Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study

, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin þ etoposide þ cyclophosphamide) regimen and TM (thiotepa þ melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for 43 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

Section: Discussionmentioning

confidence: 99%

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Sung

Son

Lee

et al. 2012

“…Ten were females and seven were males. Median age at diagnosis was 3 years (range [1][2][3][4][5][6][7][8][9]. Median time between diagnosis and megatherapy was 7 months (range 4-46).…”

Section: Patients' Characteristics and First Line Therapymentioning

confidence: 99%

“…In a pilot study, side-effects of MIBG treatment associated with highdose chemotherapy and immunotherapy also proved to be tolerable in 11 children. 8 We evaluated the toxicity observed in patients receiving a course of MIBG radiotherapy and a conditioning regimen including high-dose chemotherapy before autologous PBSC transplantation and compared it to that observed in children not receiving MIBG.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Megatherapy combining I131 metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma

Miano

Garaventa

Pizzitola

et al. 2001

Summary:Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I 131 MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBGpositive residual disease received 4.1-11.1 mCi/kg of I 131 MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m 2 followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I strategy includes inductive chemotherapy, mainly based on ozaphorines and platine derivatives followed by surgery and a consolidation phase including megatherapy with stem cell rescue. Conditioning regimens combining high-dose chemotherapy with total body irradiation have been abandoned due to unsatisfactory results and severe late effects. In a Children's Cancer Group (CCG) study, the event-free survival (EFS) of children receiving high-dose (HD) chemotherapy with peripheral blood stem cell transplantation (PBSC) rescue was 34% reaching 46% when followed by further therapy with 13 cis-retinoic acid treatment. 1 Targeted radiotherapy with I 131 metaiodobenzylguanidine (MIBG) has proven to be active in advanced neuroblastoma (NB) and insertion in the megatherapy regimen is promising. In fact, I 131 MIBG, that concentrates in the neuroblastoma cells, is potentially capable of selectively delivering a substantial radiation dose to neoplastic cells while sparing normal tissues. We report on the feasibility of this approach in 17 patients with advanced NB. Fifteen children with NB receiving a similar myeloablative conditioning regimen without I 131 MIBG are evaluated and reported as controls. Our experience suggests that including I 131 MIBG in the conditioning regimen followed by PBSC rescue in children taking up MIBG is a feasible therapeutic strategy, although attention should be paid to avoiding lung complications. Patients and methods Patients' characteristics and first line therapyFrom October 1994 to February 2000 17 patients suffering from either stage 3 (one patient) or 4 (16 patients) neuroblastoma and having positive MIBG residual disease were treated with MIBG megatherapy followed by high-dose chemotherapy with PBSC rescue. Ten were females and seven were males. Median age at diagnosis was 3 years (range 1-9). Median time between diagnosis and megatherapy was 7 months (range 4-46). NB origin was adrenal in seven cases, retroperitoneal gangliar in seven cases, abdominal in two, and unknown in one.

“…Myeloablative chemotherapy with autologous stem cell transplantation is increasingly used in patients who otherwise have a poor prognosis with standard chemotherapy alone. It is believed that myeloablative chemotherapy, eventually combined with mIBG radiotherapy 17 can eradicate residual tumor cells in CR patients, thus reducing the relapse rate. In non-CR patients post induction, therapy intensification with stem cell transplantation is used to overcome the resistance to conventional chemotherapy and to induce a CR in these patients.…”

Section: Discussionmentioning

confidence: 99%

“…In four of the patients, 300 mCi of meta[131] iodo-benzylguanidine (mIBG) therapy was given 1 week before the start of the chemoconditioning as described by us. 17 For reinfusion, isolated CD34 ϩ cells were rapidly thawed and injected without further washing. All patients received G-CSF (5 g/kg/day) starting day ϩ4 until a stable leucocyte count was reached.…”

Section: Myeloablative Therapymentioning

confidence: 99%

Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution and long-term outcome in children with high-risk neuroblastoma

Handgretinger

Lang

Ihm

et al. 2002

Self Cite

Summary:We have investigated the purging efficacy of positive selection of autologous mobilized CD34 ϩ peripheral stem cells in 22 children with high-risk neuroblastoma. CD34 ϩ cell selection was performed using the method of magnetic-activated cell sorting (MACS). The median purity of the CD34 ϩ cells post selection was 97.6% (range 81.7-99.7). For detection of contaminating neuroblastoma cells before and after CD34 ϩ selection, the chimeric anti-disialoganglioside GD2 antibody delta ch 14.18 was used. Prior to positive selection, various numbers of contaminating neuroblastoma cells were found in 17 patients. After positive CD34 ϩ cell selection, low numbers of neuroblastoma cells were only detectable in four patients. In 18 patients, high-dose chemotherapy was performed and the isolated CD34 ϩ cells were reinfused. In all patients, a rapid neutrophil recovery was seen with a median time to reach 0.5 × 10 9 /l neutrophils of 12 days (range 8-24 days). Nine of the 18 patients are free of progression with a median followup of 55 months (range 45-70 months). Two patients are alive with relapse, six patients died due to progression or relapse and one patient died due to secondary AML 10 months after transplant while in remission from neuroblastoma. In summary, we show that, through a highly effective positive selection method, a high purging efficacy can be obtained without compromising the hematopoietic reconstitution capacity of the graft. Bone Marrow Transplantation (2002) 29, 731-736.