Thalidomide therapy for myelofibrosis with myeloid metaplasia.
BACKGROUND
Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies.


METHODS
Forty-four patients who had myelofibrosis with myeloid metaplasia received treatment with thalidomide in a Phase II clinical trial at a dose of 200 mg daily with escalation by 200 mg weekly until the best tolerated dose (maximum, 800 mg) was reached.


RESULTS
Seventeen of 41 evaluable patients (41%) who received treatment for at least 15 days had a response. A complete response (without reversal of bone marrow fibrosis) was achieved in 4 patients (10%), a partial response was achieved in 4 patients (10%), and hematologic improvements in anemia, thrombopenia, and/or splenomegaly were observed in 9 patients (21%). Improvements in anemia occurred in 7 of 35 patients (20%) with hemoglobin levels <10.0 g/dL, and improvements in thrombopenia occurred in 5 of 24 patients (21%) with platelet counts <100 x 10(9)/L. Five of 24 patients (21%) became transfusion-independent. Major or minor regression of splenomegaly was noted in 9 of 29 evaluable patients (31%), and complete regression was noted in 5 patients. Responders had a lower baseline median vascular endothelial growth factor levels (77.9 pg/mL vs. 97.7 pg/mL; P <.01) and higher median basis fibroblast growth factor levels (60.8 pg/mL vs. 37.4 pg/mL; P <.01) compared with nonresponders. Nine patients (22%) had deterioration that was attributed to thalidomide (resolved after withdrawal) with either progressive cytopenias or excessive proliferation. Two patients developed Grade 3 neutropenia with recovery and resumed therapy with dose reductions, and both later achieved a complete response. Dose-related toxicities included fatigue (50%), constipation (48%), rash or pruritus (37%), sedation (35%), peripheral edema (29%), tremors (23%), peripheral neuropathy (22%), and orthostasis (16%).


CONCLUSIONS
Thalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs.
Thomas
Deborah A
DA
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. debthomas@mdanderson.org
Giles
Francis J
FJ
Albitar
Maher
M
Cortes
Jorge E
JE
Verstovsek
Srdan
S
Faderl
Stefan
S
O'Brien
Susan M
SM
Garcia-Manero
Guillermo
G
Keating
Michael J
MJ
Pierce
Sherry
S
Zeldis
Jerome
J
Kantarjian
Hagop M
HM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D055728:Primary Myelofibrosis / Q000188:drug therapy*; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide