Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia

Abstract

Autoimmune hemolytic anemia (AIHA) is a well-known complication of chronic lymphocytic leukemia (CLL). In recent years the anti-CD20 monoclonal antibody rituximab has been used for the therapy of steroid-refractory AIHA and autoimmune thrombocytopenia, either idiopathic or in association with CLL. We report the results of rituximab treatment for 14 patients suffering from CLL-associated AIHA. They developed a direct antiglobulin test positive AIHA at a mean time of 47 months (range 0-135 months) from the diagnosis of CLL. In 3 cases AIHA was diagnosed at the same time as CLL. Only 1 patient had fludarabine-related AIHA. All patients received steroids as first-line treatment. At a mean time of 46 days (range 1-210 days) from the diagnosis of AIHA all patients received rituximab at a dosage of 375 mg/m 2 /weekly for 4 weeks. All patients except 3 (2 died of cardiac failure or sepsis soon after the third cycle and 1 HCV-positive patient experienced a rise in serum amino transferases) completed the scheduled four programmed cycles. First injection side effects of rituximab were minimal. All but 2 patients showed an increase in hemoglobin levels in response to rituximab (mean value 3.6 g/dl; range 0.7-10 g/dl) and a reduction in the absolute lymphocyte count and lymph nodes and spleen volume. Nine patients required packed red cell transfusions before starting rituximab; 5 no longer needed transfusions just after the second cycle and another patient after the fourth cycle. Three patients (22%) were considered to fully respond and 7 (50%) only responded partially. At a mean follow-up of 17 months, 8 patients were still alive, 6 of them transfusion-free. Our results prove that the anti-CD20 monoclonal antibody is an effective and well-tolerated alternative treatment for CLL-associated AIHA. Am. J. Hematol. 81:598-602, 2006. V V C 2006 Wiley-Liss, Inc.

Rituximab in the treatment of autoimmune haematological disorders

“…Further investigations are needed to determine whether rituximab maintenance therapy prolongs remission duration in AIHA. In addition to the data reported above showing that patients can respond to re-treatment with rituxumab, preliminary data in small series of AIHA and CAD patients show that durable responses can also be achieved after extended rituximab treatment (Quartier et al, 2001;D'Arena et al, 2006D'Arena et al, , 2007Schöllkopf et al, 2006). In addition, a case report has described a patient with mantle cell lymphoma who developed acquired AIHA that was successfully treated with rituximab …”

“…Responses were observed both in patients with idiopathic AIHA (Quartier et al, 2001;Shanafelt et al, 2003;Zecca et al, 2003;Narat et al, 2005;Berentsen et al, 2006;Schöllkopf et al, 2006;D'Arena et al, 2007) and in those with AIHA secondary to a range of conditions, including bone marrow transplant (Quartier et al, 2001;Zecca et al, 2003), autoimmune disorders (Shanafelt et al, 2003;Zecca et al, 2003), chronic lymphocytic leukaemia (Gupta et al, 2002;Trapè et al, 2003;Zaja et al, 2003b;Narat et al, 2005;D'Arena et al, 2006) and other lymphoproliferative disorders (Trapè et al, 2003;Narat et al, 2005;Schöllkopf et al, 2006). Patients with warm AIHA responded well to rituximab treatment regardless of prior therapy (Quartier et al, 2001;Gupta et al, 2002;Shanafelt et al, 2003;Trapè et al, 2003;Zaja et al, 2003b;Zecca et al, 2003;Narat et al, 2005;D'Arena et al, 2006). Likewise, rituximab was effective in patients with CAD regardless of whether they had previously been treated with immunosuppressant drug regimens and/or corticosteroids (Berentsen et al, 2004;Schöllkopf et al, 2006).…”

“…Although most patients with AIHA receive rituximab as monotherapy, rituximab has also been used in combination with corticosteroids, immunosuppressant drugs and interferon-a (Gupta et al, 2002;Zecca et al, 2003;Berentsen et al, 2004;Narat et al, 2005;D'Arena et al, 2006). In patients with underlying lymphoproliferative disorders in particular, treatment with a combination of rituximab and other agents may offer additional benefits (Gupta et al, 2002;Narat et al, 2005).…”

Disease-Specific Complications of Chronic Lymphocytic Leukemia

“…36 In a small study, rituximab was used in combination with cyclophosphamide and dexamethasone with good results. 37 More recently alemtuzumab has been reported as effective in controlling refractory AHA.…”

Rituximab for the treatment of autoimmune cytopenias

“…Conversion to a negative direct antiglobulin test was achieved in five patients. 28 The same group performed a retrospective study of 11 steroid-refractory adults with idiopathic AIHA.…”