612. Acute Lymphoblastic Leukemia: Clinical Studies: Therapeutic Strategies

Nicholas J. Short, et al.
Conclusion cited from the abstract: Reduced-intensity chemotherapy with hyper-CVD plus INO, with or without blinatumomab, is safe and effective in older adults with newly diagnosed Ph-negative ALL, with an overall response rate of 98% and 3-year OS rate of 54%. Further optimization of this regimen with less chemotherapy in patients 70 years and older is warranted to further decrease the rate of death in remission.
Anne Angiolillo, et al.
Conclusion cited from the abstract: AALL0932 demonstrated that the AR subset of patients with SR B-ALL who received VCR/DEX pulses every 12 weeks maintained outstanding outcomes similar to those who received pulses every 4 weeks. The decreased frequency of VCR/DEX pulses will be incorporated into frontline B-lineage COG ALL trials thereby dramatically improving patient and family quality of life.
Peihua Lu, et al.
Conclusion cited from the abstract: This study has demonstrated that FasT CAR-T cells with superior expansion capability and younger/less exhausted phenotypes can be generated rapidly. This first-in-human clinical study showed that FasT CAR-T is safe and highly effective for treating patients with B-ALL.
Josep-Maria Ribera, et al
Conclusion cited from the abstract: This trial, in which post-induction therapy was only based on MRD results assessed by FCM, suggests that avoiding alloHSCT does not hamper the outcome of HR Ph-neg adult ALL pts with adequate MRD response after induction and after consolidation. Better post-remission alternative therapies are specially needed for patients with poor MRD clearance.

Supported by grants PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain.


Naomi Michels, et al.
Conclusion cited from the abstract:  The MRD levels did not differ between DS ALL and non-DS ALL patients when matched for (cyto)genetics and other risk factors. In accordance, the overall relapse rate of DS ALL patients did not differ from that of matched non-DS ALL patients. Similar to non-DS ALL, IKZF1 deletion is an adverse risk factor for DS-ALL, indicating the need for treatment aimed at reducing the high relapse risk. DS ALL patients suffer more frequently from death in induction and from treatment while in remission, which jeopardizes treatment intensification. Therefore, the efficacy of targeted, less toxic therapies such as immunotherapies should be assessed in DS ALL.
Shuhong Shen, et al.
Conclusion cited from the abstract:  Intensive chemotherapy including dasatinib at 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared to imatinib at 300 mg/m2per day and provided excellent control of central-nervous-system leukemia without the use of prophylactic cranial irradiatio.
Session: 618.

Chunjie Li, et al. 

Conclusion cited from the abstract: We first identified that GATA3 rs3824662 associated with the risk of MRD in the childhood ALL cohorts of Han ethnicity. Mechanistic study showed that inherited GATA3 variants possibly contributed to L-Asp resistance via autophagy activation induced by promoting GATA3 enhancer activity, providing new insights into the rationale for the future development of combinational treatment of L-Asp and anti-autophagy regimen in ALL patients.



Oral presentation from the session Molecular Pharmacology, Drug Resistance with Co-Authors Beat Bornhauser & Jean-Pierre Bourquin from the Department of Pediatric Oncology, University Children's Hospital Zurich, Zurich, Switzerland:

Laura Hinze, et al. 
Conclusion cited from the abstract: Our data support a model in which inducible phase separation of GSK3α and heat shock proteins represents a previously unrecognized response to amino acid starvation that concentrates the cellular machinery for protein degradation, thus allowing efficient catalysis of this alternative source of amino acids in response to amino acid starvation.