Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.

In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.

IntroductionOver the last decade, major advances in the treatment of multiple myeloma (MM) have been reported with the use of autologous stem-cell transplantation [1][2][3][4] and, more recently, of novel agents targeting the tumor clone and the bone marrow microenvironment. 5 In this setting, thalidomide represents a new treatment paradigm because of its alternative mechanisms of action that include disruption of myeloma-bone marrow stromal cell interactions, inhibition of cytokine secretion, and immunomodulatory effects. The observation that increased bone marrow angiogenesis correlates with advanced phases of MM, 6 along with the welldocumented in vitro antiangiogenic activity of thalidomide, 7 led to the investigational use of this agent in patients with advanced and refractory MM. 8 Response rates in the 30% range initially reported by Singhal et al 8 were extended and confirmed by other groups (for a review, see Cavenagh and Oakervee 9 and Dimopoulos et al 10 ). Subsequent combination of thalidomide with dexamethasone increased the rate of response up to 50% to 55%, 11,12 suggesting a synergism between these agents and providing the rationale for their use as primary therapy for patients with symptomatic MM. Results of 3 phase-2 studies with thalidomide-dexamethasone (Thal-Dex) in preparation for subsequent autologous transplantation 13-15 and a randomized comparison of Thal-Dex with dexamethasone alone 16 were promising in terms of response rate and collection of adequate quantities of peripheral blood stem cells (PBSCs). Based on these data, Thal-Dex has been proposed, and is currently accepted at many centers, as a front-line treatment option for patients with symptomatic MM, particularly if it is planned to offer subsequent high-dose therapy with autologous transplantation. However, no comparative study of Thal-Dex with vincristinedoxorubicin-dexamethasone (VAD), the reference treatment used so far to reduce tumor cell mass before autologous transplantation, has been reported. To address this issue, we performed a retrospective matched case-control analysis of 200 patients with symptomatic MM who were primarily treated with Thal-Dex (n ϭ 100) or VAD (n ϭ 100) in preparation for autologous stem-cell transplantation as part of 2 consecutive studies conducted from 1996 to 2004. Table 1; the 2 groups were comparable with respect to the major presenting variables known to potentially affect clinical outcome. Both studies were approved by local ethical committees of participating centers. Informed consent was provided according to the Declaration of Helsinki. Patients, materials, and methods Patients and criteria of matching Study design and treatment regimensBy design of both studies, Thal-Dex and VAD were planned to be administered for 4 months in an attempt to reduce tumor cell mass before collection of PBSCs and subsequent autologous transplantation. Details on treatment regimens were given elsewhere. 4,15 Briefly, thalidomide was given orally at the starting dose of 100 mg/d for 14 days and then increa...

Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-␣ (IFN-␣), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-␣ alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-␣ treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients. (Blood. 2001;98:3074-3081)