Immunosuppression and infectious complications in patients with stage IV indolent lymphoma treated with a fludarabine, mitoxantrone, and dexamethasone regimen

Abstract

Background: Myelosuppression and immunosuppression occur with purine analogs. The objective of the current study was to investigate the effects of combined fludarabine, mitoxantrone, and dexamethasone (FND) followed by interferon/dexamethasone on myelosuppression (absolute neutrophil counts), immunosuppression (CD4 and CD8 counts), and infectious complications in patients with previously untreated, Stage IV indolent lymphoma.

Methods: Seventy-three patients were treated. All patients received Pneumocystis carinii pneumonia (PCP) prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil counts were correlated with infectious complications.

Results: The median follow-up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The median baseline CD4 count was 764/microL. This CD4 level decreased to 238/microL at 1 year and to 264/microL at 2 years; and it rose to 431/microL by 3 years and to 650/microL at 4 years. CD8 counts did not change significantly. The median baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to 693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4 years. Fourteen patients (19%) developed Grade 3-4 infections, the majority during FND therapy with neutropenia and/or accompanied by CD4 counts < 200/microL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3-4 infections, Grade 1-2 infections, or no infections.

Conclusions: Most infections with FND occurred during FND, in the setting of neutropenia, often with concurrent low CD4 counts. The overall safety profile for FND was good. However, patients should be monitored for opportunistic infections, and prophylactic antibiotics are recommended, particularly against PCP.