TY - JOUR
T1 - Thalidomide in myelofibrosis with myeloid metaplasia
T2 - A pooled-analysis of individual patient data from five studies
AU - Giovanni, Barosi
AU - Michelle, Elliott
AU - Letizia, Canepa
AU - Filippo, Ballerini
AU - Paolo, Piccaluga Pier
AU - Giuseppe, Visani
AU - Monia, Marchetti
AU - Gabriele, Pozzato
AU - Fancesca, Zorat
AU - Ayalew, Tefferi
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Trials to determine the effect of thalidomide in patients with Myelofibrosis with Myeloid Metaplasia (MMM) have produced inconclusive results due to different criteria for response and heterogeneous study participants. We undertook a pooled-analysis to assess the effects of such treatment on a larger series of cases and with a uniform assessment of response. We used updated data on 62 individual patients from 5 phase II trials that evaluated thalidomide therapy in MMM patients. Response was judged on individual disease parameters, on the improvement of the Dupriez risk categories and on the improvement of a 6 point "severity score" based on myeloproliferative and myelodepletive indexes of the disease. Overall, using standard dose of thalidomide, i.e. starting with no less than 100 mg/day, 49 patients (79%) had more than 4 weeks of therapy. Twenty-nine percent of patients with moderate to severe anemia showed an increase in hemoglobin or reduction/abolishment of blood transfusion requirements, 38% with moderate to severe thrombocytopenia had an increase in platelet counts, and 41% with high grade splenomegaly demonstrated a measurable reduction in splenic size. These effects led to an absolute decrease in the "severity" score in 44.9% of the patients. Major disease severity and high degrees of splenomegaly before therapy predicted response with a probability of 61.9%. However, worsening of the "severity" score was observed in 20.4% of the patients, 18% having a "myeloproliferative reaction" with leukocytosis and/or thrombocytosis. Sixty-six percent of the patients discontinued the drug before 6 months of treatment due to intolerance. In conclusion, there is a small but clear improvement of disease severity with thalidomide therapy in MMM. The potential for myeloproliferative reactions and the unfavorable dose-related toxicity profile argue for future studies using lower doses of this drug.
AB - Trials to determine the effect of thalidomide in patients with Myelofibrosis with Myeloid Metaplasia (MMM) have produced inconclusive results due to different criteria for response and heterogeneous study participants. We undertook a pooled-analysis to assess the effects of such treatment on a larger series of cases and with a uniform assessment of response. We used updated data on 62 individual patients from 5 phase II trials that evaluated thalidomide therapy in MMM patients. Response was judged on individual disease parameters, on the improvement of the Dupriez risk categories and on the improvement of a 6 point "severity score" based on myeloproliferative and myelodepletive indexes of the disease. Overall, using standard dose of thalidomide, i.e. starting with no less than 100 mg/day, 49 patients (79%) had more than 4 weeks of therapy. Twenty-nine percent of patients with moderate to severe anemia showed an increase in hemoglobin or reduction/abolishment of blood transfusion requirements, 38% with moderate to severe thrombocytopenia had an increase in platelet counts, and 41% with high grade splenomegaly demonstrated a measurable reduction in splenic size. These effects led to an absolute decrease in the "severity" score in 44.9% of the patients. Major disease severity and high degrees of splenomegaly before therapy predicted response with a probability of 61.9%. However, worsening of the "severity" score was observed in 20.4% of the patients, 18% having a "myeloproliferative reaction" with leukocytosis and/or thrombocytosis. Sixty-six percent of the patients discontinued the drug before 6 months of treatment due to intolerance. In conclusion, there is a small but clear improvement of disease severity with thalidomide therapy in MMM. The potential for myeloproliferative reactions and the unfavorable dose-related toxicity profile argue for future studies using lower doses of this drug.
KW - Myelofibrosis with myeloid metaplasia
KW - Myeloproliferative reaction
KW - Pooled-analysis
KW - Splenomegaly
KW - Thalidomide
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U2 - 10.1080/1042819021000040008
DO - 10.1080/1042819021000040008
M3 - Article
C2 - 12613516
AN - SCOPUS:0036890863
SN - 1042-8194
VL - 43
SP - 2301
EP - 2307
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 12
ER -