Venetoclax with chemotherapy in relapse/refractory early T-cell precursor acute lymphoblastic leukemia

Arora, Sankalp; Vachhani, Pankit; Bachiashvili, Kimo; Jamy, Omer

doi:10.1080/10428194.2021.1897807

Cited by 14 publications

(7 citation statements)

References 8 publications

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“…Meanwhile, the blast population was completely lost from the bone marrow after short course of venetoclax therapy. Hence, one may expect that treatment by venetoclax at pretransplant stage in this category of atients would be also effective, as demonstrated in several recent studies [11][12][13][14][15][16][17][18][19][20]. Our observation supports the idea [12] that venetoclax may be useful when preparing for HSCT in bcl-2positive ALL.…”

Section: Discussionsupporting

confidence: 87%

“…Hence, one may expect that treatment by venetoclax at pretransplant stage in this category of atients would be also effective, as demonstrated in several recent studies [11][12][13][14][15][16][17][18][19][20]. Our observation supports the idea [12] that venetoclax may be useful when preparing for HSCT in bcl-2positive ALL. We have demonstrated that myeloablative conditioning regimen is effective with regard to BAALCexpressing EPs, at least in the near-e-T-ALL case.…”

Section: Discussionsupporting

confidence: 87%

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Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

NN¹,

VV²,

AI³

et al. 2022

Insights Blood Disord

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Clinical and laboratory data are presented of a 29 year female patient with BAALC- and BCL-2-positive T-cell acute lymphoblastic leukemia developed from early leukemic progenitors which was treated unsuccessfully with high-dose chemotherapy and allogeneic stem cell transplant (allo-HSCT), but revealed an impressive effect of venetoclax. For reasons beyond our control, allo-HSCT with myeloablative fludarabine-busulfan (14 mg/ kg) conditioning regimen was performed at the peak of relapse when blast count in bone marrow aspirate was 77.5%, whereas level of BAALC-expressing earlier progenitors (EP) reached 186%. HSCT was ineffective, since the number of blasts on day+30 reached 86%, whereas the burden of BAALC-expressing EP decreased to the cutoff values. Later, at post-transplant stage, an impressive response to venetoclax coupled with hypomethylating agent was observed. Following allo-HSCT and combined venetoclax therapy a severe pancytopenia developed, which required the second transplantation of peripheral blood stem cells from her haplo-matched father. After transplantation hematopoietic recovery started on day 10+. Although bone marrow aspirate at this point was hypo cellular, it contained all types of granulocytic and erythroid elements and 2.2% of blasts only.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

NN¹,

VV²,

AI³

et al. 2022

Insights Blood Disord

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“…ETP-ALL tends to be resistant to chemotherapy, and novel agents such as BCL-2 inhibitors have shown a good response for this disease. Another important and potentially curative treatment is allo-HSCT ( 21 , 22 ). In this study, we summarized the characteristics of 57 T-ALL patients who received allo-HSCT at our center and compared the heterogeneity between ETP and non-ETP.…”

Section: Discussionmentioning

confidence: 99%

Comparison of characteristics and outcomes on ETP-ALL/LBL and non-ETP ALL patients receiving allogeneic hematopoietic stem cell transplantation

Chen

Liu²,

Ma³

et al. 2023

Front. Oncol.

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ObjectiveThis study aims to compare the characteristics of early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) and non-ETP ALL patients and the outcomes of these patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodA total of 57 patients with T-cell acute lymphoblastic leukemia/lymphoma receiving allo-HSCT at our center between January 2016 and March 2022 were enrolled in the study. Twenty-eight patients were diagnosed as ETP-ALL/LBL (28/57, 49.12%) in the cohort.ResultsThe baseline characteristic was not significantly different between the two groups. The median time for myeloid engraftment was 14 days (ranged from 11 to 21) versus 14 days (ranged from 10 to 20) (P = 0.067) and 18 days (ranged from 12 to 27) versus 15.5 days (ranged from 12 to 72) (P = 0.183) for platelet engraftment in the ETP-ALL/LBL and non-ETP ALL groups, respectively. There was no significant difference in 5-year overall survival (54.74% ± 10.33% vs. 64.20% ± 10.30%, P = 0.786), relapse-free survival (56.22% ± 10.11% vs. 57.17% ± 12.71%, P = 0.841), cumulative incidence of relapse (30.14% ± 9.85% vs. 22.79% ± 8.24%, P = 0.774), and non-relapse mortality (19.52% ± 8.99% vs. 25.95% ± 14.44%, P = 0.967) between the two groups. The incidence of acute graft versus host disease (aGVHD) (P = 0.922), II–IV aGVHD (P = 0.940), III–IV aGVHD (P = 0.664), cytomegalovirus infection (P = 0.862), Epstein–Barr virus infection (P = 0.610), and severe bacterial infection (P = 0.145) was also similar.ConclusionThe prognosis of patients with ETP-ALL/LBL was similar to non-ETP ALL patients when they received allo-HSCT.

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“…Apart from those backgrounds, there are relatively many reports on venetoclax clinical activity in T-ALL (mainly case series), but it is difficult to conclude whether this represents a more general sensitivity in T-ALL or if this is a bias of clinical decisions or reporting. However, many authors believe that venetoclax should be considered in recurrent or refractory T-ALL [ 2 , 21 , 37 , 38 , 39 , 40 , 41 ]. It is not known if there are common genomic/molecular features of those responsive T-ALL cases, apart from those mentioned above, and from the pre-clinical data on ETP-ALL and RPL10 -mutated T-ALL.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

et al. 2023

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Venetoclax, the best established BH3 mimetic, is a practice-changing proapoptotic drug to treat blood cancers in adults. In paediatrics, the data are less but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the interventions could be potentially molecularly guided as vulnerabilities to BH3 mimetics were reported. Currently, venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated thus far with venetoclax in Poland. We set out to gather this data to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data of November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with haematologic complete remission (CR), was reported in five patients out of ten, whereas five patients did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe that BH3 mimetics have clinical activity in children and should be available to paediatric haemato-oncology practitioners in well-selected applications.

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Venetoclax with chemotherapy in relapse/refractory early T-cell precursor acute lymphoblastic leukemia

Cited by 14 publications

References 8 publications

Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

Comparison of characteristics and outcomes on ETP-ALL/LBL and non-ETP ALL patients receiving allogeneic hematopoietic stem cell transplantation

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

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