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580 Part VI: The Erythrocyte Chapter 40: Paroxysmal Nocturnal Hemoglobinuria 581

severity of the disease waxes and wanes as the normal cells and the PNH to which the drug enhances survival cannot be accurately determined
clone alternately appear to gain ascendancy. Rarely, the abnormal clone from these studies as the experimental design did not include a ran-
disappears altogether, and the patient appears to be cured. Transforma- domized control group of patients. Eculizumab does not appear to
tion to acute leukemia is uncommon (in the range of 1 percent). In some affect either the marrow failure component of the disease or the clonal
instances, but not in others, leukemic blasts are GPI-AP–deficient. 46 hematopoiesis that underlies disease pathophysiology. Although PNH
As with so many other diseases, initial reports on PNH tended is a clonal disease, it is not a malignant disease, as previously discussed,
to emphasize the more severely affected patients, so the prognosis was and it is this characteristic of PNH that allows for successful long-term
generally deemed to be very grave. As physicians developed a higher symptomatic management in the absence of a treatment strategy aimed
index of suspicion concerning this disorder, and as simplified meth- at eradicating the PIGA mutant hematopoietic stem cells.
ods for diagnosis became available, milder cases were diagnosed with
a better long-term outlook. Nonetheless, even today, the disease must REFERENCES
be considered a very serious one. The most common lethal event is a
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96.4 percent (range: 41.8 to 100 percent). Twenty-four patients (30 percent) phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor
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transfusion requirement from 19.3 units to 5.0 units. Of 61 patients globinuria caused by a germline mutation and a somatic mutation in PIGT. Blood
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Survival of the 79 patients treated with eculizumab was the same 21. Chen R, Nagarajan S, Prince GM, et al: Impaired growth and elevated fas receptor
as that of a group of age- and sex-matched controls from the general expression in PIGA(+) stem cells in primary paroxysmal nocturnal hemoglobinuria. J
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coccal infection with Neisseria meningitidis serogroup B, and thereafter, 22. Heeney MM, Ormsbee SM, Moody MA, et al: Increased expression of anti-apoptosis
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A multicenter study involving 195 patients followed for 66 months 23. Horikawa K, Nakakuma H, Kawaguchi T, et al: Apoptosis resistance of blood cells from
largely confirmed these findings. 86 patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodys-
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fusion requirements through inhibition of intravascular hemolysis and mal nocturnal hemoglobinuria. Blood 92:2541, 1998.
by virtually eradicating thromboembolic complications. Eculizumab 25. Yamamoto T, Shichishima T, Shikama Y, et al: Granulocytes from patients with parox-
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treatment may also reduce disease related mortality although the extent spontaneous apoptosis. Exp Hematol 30:187, 2002.

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