Effect of pre-transplant cumulative doses of chemotherapeutic drugs on early and long-term hematological recovery after autologous bone-marrow transplantation for lymphoma

Abstract

BACKGROUND AND OBJECTIVES: It has recently been demonstrated that autologous bone-marrow transplantation (ABMT) is feasible in heavily pretreated patients who do not mobilize peripheral blood progenitor cells (PBPC), suggesting that bone marrow (BM) progenitor-cells are not as sensitive to chemotherapy as are PBPC. However, information regarding the impact of previous chemotherapy on the performance of BM grafts is scanty. DESIGN AND METHODS: We have retrospectively analyzed 40 consecutive lymphoma patients treated with the BEAM regimen and ABMT at our institution. The impact of the chemotherapeutic drugs (individual cumulative doses) received before transplant on stem-cell yield and hematologic recovery was investigated. Univariate analysis failed to identify any variable that significantly affected progenitor-cell content. RESULTS: Regarding the impact of pre-transplant chemotherapy on early engraftment, only cumulative doses of cytarabine (r=0.28, p=0.04) and cisplatin (r=0.32,p=0.02) had a negative influence on neutrophil recovery (to >0.5x10(9)/L), but the significance of this was not maintained in multivariate analysis. We did not find any chemotherapeutic drug that negatively affected platelet recovery (to >20x10(9)/L). By contrast, administration of several drugs, including doxorubicin, procarbazine, nitrogen mustard, cytarabine and cisplatin, significantly delayed complete trilineage reconstitution. In multivariate analysis, only previous doxorubicin retained statistical significance (p=0.014). INTERPRETATION AND CONCLUSIONS: Our results show that pre-transplant chemotherapy has little or no influence on progenitor-cell yield and short-term engraftment after ABMT.In contrast, we found that cumulative doxorubicin doses have an independent influence on long-term engraftment. In heavily pretreated lymphoma patients in whom poor PBPC mobilization is expected, BMT may represent an attractive option.