Abstract
The outcome of hr cancer pts undergoing intensified chemotherapy (CTx) with risk factors, such as advanced disease, incomplete remission, tumor resistance and/or prior clinical complications can be dismal and remains a challenge. The prognostic factors for determining TRM, ER and FBR in hr cancer pts undergoing auto-PBSCT, allogeneic (allo)-PBSCT or intensified CTx have not yet been identified. Here, we analysed 50 cancer pts who died within three months of auto-PBSCT or had primary FBR, with a total of 796 pts undergoing auto-transplants over a 10 year period (6/93–5/2003) at our center. Median patient (pt) age at transplant was 52 years (y; range; 18–75), with underlying lymphoma, solid tumors or leukemias in 30, 14 and 6 pts, respectively. The disease stage in 90% (n=45) was advanced, bulky disease was present in 52%. Median performance status of all pts was 70%. An elevated LDH (median 365U/l) at diagnosis was present in 78% of pts. Treatment before auto-PBSCT consisted of a median number of 7 CTx cycles and radiation in 32% of pts. A median number of 4.1x10e6/kg bw PBSCs were transfused, with total CFUs (/1.5e5) of 128. Median platelet counts before PBSCT were 98x10e9/L, with persisting BM involvement in 38% and hypocellularity in 46% of pts. Transplant complications, leading to TRM, ER or FBR were observed in 18, 25 and 7 pts, respectively and resulted in early death in all pts, except one with CML and FBR, who was salvaged with back-up PBSCs. Thirteen pts were examined post-mortem and showed hypo- vs normocellular BM in 8 vs. 3 pts, respectively. Of note, FBR was observed in older pts (59 y), who were mostly heavily pretreated and had AML or CML (4 pts). They had been retransfused with lower CD34+ cells (2.9x10e6/kg), showed lower BFU-Es, CFU-GMs and GEMMs (30, 40, 3, respectively) and low platelet counts (27x10e9/L) before PBSCT due to active underlying disease (71%) and/or BM hypocellularity (71%). During post-transplant cytopenia all pts with FBR showed serious infections. These results suggest that the above risk factors are associated with TRM, ER and FBR. LDH and low platelet counts were significantly different between the three groups. In vitro culture data (cell expansion, CFU, LTC-IC) correlated with our clinical results. With a TRM of 2.26% and FBR in 0.88% in this hr pt cohort, auto-PBSCT is in general a very safe procedure. Nevertheless distinct risk factors can be determined and need to be considered before autotransplantation. Our results may also be valid for allo-SCT and intensified dose-dense chemotherapies.
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