A disease that is often very difficult to separate from CML is agnogenic (idiopathic) myeloid metaplasia (AMM). It is most common in persons aged 50-60 years. The syndrome results from bone marrow failure and subsequent extramedullary hematopoiesis on a large scale in the spleen and sometimes in the liver and lymph nodes. Actually, the extramedullary hematopoiesis is compensatory and therefore is not idiopathic (agnogenic), but the bone marrow failure is agnogenic. The bone marrow typically shows extensive replacement by fibrous tissue (myelofibrosis), but in an early stage AMM may show a normally cellular or even hypercellular marrow and such minimal fibrosis that reticulum stains are required to demonstrate abnormality. The average life span after diagnosis is 5-7 years. One percent to 5% of patients eventually develop acute leukemia.

Although marrow fibrosis is typically associated with AMM, varying degrees of fibrosis have been reported in 15%-30% of patients with polycythemia vera and in some patients with CML, hairy cell leukemia, acute leukemia, metastatic carcinoma to bone marrow, and multiple myeloma.

In AMM there is a normochromic anemia of mild to moderate degree and usually a moderate degree of reticulocytosis. The peripheral blood smear typically contains a moderate number of polychromatophilic RBCs and varying numbers of later-stage nucleated RBCs as well as moderate RBC anisocytosis and poikilocytosis. Teardrop RBCs are characteristic of AMM and are usually (although not always) present in varying numbers. The WBC counts in AMM are most often in the 12,000-50,000/mm3 (12-50 Ч 109/L) range (approximately 40% of cases), but a substantial proportion of patients have counts within reference limits (20%-35% of cases), and a significant number have leukopenia (10%-30% of cases). About 7% have WBC counts over 50,000/mm3 (literature range, 0%-18%). Peripheral blood differential counts usually show mild or moderate myeloid immaturity centering on metamyelocytes and band forms with some myelocytes present, similar to the picture of CML. The number of basophils is increased in approximately 35% of cases. The number of platelets is normal in 40%-50% of cases, increased in approximately 40% (literature range, 8%-48%), and decreased in 20%-25% (literature range, 10%-40%). Giant platelets are often found. Splenomegaly is present in more than 95% of cases (literature range, 92%-100%), and hepatomegaly is also common (approximately 75% of cases; literature range, 55%-86%). Splenomegaly is present even when the WBC count is relatively low. Lymphadenopathy is not common (approximately 10% of cases; literature range, 0%-29%).

One uncommon variant of AMM has been reported under the name of “acute myelofibrosis.” The typical picture is pancytopenia, normal peripheral blood RBC morphology, lack of splenomegaly, and typical myelofibrosis on bone marrow examination. Most of the patients were over age 50, and most died in less than 1 year. All of the patients had blast cells in the peripheral blood, in most cases less than 15% but occasionally in greater numbers. Cases of acute myelofibrosis are difficult to separate from atypical cases of AMM (which occasionally terminates in a blast crisis, like CML), atypical cases of AML (in which a fibrotic bone marrow occasionally develops), and some patients with CML who develop some degree of marrow fibrosis and then progress to a blast crisis.