Clinical and molecular aspects of 23 patients affected by paroxysmal nocturnal hemoglobinuria.
We reviewed clinical and molecular data of 23 consecutive unrelated patients affected by paroxysmal nocturnal hemoglobinuria (PNH) (19 with hemolytic PNH, 3 with aplastic anemia/PNH, and 1 with myelodysplasia/PNH syndrome) with a mean follow-up of 11.8 years. Five patients had thrombotic episodes, and 10 needed regular blood transfusions; 2 died for cerebral hemorrhage and kidney failure, and 2 spontaneously recovered from PNH. Twenty different PIG-A gene mutations were detected in 21/23 patients: 15 frameshift, 1 splicing, 2 nonsense, and 2 missense mutations. Two mutations (DelG341 and IVS2 +1g-a) were detected twice. A PIG-A mutated clone was also revealed in the two patients in complete clinical remission. One patient with aplastic anemia/PNH syndrome was treated with two courses of antilymphocyte globulin and cyclosporin with partial sustained response. Six patients were given rHu-EPO 150 U/kg/day s.c. for at least 6 months: one became transfusion-independent for 8 months and then discontinued treatment for clinical complications; one displayed a mean rise of Hb of 1.5 g/dL and is currently maintaining Hb levels higher than 9 g/dL after 54 months of therapy. Mutation specific quantitative-competitive PCR showed that the rise of hemoglobin was related to an increase of PIG-A negative molecules, suggesting that the efficacy of rHu-EPO therapy may be due to the stimulation of the abnormal clone.
Department of Hematology, IRCCS Ospedale Maggiore of Milan, Milan, Italy.
Carla
C
Boschetti
Elisa
E
Fermo
Paola
P
Bianchi
Cristina
C
Vercellati
Fiorenza
F
Barraco
Alberto
A
Zanella
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D016903:Drug Monitoring; D004921:Erythropoietin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D013927:Thrombosis / Q000209:etiology / Q000628:therapy; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D006454:Hemoglobins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C080086:phosphatidylinositol glycan-class A protein; D004921:Erythropoietin; D016572:Cyclosporine