Experimental HDCSCR

The HDC/SCR concept has been extended using the more rapid recovery and lower tumor burden afforded by PBSC in studies which use sequential cycles of HDC/SCR. The approach is called tandem transplant and allows for greater dose intensification in the consolidation phase. This approach was initially tried using bone marrow as a stem cell source, and encountered a 24% rate of TRM (Philip et al. 1993); however, the switch to PBSC has allowed more rapid recovery from HDC/SCR, and several groups have tested tandem HDC/SCR supported by PBSC (Grupp et al. 2000b; Kletzel et al. 2002). The largest of these studies was conducted over 6 years at four cooperating institutions (see Fig. 11.6.1 for the schema and an EFS curve as of the most recent update). Important characteristics of the study included early collection of PBSC (generally after the third cycle of induction), use of CD34 selection of PBSC as a purging method, and two fully myeloablative consolidation regimens (carboplatin/etoposide/cyclophosphamide and melphalan/ TBI). The 3-year EFS rate from diagnosis in this sequentially treated group of 91 patients was 56% (see Fig. 11.6.1; Grupp et al. 2000b; S. Grupp, unpublished data). The TRM was 6%, including one death from EBV lymphoproliferative disease (EBV-LPD). EBV-LPD is a very uncommon complication of autologous HDC/SCR and three cases total were observed among 91 patients, suggesting that the combination of CD34 selection and tandem transplant is more immunosuppressive than HDC/SCR using unpurged PBSC (Kanold et al. 2000; Powell et al. 2004). A similar study was conducted by Kletzel et al., using three HDC/SCR regimens in sequence (Fig. 11.6.2; Table 11.6.2; M. Kletzel, unpublished data). Among 26 patients in the published report, 19 completed HDC/SCR #2,17 went on to HDC/SCR #3, and one late TRM was observed. Eight of the patients received at least one course of anti-GD2 monoclonal antibody following induction chemotherapy and surgery. The EFS in this group of patients at 3 years was 57%.



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