Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma

Abstract

Although high-dose therapy and autologous stem cell transplant (ASCT) is superior to conventional chemotherapy for treatment of myeloma, most patients relapse and the time to relapse depends upon the initial prognostic factors. The administration of non-cross-resistant chemotherapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after single autologous peripheral blood stem cell transplant (auto-PBSCT) in 103 mostly newly diagnosed myeloma patients (67 patients were p6 months from the initial treatment). Patients received conditioning with BCNU, melphalan7gemcita-bine and auto-PBSCT followed by two cycles of the DCEP7G regimen (dexamethasone, cyclophosphamide, etoposide, cisplatin7gemcitabine) at 3 and 9 months posttransplant and alternating with two cycles of DPP regimen (dexamethasone, cisplatin, paclitaxel) at 6 and 12 months post-transplant. With a median follow-up of 61.2 months, the median event-free survival (EFS) and overall survival (OS) are 26 and 54.1 months, respectively. The 5-year EFS and OS are 23.1 and 42.5%, respectively. Overall, 51 (49.5%) patients finished all CC, suggesting that a major limitation of this approach is an inability to deliver all planned treatments. In order to improve results following autotransplantation, novel agents or immunologic approaches should be studied in the post-transplant setting.

Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

“…To determine whether the early lymphocyte recovery which followed day +2 adoptive T cell transfer had an effect on hematopoietic recovery, we compared the times to absolute neutrophil counts (ANC) ≥ 500/µl for 2 consecutive days for the current study patients with an historical control population of 102 myeloma patients who had standard autografts without additional T cells (31). The median number of days to neutrophil recovery in the current trial was 12 days [range 10–18] versus 12 days in the historical cohort [P = 0.49].…”

Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma

“…9 To eliminate the effect of the myeloma paraprotein, we compared IgG recovery for the patients with non-IgG myeloma, IgA recovery for the patients with non-IgA myeloma, and IgM recovery for all patients. Early polyclonal recovery rates were significantly greater for the IgG, IgA, and IgM fractions among the patients who received T-cell transfers on day 2 after transplantation compared with the historical control patients ( Table 4).…”

“…Efforts to improve the results of autotransplantation for myeloma and other hematologic malignancies include the use of posttransplantation consolidation chemotherapy or maintenance therapy based on targeted agents such as thalidomide and lenalidomide. [9][10][11][12] These agents may increase the level of response and the time to progression, but their effect on long-term survival and cure is unknown. Higher lymphocyte counts may predict better disease-free and overall survival (OS) for myeloma both early after autotransplantation and at diagnosis.…”

Current Trends in Multiple Myeloma Management

“…97 -99 It can be used in consolidation therapy after auto-SCT. 100,101 Other effective cisplatin-containing 102,103 Furthermore, the combination of cisplatin with the nucleoside analogue, gemcitabine, was active in patients not responding to gemcitabine alone 104 and in vitro experiments showed that U266 multiple myeloma cells could be sensitized to cisplatin-induced apoptosis by the STAT3 pathway inhibitors, piceatannol and tyrphostin. 105…”