Cold hemagglutinin disease is a chronic hemolytic anemia that is refractory to the usual treatments for hemolytic anemia mediated by a warm-reactive antibody; it may be associated with a low-grade lymphoma. Two previous case reports point to a possible role for this agent in the treatment of cold hemagglutinin disease.1,2 Rituximab is an anti-CD20 monoclonal antibody of proven efficacy in the treatment of low-grade B-cell lymphomas.3 We report a remission of cold hemagglutinin disease in response to single-agent therapy with rituximab.
In 1987, a 39-year-old man presented with idiopathic acquired cold hemagglutinin disease. Physical examination revealed pallor and jaundice. There was no lymphadenopathy or organomegaly. He had a hemoglobin concentration of 67 g/L, a hematocrit of 20.1% and a reticulocyte count of 9.7%. His white blood cell count was 5.1 х 109/L with 62% neutrophils, 35% lymphocytes, 2% monocytes and 1% eosinophils. Hemagglutination was noted and improved with prewarming. The direct antiglobulin test was positive to complement 4+. The titre of cold agglutinins was persistently greater than 1:2048 and the thermal amplitude was reactive in saline and albumin to 37°C. The bilirubin concentration was 86 μmol/L (normally 0–17 μmol/L) and the lactate dehydrogenase concentration was 306 U/L (normally 90–180 U/L). The bone marrow biopsy specimen was hypercellular with no abnormal infiltrates. The chest x-ray film and the CT scan of the abdomen appeared normal.
The patient was given folic acid and a regimen to minimize cold exposure. He failed to respond to chlorambucil and showed minimal responsiveness to prednisone on occasions when hemolysis was severe. His condition was managed in a symptomatic fashion until 1996, when he failed a trial of cyclosporin A. He was reassessed in 1998 and was noted to have an enlarged spleen. Bone marrow aspiration showed a dry tap, and the bone marrow biopsy demonstrated replacement with a small-cleaved follicular centre cell lymphoma. At the time of his reassessment the patient was taking 50 mg of prednisone daily, and his hemoglobin level had improved transiently. A course of oral chlorambucil therapy (4 mg/d) resulted in a drop in his hemoglobin concentration to 51 g/L and was discontinued.
Rituximab therapy (375 mg/m2 weekly for 4 weeks) was begun on Dec. 15, 1999. The dose of prednisone was reduced from 50 mg/d to 30 mg/d alternating with 15 mg/d on alternate days over 4 weeks. Prednisone was withdrawn completely over 4 months. At the time this treatment was initiated, the patient's hemoglobin level was 82 g/L; it increased to 125 g/L by the 18th day after treatment began. One year later his hemoglobin concentration was 93 g/L; the patient was off all treatment and exhibited no symptoms.
This successful induction of remission suggests that rituximab may be an effective treatment for chronic and refractory cold hemagglutinin disease occurring in association with follicular centre cell lymphoma. The use of this agent to treat idiopathic acquired cold hemagglutinin disease requires evaluation.
Signatures
Terence G. Sparling
Head Division of Medical Oncology Shaikh Khalifa Medical Center Abu Dhabi, United Arab Emirates
Marina Andricevic
Clinical pharmacist Burnaby Regional Cancer Centre Burnaby, BC
Hilary Wass
Clinical hematologist Victoria, BC
References
- 1.Lee EJ, Jueck B. Rituxan in the treatment of cold agglutinin disease [letter]. Blood 1998; 92(9):3490-1. [PubMed]
- 2.Layios N, Van Den Neste E, Jost E, Deneys V, Scheiff JM, Ferrant A. Remission of severe cold agglutinin disease after rituximab therapy. Leukemia 2001;15(1):187-8. [DOI] [PubMed]
- 3.McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to four-dose treatment program. J Clin Oncol 1998;16:2825-33. [DOI] [PubMed]