Patients with acute lymphoblastic leukemia (ALL) experience one of the most aggressive malignant disorders of blood and bone marrow, characterized by the overproduction of immature white blood cells. Most ALL cases are of B-cell origin, and half of the patients diagnosed with ALL are children, especially infants aged 1-4 years. Standard-of-care therapies, including intensive chemotherapy, risk stratification, minimal residual disease monitoring, and supportive clinical care, have offered remarkable advances in the treatment of ALL and allowed for complete hematologic remission (CR) in most pediatric and adult patients. Despite these advanced treatment results and the increased overall survival (OS) of newly diagnosed patients, those suffering from relapsed or refractory disease (R/R ALL) do not share the same success. R/R ALL presents with a dismal prognosis and an OS of 3 to 12 months, depending mainly on the duration of the first remission. To overcome this medical challenge, targeted therapies have started to enter the arena, aiming at generating better patient outcomes with less toxicity and a greater probability of proceeding to allogeneic hematopoietic stem cell transplantation (alloHSCT).

This Research Topic focuses on the current landscape of novel targeted immunotherapies and molecular therapies for R/R ALL, their appropriate use in children and adult patients, and how they are incorporated into recent clinical practice. In addition, it aims to expand knowledge on the molecular pathways involved in ALL and how these pathways are being therapeutically targeted. Bispecific T-cell engager (BiTE) immunotherapy constructs crosslink the CD3 component of cytotoxic T-cells with the CD19 antigen on the surface of tumor cells, resulting in the activation of T-cells and the release of cytotoxic proteins. Inotuzumab ozogamicin is an anti-CD22 antibody conjugated to calicheamicin. It binds to cell surface CD22, and the drug is internalized into leukemic cells while calicheamicin is released, resulting in DNA damage and subsequent cell apoptosis. Chimeric antigen receptor T-cells (CAR T-cells) immunotherapy aims at harvesting patient-specific T-cells and reengineering them to express a new antigen recognition receptor to encounter and destroy the CD19 antigen on the leukemic cell surface. Tyrosine kinase inhibitors (TKIs) disrupt the signal transduction pathways of protein kinases in several ways and are used for the treatment of Philadelphia chromosome-positive (Ph+) ALL in children and adults.

Our aim is to advance the understanding of novel and effective treatment strategies in the ALL setting for children and adult patients, and to highlight the important challenges to be addressed in the upcoming years.

The objectives of this Research Topic are as follows:

1. Promote knowledge of the novel treatment strategies for children and adults with R/R ALL.
2. Identify and characterize potential mechanisms of resistance to immunotherapies, and potential adverse effects and toxicity.
3. Provide information on the appropriate use of different immunotherapies according to specific clinical conditions.
4. Explore future perspectives on whether immunotherapies could be incorporated as frontline therapies in parallel with or sequentially to standard-of-care treatment.

Clinicians, molecular biology, and hematology researchers are kindly invited to contribute to this article collection by submitting original research, reviews, clinical trials, mini-reviews, case, and systematic review articles.

All above-mentioned article types will be considered for this Research Topic. For more information regarding particular article types, please visit: https://www.frontiersin.org/journals/medicine/for-authors/article-types

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