Durable remissions in <i>TCF3-HLF</i> positive acute lymphoblastic leukemia with blinatumomab and stem cell transplantation

Mouttet, Brice; Vinti, Luciana; Ancliff, Philip; Bodmer, Nicole; Brethon, Benoît; Cario, Gunnar; Chen-Santel, Christiane; Elitzur, Sarah; Hazar, Volkan; Kunz, Joachim; Möricke, Anja; Stein, Jerry; Vora, Ajay; Yaman, Yöntem; Schrappe, Martin; Anak, Sema; Baruche, André; Locatelli, Franco; Stackelberg, Arend von; Stanulla, Martin; Bourquin, Jean‐Pierre

doi:10.3324/haematol.2018.210104

Cited by 55 publications

(56 citation statements)

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“…Achievement of CR in three of four patients with constitutional trisomy 21 suggests that blinatumomab could be particularly useful to treat these fragile patients at risk of experiencing severe toxicities when exposed to aggressive chemotherapy 12 . Remarkably, both patients with t(17;19) rearrangement obtained CR with MRD response, this finding corroborating recent data on blinatumomab efficacy in this peculiar patient subset 13 .…”

Section: Dear Editorsupporting

confidence: 89%

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

et al. 2020

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Section: Dear Editorsupporting

confidence: 89%

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

et al. 2020

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“…The results of the RIALTO trial also show a trend toward improved OS and RFS for patients who received HSCT after blinatumomab as compared with those who did not 21 . Moreover, durable remissions in TCF3‐HLF‐positive ALL with blinatumomab and subsequent HSCT have recently been reported, a rare subtype of leukemia characterized by a high rate of treatment failure 22 . In line with previous works, we did not observe exacerbations of graft‐vs‐host disease 23,24 …”

Section: Discussionsupporting

confidence: 89%

Blinatumomab in pediatric patients with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia

Queudeville

Schlegel

Heinz

et al. 2021

European J of Haematology

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Objective Pediatric patients with relapsed or refractory acute lymphoblastic leukemia have a poor prognosis. We here assess the response rates, adverse events, and long‐term follow‐up of pediatric patients with relapsed/refractory acute lymphoblastic leukemia receiving blinatumomab. Methods Retrospective analysis of a single‐center experience with blinatumomab in 38 patients over a period of 10 years. Results The median age at onset of therapy was 10 years (1‐21 years). Seventy‐one percent of patients had undergone at least one hematopoietic stem cell transplantation (HSCT) prior to treatment with blinatumomab. We observed a response to blinatumomab in 13/38 patients (34%). The predominant side effect was febrile reactions, nearly half of the patients developed a cytokine release syndrome. Eight events of neurotoxicity were registered over the 78 cycles (15%). To date, nine patients (24%) are alive and in complete molecular remission. All survivors underwent haploidentical HSCT after treatment with blinatumomab. Conclusions Despite heavy pretreatment of most of our patients, severe adverse events were rare and response rates encouraging. Blinatumomab is a valuable bridging salvage therapy for relapsed or refractory patients to a second or even third HSCT.

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“…According to drug screening results, TCF3-HLF-bearing tumour cells obtained from paediatric patients show resistance to standard therapy, including nucleotide analogues (e.g., cytarabine) and mitotic spindle inhibitors (e.g., vincristine) but are sensitive to glucocorticoids [15]. Studies to date show that the use of tyrosine kinase inhibitors or CD19directed immunotherapy can improve the quality of remission in TCF3-HLF-positive ALL patients [16]. Moreover, TCF3-HLF-positive cells are sensitive to PARP inhibitors (olaparib and veliparib) in vitro, but monotherapy with these drugs was not effective in in vivo studies [17].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL

et al. 2020

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Background: The use of high-throughput analytical techniques has enabled the description of acute lymphoblastic leukaemia (ALL) subtypes. The TCF3-HLF translocation is a very rare rearrangement in ALL that is associated with an extremely poor prognosis. The TCF3-HLF fusion gene in the described case resulted in the fusion of the homeoboxrelated gene of TCF3 to the leucine zipper domain of HLF. The TCF3-HLF fusion gene product acts as a transcriptional factor leading to the dedifferentiation of mature B lymphocytes into an immature state (lymphoid stem cells). This process initiates the formation of pre-leukaemic cells. Due to the rarity of this chromosomal aberration, only a few cases have been described in the literature. The advantage of this work is the presentation of an interesting case of clonal evolution of cancer cells and the cumulative implications (diagnostic and prognostic) of the patient's genetic alterations. Case presentation: This work presents a patient with diagnosed with TCF3-HLF-positive ALL. Moreover, the additional genetic alterations, which play a key role in the pathogenesis of ALL, were detected in this patient: deletion of a fragment from the long arm of chromosome 13 (13q12.2-q21.1) containing the RB1 gene, intragenic deletions within the PAX5 gene and NOTCH1 intragenic duplication. Conclusions: A patient with coexistence of chromosomal alterations and the TCF3-HLF fusion has not yet been described. Identifying all these chromosomal aberrations at the time of diagnosis could be sufficient to determine the cumulative effects of the described deletions on the activity of other oncogenes or tumour suppressors, as well as on the clinical course of the disease. On the other hand, complex changes in the patient's karyotype and clonal evolution of cancer cells call into question the effectiveness of experimental therapy.

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Durable remissions in TCF3-HLF positive acute lymphoblastic leukemia with blinatumomab and stem cell transplantation

Cited by 55 publications

References 15 publications

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

Blinatumomab in pediatric patients with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia

Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL

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