title: Autologous bone marrow transplantation followed by interleukin-2 in children with advanced leukemia: a pilot study.
abstract: In an attempt to prolong disease-free survival in children with acute leukemia, we tested the feasibility of interleukin-2 (IL-2) administration after an autologous bone marrow transplantation (ABMT). We report the clinical and biological data obtained in three children with acute myelocytic leukemia (AML) in second complete remission (CR) and in seven children with acute lymphocytic leukemia (ALL) in second or subsequent CR, who received IL-2 at a median interval of 78 days (range 38-125) from ABMT. Patients were treated with 1-2 cycles of IL-2 given by continuous infusion over a 5-day period using a daily escalating protocol, from 100 micrograms/m2 per day to the maximum tolerated dose, followed after 3 weeks by low-dose IL-2 for 5 days monthly over a 6-h infusion on an out-patient basis. Side effects greater than grade 2 (WHO system), consisting of thrombocytopenia, fever, cutaneous rash, nausea and vomiting, diarrhoea were common during the high-dose IL-2 cycles, but resolved 24-48 h after stopping IL-2. Only one patient developed liver toxicity (grade 3, WHO) on day +3 of the first cycle which prompted us to stop the administration of IL-2. An increase in lymphocytes and eosinophils was also observed. IL-2 treatment was followed by a normalization of NK function and by the generation of a high proportion of endogenous LAK cells. All seven ALL patients relapsed at a median of 5 months (range 1-23). Two AML patients relapsed at 1 and 11 months, while the other is still in continuous CR at 23 months after IL-2 treatment. Our IL-2 schedule for treatment of leukemia in children after ABMT is thus feasible but its efficacy requires further investigation.
authors.affiliation: Department of Human Biopathology, University La Sapienza, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Meloni
authors.forename: R
authors.initials: R
authors.lastname: Foà
authors.forename: S
authors.initials: S
authors.lastname: Tosti
authors.forename: M
authors.initials: M
authors.lastname: Vignetti
authors.forename: F
authors.initials: F
authors.lastname: Mancini
authors.forename: A
authors.initials: A
authors.lastname: Guarini
authors.forename: D
authors.initials: D
authors.lastname: Marchis
authors.forename: F
authors.initials: F
authors.lastname: Gavosto
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008297:Male; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins