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Open research questions in Acute Lymphoblastic Leukemia research

164 gap statements mined from Acute Lymphoblastic Leukemia research papers in our 4.5M-paper local library, which holds 1,041 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • There is a lack of studies on the use of chidamide as maintenance therapy in T-ALL/T-LBL patients after allo-HSCT. The efficacy and safety of chidamide in this setting are unknown.

    Safety and efficacy of chidamide for maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with T-ALL/T-LBL · 2026 · DOI

  • There is a lack of publications on the use of blinatumomab in pediatric B-ALL. There is a need for more research on the safety and effectiveness of blinatumomab in an outpatient setting.

    Ambulatory use of blinatumomab in paediatric patients with relapsed or refractory B-cell acute lymphoblastic leukaemia at a single centre in South Africa · 2026 · DOI

  • Furthermore, it remains unclear whether IO-resistant cells exhibit cross-resistance to other therapies for R/R ALL, such as Blinatumomab or CAR-T therapy, both of which target CD19.

    Targeting drug efflux and DNA repair enhances inotuzumab ozogamicin activity in IO-resistant B-ALL cell lines · 2026 · DOI

  • Page 19 Translational Relevance There is a growing interest in BH3 mimetics in hematological malignancies, although genomic predictors of responses are not well established.

    Genomic Subtype Influences BH3 Mimetic Drug Sensitivity and Synergy with Cytotoxic Chemotherapeutics in T-cell Acute Lymphoblastic Leukemia · 2026 · DOI

  • Acute neurotoxicity is a significant adverse event in pediatric patients with ALL. The causes of acute neurotoxicity are not well understood. There is a need to develop strategies to prevent and manage acute neurotoxicity.

    Etiological Profile and Clinical Outcomes Of Acute Neurotoxicity During Pediatric ALL Treatment in a Developing Country · 2026 · DOI

  • There is a need to understand the causes and outcomes of acute neurotoxicity in pediatric patients with ALL. The existing literature has limitations, including short follow-up periods and limited sample sizes.

    Etiological Profile and Clinical Outcomes Of Acute Neurotoxicity During Pediatric ALL Treatment in a Developing Country · 2026 · DOI

  • The mechanisms underlying leukemia development and progression are not fully understood. The in utero origin and two-hit hypotheses in pediatric ALL need further clinical evidence.

    Concordant ETV6::RUNX1-positive acute lymphoblastic leukemia in monozygotic twins: a case report and review of the literature · 2026 · DOI

  • However, the target imatinib concentration required for therapeutic efficacy in the CNS remains unknown. Although the clinical relevance of these thresholds for CNS disease remains uncertain, this finding supports the notion of limited pharmacologically active exposure in the CNS.

    Central nervous system penetration of imatinib in acute lymphoblastic leukemia: Pharmacokinetic analysis and clinical implications · 2026 · DOI

  • The study faced challenges in collecting and analyzing data from a limited sample size. The study had to overcome the challenge of detecting copy number alterations (CNAs) in ALL patients. The study faced the challenge of interpreting the prognostic significance of biomarker expression in ALL patients.

    Combination of p-STAT5, CRLF2 and copy number alterations as a potential indicator of a high-risk subgroup of acute lymphoblastic leukemia · 2026 · DOI

  • The study had a limited sample size of 115 patients. The study only included precursor-B-ALL patients. The follow-up period ranged from 0.1 to 34 months.

    Combination of p-STAT5, CRLF2 and copy number alterations as a potential indicator of a high-risk subgroup of acute lymphoblastic leukemia · 2026 · DOI

  • Germline loss-of-function variants cause Noonan syndrome, with emerging evidence implicating LZTR1 in predisposition to childhood acute lymphoblastic leukemia (ALL), though its role in hematopoiesis remains poorly defined.

    LZTR1 functions as a two-hit tumor suppressor in childhood acute lymphoblastic leukemia · 2026 · DOI

  • Haematological toxicity is a significant challenge in treating children with ALL. Hyperleukocytosis at diagnosis is associated with increased relapse risk. Treatment delays and need for blood product support are common.

    Outcomes of an acute lymphoblastic leukaemia cohort between 2008 and 2017 at a South African paediatric oncology unit · 2026 · DOI

  • Standard intensive supportive care often fails to halt progressive organ damage, while clinical data regarding therapeutic plasma exchange (TPE) as a rescue intervention in pediatric populations remain scarce.

    Single-session therapeutic plasma exchange as salvage therapy for pegaspargase-induced severe acute pancreatitis accompanied by multiple organ dysfunction in a pediatric patient with B-cell precursor acute lymphoblastic leukemia: a case report · 2026 · DOI

  • Inherited genetic variation substantially increases the risk for developing childhood B-cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, yet the underlying mechanisms remain poorly understood.

    Single-cell multiomic mapping of genetic predisposition to childhood B-cell acute lymphoblastic leukemia · 2026 · DOI

  • B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, yet the mechanisms by which inherited risk variants predispose to leukemia development remain poorly understood.

    A functional genomics screen of human B-cell differentiation reveals convergent mechanisms of inherited childhood leukemia predisposition · 2026 · DOI

  • The clinical value of next-generation sequencing for measurable residual disease (NGS-MRD) monitoring in T-cell acute lymphoblastic leukemia remains to be fully established.

    Measurable residual disease detected by next-generation sequencing in T-cell acute lymphoblastic leukemia · 2026 · DOI

  • Determining what chemical exposures are toxic to children requires a variety of research approaches. Each center consists of three to four unique but integrated research projects related to the center’s theme. Children’s Centers are supported by cores that provide infrastructure, services, and resources to the research projects to help them meet their long–term goals.

    Environmental Pesticide Exposure in the Etiology of Pediatric Brain Tumors and Leukemia: A Scoping Review of Epidemiological Studies · 2026 · DOI

  • The key issue is whether increased mRNA stability is sufficient to explain fusion-gene oncogenicity across genetically diverse pediatric leukemia contexts.

    Interpreting fusion-transcript stability as one layer of leukemogenic fitness. Comment on: "Chromosomal rearrangement-enhanced mRNA stability drives the oncogenic potential of fusion genes in pediatric leukemia" · 2026 · DOI

  • Hypoglycemia is a rarely reported complication of asparaginase (ASP) therapy in children with acute lymphoblastic leukemia/lymphoma (ALL/LLy).

    Recurrent Hypoglycemia Following Asparaginase Therapy for Lymphoid Malignancies in Childhood: The Texas Children's Hospital Experience · 2026 · DOI

  • The disease has a significant impact on the immune system, causing symptoms such as anemia, frequent infections, and bone pain. The reduction of side effects and toxicity of treatments remains a concern. The development of personalized strategies and innovative therapies is challenging.

    Manejo de pacientes pediátricos com leucemia linfocítica aguda na atualidade: revisão da literatura · 2026 · DOI

  • The optimal timing and possible combination strategies of targeted therapies. The long-term toxicities and resistance mechanisms of targeted therapies. The optimal integration of targeted therapies into existing treatment protocols.

    Targeted therapies in pediatric cancers · 2026 · DOI

  • Small sample sizes in some studies - Incomplete reporting of Hardy-Weinberg equilibrium testing - Lack of multivariable adjustment for potential confounders - Inconsistent toxicity grading…

    Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization · 2026 · DOI

  • Prospective evaluation of the identified variants - Replication of associations across different populations - Investigation of the underlying mechanisms of treatment-related…

    Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization · 2026 · DOI

  • The study had a limited sample size, - The difference in EFS between patients with positive TRG/TRD MRD and those with negative MRD did not reach statistical significance, likely due to the limited sample size, - NGS-MRD might not fully capture the risk of extramedullary…

    Measurable residual disease detected by next-generation sequencing in T-cell acute lymphoblastic leukemia · 2026 · DOI

  • Investigating the underlying mechanisms of the FOXF1/FENDRR subtype, - Developing targeted interventions for patients with FOXF1/FENDRR, - Analyzing larger cohorts to confirm…

    IGH :: FENDRR and specific KRAS mutations define a novel B-ALL molecular subtype with poor chemotherapy response · 2026 · DOI

Most-cited papers in Acute Lymphoblastic Leukemia research

Most recent work

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Open questions raised by papers listed on this page include: (1) There is a lack of studies on the use of chidamide as maintenance therapy in T-ALL/T-LBL patients after allo-HSCT (“Safety and efficacy of chidamide for maintenance therapy after allogeneic…”, 2026); (2) There is a lack of publications on the use of blinatumomab in pediatric B-ALL (“Ambulatory use of blinatumomab in paediatric patients with relapsed or…”, 2026); (3) It remains unclear whether IO-resistant cells exhibit cross-resistance to other therapies for R/R ALL, such as Blinatumomab or CAR-T therapy, both of which target CD19 (“Targeting drug efflux and DNA repair enhances inotuzumab ozogamicin activity in…”, 2026); (4) Page 19 Translational Relevance There is a growing interest in BH3 mimetics in hematological malignancies, although genomic predictors of responses are not well established (“Genomic Subtype Influences BH3 Mimetic Drug Sensitivity and Synergy with…”, 2026); (5) There is a need to develop strategies to prevent and manage acute neurotoxicity (“Etiological Profile and Clinical Outcomes Of Acute Neurotoxicity During…”, 2026). 164 gap statements have been mined from Acute Lymphoblastic Leukemia research papers in our 4.5M-paper local library, which holds 1,041 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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