AUTOLOGOUS PROGENITOR-CELL TRANSPLANTATION - PRIOR EXPOSURE TO STEM CELL-TOXIC DRUGS DETERMINES YIELD AND ENGRAFTMENT OF PERIPHERAL-BLOOD PROGENITOR-CELL BUT NOT OF BONE-MARROW GRAFTS

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphom a (NHL). Because many patients with relapsed or refractory lymphoma ar e candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be take n into account. In a retrospective study, we have analyzed the influen ce of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autog rafted with BM, hematopoietic recovery was significantly accelerated i n recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles (less t han or equal to 1 v >1) was the predominate prognostic factor affectin g colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34(+) cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to >0.5 x 10(9)/L (9 v. 11 days, P = .0086 ), platelet recovery to >20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L , P = .031) using univariate analysis. Previous radiotherapy was assoc iated with significantly lower CFU-GM and CD34(+) cell yields but had no influence on engraftment. Patient age, patient sex, disease activit y, or chemotherapy other than Dexa-BEAM did not have any prognostic im pact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34(+) cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemot herapy or any other variable tested. However, prognostic factors favor ing the use of BM instead of PBPC were not identified using joint regr ession models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure t o salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and perform ance of PBPC grafts. Marrow progenitor cells appear to be less sensiti ve to stem cell-toxic chemotherapy, PBPC should be harvested before re peated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM. (C) 1995 by The American Society of Hematology.