New frontiers in pediatric Allo-SCT: novel approaches for children and adolescents with ALL

Pulsipher, Michael A.; Wayne, Alan S.; Schultz, Kirk R.

doi:10.1038/bmt.2014.114

Cited by 18 publications

(13 citation statements)

References 57 publications

(58 reference statements)

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“…The potential for cure of R/R BCP ALL is greatest using intensive induction followed by allogeneic hematopoietic stem cell transplantation (HSCT). Survival after HSCT for relapsed ALL is improved if the patient is transplanted in a minimal residual disease (MRD)-negative remission (3).…”

Section: Introductionmentioning

confidence: 99%

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

O’Leary

Lü

Huang

et al. 2019

Clinical Cancer Research

199

114

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Tisagenlecleucel (Kymriah; Novartis Pharmaceuticals) is a CD19-directed genetically modified autologous T-cell immunotherapy. On August 30, 2017, the FDA approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory in second or later relapse. Approval was based on the complete remission (CR) rate, durability of CR, and minimal residual disease (MRD) <0.01% in a cohort of 63 children and young adults with relapsed or refractory ALL treated on a single-arm trial (CCTL019B2202). Treatment consisted of fludarabine and cyclophosphamide followed 2 to 14 days later by a single dose of tisagenlecleucel. The CR rate was 63% (95% confidence interval, 50%-75%), and all CRs had MRD <0.01%. With a median follow-up of 4.8 months, the median duration of response was not reached. Cytokine release syndrome (79%) and neurologic events (65%) were serious toxicities reported in the trial. With implementation of a Risk Evaluation and Mitigation Strategy, the benefit-risk profile was considered acceptable for this patient population with such resistant ALL. A study of safety with 15 years of follow-up is required as a condition of the approval. See related commentary by Geyer, p. 1133 Nonclinical Pharmacology and Toxicology Nonclinical safety studies were conducted with lentivirustransduced T cells prepared from healthy donors and patients in

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Section: Introductionmentioning

confidence: 99%

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

O’Leary

Lü

Huang

et al. 2019

Clinical Cancer Research

199

114

View full text Add to dashboard Cite

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“…Yet the complications of allogeneic BMT have also decreased since 2000, with better management of sinusoidal obstruction syndrome, infections, and GVHD. 96 Nevertheless, patients who undergo BMT have a distinct risk of mortality associated with the procedure. The 1-year TRM for higher-risk acute leukemia in CR is 10% and the TRM rate in the CML IV study 92 was 7% (4/56) for allogeneic BMT in CR1.…”

mentioning

confidence: 99%

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

Hijiya

Schultz

Metzler

et al. 2016

Blood

165

176

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Chronic myelogenous leukemia (CML) in children is relatively rare. Because of a lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate that some genetic differences exist in pediatric and adult CML. Because children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid lifelong exposure to TKIs and their associated adverse effects. Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.

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“…Although allo-HSCT is the only curative option for relapsed or refractory adult ALL, outcomes remain poor and reported rates of DFS after allo-HSCT for patients in CR2 or with advanced disease range from 17-35% [34,35]. According to pediatric ALL patients receiving allo-HSCT, the rates of DFS were around 62-64% in patients with very high-risk ALL in CR1, 59% in induction faiure [1,36,37]. Our protocol yielded satisfactory outcomes for high-risk and refractory ALL with one-year OS and DFS rates after transplantation of 70.7%.…”

Section: Discussionmentioning

confidence: 99%

“…Although transplant-related mortality (TRM) has been significantly decreased in the past decades, relapse is high after HSCT for ALL. Relapse rates in children with highrisk ALL undergoing allo-HSCT are 25-40% [1]. Developing strategies to further decrease relapse and improve survival are vital.…”

Section: Introductionmentioning

confidence: 99%

Haploidentical hematopoietic SCT using helical tomotherapy for total-body irradiation and targeted dose boost in patients with high-risk/refractory acute lymphoblastic leukemia

Jiang

Jia

Yue

et al. 2018

Bone Marrow Transplant

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A novel conditioning regimen using helical tomotherapy (HT) was developed to deliver 10 Gy for total body irradiation (TBI) and simultaneously augment dose to 12 Gy for targeted dose boost to total marrow, central nervous system leukemia, and extramedullary disease sites in patients with high-risk or relapsed/refractory acute lymphoblastic leukemia (ALL) receiving haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fourteen patients were included, eight of these patients were in first complete remission (CR1), one was in CR2, one had a partial response and four patients had refractory disease at transplantation. The median delivered average dose was 11.395 Gy (range 10.06-12.17). The median planning target volume D95 was 8.2 Gy (range 7.52-9.01). The median delivered dose to skeleton bone with active bone marrow sites was 12.685 Gy (range 11.12-13.52). The results of this trial suggest that using HT TBI confers satisfactory immunosuppression and excellent eradication of malignant cells in patients with high-risk ALL undergoing allo-HSCT, especially in those with refractory ALL. After a median follow-up of 14.6 months (range 4-28), four patients experienced non-relapse mortality, ten patients are alive in durable CR including remission of extramedullary leukemic infiltration. One-year overall survival and disease-free survival rates post-transplantation were both 70.7%.

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New frontiers in pediatric Allo-SCT: novel approaches for children and adolescents with ALL

Cited by 18 publications

References 57 publications

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

Haploidentical hematopoietic SCT using helical tomotherapy for total-body irradiation and targeted dose boost in patients with high-risk/refractory acute lymphoblastic leukemia

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