The prognostic significance of autologous bone marrow transplant in advanced neuroblastoma.

This report provides strong evidence for conducting a controlled randomized clinical trial of autologous bone marrow transplantation versus conventional chemotherapy in childhood neuroblastoma, which is disseminated beyond the intracavity nodes, and which is diagnosed in children older than 12 months of age. On the basis of two Pediatric Oncology Group (POG) studies, one a surgery plus conventional chemotherapy study (POG 8441) and the other an elective autologous transplant pilot protocol (POG 8340), there was no significant prognostic benefit of switching in remission from the surgery plus chemotherapy protocol to the transplant protocol (P = .91) or of switching in remission from the surgery plus chemotherapy protocol to any transplant (P = .75). The analysis is based on 116 patients achieving a complete or partial remission, 32 of whom received transplants on the pilot protocol, and 17 of whom received transplants outside the pilot protocol. While potential selection bias precludes cause-effect conclusions, these data strongly suggest that a large randomized trial of autologous bone marrow transplantation should be conducted before accepting this form of therapy as standard.

High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.

Immunomagnetic purging of bone marrow: a model for negative cell selection.

Many in vitro techniques have been developed for removing cancer cells from the marrow of patients who are to undergo autologous bone marrow transplantation (ABMT). These purging techniques can be classified as immunological or pharmacological. The immunomagnetic technique has been widely used in neuroblastoma patients. It depends on an interaction between target neuroblastoma cells in the marrow and a complex of specific monoclonal antibodies and magnetized microspheres, the target cells being selectively removed by passage through a magnetic field. Laboratory studies with neuroblastoma and acute lymphoblastic leukemia cells have shown the high efficiency of this technique in selectively removing cancer cells while retaining adequate numbers of normal hematopoietic cells for subsequent reinfusion into the patient. Clinical studies in several hundred neuroblastoma patients, as well as small numbers of acute lymphoblastic leukemia, breast cancer, and myeloma patients, suggest that this is a clinically safe and effective technique. However, no clinical trial has been conducted comparing ABMT with and without in vitro marrow purging. Until such time, we will regard immunomagnetic purging as "standard of care" for neuroblastoma patients receiving ABMT.

Granulocyte transfusion in treatment of infected neutropenic children.

Thirty episodes of infection in severely neutropenic children with acute leukaemia and aplastic anaemia resistant to antibiotics were treated with total of 51 granulocyte transfusions collected from normal donors by means of an Aminco continuous flow cell separator. The mean granulocyte increment in the recipients was 820/mm3 at 1 hour and 307/mm3 at 15 hours post-transfusion and it showed a correlation with the number of cells transfused, the size of the child, and his pretransfusion granulocyte count. Fifteen (50%) episodes responded clinically by 24 hours and 23 (77%) by 5 days post-transfusion. Two more children recovered more slowly and 5 died. Poor response was associated with multiple-site infections and with a prolonged period of infection before granulocyte transfusion, but the primary diagnosis did not influence the outcome. We conclude that granulocyte transfusion significantly reduces the mortality and morbidity from infection in neutropenic children with acute leukaemia.