Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab

Abstract

Background: Pure red cell aplasia and moderate aplastic anemia are marrow failure states with an immune pathogenesis. Previously, we described short-term improvements in blood counts in two pilot studies treating moderate aplastic anemia (mAA) and pure red cell aplasia (PRCA) patients with daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor; we now report our long-term experience with a larger cohort of patients.

Design and methods: After a median follow-up period of 4.8 years, 19 of 45 (42%) evaluable mAA patients and 10 of 26 (38%) patients with PRCA responded by three months and 2 additional mAA patients responded by six months following administration of the drug.

Results: Seven of 28 (25%) mAA patients achieved long-term packed red blood cell PRBC transfusion independence, and all PRCA responders achieved long-term transfusion PRBC transfusion independence.

Conclusions: Red cell transfusion-independence prior to treatment in mAA patients predicted response. The only significant adverse treatment-related events were transient rashes and arthralgias. Daclizumab is safe and effective, and produces lengthy remissions in patients with PRCA and mAA.

Figure 1.

Response of patients with mAA and PRCA treated with daclizumab (A) Patients treated with one course of daclizumab infusions were assessed for response at three months following the last infusion and again at six months. Responses were determined as described in Design and Methods section. (A) Responses of mAA patients. (B) Fate of NR patients. (C) Responses of patients with PRCA.

Figure 2.

Cumulative response curves for patients with mAA and PRCA. Routine complete blood counts were obtained weekly on patients with mAA (top panel) and PRCA (bottom panel) for the first three months and every other week between three and six months. Cumulative response curves were generated from these blood counts.

Figure 3.

Erythematous cutaneous eruption in a patient after treatment with daclizumab. (A) Patient who received daclizumab for PRCA developed severe erthroderma requiring two weeks of prednisone therapy two months following the last infusion. (B) Typical pathological specimens showing: 1) Vesiculation, 2) Eosinophilic infiltration, and 3) Spongiosis.

Figure 4.

Survival curves for patients with PRCA and mAA treated with daclizumab. Five-year survival for daclizumab-treated mAA and PRCA patients was over 90%; however, there were too few deaths to demonstrate differences in survival between responders and non-responders.