Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: Implications for therapy

Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Blood (Impact Factor: 10.45). 09/2002; 100(4):1168-71. DOI: 10.1182/blood-2002-01-0335
Source: PubMed


Ten percent of newly diagnosed myeloma patients treated with any type of chemotherapy develop deep venous thrombosis (DVT). Thalidomide has proven activity in refractory multiple myeloma (MM), and although single-agent thalidomide has minimal prothrombogenic activity, its combination with cytotoxic chemotherapy is associated with a significantly increased risk of DVT. We analyzed the incidence of DVT in 232 MM patients who received a combination of chemotherapy and thalidomide on 2 protocols that differed only by the inclusion of doxorubicin in one. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide) was offered to patients with preceding standard dose therapy, but no prior autotransplantation, while DCEP-T (dexamethasone/cyclophosphamide/etoposide/cisplatin/thalidomide) was administered for relapse after transplantation. If there were signs or symptoms suggestive of DVT, patients received additional investigations, including Doppler ultrasonography, followed by venography if indicated. Only patients on DT-PACE but not DCEP-T experienced an increased incidence of DVT. A statistical association between the incidence of DVT and combination chemotherapy including doxorubicin (P =.02) was observed; this association was confirmed on multivariate analysis. MM patients treated with thalidomide and doxorubicin have a high risk of developing DVT.

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    • "[12] However, it was seen that incidence of VTE in MM doesn't increase solely with Thalidomide. [13] When Thalidomide is combined with chemotherapeutic agents such as Doxorubicin or melphalan with prednisone, there was a sharp increase in the incidence of VTE [14] [15]. MM usually presents with end organ damage like bone symptoms such as pain, pathologic fracture, renal dysfunction, chronic fatigue from anemia or symptoms of hypercalcemia. "
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    ABSTRACT: Multiple Myeloma usually presents with end organ damage like bone symptoms such as pain, pathologic fracture, renal dysfunction, chronic fatigue from anemia or symptoms of hypercalcemia. Although frequently associated with venous thromboembolisms, the presentation of multiple myeloma with pulmonary embolism as its initial manifestation is extremely rare. We report the case of a 60 y/o Hispanic male who presented with a Pulmonary Embolism, further diagnostic test revealed an underlying diagnosis of Multiple Myeloma.
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    • "The incidence of DVT (21%) was high among patients in the current study. The risk of DVT is known to be high with cancer (Naess et al., 2007), with central venous catheters (Monreal et al., 2006), and with chemotherapy and thalidomide (Zangari et al., 2003), particularly with doxorubicin and thalidomide (Zangari et al., 2002). Additional studies are being conducted using medical record reviews to compare the incidence of DVT among patients in the current study with patients who were treated with the same high-dose chemotherapy and autologous PBSCT protocol but did not receive ESA therapy according to the current study's algorithm. "
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    ABSTRACT: To determine the effect of aerobic and strength resistance training and epoetin alfa (EPO) therapy on transfusions, stem cell collections, transplantation recovery, and multiple myeloma treatment response. Randomized clinical trial. A myeloma research and therapy center in the south central United States. 135 patients with multiple myeloma, 120 evaluable. Random assignment to exercise or usual care groups. All patients received EPO based on an algorithm. Aerobic capacity, using the six-minute walk test, was assessed prior to induction chemotherapy, prior to stem cell mobilization, and following stem cell collection for all patients and before and after transplantation for patients continuing in the study. Data analysis included analysis of variance to compare other outcome variables by groups. Number of red blood cell and platelet transfusions during transplantation, number of attempts at and total number of days of stem cell collection, time to recovery after transplantation, and response to intensive therapy for multiple myeloma. Recovery and treatment response were not significantly different between groups after transplantation. The exercise group had significantly fewer red blood cell transfusions and fewer attempts at stem cell collection. Serious adverse events were similar in each group. Exercise with prophylactic EPO therapy reduces the number of RBC transfusions and attempts at stem cell collection for patients receiving intensive treatment for multiple myeloma. Exercise is safe and has many physiologic benefits for patients receiving multiple myeloma treatment.
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    • "This was first recognized in our initial phase II study involving 15 patients receiving concurrent thalidomide, Adriamycin, and dexamethasone, in which a 27% incidence of DVT was noted (Osman et al, 2001). This complication was confirmed in association with other regimens (Zangari et al, 2002). None of the patients in these reports received prophylactic anticoagulation. "
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