Incorporation of high‐dose <sup>131</sup>I‐metaiodobenzylguanidine treatment into killer immunoglobulin‐like receptor/HLA‐ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation

Lee, Ji Won; Kang, Eun‐Suk; Sung, Ki Woong; Yi, Eun Sang; Lee, Soo Hyun; Yoo, Keon Hee; Koo, Hong Hoe

doi:10.1002/pbc.26399

Cited by 9 publications

(9 citation statements)

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“…RT dose and volume were determined according to previous RT prior to relapse/progression. 6 7 A detailed review of the clinical data was performed to ascertain the presenting features, degree of surgical resection, pathology, chemotherapy regimen, RT, the response to salvage treatment, and any events (relapse/progression, second malignancy, treatment-related mortality, and death).…”

Section: Methodsmentioning

confidence: 99%

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Cho

Lee

et al. 2018

J Korean Med Sci

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BackgroundBy estimating the survival rates and exploring prognostic factors in pediatric patients with relapsed or progressed solid tumors, our purpose was to generate background data for future studies.MethodsWe reviewed the medical records of 258 patients with solid tumors who experienced relapse/progression and received subsequent salvage treatment between 1996 and 2016.ResultsA total of 60 patients remained progression-free during first-line salvage treatment, while the remaining 198 patients experienced relapse/progression again; 149 underwent second-line salvage treatment. A total of 76 patients underwent high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), and 44 patients received allogeneic SCT. The 10-year progression-free survival (PFS) and overall survival (OS) from relapse/progression were 18.4% ± 2.7% and 24.5% ± 3.0%, respectively. Survival rates were relatively higher in patients with anaplastic ependymoma, initially non-high-risk neuroblastoma, osteosarcoma, Wilms tumor and retinoblastoma. A multivariate analysis showed that relapse/progression during initial treatment, metastatic relapse/progression, and impossible debulking surgery were independent poor prognostic factors for both PFS and OS. Patients who exhibited a complete response or partial response during conventional salvage treatment showed significantly higher survival after SCT than those with stable disease or progressive disease (10-year OS: 54.8% ± 7.0% vs. 7.0% ± 3.5%, P < 0.001).ConclusionThe prognosis of relapsed/progressed pediatric solid tumors still remains unsatisfactory. New, effective treatment strategies are needed to overcome limitations of current approaches. Hopefully, the background data generated herein will be used in future clinical trials involving patients with relapsed/progressed solid tumors.

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Section: Methodsmentioning

confidence: 99%

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Cho

Lee

et al. 2018

J Korean Med Sci

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“…HaploHSCT has been studied as a potential treatment modality exploiting the graft‐versus‐tumor effect from NK‐cell alloreactivity . Initial experience with haploHSCT highlighted the need to minimize TRM due to GvHD and infection associated with GvHD treatment . Ex vivo engineering of stem cell graft, initially by CD34 positive selection, has evolved to become a feasible tool to mitigate GvHD in haploHSCT, with the disadvantage of delayed immunoreconstitution and depleted alloreactive NK cells .…”

Section: Discussionmentioning

confidence: 99%

“…Various graft manipulation protocols have since been designed to improve the outcome in patients undergoing haploHSCT . The literature about haploHSCT in NB is scarce and limited to small series and case reports (Table ).…”

Section: Discussionmentioning

confidence: 99%

“…These factors, in addition to tumor expression of major histocompatibility complex class I‐related chain A, which interacts with NK‐cell immunoreceptor NKG2D to induce tumor recognition, could influence the outcome of haploHSCT in NB . KIR‐ligand mismatch was considered in a series of 7 patients with relapsed NB who underwent serial high‐dose 131 I‐MIBG treatment and haploHSCT with unmanipulated grafts . Unsurprisingly, 6 of the patients developed acute GvHD, and 4 had chronic GvHD; infective complications were common because of the immunosuppression required.…”

Section: Discussionmentioning

confidence: 99%

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Selective T cell‐depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma

Liu

Lee

Kwok

et al. 2018

Pediatric Transplantation

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Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αβ/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αβ/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB.

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“…Neuroblastoma cells have been reported to have decreased class I HLA expression, which suggests that NK cell therapy may be effective in killing neuroblastoma cells [16]. Our previous study showed that KIR/HLA-ligand mismatched haplo-SCT might improve outcomes in children with recurrent neuroblastoma; however, most relapse/progression occurred in the early post-transplant period, suggesting the need for further effective treatment to prevent early relapse after haplo-SCT [17].…”

Section: Introductionmentioning

confidence: 99%

Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma

et al. 2019

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IntroductionUnder the hypothesis that early natural killer cell infusion (NKI) following haploidentical stem cell transplantation (haplo-SCT) will reduce relapse in the early post-transplant period, we conducted a pilot study to evaluate the safety and feasibility of NKI following haplo-SCT in children with recurrent neuroblastoma who failed previous tandem high-dose chemotherapy and autologous SCT.MethodsWe used the high-dose 131I-metaiodobenzylguanidine and cyclophosphamide/fludarabine/anti-thymocyte globulin regimen for conditioning and infused 3 × 107/kg of ex-vivo expanded NK cells derived from a haploidentical parent donor on days 2, 9, and 16 post-transplant. Interleukin-2 was administered (1 × 106 IU/m2/day) subcutaneously to activate infused donor NK cells on days 2, 4, 6, 9, 11, 13, 16, 18, and 20 post-transplant.ResultsSeven children received a total of 19 NKIs, and NKI-related acute toxicities were fever (n = 4) followed by chills (n = 3) and hypertension (n = 3); all toxicities were tolerable. Grade ≥II acute GVHD and chronic GVHD developed in two and five patients, respectively. Higher amount of NK cell population was detected in peripheral blood until 60 days post-transplant than that in the reference cohort. Cytomegalovirus and BK virus reactivation occurred in all patients and Epstein-Barr virus in six patients. Six patients died of relapse/progression (n = 5) or treatment-related mortality (n = 1), and one patient remained alive.ConclusionNKI following haplo-SCT was relatively safe and feasible in patients with recurrent neuroblastoma. Further studies to enhance the graft-versus-tumor effect without increasing GVHD are needed.

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Incorporation of high‐dose ¹³¹I‐metaiodobenzylguanidine treatment into killer immunoglobulin‐like receptor/HLA‐ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation

Cited by 9 publications

References 34 publications

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Selective T cell‐depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma

Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma

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Incorporation of high‐dose 131I‐metaiodobenzylguanidine treatment into killer immunoglobulin‐like receptor/HLA‐ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation

Cited by 9 publications

References 34 publications

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid Tumors: a 20-year, Single-Center Study

Selective T cell‐depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma

Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma

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Incorporation of high‐dose ¹³¹I‐metaiodobenzylguanidine treatment into killer immunoglobulin‐like receptor/HLA‐ligand mismatched haploidentical stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation