^th.

"The aim of this study was to assess the incidence, presenting characteristics, treatment outcomes, and factors that can be used for predicting survival for patients with Richter's syndrome," Dr. Tsimberidou said.

Following a database search of patients with CLL and RS who presented at the MD Anderson Cancer Centre between 1977 and 2004, the patients with possible RS, the researchers found that 5.3% of subjects with CLL had RS (193 of 3656). Of these, 143 had Richter's large-cell lymphoma that was proven by biopsy or fine-needle aspiration.

The presenting characteristics of these 143 patients indicated that approximately 50% of them had an age greater than 60 years, haemoglobin level below 11 g/dL, received 2 or more prior therapies, lactate dehydrogenase levels of at least 1.5 times the upper limit of normal, and tumour size of at least 5 cm.

Approximately 40% of patients with RS had platelet counts of less than 100,000, their time to transformation was at least 5 years, and beta2-microglobulin levels were 3 times the upper limit of normal. Twenty-one percent had a performance status greater than 1.

One hundred thirty subjects had prior treatment, including chemotherapy alone (61%), chemotherapy plus rituximab (36%), and immunotherapy alone with rituximab and campath (3%). Some patients underwent subsequent allo-SCT in remission (7%), as salvage (6%), or as auto-SCT in remission (2%).

There were no significant differences between the chemotherapy and chemotherapy/rituximab groups for either mean complete response (11% vs 13%, respectively) or mean overall response (34% vs 47%, respectively). The combination of these treated RS patients gave a complete response of 12% and an overall response of 39%, with a median failure-free survival of 7.1 months (95% confidence interval [CI], 5-10 months).

Median overall survival was 9.1 months (95% CI, 8-11 months) for the full group of 143 RS patients. When divided according to subsequent transplantation, the patients that received allo-SCT in remission showed significantly (P =.004) greater survival than both the therapy responders without SCT and those that received SCT.

In multivariate analysis, of the large range of significant factors for response and survival in the previously treated patients, the significant risk factors for poor survival were performance status greater than 1 (P =.006), lactate dehydrogenase level of at least 1.5 times the upper limit of normal (P =.003), platelet count below 100,000 (P =.012), tumour size of 5 cm or greater (P =.022), and 2 or more prior therapies (P =.024).

However, when the SCT was included in this multivariate analysis, platelet count lost its significance, and the absence of allo-SCT in remission became a significant risk factor for poor survival (P =.002).

As the use of chemotherapy with or without immunotherapy followed by allo-SCT resulted in improved survival when compared with the other therapies used in this trial, Dr Tsimberidou concluded, "Allogenic stem cell transplantation should be offered to all RS patients with available donors as postremission therapy."

She further stressed the need to identify prognostic factors for CLL patients at risk of RS so that they can be offered allo-SCT prior to this transformation.


[Study title: Outcome in Patients With Richter's Syndrome Treated With Chemotherapy and/or Immunotherapy With or Without Stem Cell Transplantation. Abstract 043]

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