What you decided at the review gate

These are the discovery findings as they were approved. Mapping & Synthesis built on them, so they cannot be changed for this run.

Acute Lymphoblastic Leukemia United States All RUN-C8D50E0C
Discovery approved

Mapping & Synthesis has built on these findings. Decisions made here are final for this run.

Export all insights to PPT See Mapping & Synthesis

9 key insights from the discovery phase

Each card is one slot the research owes, filled from its stage document. Ready cards carry forward as written unless you change them; a card marked Needs review says why.

01

Epidemiology

Acute lymphocytic leukemia in the United States has a reported incidence rate of 1.9 per 100,000 men and women per year and a death rate of 0.4 per 100,000 men and women per year. SEER reported 126,118 people living with acute lymphocytic leukemia in 2023 and a 5-year relative survival of 73.2% during 2016–2022.

Clinical Landscape
Ready | 9 sources |includes web evidence
1.9 per 100,000 per year
Incidence rate
0.4 per 100,000 per year
Death rate
126,118
Estimated US prevalence
73.2%
5-year relative survival
<20 years
Most frequently diagnosed age group
2 to 5 years
Peak pediatric incidence age
What this means

Claims-based cohorting should distinguish pediatric, adolescent and young adult, and adult populations because disease incidence and outcomes differ by age setting. Subpopulation segmentation is also relevant for adult Philadelphia chromosome-negative B-cell ALL because outcome data were reported separately for this subgroup.

Worth checking: Check that prevalence year remains 2023 in the cited SEER extract.

Sources
Orphanet / Orphadata NCI SEER CDC / NCHS WHO Global Health Observatory
02

Patient Population & Segmentation

The supplied evidence segments ALL populations by age group, lineage, molecular subtype, MRD status, and risk category. B-cell lineage disease represented 79.3% of cases and T-cell lineage disease represented 20.7% in the cited immunophenotyping dataset.

Clinical Landscape
Ready | 7 sources |includes web evidence
What this means

Claims-based line-of-therapy analyses should preserve biologic and risk subgroup definitions, including B-cell versus T-cell lineage, Philadelphia chromosome status, MRD status, and age setting. These cohort-defining forks are directly linked to treatment selection and transplant consideration in the supplied evidence.

Worth checking: Expert review should confirm whether the lineage proportions are intended as representative or study-specific.

Sources
WHO National Cancer Institute (NCI) Orphanet / Orphadata ASH / Blood (American Society of Hematology)
SegmentApproximate shareDefining feature
Children and adolescentsMost common populationMost frequently diagnosed among people aged <20
Childhood ALL peak incidenceNot quantifiedPeak incidence between 2 and 5 years of age
B-cell acute lymphoblastic leukemia (B-ALL)79.3%CD19, CD22, cytoplasmic CD79a markers
T-cell acute lymphoblastic leukemia (T-ALL)20.7%Cytoplasmic CD3 and CD5 markers
Philadelphia chromosome-negative B-cell ALLNot quantifiedAdult B-cell ALL molecular subgroup
ZNF384-rearranged B-cell ALLRare subtypeEP300::ZNF384 and TCF3::ZNF384 fusion partners
MRD-negative patientsNot quantifiedTreatment segmentation by MRD status
Patients in MRD-positive CR1Not quantifiedHigher-risk treatment cohort
03

Disease Definition & Taxonomy

ALL is described as a group of rare Non-Hodgkin lymphoma characterized by malignant proliferation of lymphoid cells blocked at an early stage of differentiation. The supplied evidence classifies disease by lineage, molecular subgroup, and treatment-relevant biologic features.

Clinical Landscape
Ready | 9 sources |includes web evidence
What this means

Disease taxonomy in claims research should retain lineage, molecular subgroup, and MRD-based risk segmentation because these categories define treatment pathways and transplant eligibility. The evidence also supports separating adult Philadelphia chromosome-negative B-cell ALL from broader ALL populations.

Worth checking: Review whether ALL should be labeled as leukemia versus rare Non-Hodgkin lymphoma in downstream taxonomy standards.

Sources
Orphanet / Orphadata WHO National Cancer Institute (NCI) NCI SEER
ClassificationCategoryNote
Acute lymphoblastic leukemiaRare Non-Hodgkin lymphomaMalignant lymphoid proliferation affecting marrow and blood
B-cell acute lymphoblastic leukemiaLineage subtypeDefined using CD19, CD22, cytoplasmic CD79a
T-cell acute lymphoblastic leukemiaLineage subtypeDefined using cytoplasmic CD3 and CD5
Philadelphia chromosome-negative B-cell ALLMolecular subgroupAdult treatment-linked subgroup
ZNF384-rearranged B-cell ALLMolecular subgroupIncludes EP300::ZNF384 and TCF3::ZNF384 fusions
MRD-positive CR1 diseaseRisk subgroupUsed for treatment stratification
Higher-risk subsetsRisk categoryMay require allogeneic transplantation
04

Diagnostic Foundation

The supplied evidence describes a diagnostic workflow based on bone marrow assessment, morphology, cytochemical testing, immunophenotyping, cytogenetics, and lumbar puncture evaluation.

Clinical Landscape
Ready | 5 sources |includes web evidence
  1. Bone marrow aspiration
  2. Morphology assessment
  3. Cytochemical analysis
  4. Flow cytometric immunophenotyping
  5. Lineage marker evaluation
  6. Cytogenetics testing
  7. Immunohistochemistry assessment
  8. Lumbar puncture evaluation
What this means

Claims algorithms for incident ALL may need combinations of marrow procedures, flow cytometry, cytogenetic testing, and CNS-directed evaluation to improve diagnostic specificity. Lineage-defining immunophenotyping is central to distinguishing B-cell versus T-cell disease cohorts.

Worth checking: The sequence of diagnostic steps was inferred from the supplied workup descriptions rather than a formal guideline.

Sources
WHO Orphanet / Orphadata Europe PMC ASH / Blood (American Society of Hematology)
05

Natural History & Disease Journey

The supplied materials describe an ALL disease course involving diagnostic confirmation, lineage and molecular classification, MRD-based risk assessment, frontline treatment selection, and escalation for higher-risk or suboptimal responders.

Clinical Landscape
Ready | 8 sources |includes web evidence
  1. Initial symptom presentation
  2. Bone marrow confirmation
  3. Immunophenotypic lineage assignment
  4. Molecular subgroup classification
  5. MRD status assessment
  6. Frontline treatment selection
  7. Response-based risk stratification
  8. Transplant consideration for high-risk
What this means

Claims-based line-of-therapy construction should incorporate transitions driven by MRD status, biologic subgrouping, and response assessment because these factors determine escalation and transplant pathways. Age setting and molecular classification also define distinct treatment journeys.

Worth checking: Relapse sequencing details were limited in the supplied evidence.

Sources
Orphanet / Orphadata National Cancer Institute (NCI) NCI SEER CDC / NCHS
06

Treatment Landscape

The supplied evidence describes ALL treatment as stratified by Philadelphia chromosome/BCR::ABL1 status, lineage subtype, age group, and MRD context across induction, consolidation, maintenance, transplant, and relapsed/refractory settings. Therapeutic modalities identified include multiagent chemotherapy, tyrosine kinase inhibitors for Ph+ ALL, immunotherapy, CAR-T therapy, transplant approaches, and lineage-specific agents.

Treatment Evidence
Ready | 9 sources |includes web evidence
What this means

Claims-based line-of-therapy construction should segment patients by Ph/BCR::ABL1 status, lineage subtype, age group, MRD context, relapsed/refractory status, CAR-T exposure, and transplant exposure. The evidence supports mapping treatment journeys across induction, consolidation, maintenance, and reinduction phases.

Worth checking: Confirm whether AYA-focused ASH recommendations should be operationalized separately from adult NCCN pathways.

Sources
FDA Drug Labeling (openFDA) ESMO FDA National Cancer Institute (NCI)
Therapy classExamplesKey populations / role
Multiagent chemotherapyPrednisone, vincristine, and an anthracyclineAdult ALL remission induction
Pediatric-inspired asparaginase-containing regimensAsparaginase-containing regimensFrontline therapy for adolescents and young adults (AYAs) with ALL
Tyrosine kinase inhibitors (TKIs)Imatinib, dasatinib, ponatinibPhiladelphia chromosome-positive (Ph+) ALL
Immunotherapy / targeted reinductionBlinatumomab and/or inotuzumabRelapsed/refractory AYA ALL reinduction
CAR-T cellular therapyTECARTUS (brexucabtagene autoleucel)Adult relapsed or refractory B-cell precursor ALL
Lineage-specific therapyNelarabineRelapsed/refractory T-ALL/T-LBL after at least two chemotherapy regimens
Transplant consolidationAllogeneic hematopoietic stem cell transplantation (HSCT)Higher-risk subsets or patients with suboptimal responses; consolidation/transplant decision point
07

Guideline / Standard of Care

The supplied evidence identifies NCCN adult ALL guidelines Version 2.2024, NCCN Pediatric ALL guideline Version 2.2025, and ASH 2026 ALL guidelines as major U.S. standards governing treatment selection. Pathways branch by Ph/BCR::ABL1 status, lineage, age group, MRD status, and relapsed/refractory setting.

Treatment Evidence
Ready | 9 sources |includes web evidence
What this means

Guideline-driven cohort logic should incorporate biomarker testing and MRD assessment at diagnosis and during treatment transitions because treatment branching depends on these factors. Separate cohort definitions may be required for pediatric, AYA, and adult populations and for Ph+ versus Ph-negative disease.

Worth checking: Check whether the cited ASH 2026 recommendations are intended only for AYAs and should not be generalized to all adults with ALL.

Sources
ESMO FDA Drug Labeling (openFDA) FDA National Cancer Institute (NCI)
Guideline / bodyPopulationRecommended approach
NCCN Clinical Practice Guidelines in Oncology for Acute Lymphoblastic Leukemia Version 2.2024Adults with Ph-positive and Ph-negative ALLTreatment strategies stratified by Philadelphia chromosome status, age, MRD assessment, and supportive care consideratio
NCCN Pediatric Acute Lymphoblastic Leukemia guideline Version 2.2025Pediatric BCR::ABL1-positive and BCR::ABL1-negative B-cell lineage, T-cell lineage, and infant ALLRisk assessment and stratification of risk-adapted therapy
American Society of Hematology 2026 frontline management guidelineAdolescents and young adults (AYAs) with B-ALL/T-ALL or T-LBL/LLy receiving frontline therapyPediatric-inspired regimens containing asparaginase are recommended as frontline therapy compared with traditional adult
American Society of Hematology 2026 relapsed/refractory guidelineAYAs with relapsed/refractory ALLBlinatumomab and/or inotuzumab over chemotherapy for reinduction
NCCN and ASH pathway structureALL across treatment phasesPretreatment, induction, consolidation, maintenance therapy, and allogeneic HSCT decision points guided by biomarker and
08

Approved Therapy & Label Intelligence

The supplied evidence identifies FDA-approved therapies for ALL spanning Ph+ disease, relapsed/refractory T-ALL/T-LBL, pediatric relapsed/refractory ALL, maintenance therapy, and adult relapsed/refractory B-cell precursor ALL. Recent regulatory activity includes a 2024 FDA accelerated approval for ponatinib with chemotherapy in newly diagnosed adult Ph+ ALL.

Treatment Evidence
Ready | 7 sources |includes web evidence
What this means

Approved therapy mapping supports claims segmentation by biomarker-defined disease, age group, lineage, and treatment setting. Frontline versus relapsed/refractory distinctions are essential because several approvals are limited to specific lines and subpopulations.

Worth checking: Verify whether unavailable approval dates for TECARTUS should be supplemented from an external FDA source.

Sources
FDA Drug Labeling (openFDA) FDA Drugs@FDA (openFDA) ESMO ClinicalTrials.gov
TherapyIndication / populationSettingApprovalRecent label change
Ponatinib (ICLUSIG)Adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with chemothFrontline newly diagnosed adult Ph+ ALLFDA accelerated approval 2024-03-192025-10-10 ICLUSIG SUPPL 38 efficacy supplement; specific ALL scope not provided
Dasatinib (SPRYCEL)Adults with Ph+ ALL with resistance or intolerance to prior therapy; pediatric patients 1 year of age and older with newRelapsed/refractory adult Ph+ ALL and frontline pediatric Ph+ ALLInitial U.S. Approval: 20062024-07-31 SPRYCEL SUPPL 28 labeling action; specific ALL scope not provided
Imatinib mesylate (Gleevec/imatinib)Adult relapsed/refractory Philadelphia chromosome positive acute lymphoblastic leukemia and pediatric newly diagnosed PhRelapsed/refractory adult Ph+ ALL and frontline pediatric Ph+ ALLInitial U.S. Approval: 2001Multiple FDA supplement approval dates including SUPPL 63 AP 2024-03-01; ALL scope not specified
Nelarabine (ARRANON)Adult and pediatric patients age 1 year and older with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblasRelapsed/refractory T-ALL/T-LBL after at least two regimensInitial U.S. Approval: 20052025-03-11 ARRANON SUPPL 14 labeling action; specific ALL scope not provided
Clofarabine injectionPediatric patients 1 to 21 years old with relapsed or refractory ALL after at least two prior regimensPediatric relapsed/refractory ALLInitial U.S. Approval: 2004No recent label change identified in supplied evidence
Methotrexate InjectionAdult and pediatric ALL as part of a combination chemotherapy regimen or maintenance regimenCombination chemotherapy and maintenance settingsInitial U.S. Approval: 1953No recent label change identified in supplied evidence
TECARTUS (brexucabtagene autoleucel)Adult relapsed or refractory B-cell precursor ALLRelapsed/refractory adult B-cell precursor ALLApproved; approval date not provided in supplied evidenceNo recent label change identified in supplied evidence
09

Key Clinical & Treatment Insights

The discovery phase established that Acute Lymphoblastic Leukemia treatment pathways, outcomes, and regulatory positioning are highly stratified by age group, lineage subtype, Philadelphia chromosome/BCR::ABL1 status, molecular subgroup, MRD context, and relapsed/refractory status.

Celestra Synthesis
Ready | 16 sources
  1. The supplied evidence segments ALL populations by age group, lineage, molecular subtype, MRD status, and risk category, with B-cell lineage disease representing 79.3% of cases and T-cell lineage disea
  2. Diagnostic classification frameworks rely on bone marrow assessment, morphology, cytochemical testing, immunophenotyping, cytogenetics, and lumbar puncture evaluation, with lineage assignment supporte
  3. Treatment selection pathways are stratified across induction, consolidation, maintenance, transplant, and relapsed/refractory settings by Philadelphia chromosome/BCR::ABL1 status, lineage subtype, age
  4. The supplied evidence identifies molecular subgrouping that includes Philadelphia chromosome-negative B-cell ALL and ZNF384-rearranged B-ALL with EP300::ZNF384 and TCF3::ZNF384 fusion partners.
  5. NCCN adult ALL Version 2.2024, NCCN Pediatric ALL Version 2.2025, and ASH 2026 guidelines govern treatment selection using branching logic based on Ph/BCR::ABL1 status, lineage, age group, MRD status,
  6. FDA-approved therapies identified in the supplied evidence span specific ALL subpopulations and settings including Ph+ disease, relapsed/refractory T-ALL/T-LBL, pediatric relapsed/refractory ALL, main
What this means

Downstream modelling should preserve ALL subpopulation stratification variables and setting-specific treatment branches because diagnostic classification, guideline pathways, and approved therapies are differentiated by lineage, molecular status, age group, MRD context, and relapsed/refractory statu

Sources
Orphanet / Orphadata NCI SEER CDC / NCHS WHO Global Health Observatory

Source conflicts (0)

Discovery surfaced no disagreements between sources.