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Unfortunately, no classification system will be entirely inclusive, and the WHO recognizes this with the group of AML, not otherwise categorized. This group corresponds in most cases to the same morphologic entity as is delineated in the FAB schema. Indeed, this is pointed out as a limitation of the system, one which gives the clinician no help in planning therapy for a given case of AML. However, those who developed the WHO classification point out that the system is meant to be of worldwide application, and that there will be places where the diagnostic facilities are not yet sophisticated enough to provide information to make a more specific categorization. This last category of AML does include the entity of acute erythroid leukemia, and recognizes that there are two subtypes. Pure erythroid leukemia has at least 80% immature erythroid precursors with minimal differentiation and no significant myeloblastic component, as distinguished from the second subtype, which has at least 50% immature erythroid precursors and 20% myeloblasts in the nonerythroid population.

Modifications of the WHO classification will continue to be made with advances in our knowledge of the biology and treatment of AML. An International Working Group has recently recommended some definitions of terminology. Thus, de novo AML is defined as "AML in patients with no clinical history of prior MDS, myeloproliferative disorder, or exposure to potentially leukemogenic therapies or agents." Secondary AML is defined as those patients with AML who do have prior MDS or exposure to leukemogenic therapies and should be categorized as "AML secondary to prior existing MDS, myeloproliferative disorder, or the development of AML secondary to proven leukemogenic exposure."86

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14. Miller RW: Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960-1967. J Natl Cancer Inst 46(1):203-209, 1971.

15. Greaves MF, Maia AT, Wiemels, JL, et al.: Leukemia in twins: lessons in natural history. Blood 102(7):2321-2333, 2003.

16. Harnden DG: Inherited factors in leukaemia and lymphoma. Leuk Res 9(6):705-707, 1985.

17. Horwitz M: The genetics of familial leukemia. Leukemia 11(8):1347-1359, 1997.

18. Novik Y, Marino P, Makower DF, et al.: Familial ery-throleukemia: a distinct clinical and genetic type of familial leukemias. Leuk Lymphoma 30(3/4):395-401, 1998.

19. Zipursky A, Poon A, Doyle J: Leukemia in Down syndrome: a review. Pediatr Hematol Oncol 9(2):139-149,

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