Autologous bone marrow rescue in the treatment of advanced tumors of childhood

Abstract

High-dose multiagent chemotherapy followed by autologous marrow rescue was used in the treatment of 13 patients with Stage III or IV childhood tumors. Encouraging results are being obtained in abdominal lymphoma (1/3 complete remissions (CR); rhabdomyosarcoma (2/4 CR); and retinoblastoma (1/2 CR). In neuroblastoma, the results are disappointing, with only one of four patients in CR; this patient developed a lymphoma associated with Epstein-Barr virus infection. Marrow reconstitution was obtained in 11 patients, with recovery of neutrophils to greater than 0.5 x 10(9)/liter between six and 30 days and platelet recovery to greater than 50 x 10(9)/liter between seven and 38 days. Investigations on the numbers of cells or committed granulocyte precursors ()CFU-c's) infused and parameters of hematologic recovery show poor correlation and suggest that a more accurate and reliable assay for the predictability of cryopreserved marrow to reconstitute marrow function within a reasonable time is necessary. Nonhematologic toxicities of high-dose multiagent chemotherapy are the principal dose-limiting factors.

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

“…Haematological toxicity of melphalan at doses > 100 mg m-2 has been reported in the literature predominantly using autologous bone marrow rescue (ABMR). There seems little doubt from the experience at the Royal Marsden Hospital that ABMR significantly reduces the periods of neutropenia and thrombocytopenia (McElwain et al, 1979), and time to recovery of a normal peripheral count appears to relate to the number of nucleated cells which are re-infused into the patient (Ekert et al, 1982). Although several of these studies have used doses of melphalan > 120 mg m2, the majority have employed different doses in sequential patient groups.…”

Investigations of the simian ontogenic switch from fetal to adult hemoglobin at the progenitor cell level.

“…Cell culture. Bone marrow mononuclear cells were isolated by centrifugation on Ficoll-Hypaque and either used directly or slowly cryopreserved and later thawed (18). Mononuclear cells from either source were washed and suspended in a-medium, and then plated in methyl cellulose at 100,000 cells/ml (final concentration) using methods similar to those described for human cultures (10).…”

Chemotherapy for Retinoblastoma

“…The optimal multiagent chemotherapy combination for retinoblastoma is not yet defined [2]. Some investigators have explored the inclusion of myeloablative therapy with autologous bone marrow rescue [13][14][15]. However, response needs to be documented before such consolidation strategies have a place.…”