A PHASE-I PHASE-II STUDY OF MULTICYCLIC DOSE-INTENSIVE CHEMOTHERAPY SUPPORTED WITH G-CSF, OR G-CSF AND HEMATOPOIETIC PROGENITOR CELLS IN WHOLE-BLOOD, IN 2 CONSECUTIVE COHORTS OF PATIENTS/

We investigated the reconstitutive potential of haematopoietic progeni tor cells collected in autologous whole blood during multicycle dose-i ntensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses o f ifosfamide every 14 days. Cisplatin was administered in 3% sodium ch loride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h, The first cohort of patients received granulocyte colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was reached in c ohort 1, the study continued with a second cohort of patients, in whom , in addition to G-CSF on days 4-14, 500 mi of G-CSF and chemotherapy- 'primed' whole blood was collected on day 15, i.e. on day 1 of treatme nt cycles two to six, before cisplatin administration. This volume of blood was kept unprocessed at 4 degrees C and reinfused 20-24 h after the completion of ifosfamide. In cohort 1, dose-limiting toxicity (DLT ) was reached at ifosfamide 6.0 g m(-2) with two out of six of the pat ients developing neutropenic fever. Although in cohort 2 no neutropeni c fever was encountered, neither the frequency nor the duration of gra de 4 neutropenia and thrombocytopenia were reduced. Cumulative astheni a resulted in DLT at 7.0 g m(-2). The median number of CD34+ cells in 500 mi of whole blood after the first cycle (i.e. at start of cycle 2) was 1.15 x 10(6) kg(-1). This number was significantly greater after the second cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually de creased after cycles three to six. After storing whole blood, the numb er of CD34+ cells had not decreased (median + 10%). We conclude that t he method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clin ically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.