Treatment of children with neuroblastoma with high dose chemotherapy followed by peripheral blood stem cell hematopoietic rescue

Abstract

Since advanced neuroblastoma often involves the marrow, the use of peripheral blood The International Journal of Cell Cloning (PBSC) in lieu of marrow for autologous cellular support after intensive chemotherapy offers a potentially attractive alternative. We developed a method, in light of the young age and small size of patients with neuroblastoma, to collect PBSC from small children; applied this method to the clinical collection of PBSC; and attempted hematologic rescue using the collected cells1–2. Collections were performed on the Fenwal CS3000, and the machine was primed with irradiated red cells, fresh frozen plasma, and, with very small patients, albumin (to minimize the amount of citrate returned). In small patients, heparin was used in lieu of some of the citrate anticoagulant for the same reason. Collections were performed through dual lumen central lines without major complications, and with complete avoidance of blood pressure and pulse instability or citrate toxicity. Among the first five patients, patient size ranged from 8.3 to 24 kg, and the total number of mononuclear cells collected ranged from 2.8 to 7.4 × 108 cells per kg in 5 to 7 procedures per patient. The preparative regimen consisted of high dose cyclophosphamide, etoposide, and cisplatin. Pediatric patients with solid tumors without marrow involvement treated with similar preparative regimens and marrow rescue (1.0 to 3.0 × 108 nucleated cells per kg) were compared retrospectively as controls. Cryopreserved cell preparations were thawed at the bedside in 37°C saline and infused rapidly in a central line. Hematopoietic recovery was comparable to the marrow-treated control patients, except for one PBSC patient in whom platelet recovery was delayed, and another in whom neutrophil recovery was delayed. The PBSC patients all relapsed and died but one, who was alive and disease-free 27 months following transplant. Of the three marrow-treated neuroblastoma control patients, one was alive and disease-free one year following transplant. Because of the small numbers of patients studied, definitive conclusions about the effect of this treatment technique on disease outcome is not possible. However, the data suggest that PBSC rescue may be an acceptable if not preferable treatment for advanced neuroblastoma, even in very small children.