scholarly journals T-Cell Acute Lymphoblastic Leukemia—Current Concepts in Molecular Biology and Management

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1621
Author(s):  
Parveen Shiraz ◽  
Waqas Jehangir ◽  
Vaibhav Agrawal
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Children And Young Adults

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are steadily improving, patients with relapsed and refractory T-ALL fare poorly. Newer targeted therapies are being studied in large clinical trials and have the potential to further improve outcomes. The role of allogeneic stem cell transplant (HSCT) is evolving due to the increased use of pediatric-inspired regimens and MRD monitoring. In this review we will discuss the biology, treatment, and outcomes in pediatric and adult T-ALL.

scholarly journals T-cell acute lymphoblastic leukemia

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 580-588 ◽  
Author(s):  
Elizabeth A. Raetz ◽  
David T. Teachey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Disease Response ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Relapsed Disease ◽  
Modern Genomic

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.

scholarly journals Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 5 (17) ◽  
pp. 3436-3444
Author(s):  
Hasmukh Jain ◽  
Manju Sengar ◽  
Vasu Babu Goli ◽  
Jayashree Thorat ◽  
Prashant Tembhare ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Confidence Interval ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Optimal Number ◽  
Cell Transplant ◽  
Historical Cohort ◽  
Cell Acute Lymphoblastic Leukemia

Abstract The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib’s activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(http://ctri.nic.in/Clinicaltrials).

scholarly journals Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplant

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Leena T. Rahmat ◽  
Anna Nguyen ◽  
Haifaa Abdulhaq ◽  
Sonam Prakash ◽  
Aaron C. Logan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia

Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine. Assessment of measurable residual disease by next generation sequencing showed no evidence of residual disease of a sensitivity of 1 × 10−6. While the combination of venetoclax and hypomethylating agents has shown promise in the treatment of relapsed/refractory AML, and to our knowledge, this is the first report of this combination demonstrating clinical activity in relapsed/refractory T-ALL.

scholarly journals Bispecific T-cell engaging antibodies in B-cell precursor acute lymphoblastic leukemias: focus on blinatumomab

2020 ◽  
Vol 11 ◽  
pp. 204062072091963
Author(s):  
Jose-Maria Ribera ◽  
Eulalia Genescà ◽  
Jordi Ribera
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Development Program ◽  
Cell Transplant ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Clinical Development Program

Bispecific T-cell engaging antibodies are constructs engineered to bind to two different antigens, one to a tumor-specific target and the other to CD3-positive T cells or natural killer (NK) cells. Blinatumomab engages CD19 and CD3, performing effective serial lysis. The clinical development program in acute lymphoblastic leukemia (ALL) includes clinical trials in relapsed or refractory (R/R) patients and in B-cell precursor (BCP) ALL patients with measurable residual disease. Several trials are currently being conducted in de novo BCP-ALL, either in induction, consolidation, or before or after hematopoietic stem cell transplant. Combination with other targeted therapies or with other immunotherapeutic approaches are also underway. Several strategies are aimed to optimize the use of blinatumomab either by overcoming the mechanisms of resistance (e.g. inhibition of PD-1/PD-L1) or by improvements in the route of application, among others.

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