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1.  Immunotherapy with low-dose recombinant interleukin 2 after high-dose chemotherapy and autologous stem cell transplantation in neuroblastoma. 
British Journal of Cancer  1998;78(4):528-533.
The purpose of this study was to evaluate in a phase I-II trial whether low doses of recombinant human interleukin 2 (rHuIL-2) over a prolonged period of time are safe and effective in eradicating or controlling minimal residual disease in children with neuroblastoma given high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). From January 1992 to July 1996, 17 consecutive patients, with either stage IV or relapsed neuroblastoma, were enrolled. Patients received rHuIL-2 after a median time interval (min-max) of 105 days (56-153) after HDCT and ASCT. The protocol consisted of 2 'priming' courses of rHuIL-2 at escalating doses administered intravenously at 72-h intervals, followed by 'maintenance' with 11 monthly and six bimonthly boosting 5-day courses administered subcutaneously on an outpatient basis. At April 1997, 7 out of the 17 patients had completed the treatment schedule, four had discontinued treatment because of toxicity and four because of relapse; the remaining two patients are still on treatment, having completed 15 courses. Expansion of T lymphocytes, together with an increase in both natural killer cells and in activated T lymphocytes was evidenced. After a median (min-max) follow-up time of 30 (16-64) months, 12 out of 17 patients are alive and well. Two patients relapsed and died 14 and 35 months after transplant. Three patients are alive after having relapsed at 41, 21 and 13 months. The actuarial 2-year event-free survival and overall survival are 67% and 92% respectively. Intermittent administration of low doses of rHuIL-2 given for a long period of time is well tolerated and seems capable of controlling minimal residual disease after HDCT and ASCT in children with high-risk neuroblastoma.
PMCID: PMC2063104  PMID: 9716039
2.  Prognostic relevance of pretreatment proliferative rapidity of marrow blast cells in childhood acute lymphoblastic leukaemia. 
British Journal of Cancer  1994;70(6):1198-1202.
Cell proliferation rate is a well-established prognostic factor in cancer, but it has not been considered to identify the risk group of childhood acute lymphoblastic leukaemia (ALL) at presentation. We carried out a study to demonstrate the prognostic importance of the rapidity of cell proliferation in patients with ALL. To measure the rapidity of cell proliferation we used the parameter relative to the area of silver-stained nucleolar organiser regions (AgNORs) as evaluated by morphometric analysis on smeared marrow blast cells. The mean AgNOR area of leukaemic marrow cells was measured in 119 children. By using a cut-off value of 3 microns2, we identified a group of 91 children with low proliferating blast activity (mean AgNOR value 2.11 microns2) and a group of 28 children with high proliferating activity (mean AgNOR value 3.29 microns2). The group of patients with a mean AgNOR value > 3 microns2 was characterised by a higher number of deaths, more frequent relapse and shorter time interval to relapse than the group of patients with mean AgNOR value < 3 microns2 (P < 0.01). Multivariate analysis performed to include T-cell immunophenotype, FAB morphology, leucocyte count and presence of mediastinal mass showed that the mean AgNOR value was the only independent predictor of unfavourable event-free survival probability (P > 0.01). Our results indicate that the rapidity of marrow blast cell proliferation is an important prognostic parameter in childhood ALL and should be routinely introduced in the group risk definition.
PMCID: PMC2033703  PMID: 7981077

Results 1-2 (2)