Abstract
Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing's sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT) allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an event-free survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemotherapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.
Highlights
Positive selection of CD34+ stem cells results in an approximately 3-4 log reduction of CD3+ cells, which reduces the risk of GVHD but increases the risk of graft failure.[3,4,5]
Gesù Pediatric Hospital, Rome, Italy; n 3Immunohematology and Transfusion o Medicine Service, Policlinico Tor Vergata, Rome, Italy; 4LIBT, International Center e for Transplantation in Thalassemia s and Sickle Cell Anemia, Mediterranean u Institute of Hematology, Policlinico l Tor Vergata, Rome, Italy rcia Introduction e The cure for thalassemia involves correcting m the genetic defect in a hematopoietic stem cell that results in reduced or absent β-globin synm thesis and an excess of α-globin dimers
In a second prospective phase of this pilot study, we evaluated the use of haploidentical CD3+/CD19+-depleted marrow graft combined with CD34-selected mobilized PBSCs and CD3+ marrow cells that were added back at the time of infusion.[6,7]
Summary
All donors received recombinant human GCSF 15 μg/kg/day in two daily subcutaneous boluses to mobilize PBSCs. CD34+ cells from leukapheresis and bone marrow harvests were select using the CliniMACS one-step procedure (Milteny Biotech, Germany) for 14 donors. Twostep selection (CD34 positive selection leukapheresis followed by negative selection using anti-CD3 and anti-CD19 monoclonal antibodies) of bone marrow cells was employed for busulfan (BU) 1 mg/kg were administered orally 3 times daily over 4 days (total dose 14 mg/kg over 4 days) in the first 17 patients, and corresponding dose of busulfan give intravenous in the following 14 patients, followed by intravenous cyclophosphamide (CY) 50 mg/kg daily on each of the 4 days (total dose 200 mg/kg), and 10 mg/kg thiotepa, and 12.5 mg/kg anti-thymocyte globulin daily from days -5 to -2, (ATG-Fresenius S). All patients received cyclosporine for GVHD prophylaxis for the first two months post transplantation
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