Summary:Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapsefree survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after highdose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count Ͼ0.5 × 10 9 /l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.
Three successive strategies used to treat acute myelogenous leukemia (AML) patients who entered complete remission are compared with respect to their long term efficacy (> 5 years). Additionally, the ability of two in vitro assays to identify patients who would be long term remitters was assessed. With respect to the proportion of patients in long term remission, 5 years of maintenance therapy, intensive consolidation therapy plus 3 years of additional therapy, and 4 courses of consolidation therapy produced equivalent results with 18 to 22% of patients in remission at 7 years. Patients whose leukemia cells retained high levels of cytosine arabinoside triphosphate (araCTP) and who received maintenance therapy were less likely to experience early relapse than comparably treated patients whose leukemia cells failed to retain araCTP. The failure of leukemia cells to clone in vitro was also associated with a lower early relapse rate for patients who received maintenance therapy. Neither the ability of leukemia cells to retain araCTP nor their ability to clone in vitro were of prognostic significance for patients treated with 4 courses of intensive consolidation therapy.
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