Rituximab for Child with Chronic Relapsing Autoimmune Hemolytic Anemia
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Pediatric Hematology and Oncology, 28:164–166, 2011 Copyright C Informa Healthcare USA, Inc. ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2010.518339 LETTER TO THE EDITOR Non-Malignant Hematology and Infection Rituximab for Child with Chronic Relapsing Autoimmune Hemolytic Anemia Shahla Ansari, MD, Maryam Tashvighi, MD, Bahram D. Arbani, MD, Adel Bagher Salimi, MD, and Mohamadreza Golpaygani Department of Hematology and Oncnlogy, Ali Asghar Children’s Hospital, Iran University, Tehran, Iran Autoimmune hemolytic anemia (AIHA) is a process of accelerated red cell destruc- tion arising from the production of autoantibody against red cell antigens. Warm au- toimmune hemolytic anemia is the most common autoimmune hemolytic anemia [1–3]. e hemolysis is predominantly extravascular and is mediated by immunoglob- ulin G (IgG) auto antibodies that are maximally reactive 37 ◦ C [1–3]. e mainstay of therapy is immunosuppressive with corticosteroids, although up to 50% require maintenance therapy. Spelenectomy is effective second-line therapy, pro- viding remission in up to 60%; other second-line agents include danazol, cyclosporine, azathioprine, and intravenous immunoglobulin [3]. Rituximab is a humanized monoclonal antibody directed against CD20. e anti- gen is expressed on lymphoid B cell. Binding of rituximab to cell expressing CD20 re- sults in cell death via a combination of antibody-dependent cell cytotoxicity, comple- ment activation, and apoptosis [2–4]. In particular, good results have been reported in the management of both idiopathic and secondary warm antibody-dependent AIHA [4–6]. Five patients (2 male, 3 female) developed an IgG warm-type AIHA at a mean age of 9 years (range 3–14 years). A direct antiglobulin test (DAT) was positive and laboratory signs of hemolysis (high serum levels of lactate dehydrogenase and indirect bilirubin and reticulocytosis) were found in all cases. As first-line treatment, all patients received steroids at therapeutic dosages (methyl prednisolone 30 mg/kg/3 day). As second-line treatment was IgG 400 mg/kg/5 days intravenously infused and azathioprine 1 mg/kg/day. After 2 years from diagnosis of AIHA, all patients received rituximab. Table 1 shows hemoglobin (Hb) (g/dL) and bilirubin (mg/dL) levels before and after rituximab treat- ment. All patients received 4 cycles first. Infusion side effects of rituximab were ob- served in one case with seizure. All patients showed an increase in Hb levels in response to rituximab. Two patients showed a slow response, with Hb normaliza- tion requiring more than 6 months. ree patients required transfusion before starting drug. ree cases had converted from a positive to a negative DAT 6 months after 4- cycle administration of rituximab. Received 15 January 2010; accepted 21 August 2010. Address correspondence to Shahla Ansari, MD, Department of Hematology and Oncnlogy, Ali Asghar Children’s Hospital, Zafar Street, Post Code 19166, Iran University, Tehran, Iran. E-mail: [email protected] Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Sydney on 09/03/14 For personal use only.
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Transcript of Rituximab for Child with Chronic Relapsing Autoimmune Hemolytic Anemia
Pediatric Hematology and Oncology, 28:164–166, 2011Copyright C© Informa Healthcare USA, Inc.ISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.3109/08880018.2010.518339
LETTER TO THE EDITORNon-Malignant Hematology and Infection
Rituximab for Child with Chronic RelapsingAutoimmune Hemolytic Anemia
Shahla Ansari, MD, Maryam Tashvighi, MD, Bahram D. Arbani, MD,Adel Bagher Salimi, MD, and Mohamadreza Golpaygani
Department of Hematology and Oncnlogy, Ali Asghar Children’s Hospital, Iran University,Tehran, Iran
Autoimmune hemolytic anemia (AIHA) is a process of accelerated red cell destruc-tion arising from the production of autoantibody against red cell antigens. Warm au-toimmune hemolytic anemia is the most common autoimmune hemolytic anemia[1–3]. The hemolysis is predominantly extravascular and is mediated by immunoglob-ulin G (IgG) auto antibodies that are maximally reactive 37◦C [1–3].
The mainstay of therapy is immunosuppressive with corticosteroids, although up to50% require maintenance therapy. Spelenectomy is effective second-line therapy, pro-viding remission in up to 60%; other second-line agents include danazol, cyclosporine,azathioprine, and intravenous immunoglobulin [3].
Rituximab is a humanized monoclonal antibody directed against CD20. The anti-gen is expressed on lymphoid B cell. Binding of rituximab to cell expressing CD20 re-sults in cell death via a combination of antibody-dependent cell cytotoxicity, comple-ment activation, and apoptosis [2–4]. In particular, good results have been reported inthe management of both idiopathic and secondary warm antibody-dependent AIHA[4–6].
Five patients (2 male, 3 female) developed an IgG warm-type AIHA at a mean age of9 years (range 3–14 years). A direct antiglobulin test (DAT) was positive and laboratorysigns of hemolysis (high serum levels of lactate dehydrogenase and indirect bilirubinand reticulocytosis) were found in all cases.
As first-line treatment, all patients received steroids at therapeutic dosages (methylprednisolone 30 mg/kg/3 day). As second-line treatment was IgG 400 mg/kg/5 daysintravenously infused and azathioprine 1 mg/kg/day.
After 2 years from diagnosis of AIHA, all patients received rituximab. Table 1 showshemoglobin (Hb) (g/dL) and bilirubin (mg/dL) levels before and after rituximab treat-ment. All patients received 4 cycles first. Infusion side effects of rituximab were ob-served in one case with seizure. All patients showed an increase in Hb levels inresponse to rituximab. Two patients showed a slow response, with Hb normaliza-tion requiring more than 6 months. Three patients required transfusion before startingdrug. Three cases had converted from a positive to a negative DAT 6 months after 4-cycle administration of rituximab.
Received 15 January 2010; accepted 21 August 2010.Address correspondence to Shahla Ansari, MD, Department of Hematology and Oncnlogy, AliAsghar Children’s Hospital, Zafar Street, Post Code 19166, Iran University, Tehran, Iran. E-mail:[email protected]
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S. Ansari et al.
All of the patients were in complete remission after 8 months, 1 patient after 13months was in complete remission. Finally at a mean follow-up of 432.4 days (range240–892 days) at the present time, all of the patients were alive and transfusion free,although 2 patients remained in positive DAT (+1). However, clinical and laboratorysigns of hemolysis are absent.
The mechanism of effective treatment with rituximab in AIHA is still not completelydefined. The simplest explanation is that the source of pathogenesis antibodies is re-moved [7–9].
Zecca et al. reported 15 patients with median age ranging from 3 months to 14 yearstreated with rituximab for 2 to 4 weeks after steroid and immunoglobulin failure. Thir-teen patients responded to therapy, 3 patients relapsed and second remission was ob-tained again with rituximab [7]. Arena et al. described 11 cases receiving rituximab forsteroid-refractory AIHA of the warm type. All patients showed an increase in responseto rituximab; at the last follow-up, 73% were considered complete remission and 27%partial responders [4].
In our study, the efficacy and safety of rituximab was prospectively elevated in 5 ofchildren with AIHA, all patients were steroid refractory, some of them were also givenimmunosuppressive agents and intravenous immunoglobulin. All patients receivedat least 4 infusions of rituximab. However, treatment was successfully performed, ob-taining a long-lasting remission. An overall response of 100% was achieved. In our se-ries of patients we did not observe an increased risk of infectious complication. Onlyone child had meningitis infection 2 weeks after rituximab infusion. This infection wassuccessfully cured with antibiotic treatment.
In conclusion, data from this study show that anti-CD20 rituximab is an effectiveand safe alternative treatment option for idiopathic AIHA, particularly for steroid-refractory disease. The therapy is safe, without complication, and response is sus-tained, avoiding the long-term side effects of steroids and or other immunosuppres-sive agents.
Declaration of InterestThe authors report no conflicts of interest. The authors alone are responsible for thecontent and writing of the paper.
REFERENCES
[1] Autoimmune hemolytic anemia. In: Orkin SH, Nathan DG, Ginsburg D, Look AT, eds. Hematology ofInfancy and Childhood. 7th ed. Philadelphia: WB Sanders; 2009:618–632.
[2] Dacie J. The immune hemolytic anemia’s: a century of exciting progress in understanding. Br Hematol.2001;114:770–785.
[3] Ramanathan S, Koutts J, Hertzberg MS. Two cases of refractory warm autoimmune hemolytic anemiatreated with rituximab. Am J Hematol. 2005;78:123–126.
[4] Arena GD, Califano C, Annunziata M, et al. Rituximab for warm-type idiopathic autoimmunehemolytic anemia: a retrospective study of 11 adult patients compilation. European Journal of Hema-tology 2007;79:53–58.
[5] Zecca M, De Stefano P, Nobili B, Locatelli F. Anti-CD20 monoclonal antibody for the treatment ofsevere immune-mediated pure red cell aplasia and hemolytic anemia. Blood. 2001;97:3995–3997.
[6] Shanafelt TD, Madueme HL, Wolf RC, Tefferi A. Rituximab for immune cytopenia in adults: idiopathicthrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc.2003;78:1340–1346.
[7] Zecca M, Nobili B, Ramenghi U, et al. Rituximab for the treatment of refractory autoimmune hemolyticanemia in children. Blood. 2003;101:3857–3861.
[8] Ouartier P, Brethon B, Philippet P, et al. Treatment of childhood autoimmune hemolytic anemia withrituximab. Lancet. 2001;358:1511–1513.
[9] Stasi R, Pagano A, Stipa E, Amatori S. Rituximab chimeric anti CD20 monoclonal antibody treatmentfor adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98:952–957.
Pediatric Hematology and Oncology
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