Chr t(4;11)(q21;q23)

After the initial induction chemotherapy, her disease remained refractory, and the patient received salvage immunotherapy with blinatumomab and inotuzumab ozogamicin. We present this case to highlight the potential of KMT2A-rearranged B-ALL to undergo lineage switch following B-cell targeted therapy. Patients with this kind of B-ALL should therefore be closely monitored to capture potential changes in the nature of the disease and prompt appropriate treatment.

P2, N=107, Recruiting, West China Hospital of Sichuan University; West China Hospital, Sichuan University

P3, N=1033, Active, not recruiting, University College, London | Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

We report a case of t-ALL that mimicked CD34+ HPC and was mobilized by high-dose G-CSF. Up to 70% of secondary leukemias bear 11q23/KMT2A rearrangements, which occur at the multipotent stem cell stage and can result in myeloid and lymphoid leukemias. Donors who have received past chemotherapy, especially with topoisomerase II inhibitors, are at increased risk for 11q23/KMT2A leukemias.

Compared with historical data, prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved, but allo-HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.

Overall, our study identifies the first microRNAthat strikes in one hit four crucial drivers of blast transformation in t(4;11) leukemia. Therefore, MiR-27a emerges as a new promising therapeutic target for this aggressive and poorly curable form of leukemia.

In a 4-month landmark analysis, the 5-year OS rate was 32% (95% CI, 14 - 70%) in patients who underwent HSCT versus 11% (95% CI, 3 - 39) in others (p=0.10). Our study confirms the poor prognosis of ALL with any KMT2A rearrangement and the role of HSCT in these patients.

These analyses revealed that the expression of AF4-MLL for only 48 h was sufficient to significantly change the genomic landscape (transcription and chromatin) even on a longer time scale. Thus, we have to conclude that the AF4-MLL fusion protein works through a hit-and-run mechanism, probably necessary to set up pre-leukemic conditions, but being dispensable for later disease progression.

Dexamethasone good response on day 8 (n=82) was not associated with better treatment outcome (p=0.060 for EFS and p=0.332 for CIR)...We did not include MRD in this analysis as we previously showed its prognostic value (G. Tsaur et al doi.org/10.1111/bjh.17304).

These results support indication of alloHSCT in CR1 for t(4;11) BCP-ALL patients, provided a negative MRD status is achieved. Conversely, pre-alloHSCT additional therapy is warranted in MRD-positive patients.

Conclusions : Our first assessment of risk alleles for cytogenetic subsets of AML identified two novel independent risk loci associated with 11q23/KMT2A-translocated AML, and one risk locus associated with CBF-AML. These data suggest an important, subtype-specific role for transcriptional elongation in AML and that functional studies of retro transposition elements should be undertaken in leukemogenesis.

MRD status is highly predictive of outcome within KMT2A subgroups. In MRD-negative patients after induction course two, both t(10;11) KMT2A subgroups were associated with poor outcome.

We report a novel translocation t(5;11)(q35;q23)KMT2A-MAML1 in newly diagnosed infant precursor B-ALL. Long-term follow-up and a larger number of patients are needed to better understand its prognostic significance.