Pulse Cyclophosphamide Therapy in Refractory Warm Autoimmune Hemolytic Anemia: A New Perspective
Tóm tắt
Treatment of steroid refractory autoimmune hemolytic anemia (AIHA) is challenging especially with no evidence based consensus guide lines and limited resources. The aim of this study was to evaluate the efficacy of pulse cyclophosphamide therapy in patients with severe refractory warm AIHA. The prospective study was designed to evaluate the efficacy of pulse cyclophosphamide—1 g/month for four consecutive months—in 17 patients (10 males and 7 females) with severe refractory warm AIHA [13 primary AIHA and 4 (females) secondary to SLE], all studied patients failed to respond to high dose of steroid therapy ± azathioprine ± intravenous immunoglobulin ± oral cyclophosphamide. Mean hemoglobin level, reticulocytic count and direct antiglobulin test were assessed before and after cyclophosphamide treatment every month. After the 4th cycle of cyclophosphamide (82 %, 14 patients) achieved partial response while the remaining (17 %, 3 patients) showed no response, while after 6 months follow up 47 % (8 patients) show complete response, while 53 % (9 patients) showed partial response. The mean hemoglobin levels were significantly increased after the 1st, 2nd, 3rd and 4th months of pulse cyclophosphamide therapy when compared to before treatment (P < 0.01, P < 0.001, P < 0.001 and P < 0.001) respectively, and the mean reticulocyte (%) were significantly decreased after the 2nd, 3rd and 4th months (P < 0.05, P < 0.01 and P < 0.001) respectively. We conclude that pulse cyclophosphamide therapy is well tolerated and induces good response in patients with severe refractory warm AIHA.
Tài liệu tham khảo
Klein NP, Ray P, Carpenter D et al (2010) Rates of autoimmune diseases in Kaiser Permanente for use in vaccine adverse event safety studies. Vaccine 28(4):1062–1068
Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB (2007) Epidemiology of autoimmune diseases in Denmark. J Autoimmun 29(1):1–9
Valent P, Lechner K (2008) Diagnosis and treatment of autoimmune haemolyticanaemias in adults: a clinical review. Wien KlinWochenschr 120(5–6):136–151
Lechner K, Jäger U (2010) How I treat autoimmune hemolytic anemias in adults. Blood 116:1831–1838
Petz LD, Garratty G (1980) Management of autoimmune hemolytic anemias. In: Petz LD, Garratty G (eds) Acquired immune hemolytic anemias. Churchill Livingstone, New York, pp 392–440
Ahn YS, Harrington WJ, Mylvaganam R, Ayub J, Pall LM (1985) Danazol therapy for autoimmune hemolytic anemia. Ann Intern Med 102:298–301
Cooper N, Stasi R, Cunningham-Rundles S et al (2004) The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol 125(2):232–239
Moyo VM, Smith D, Brodsky I, Crilley P, Jones RJ, Brodsky RA (2002) High-dose cyclophosphamide for refractory autoimmune hemolytic anemia. Blood 100(2):704–706
McCune WJ, Bolbus J, Zeldes W, Dunne R, Bohlke P, Fox DA (1988) Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N Engl J Med 318:1423
Verlin M, Laros RK, Penner JA (1996) Treatment of refractory thrombocytopenic purpura with cyclophosphamide. Am J Hematol 1:97
Thomas ED, Storb R, Fefer A et al (1972) Aplastic anaemia treated by marrow transplantation. Lancet 1:284–289
Jones RJ, Barber JP, Vala MS et al (1995) Assessment of aldehyde dehydrogenase in viable cells. Blood 85:2742–2746
Jaime-Perez JC, Gonzalez-Llano O, Gomez-Almaguer D (2001) High-dose cyclophosphamide in the treatment of severe aplastic anemia in children. Am J Hematol 66:71
Hayag MV, Cohen JA, Kerdel FA (2000) Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris. J Am Acad Dermatol 43:1065–1069
Brodsky RA, Fuller AK, Ratner LE, Jones RJ, Leffell MS (2001) Elimination of alloantibodies by immunoablative high-dose cyclophosphamide. Transplantation 71:482–484
Rosse W, Bussel J, Ortel T (1997) Challenges in managing autoimmune disease. American Society of Hematology Education Book 92–101
Flores G, Cunningham-Rundles C, Newland AC, Bussel JB (1993) Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia: results in 73 patients. Am J Hematol 44:237–242
Schwartz RS, Berkman EM, LE Silberstein (2000) Autoimmune hemolyticanemias. In: Hoffman RH, Benz EJ Jr, Shattil SJ (eds) Hematology: basic principles and practice, 3rd edn. Churchill Livingstone, Philadelphia, pp 611–630
Petz LD (2008) Cold antibody autoimmune hemolytic anemias. Blood Rev 22(1):1–15
Packman CH (2008) Hemolytic anemia due to warm autoantibodies. Blood Rev 22(1):17–31
Akpek G, McAneny D, Weintraub L (1999) Comparative response to splenectomy in Coombs-positive autoimmune hemolytic anemia with or without associated disease. Am J Hematol 61:98–102
Zupańska B, Sylwestrowicz T, Pawelski S (1981) The results of prolonged treatment of autoimmune haemolytic anaemia. Haematologia (Budap) 14(4):425–433
Sakalová A, Hrubisko M (1975) Cyclophosphamide in the treatment of immune hemocytopenias. FoliaHaematolInt Mag KlinMorpholBlutforsch 102(5):559–564