Evidence of Graft-versus-Tumor Effect in Refractory Metastatic Neuroblastoma

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.

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

“…8,11,[17][18][19] have reported high engraftment rates with low TRM rates, but the impact of RIC-allo-SCT on survival has only been demonstrated or suggested in a few cases. [19][20][21] In our study, overall engraftment rate was 87%, with 2% primary graft failures and 11% secondary graft failures. However, our results are clearly not the same with BM/PBSC vs CB grafts.…”

Section: Discussionmentioning

confidence: 91%

Reduced-intensity conditioning followed by allogeneic transplantation in pediatric malignancies: a report from the Société Française des Cancers de l’Enfant and the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Paillard

Rochette

Lutz

et al. 2013

We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n ¼ 11), Hodgkin's lymphoma (n ¼ 15) or solid tumors (n ¼ 20). Graft sources were BM (n ¼ 21), PBSC (n ¼ 20) and cord blood (CB; n ¼ 5) from related (n ¼ 20) or unrelated (n ¼ 26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day þ 100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.

“…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

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.