Outcomes after late bone marrow and very early central nervous system relapse of childhood B-Acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433.

Outcomes after late bone marrow and very early central nervous system relapse of childhood B-Acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2020 Jan 30;: Authors: Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP Abstract Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children's Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research

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Abstract Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
Abstract Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study e...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
This article is protected by copyright. All rights reserved. PMID: 30506673 [PubMed - as supplied by publisher]
Source: Clin Med Res - Category: Research Authors: Tags: Clin Pharmacol Ther Source Type: research
Conclusions: A dose of 2.3 mg of ixazomib was well-tolerated in combination with induction chemotherapy among older patients with ALL, and is being tested in the expansion phase of this trial. The remission rate in this older adult population appears favorable in both Ph-negative and Ph-positive patients.Table.DisclosuresAmrein: Takeda: Research Funding. Fathi: Agios: Honoraria, Research Funding; Astellas: Honoraria; Boston Biomedical: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster II Source Type: research
ConclusionsChildren treated for ALL or HL who receive VCR by means of one-hour infusions or bolus injections seem to be at equal or diminished risk of developing VIPN during induction therapy. Results of longer follow-up that includes the total treatment period should demonstrate whether VIPN occurs less frequently and/or is less severe in case VCR is administered through one-hour infusions compared to administrations by bolus injections.Figure.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation Source Type: research
AbstractOn July 11, 2017, the Food and Drug Administration granted approval for blinatumomab for the treatment of relapsed or refractory (R/R) precursor B‐cell acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific CD19‐directed CD3 T‐cell engager. The basis for the approval included results from two clinical trials, TOWER and ALCANTARA. TOWER, a randomized trial comparing overall survival in patients with Philadelphia chromosome (Ph)‐negative R/R ALL receiving blinatumomab versus standard‐of‐care (SOC) chemotherapy, demonstrated a hazard ratio of 0.71 favoring blinatumomab (p = .012; me...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Leukemias, Regulatory Issues: FDA, Hematologic Malignancies Source Type: research
Conclusion This study presents the first pharmacogenetic analysis of vincristine-related peripheral neuropathy in children with ALL in an Arab country. We have shown that genetic polymorphisms in candidate genes are not associated with peripheral neuropathy secondary to chronic therapy with high-dose vincristine (2 mg/m2) during the continuation phase. Concerning CEP72, our results are in line with the findings from the St Jude cohort of children treated for ALL with higher vincristine doses during chronic treatment. Larger high-throughput genetic analyses may be warranted to evaluate variants in other candidate g...
Source: Pharmacogenetics and Genomics - Category: Genetics & Stem Cells Tags: Original Article Source Type: research
Abstract On July 11, 2017, the Food and Drug Administration granted approval for blinatumomab for the treatment of relapsed or refractory (R/R) precursor B-cell acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific CD19-directed CD3 T-cell engager. The basis for the approval included results from two clinical trials, TOWER and ALCANTARA. TOWER, a randomized trial comparing overall survival in patients with Philadelphia chromosome (Ph)-negative R/R ALL receiving blinatumomab versus standard-of-care (SOC) chemotherapy, demonstrated a hazard ratio of 0.71 favoring blinatumomab (p = .012; medi...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN. This article is protected by copyright. All rights reserved. PMID: 29999516 [PubMed - as supplied by publisher]
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research
The dose-limiting toxicity for vincristine is peripheral neuropathy which can be potentiated with concurrent usage of azole antifungals. The current retrospective study assessed the incidence of concurrent vincristine and azole antifungal usage to determine if it led to increased neurotoxicity for the Kaiser Northern California pediatric acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma patient population. Data were obtained from the electronic medical record (2007 to 2014). In total, 130 subjects received at least one dose of vincristine for ALL or Hodgkin lymphoma (median age 9, 88% ALL, 58% male, 47% Caucasian). T...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
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