Rituxan for Auto-Immune Hemolytic Anemia – pro

The evidence for use of rituximab in autoimmune hemolytic anemia has until reently been limited to case reports and small, uncontrolled clinical studies; however, there are many of them, and more recently larger trials, such as Barcellini et al have been performed and an evidence based recommendation(Crowder et al) appeared. Rituximab appeared to have efficacy in the treatment of AIHA, both idiopathic or associated with B-cell chronic lymphoproliferative disorders. Although the case series is small, interesting results have been observed in idiopathic AIHA with warm autoantibodies in children. These results have recently been confirmed by Zecca and colleagues in a group of 15 children treated with rituximab. This is the largest series of children with AIHA treated with this agent reported so far. In 13 cases, warm-reactive autoantibodies of the IgG type were demonstrated by the direct antiglobulin test. In four children a concomitant autoimmune disease was present at the time of AIHA diagnosis. All patients had previously received two or more courses of immunosuppressive therapy. Most of the patients were given three infusions of rituximab. With a median follow-up of 15 months 13 patients responded and two did not respond. Three patients relapsed 7, 8 and 10 months after completion the treatment, respectively, and all three patients were re-treated with rituximab, achieving remission. Four further children were treated by Motto et al who received four to six doses of rituximab at a dose of 375 mg/m2. All four patients became transfusion independent and were taken off prednisone completely.

Further evidence for efficacy of rituximab in the treatment of refractory AIHA comes from the patients with SLE. Perotta and colleagues observed an 18-yr-old girl with SLE who developed AIHA that did not respond to conventional treatment with steroids, azathioprine and cyclosporine. Her hemolytic disorder markedly ameliorated after treatment with rituximab, starting a few days after therapy and the patient remained disease-free 7 months later, at the time of writing the paper. A patient with AIHA associated with SLE was also among the six patients described by Quartier and colleagues. This 1-yr-old child also responded to rituximab therapy. Red blood cell transfusions were discontinued 14 d after the start of rituximab and normal hemoglobin concentration and reticulocyte counts were achieved within 4 months. In recent years, three manuscripts have focused on larger patient cohorts. D’Arena and colleagues described the use of rituximab in warm-type idiopathic AHA. All patients were refractory to steroids and/or immunosuppressive drugs and all were given weekly rituximab 375 mg/m2 for four consecutive weeks. An increase in hemoglobin levels was observed in all cases, with a mean increment of 3.3 g/dL. At a mean followup of 604 days, 8 patients were still in complete remission and 3 in partial remission. Recently, the effects of 68 courses of rituximab in 53 Belgian patients with AHA were reported. All patients were given rituximab after failing at least one previous line of treatment, including splenectomy in 19% of them. Overall response rates were 79%, with a median followup since first rituximab administration of 15 months. Progression-free survival at 1 and 2 years was 72% and 56% respectively [16]. The efficacy and safety of rituximab was also evaluated in a retrospective study including 27 adults with warm antibody AHA refractory to several previous lines of therapy. Overall, 8 patients achieved a complete response and 17 a partial response. After a mean followup of 21 months, 5 patients relapsed and 3 of them were successfully retreated with rituximab.

Positive reports and studies continue to be regularly published. A recent review article, albeit focusing mostly on pateints with lymphoma, says: ” although it should be noted that patients unsuccessfully treated with rituximab are much less likely to be reported, the analysis of the available literature suggests that this monoclonal antibody represents a valid therapeutic option in the treatment of AHA…. Considering both the pathogenetic mechanisms underlying AHA…. as well as the poor response rates offered by other therapeutic alternatives, we conclude that rituximab can be considered a valid strategy”.

G. D’Arena, C. Califano, M. Annunziata et al., “Rituximab for warm-type idiopathic autoimmune hemolytic anemia: a retrospective study of 11 adult patients,” European Journal of Haematology, vol. 79, no. 1, pp. 53–58, 2007.

D. Dierickx, G. Verhoef, A. van Hoof et al., “Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study,” Journal of Internal Medicine, vol. 266, no. 5, pp. 484–491, 2009.

G. Bussone, E. Ribeiro, A. Dechartres et al., “Efficacy and safety of rituximab in adults’ warm antibody autoimmune haemolytic anemia: retrospective analysis of 27 cases,” American Journal of Hematology, vol. 84, no. 3, pp. 153–157, 2009.

Zaja F, Iacona I, Masolini P, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica. 2002;87(2):189-195.

Arzoo K, Sadeghi S, Liebman HA. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis. 2002;61(10):922-924.

Claudio Fozza and Maurizio Longinotti, Use of Rituximab in Autoimmune Hemolytic Anemia Associated with Non-Hodgkin, Advances in Hematology Volume 2011 (2011),  Lymphomas,

Barcellini W, Zaja F, Zaninoni A, et al. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies. Blood 2012; 119:3691.

Mark Crowther, Y. L. Tracey Chan, Ian K. Garbett, Wendy Lim, Mark A. Vickers and Mark A. Evidence-based focused review of the treatment of idiopathic warm Autoimmune hemolytic anemia in adults 2011 118: 4036-4040

 

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