Long-term results of CD34(+) cell transplantation in children with neuroblastoma

Background. This is the first report of the long-term results of CD34(+) ce ll transplantation in children with neuroblastoma. We investigated the hema tologic and immune recovery, posttransplant morbidity, and clinical outcome of these children. Procedure. Twenty-three children with advanced neurobla stoma had PBPCs (20 patients) or BM (3 patients) collected, followed by CD3 4(+) cell selection on Ceprate column. The purge of residual neuroblastoma cells was evaluated using an RT-PCR for tyrosine hydroxylase (TH) mRNA assa y. Reinfusion of CD34(+) cells followed busulfan + melphalan myeloablative chemotherapy. Results. A median of 2.9 x 10(6) CD34(+) cells/kg was reinjec ted. Median days to achieve ANC > 0.5 x 10(9)/liter and platelets > 50 x 10 (9)/liter were 13 (range 9-33) and 59 (range 22-259), respectively. Circula ting T cells were primarily CD4(-)/CD8(+) with fewer than 0.2 10(9)CD4(+) c ells/liter throughout the first 6 months. CD19(+) cells and CD56(+) cells w ere not detectable up to day +35 posttransplant. At 1 year posttransplant, 10 evaluable patients had stable hematopoiesis with 2.3 x 10(9) ANC/liter ( range 0.8-4.1), 1.4 x 10(9) lymphocytes/liter (range 0.5-2.0) and 251 x 10( 9) PLT/liter (range 35-490). After the completion of hematopoietic reconsti tution, six events of severe septicemia/septic shock were noted. Six childr en had severe VZV infections, and 2 had EBV-associated lymphoproliferation. Thirteen patients are alive with a median follow-up of 40 months (range 2- 54). Ten patients have died; 8 relapsed or developed progressive disease, 1 died from non-documented pneumopathy at day 56, and 1 developed AML-M4 at 3 years posttransplant. Conclusions. In children, CD34(+) cell transplantat ion can be accomplished with a reduction of neuroblastoma cell inoculum in the selected graft as assessed by RT-PCR analysis. CD34(+) cell grafts prov ide successful neutrophil reconstitution. However, delayed platelet recover y, persistent decrease in CD4(+) lymphocyte levels and a high incidence of serious and life-threatening late infections were observed in these childre n. There remains a critical need to evaluate any real clinical benefit of C D34(+) cell autografts in neuroblastoma patients. (C) 2000 Wiley-Liss, Inc.