Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy

Abstract

consequently in many plasma pools. 2 More refined products (eg, albumin) were, however, consistently TTV-negative. 2,3 These findings confirm longstanding experience, derived from numerous viral validation studies, of the Cohn HSA manufacturing process as one with a high capacity for removing viruses. The explanation for the recent unexpected findings 1 thus remains enigmatic. Using the same 2 TTV primer sets and a third independent in-house primer system, we confirmed earlier reports 2,3 from research groups at regulatory bodies who unanimously found HSA to be TTVnegative. Response:First-generation recombinant factor VIII concentrates are free from viral contaminations?Kreil et al (from Baxter BioScience) failed to detect TT virus (TTV) DNA in 11 lots of a Baxter first-generation recombinant factor VIII concentrate (rFVIII) (Recombinate) as well as in 13 lots of human serum albumin (HSA), a difference from our previously reported results. 1 As regards the rFVIII, the results of Kreil et al are not significantly different from ours (3 out of 13 were positive for TTV DNA). However, with regard to the contamination by TTV in HSA lots, the difference between the results obtained by the 2 groups is more evident. Kreil et al cite, as we too have done, the paper of Pisani et al, 2 who failed to detect TTV DNA in HSA, in order to strengthen their own conclusions. As we already stressed, Pisani et al used only the N22 polymerase chain reaction (PCR), which is unable to detect a high number of TTV variants. 3 In this case the difference in the methods used may well justify the different results. In addition, it is well known that, even using the same methods, the results obtained from different laboratories are not fully comparable if international standards are not available and used, as in the case of TTV so far. Furthermore, when the size of the study is so small, a negative result can be affected by a type II statistical error. According to the "rule of 3," the one-sided 95% confidence intervals of the Kreil et al study are 0 and 27.3. 4 Similar viral safety problems emerged concerning the possible contamination of several blood products by parvovirus B19. As regards the possibility of B19 contamination, we failed to detect B19 DNA in either rFVII or HSA, even using very sensitive nested PCR, whereas other groups reported different results. 5,6 It is likely that the residual amount of virus (or better, of viral genome) (TTV or B19 virus or perhaps other viruses) in such products after the manufacturing process is very low, near to the limit of sensitivity of the analytical methods available at present.Such a condition, in addition to the lack of standardization of methods, makes a comparison of results obtained in different laboratories very hazardous.We would like to emphasize again the need for continuous drug-surveillance with prospective protocols of informative hemophiliacs, treated for the first time even with rDNA-derived clotting factor concentrates. In addition, there is also the need to implement the stan...

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma

“…This notion is supported by the combined analysis of published data, including our own study, on thalidomide combinations with or without doxorubicin, as shown in Table V. Irrespective of the particular combination therapy, the risk of venous thromboembolism in multiple myeloma seems to be enhanced during the early course of induction therapy, a phenomenon that may relate to tumour burden and tumour cell reduction (Cavo et al, 2002;Zangari et al, 2002b). In line with this hypothesis, four of the five venous thromboembolic events observed in the present study occurred during the first or second treatment cycle in responding patients.…”

“…In line with this hypothesis, four of the five venous thromboembolic events observed in the present study occurred during the first or second treatment cycle in responding patients. Importantly, the thrombotic risk seems to be linked to the disease and its treatment, rather than to pre-existing thrombophilic risk factors (Cavo et al, 2002;Zangari et al, 2002b). This conclusion would at least appear to be true for HyperCDT therapy as none of four patients with venous thromboembolism who were tested for thrombophilic abnormalities had evidence of natural anticoagulant deficiencies, antiphospholipid antibodies, activated protein C resistance, or factor V Leiden and prothrombin 20210 mutations respectively.…”

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

“…This complication has been described in 3-5% of patients treated with thalidomide alone, 11 but it appears to be significantly more frequent when thalidomide is associated with dexamethasone or chemotherapy (21-28%). [50][51][52][53] Thus, the incidence of DVT registered in our series (7%) is relatively low, and could be considered as another advantage of this oral regimen.…”

Prevention of venous thromboembolism with low molecular-weight heparin in patients with multiple myeloma treated with thalidomide and chemotherapy

“…6,7 Others have tried fixed low-dose warfarin as VTE prophylaxis but reported conflicting results. Zamagni et al used 1.25 mg warfarin daily and demonstrated a decrease in VTE incidence of 26-9% when treating de novo MM patients with dexamethasone and thalidomide.…”

“…2,3 Recently, several reports demonstrated that cytotoxic T lymphocytes (CTLs) specific for survivin-derived determinants are capable of efficiently killing leukemia targets endogenously expressing survivin. [3][4][5][6][7] In the current study, we identified a new HLA-A2-binding epitope, survivin [5][6][7][8][9][10][11][12][13][14] (TLPPAWQPFL). Using the T2 cellbinding assay, we found that survivin [5][6][7][8][9][10][11][12][13][14] showed comparable binding activity as the positive control peptide FluM1 58-66 (GILGFVFTL, data not shown).…”