Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia

Abstract

We examined the clinical response of fludarabine-refractory CLL patients treated with high-dose methylprednisolone (HDMP) and rituximab. Fourteen patients were treated with three cycles of rituximab (375 mg/m(2) weekly for 4 weeks) in combination with HDMP (1 gm/m(2) daily for 5 days). All patients were refractory to fludarabine and 86% had high-risk disease by the modified Rai classification. In all, 79% of the patients had CLL cells that expressed ZAP-70 and three patients had poor prognostic cytogenetics. The overall response rate was 93% and the complete remission rate was 36%. The median time-to-progression was 15 months and the median time-to-next treatment was 22 months. Median survival has not been reached after a median follow up of 40 months. Four patients have died of progressive disease. Patients tolerated the treatment well and serious adverse events were rare. This allowed patients to receive all planned treatments on schedule with no dose modifications. All but one patient responded to treatment and the overall survival and time-to-progression were superior to those of other published salvage regimens.

Figure 1

Comparison of clinical and laboratory parameters before treatment and at the end of the follow up period. (a) White blood cells count (WBC); (b) Hemoglobin values; (c) Platelet counts. (d) Lymph node area; sum of the large lymph nodes from each anatomic area; (e) Spleen size measured in centimeters below the left costal margin (BLCM). Statistical analysis was performed using paired t-test, two tailed P-values.

Figure 2

Survival curves for each of the indicated outcomes. The analysis was created using the product limit method of Kaplan–Meier. Median time-to-progression (TTP)-15 months. Median time-to-survival (OS) has not been reached (median follow up 40 months after treatment and 78 months after diagnosis). Median time to next treatment (TNTx) 22 months.