Splenectomy for patients with myelofibrosis with myeloid metaplasia: pretreatment variables and outcome prediction.

Since according to the early studies, the outcome after splenectomy in the individual patient with myelofibrosis with myeloid metaplasia (MMM) is unpredictable, we assessed retrospectively the pre-intervention characteristics that best predicted adverse events, hematological consequences, and survival in 71 splenectomized MMM patients. The findings indicate that the operative risk of splenectomy for both mortality (8.4%) and morbidity (39.3%) was unpredictable. New hemorrhagic or thrombotic complications occurred in 16.9% of surviving patients and were predicted by age < 50 years, a normal to high platelet count (> 200 x 10(9)/l) and huge splenomegaly (> 16 cm from the costal margin). Massive liver enlargement occurred in 24% of patients and has to be expected in patients splenectomized for transfusion-dependent anemia. Anemia improved substantially in 45% and 52% of patients at 3 months and at 1 year, respectively, and was predicted by severe anemia, low platelet count (< 100 x 10(9)/l) or normal to high white blood cell (WBC) count (> 4 x 10(9)/l). Survival from splenectomy was superior in patients < 45 years with WBC < 10 x 10(9)/l count. An unexpectedly high rate of blastic transformation was observed. It accounted for 42.8% of the deaths. The results suggest trials for prophylactic cytoreductive treatment in young patients and when platelet count is normal to increased. Further study is needed for elucidating the possible role played by splenectomy in inducing blastic transformation.

An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression.

Among 761 consecutive patients with chronic myeloproliferative disorders (CMD), it was found that 18 (nine men and nine women) did not fulfill at presentation the established diagnostic criteria for the typical forms. In seven patients, the diagnosis of CMD was made on the basis of an intense and persistent thrombocytosis that complicated splenectomy. The other 11 patients had various combinations of the following signs suggesting CMD: splenomegaly, bone marrow myeloid hyperplasia and/or slight myelofibrosis, mild thrombocytosis and/or leukocytosis, and rare immature myeloid cells in the peripheral blood. All patients were younger than 46 years of age (median age, 31.5 years; range, 20 to 45 years). A major thrombotic event was the most frequent presenting feature (eight of 18 cases), and thrombotic complications supervened in seven of the eight splenectomized patients (six in the portal system), raising the overall rate of patients with thrombotic events in their history to 11 of 18. At a median follow-up of 50 months (range, 24 to 241 months), three patients had died of thrombotic complications (two after splenectomy). The 15 surviving patients had stable disease, and 12 of them were not receiving cytoreductive therapy. Spontaneous growth of circulating burst-forming units erythroid was demonstrated in one patient, and erythroid responsiveness to erythropoietin appeared higher than in the normal controls in four. Spontaneous in vitro platelet aggregation in whole blood and/or platelet-rich plasma was seen in five of seven patients. It was concluded that a difficult to identify, slowly progressive form of CMD occurs in young people, that it carries a high risk of thrombosis, and that splenectomy is a high risk procedure in these cases.

Induction and maintenance alpha-interferon therapy in myelofibrosis with myeloid metaplasia.

In 12 patients having myelofibrosis with myeloid metaplasia (MMM), recombinant- alpha interferon (r-alpha INF) was given for 16 weeks at an initial dose of 3 x 10(6) U/day as a cytoreductive agent. At the end of the 16th wk, Hb showed minor changes; WBC were reduced from 43 x 10(9)/l, range 6.4-69.4, to 16 x 10(9)/l, range 5-39 (p = 0.05); platelets decreased from 845 x 10(9)/l, range 215-1748, to 370 x 10(9)/l, range 96-730 (p = 0.005). 2 cases responded at the starting dose, while the effective dose was 5 x 10(6) U/d in the others. Minor changes in spleen size were noted, while no significant changes in bone marrow fibrosis occurred. After induction therapy, 3 patients were allocated to maintenance therapy (from 10 up to 34 months). To maintain platelet count lower than 500 x 10(9)/l, the required r-alpha-INF dose was constantly 10 MU/wk, while the same result was not achieved in 1 case with hydroxyurea, 1 g/die. The association with hydroxyurea, 500 mg/die, allowed reduction of the r-alpha INF dose to 6 MU/die in 1 other case.