New consecutive high-dose chemotherapy modality with fractionated blood stem cell support in the treatment of high-risk pediatric solid tumors: a feasibility study

Abstract

For the treatment of childhood solid tumors, we performed a pilot feasibility study of consecutive high-dose therapies, in which each course was followed by transplantation with granulocyte colony-stimulating factor-mobilized peripheral blood cells which had been separated into CD34-positive and -negative fractions by an Isolex system (Baxter). Positive selection of CD34⁺ cells has been associated with inevitable cell loss. To overcome this loss, CD34⁺ cells that had migrated into the negative fraction were saved and used for the first transplant, which was followed by a second transplant after a 3- to 5-month interval. In this phase I feasibility study, the results in six children were evaluated for safety and engraftment. Multi-drug cytoreductive regimens using ranimustine (MCNU), melphalan, thiotepa, carboplatin, cyclophosphamide or VP-16 were comparable between the two transplant procedures in terms of their intensity. The number of CD34⁺ cells in the ‘CD34(⁺) fraction’ was 3.31 × 10⁶/kg (0.63–4.3 × 10⁶/kg), while this number in the ‘CD34(⁻) fraction’ could not be evaluated correctly due their scarcity (<0.1%). the median numbers of infused mnc and cfu-gm were, respectively, 4.2 × 10⁶/kg and 1.75 × 10⁵/kg in the CD34(⁺) fraction, and 4.8 × 10⁸/kg and 3.35 × 10⁵/kg in the CD34(⁻) fraction. The number of days required to achieve an ANC >0.5 × 10⁹/l and a platelet count >20 × 10⁹/l and >50 × 10⁹/l were, respectively, 14.5, 15.0 and 19.5 in the first transplant with CD34⁻ cells, and 13.5, 18.0 and 25.0 in the second transplant with CD34⁺ cells, with no essential difference between the two treatments. Although the small number of patients, the variation in clinical status and treatment, and the short follow-up invalidate any evaluation of the therapeutic benefit of this strategy, the encouraging results support the feasibility of this strategy, which enables an escalation of dose intensity with an improved cost/benefit ratio.