Graft-versus-tumour effect in refractory metastatic neuroblastoma

Marabelle, Aurélien; Paillard, Catherine; Tchirkov, Andréï; Hallé, Pierre; Chassagne, J; Deméocq, F.; Kanold, Justyna

doi:10.1038/sj.bmt.1705681

Cited by 26 publications

(28 citation statements)

References 7 publications

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“…2,3 Given a higher rate of TRM with allogeneic hematopoietic SCT and the occurrence of GVHD, autologous is the preferred therapeutic option for those in need of hematopoietic SCT: only 25 allogeneic transplantations were therefore performed for neuroblastoma in Europe in 2006. [4][5][6][7][8][9] However, progress has been made in allogeneic transplantation both from a better understanding of immunogenicity and decreased transplant toxicity. First, it has been shown that the GVT effect of allogeneic transplantation may be enhanced by several therapeutic modalities: rapid immunosuppression withdrawal, donor lymphocyte infusion, 10,11 natural killer (NK) cell alloreactivity, 9,12 minor histocompatiblity Ag targeting.…”

Section: Introductionmentioning

confidence: 99%

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Jubert

Wall

Grimley

et al. 2010

Bone Marrow Transplant

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Relapsed or refractory neuroblastoma is uniformly fatal. We hypothesized that allogeneic response could provide a platform for immunotherapy in neuroblastoma. We therefore undertook a pilot trial of unrelated cord blood transplantation after reduced intensity conditioning regimen (RIC) in children with relapsed neuroblastoma to assess engraftment and tolerability in this heavily pretreated population. The RIC included CY (50 mg/kg, day À6), fludarabine (40 mg/m 2 , days À6 to À2), total body irradiation (200 cGy, day À1), and rabbit antithymocyte globulin (2.5 mg/kg, days À3 to À1). Six patients were enrolled: four were in partial responsive relapse, one with a mixed response and one in refractory relapse. All patients tolerated the regimen well and had donor engraftment with full neutrophil and plt recovery (median time 12 and 35 days, respectively). One patient never experienced neutropenia and another did not need plt transfusions. All patients progressed after transplant (median time 55 days, 26-180 days). Natural killer (NK) cell counts were normal within 2 months, whereas T-cell recovery was slower. In conclusion, unrelated cord blood engrafts after RIC in children with refractory neuroblastoma. Future research should be aimed at transplanting patients with minimal residual disease, using less intensive immunosuppression and adding NK-cell based post transplant immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Jubert

Wall

Grimley

et al. 2010

Bone Marrow Transplant

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“…The second reason was to attempt to induce the GVT effect. Recently, there were some clinical reports of a GVT effect against neuroblastoma as follows: minimal residual disease in BM disappeared after the cessation of immunosuppressant 13 or after donor lymphocyte infusion, 14 and abnormal uptake on MIBG imaging disappeared 3 years after haploidentical PBSCT from the patient's father. 12 In our case 1, the urinary HVA level became normal at 3 years after uCBT.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 However, allo-SCT was recently reported to induce a graft-versus-tumor (GVT) effect against advanced neuroblastoma in some cases. [12][13][14] We performed a tandem transplantation consisting of autologous PBSCT (auto-PBSCT) followed by allogeneic cord blood transplantation (CBT) in three consecutive pediatric patients with stage 4 neuroblastoma exhibiting high MYCN amplification. They are alive without disease recurrence for 37-60 months after CBT.…”

Section: Introductionmentioning

confidence: 99%

Successful tandem (autologous-cord blood) SCT in advanced neuroblastomas with highly amplified MYCN

Goi

Inukai

Honna

et al. 2010

Bone Marrow Transplant

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Although autologous tandem hematopoietic SCT has improved the prognosis of patients with advanced highrisk neuroblastoma, the results remain unsatisfactory. In an attempt to induce the graft-versus-tumor effect, we performed autologous PBSCT followed by allogeneic cord blood transplantation in three consecutive advanced neuroblastoma cases with marked BM infiltration and high MYCN amplification. Severe acute complications did not occur in any patient and they have maintained diseasefree survival for 37-60 months. This strategy appears to be feasible and effective for the treatment of extremely high-risk neuroblastoma cases.

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“…43 In a more recent report, development of GVHD correlated temporally with disease response in a patient who had undergone a reduced-intensity allogeneic bone marrow transplant. 44 In a similar regard, the group at Columbia has been testing reduced intensity allogeneic cord blood transplants in patients with a wide range of diagnoses, including neuroblastoma. 45,46 The data continue to show improving outcomes with increasing intensity of consolidation regimens assisted by PBSC-based autologous SCT rescue.…”

Section: Dosing Of Pbscmentioning

confidence: 99%