The role of second autografts in the management of myeloma at first relapse.

We report an analysis of the value of a second high-dose melphalan autograft, performed at relapse, on a series of newly diagnosed myeloma patients entered into the high-dose program at our center. We conclude that relapse-free survival after the first autograft is a major prognostic factor in determining outcome.

The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis.

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide - thalidomide - dexamethasone) and infusional CVAMP (cyclophosphamide - vincristine - doxorubicin - methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.

Collection of peripheral blood stem cells in new patients with myeloma receiving minimal or no prior cytoreductive therapy.

The aim of the study was to evaluate whether adequate stem cells (CD34+) could be harvested at presentation in myeloma patients such that high dose melphalan (HDM) with autologous stem cell rescue can be offered as primary therapy. The regimes either involved no prior cytoreductive chemotherapy (steroids only, n = 31) or a single course of VAD (n = 22). The median number of CD34 cells collected with steroids was 1.3 x 10(6) (0.2-5.6) compared to 4.6 x 10(6) (0.3-19.2) cells/kg with VAD (P < 0.0001). We conclude that it is possible to collect stem cells from myeloma patients at presentation with minimal prior therapy. Using this strategy, of a single prior course of chemotherapy followed by immediate harvest, it is feasible to offer early high-dose therapy in clinical situations where this is important.

Re-use of the original infusional induction chemotherapy as salvage therapy in myeloma patients relapsing after one autograft.

If standard infusional therapy (IC) has been used to treat myeloma at presentation, it is a matter of debate whether patients should receive the original induction therapy or a different drug combination in first relapse. Instinctively, most clinicians may switch treatment, particularly since the advent of new drugs for the treatment of myeloma. Hitherto, there has been no data on the efficacy of repeating standard IC in the salvage setting. We studied 62 myeloma patients whose initial treatment consisted of C-VAMP and a single high dose melphalan procedure and who were retreated with C-VAMP at the time of first relapse. Response to salvage C-VAMP was seen in 50% (95% confidence interval = 0.37-0.62) but we were unable to identify any predictors for response to salvage C-VAMP. Only patients resistant to salvage C-VAMP benefited from a second autograft. The survival of patients who responded to salvage C-VAMP was not prolonged by a second transplant. In conclusion, our data supports the use of C-VAMP for patients with myeloma in first relapse and suggest that only patients resistant to salvage C-VAMP should be offered a second autograft.

Long-term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high-dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatments.

Induction chemotherapy followed by high-dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management. An intention-to-treat analysis was performed on 383 patients with newly diagnosed myeloma eligible for HDM to determine whether the extent of response to induction therapy and HDM correlated with long-term survival. Early response [complete response (CR) and partial response (PR)] to induction therapy was predictive of overall survival (OS) [median OS, 7.47 years for responders (CR and PR) versus 4.89 years for non-responders; P = 0.035]. The attainment of CR at 3 months post-HDM correlated with a prolonged progression-free survival (PFS) (median PFS, 7.4 years in CR group versus 5.3 years in non-CR group; P = 0.023). This data suggests that, at every stage of treatment, the aim should be to achieve CR. Patients with suboptimal responses could be offered alternative therapy. We propose a multiparametric risk-adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment.