Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody)

Abstract

Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusiondependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a X2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

Disease-Specific Complications of Chronic Lymphocytic Leukemia

“…37 More recently alemtuzumab has been reported as effective in controlling refractory AHA. 38 The mode of action of any of these therapies in AHA is ill-understood. Depletion of T cells and/or interference with their function appear in some individuals to induce immune phenomena, e.g., after purine analogue therapy, and in others to control it.…”

Alemtuzumab (Campath-1H) for chronic lymphocytic leukemia: a drug in search of its optimal schedule

“…Furthermore, it has also been exploited for different indications, as it clearly has impressive activity in autoimmune phenomena accompanying CLL, such as hemolysis [17]. The classic dosing schedule proposed initially was developed empirically in the absence of pharmacokinetic data, but later on changes were also made in the schedule of drug administration, starting from 12 weeks of therapy and expanding to 18 weeks, or even using monthly injections of alemtuzumab [18].…”

Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia

“…for up to 12 weeks produced an increase of at least 2 g per 100 ml in hemoglobin concentration and eliminated the requirement for transfusion in 4-7 weeks. 61 A schedule of low-dose s.c. alemtuzumab (10 mg t.i.w. for 10 weeks) in heavily pretreated patients with CLL and transfusiondependent AIHA achieved an increase of at least 2 g per 100 ml in hemoglobin concentration and independence from transfusions in 5-8 weeks.…”

“…62 Although alemtuzumab itself may cause AIHA, according to the product label, we maintain our recommendation that alemtuzumab may be given to patients with AIHA or autoimmune thrombocytopenia who do not respond to conventional therapy. Alemtuzumab may also be considered one of several options for patients who present up front with active autoimmunity when anti-CLL therapy is also needed (level of evidence: case reports and small case series 61,62 ).…”