Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation.
A group of 256 newly diagnosed myeloma patients were enrolled in a phase III study that included 4 monthly cycles of induction chemotherapy and tandem transplant. All patients were randomized to either receive or not receive thalidomide. A total of 221 patients (86%) received no prophylactic anticoagulation (cohort I); 35 patients received low dose coumadin (cohort II). The incidence of deep vein thrombosis (DVT) was significantly higher in the thalidomide arm hazard ratio: 4.5; P < 0.0001). As low dose coumadin (1 mg/d) failed to decrease thrombotic complications in 35 patients (cohort II), low molecular weight heparin (LMWH, enoxaparin 40 mg s.c. q.d.) was instituted as DVT prophylaxis in the thalidomide-treated patients (n = 68) of the subsequent cohort (n = 130, cohort III). This intervention eliminated the difference in DVT incidence between the two arms (thalidomide and no thalidomide). Within cohorts I and II, 36 patients, in whom thalidomide was discontinued after experiencing a thrombotic episode during chemotherapy, subsequently resumed the drug on full anticoagulation; with a median follow-up of 22 months, DVT recurred in four patients (11%). After completing induction and tandem transplantation, 55 patients were re-exposed to thalidomide and chemotherapy during consolidation treatment. Thrombotic complications were observed in 4%. Our experience, although not based on a randomized study, suggests that the excess frequency of thrombosis in patients treated with chemotherapy and thalidomide can be safely reduced by the prophylactic use of LMWH. The rate of DVT recurrence observed in our study upon thalidomide resumption was sufficiently low to allow its continuation in patients who may benefit from this therapeutic intervention.
The Myeloma Institute for Research and Therapy, The University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA. zangarimauricio@uams.edu
Maurizio
M
Zangari
Bart
B
Barlogie
Elias
E
Anaissie
Fariba
F
Saghafifar
Paul
P
Eddlemon
Joth
J
Jacobson
Choon-Kee
CK
Lee
Raymond
R
Thertulien
Giampaolo
G
Talamo
Teri
T
Thomas
Frits
F
Van Rhee
Athanasios
A
Fassas
Louis
L
Fink
Guido
G
Tricot
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D013792:Thalidomide / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced*
D020533:Angiogenesis Inhibitors; D000925:Anticoagulants; D017984:Enoxaparin; D013792:Thalidomide