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MMM is classified under the group of the chronic myeloproliferative disorders along with PV & ET.
In MMM, the fibroblasts are polyclonal but the residing hematopietic cells are monoclonal.
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DIAGNOSIS
Peripheral Blood: myelophthisis including the presence of teardrops, nucleated erythrocytes, & granulocyte precursors.
Bone Marrow:
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CLINICAL FINDINGS
Anemia
Marked Splenomegaly secondary to extramedullary hematopoeisis.
Hepatomegaly
Lymphadenopathy
Ascites
Pleural Effusion
Portal Hypertension secondary to the splenomegaly or intra-hepatic obstruction
Osteosclerosis
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PROGNOSIS
Median survival times vary between 3-5 years
Prognsotic Factors:
Br J Haematol 2001 Nov;115(2):313-5
We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 & 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(3)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(3)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.
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TREATMENT
1. Allogeneic stem cell transplantation has a curative potential.
2. Combination of androgen + Corticosteroid improves anemia in 25% of patients
3. Danazol
4. EPO not usually successful
5. Hydroxyurea (500 BID) may result in reduction in spleen size & control leukocytosis & thrombocytosis. But will not reverse problems that are already present such as portal hypertension, etc
6. Splenectomy-- has a high post surgical complications
7. Surgical procedure to drill out bone marrow & then infuse atem cells? Some new data coming up....
8. Role for thalidomide:
British Journal of Haematology 115(2 ):313, 2001
Thalidomide (Thal) retains antiangiogenic, immunomodulatory & cytokine regulatory properties & recently it has been used successfully in multiple myeloma. Here, we report our experience in 10 MMM patients treated with Thal. Pts with agnogenic MMM treated in an early phase of the disease obtained significant benefits from the therapy & remain transfusion-free. In contrast, all secondary MMM failed to respond. These preliminary findings confirm that Thal plays a role in MMM therapy, although the efficacy in the different phases of the disease must be further evaluated.
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SLE & MYELOFIBROSIS (secondry meylofibrosis)
There are reports of an association between the two entities.
Leuk Lymphoma 2000 Nov;39(5-6):661-5 (Kiss E, et al):
In this study we present a case of coexisting SLE & myelofibrosis. Literature review supports the fact that the two diseases rarely occur together in the same patient. The young female patient studied was admitted with pancytopenia and a clinical picture which met the criteria of SLE. Histological examination of the bone marrow biopsy revealed severe myelofibrosis with hypocellularity of the myeloid cell lines. Treatment with immunosuppressive & colony stimulating factor led to slow but complete regeneration of the bone marrow and subsequently to an improved haematological status, and the patient was spared bone marrow transplantation.
Eur J Intern Med 2000 Apr;11(2):98-100 (Durupt S, et al)
A 29-year-old woman with SLE & pancytopenia is
reported. The hematological abnormalities were found to be due to marrow fibrosis. Pancytopenia was reversed by treatment with corticosteroids.
Nippon Ronen Igakkai Zasshi 1999 Dec;36(12):881-6:
A 67-year-old woman was admitted to our hospital with a fever. She had been experiencing arthralgia for about one month. On admission, she had a fever of 38.5 degrees C, was anemic and was experiencing tenderness in the joints of both hands, elbows and feet. Laboratory data revealed proteinuria, urinary cylinders, pancytopenia (WBC 900/mm3, Hb 9.5 g/dl, Plt 7.8 x 10(4)/mm3), liver dysfunction (GOT 414 IU/l, GPT 140 IU/l), & hyper-gamma globulinemia. Antibiotics & GSCF were administered intravenously. Bone marrow aspiration was unsuccessful, but a bone marrow biopsy revealed bone marrow fibrosis. Immunological examinations were positive for antinuclear antibodies, anti-DNA antibodies, anti-double stranded anti- DNA antibodies, as well as a decreased level of serum complement & an increased level of serum immune complexes. Tests for viral antigens & antibodies known to cause hepatitis were negative. Based on these findings, a diagnosis of SLE accompanied by liver dysfunction & bone marrow fibrosis was made. Steroid pulse therapy was initiated, but her liver function deteriorated on the first day of steroid therapy, and she died three days later. SLE accompanied by myelofibrosis is extremely rare, & only 17 and cases have been reported to date. Among these reports, the present case is the second oldest subject & the first SLE patient to suffer from both myelofibrosis and severe liver dysfunction. |
