Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial.
OBJECTIVE
A phase II dose-escalation trial was conducted to ascertain low-dose thalidomide safety and response in patients with advanced myelofibrosis with myeloid metaplasia (MMM).


METHODS
Thalidomide was administered together with current therapy to 63 patients, starting at 50 mg daily and increasing to 400 mg as tolerated.


RESULTS
Half of the patients sustained daily doses more than 100 mg and the drop-out rate was 51% at 6 months: the drop-out rate was lower in patients with high baseline fatigue score. At efficacy analysis, anemia was ameliorated in 22% of the patients and transfusions were eliminated in 39% of transfusion-dependent patients. Platelet count increased by 50 x 10(9)/L or more in 22% of patients with an initial count lower than 100 x 10(9)/L. Splenomegaly decreased by more than 50% of the initial size in 19% of patients. Reduction of an overall disease severity score occurred in 31% of patients and was associated with a significant reduction of fatigue. Disease severity amelioration was independently predicted by a high baseline myeloproliferative index (ie, large splenomegaly, thrombocytosis, or leukocytosis).


CONCLUSIONS
Low-dose thalidomide displays an acceptable toxicity profile and provides an objective and subjective advantage to a relevant portion of MMM patients.
Marchetti
Monia
M
Laboratory of Medical Informatics, Unit of Clinical Immunology and Immunohematology, IRCCS Policlinico San Matteo, viale Golgi 19, 27100 Pavia, Italy.
Barosi
Giovanni
G
Balestri
Francesca
F
Viarengo
Gianluca
G
Gentili
Sara
S
Barulli
Sara
S
Demory
Jean-Loup
JL
Ilariucci
Fiorella
F
Volpe
Antonio
A
Bordessoule
Dominique
D
Grossi
Alberto
A
Le Bousse-Kerdiles
Marie Caroline
MC
Caenazzo
Andrea
A
Pecci
Alessandro
A
Falcone
Antonietta
A
Broccia
Giorgio
G
Bendotti
Cesarina
C
Bauduer
Fredric
F
Buccisano
Francesco
F
Dupriez
Brigitte
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000517:prevention & control; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007970:Leukopenia / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000473:pathology; D012449:Safety; D012720:Severity of Illness Index; D013163:Splenomegaly / Q000517:prevention & control*; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000517:prevention & control*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D013792:Thalidomide