Long-term remission of paroxysmal nocturnal hemoglobinuria following chemoimmunotherapy for non-Hodgkin lymphoma.

s). 2008;112:Abstract 1181. 3. Nafa K, Bessler M, Deeg HJ, Luzzatto L. New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria. Blood. 1998;92:3422-3427. 4. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243. 5. Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111:1840-1847. 6. Berzuini A, Montanelli F, Prati D. Hemolytic anemia after eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2010;363:993-994. 7. Zhao M, Shao Z, Li K, et al. Clinical analysis of 78 cases of paroxysmal nocturnal hemoglobinuria diagnosed in the past ten years. Chin Med J (Engl). 2002;115:398-401. 8. Cao YR, Shao ZH, Jia HR, et al. Preliminary study of DA or HA regimen chemotherapy for the treatment of refractory and relapsed paroxysmal nocturnal hemoglobinuria. Zhonghua Xue Ye Xue Za Zhi. 2004;25:202-204. 9. Zaja F, Iacona I, Masolini P, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica. 2002;87:189-195. 10. Delgado J, Buston JG, Jimenez-Yuste V, Hernandez-Navarro F. Anti-CD20 monoclonal therapy in refractory immune thrombocytopenic purpura. Haematologica. 2002;87:215-216. Review Chemoimmunotherapy’s Potential to Impact Paroxysmal Nocturnal Hemoglobinuria David A. Rizzieri, MD,1 and Katherine Walsh, MD2 1Duke University Medical Center, Durham, North Carolina; 2Department of Internal Medicine at The Ohio State University, Columbus, Ohio The case presented by Lai and colleagues1 describes a patient with paroxysmal nocturnal hemoglobinuria (PNH) that resolved following chemoimmunotherapy (rituximab [Rituxan, Genentech], cyclophosphamide, vincristine, doxorubicin, and prednisone [R-CHOP]) administered for treatment of diffuse large B-cell lymphoma (DLBCL). In addition to achieving a complete remission of her stage IV DLBCL, the patient had a resolution of her anemia. This case report proposes further consideration of chemoimmunotherapy for PNH, prompting this commentary and review. Pathophysiology PNH is an acquired disease derived from a defect in glycosylphosphatidylinositol (GPI)-linked proteins affecting the stem cells. The red cells that evade apoptosis in PNH are deficient in GPI due to an underlying genetic defect in the PIG-A gene. The normal function of the PIG-A gene product is an enzyme active in the formation of GPI. The genetic defect can arise via a number of somatic mutations including missense and nonsense mutations. Two GPI-linked proteins are CD55 (also referred to as decay accelerating factor) and CD59 (also referred to as membrane inhibitor of reactive lysis). Both of these molecules control the status of the complement cascade.2 Historically, PNH was diagnosed by the Hams test or the sugar water test, though today the diagnosis is made almost exclusively using flow cytometry techniques where CD55 and CD59 expression levels can be quantified.