BALTIMOREThe B-cell directed monoclonal antibody rituximab
(Rituxan) can produce durable complete remissions without the need for
maintenance therapy in patients with cold agglutinin autoimmune hemolytic
anemia (AIHA) and might also represent a treatment option in warm agglutinin
AIHA, according to Edward Lee, MD. Dr. Lee is director of hematology and
medical oncology at Sinai Hospital in Baltimore, and Director of the Bone
Marrow Transplantation Program.
"Autoimmune hemolytic anemia can be a difficult disease to
treat," he explained. "When warm or IgG mediated AIHA occurs,
response to steroids and/or to splenectomy may well be favorable and lasting,
but some patients do not respond durably or may have comorbid conditions that
increase the risk of splenectomy. Patients with cold or IgM-mediated AIHA
respond poorly to most therapeutic interventions and there is no standard
effective treatment for this disease. Both forms are mediated by an antibody,
so it seemed reasonable to use selective anti-B-cell agents for refractory
Five of the six AIHA patients in a pilot study were female. The
age range was 22-83, with a median of 64 years. Three patients had low-grade
lymphomas (2 cold, 1 warm) that were identified during the course of treatment
and follow-up for AIHA. All patients had prior steroid therapy for AIHA and had
disease ranging from 3 months to 20 years.
The three patients with cold agglutinin disease had
chemotherapy (2 patients), splenectomy (2 patients), or plasmapheresis (1
patient). The three patients with warm AIHA had no other therapies before
rituximab. Those with warm AIHA were steroid dependent at time of treatment
with rituximab, and two of the three cold AIHA patients were resistant to all
previous treatment before being treated with rituximab.
Patients were given four weekly doses of rituximab (375 mg/m2).
No unusual toxicity or complications occurred, according to Dr. Lee.
Five Complete Responses
Five of the six patients had complete hematologic responses
following rituximab. This included all three patients with cold AIHA. (See
Table 1.) Responses were also observed in patients with warm AIHA. (See Table
2.) Complete response was defined as an increase of hemoglobin and hematocrit
into the normal range.
One patient required a second course of treatment, and one was
given six doses of rituximab because response was definite but not complete at
the end of the planned four doses. This patient had a complete response after
Duration of response ranged between 4 months and 2.7 years at
the time of this report. "One patient required a second treatment after 5
months and has continued in response for an additional 10 months
subsequently," Dr. Lee said. No other patients have had recurrent
The investigators concluded that response can be durable
without the need for maintenance or other treatments and can occur
independently of whether concurrent non-Hodgkin’s lymphoma is present.
Patients with longstanding disease (20 years after diagnosis) responded, as did
patients with or without NHL.
"Rituximab represents an alternative for both warm and
cold AIHA," Dr. Lee stated. "The quality of response in patients
presented here suggests that rituximab might be reasonable initial therapy for
cold agglutinin disease in that no other interventions are consistently
effective. The roll of rituximab in warm AIHA remains to be determined.
Rituximab is arguably preferable to long-term corticosteroid use and should be
considered early in the course of the disease."