Reduced-intensity conditioning allogeneic stem cell transplantation for high-risk neuroblastoma: French experience

Autologous haematopoietic stem cell transplant has improved the outcome for children with high risk neuroblastoma (NB) but long term event free survival remains lower then 50%. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has the potential to confer a durable graft versus tumor im...

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Veröffentlicht in:Bone marrow transplantation (Basingstoke) 2009-03, Vol.43 (S1), p.S154
Hauptverfasser: Paillard, C, Lutz, P, Tchirkov, A, Cojean, N, David, A, Dore, E, Isfan, F, Merlin, E, Marabelle, A, Rousseau, R, Demeocq, F, Kanold, J
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Zusammenfassung:Autologous haematopoietic stem cell transplant has improved the outcome for children with high risk neuroblastoma (NB) but long term event free survival remains lower then 50%. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has the potential to confer a durable graft versus tumor immunity, but may be limited by significant toxicity in heavily pre-treated children. Therefore we have investigated the feasibility of reduced intensity conditioning (RIC) allo-HSCT in 6 patients with refractory or relapsed NB. All patients received at least 4 lines of chemotherapy including auto-HSCT with melphalan 140mg/[m.sup.2] + busulfan 600 mg/[m.sup.2] regimen. Patients were in PR or VGPR at the time of RIC allo-HSCT. Donor cell sources were: related CB 6/6 (1pt), related BM 10/10 (3 pts), unrelated BM 10/10 (1 pt) unrelated PBSC 10/10 (1 pt). RIC allo-HSCT conditioning was : Fludarabine 180 mg/[m.sup.2], Busulfan IV 6.4 to 9.6 mg/kg, and rabbit anti-thymocyte globulin 2.5 mg/kg for related and 5 mg/kg for unrelated recipients. One pt received exclusively TBI 2 grays as conditioning regimen. GVHD prophylaxis was cyclosporin (CSA) alone 3 mg/kg IV starting on day -1. In the absence of grade > II acute GvHD, CSA was tapered 25% weekly starting on day+30. After RIC allo-HSCT four pts responded, and 2 pts progressed. Maximal peripheral chimerism was 100% at day+60. Four patients had evidence of GVHD and 4 had "evidence" of graft-versus neuroblastoma effect (disappearance or decrease of blood/ marrow tyrosine hydroxylase transcript and /or MIBG spots after the induction of aGvHD by withdrawal of immunosuppressive drugs or by DLI and reappearance of neuroblastoma after the control of GvHD by immunosuppressive drugs). Maximal grade for aGVHD was III skin and liver (1pt). One patient had chronic skin GVHD. Four patients are alive, with no evidence of disease, with median time after RIC allo-HSCT of 21.8 months [3.2-52.7] [Table 1]. Conclusion: RIC allo-HSCT appears feasible and safe in patients with advanced NB. Additional studies of therapeutic strategies used donor-derived effector cells (alloreactive NK cells or T cells) and possible graft versus-tumor effects are warranted in this group of patients.
ISSN:0268-3369