Cards from the latest part of the research come first; the discovery cards you reviewed at the gate are below them. A card marked Needs review says why.
Mapping & Synthesis (15 cards)
New since your last review
10
Diagnosis Code Footprint
The supplied evidence identifies ICD-10-CM Acute Lymphoblastic Leukemia diagnosis codes within the C91.0 family, including active disease, remission, and relapse states. Legacy ICD-9-CM concepts for active disease, remission, relapse, and personal history of lymphoid leukemia are also provided.
Diagnostic Footprint
Ready|6 sources|includes web evidence
What this means
Claims-based ALL cohorts can be stratified by disease state using explicit remission and relapse diagnosis coding. Longitudinal line-of-therapy analyses may use diagnosis-state transitions between C91.00, C91.01, and C91.02 as monitoring signals.
Worth checking: Confirm whether C91.00 should be interpreted as both active disease and failed remission in the intended analytic framework.
Acute lymphoblastic leukemia not having achieved remission
Active disease or failed-remission ALL identification
ICD-10-CM
C91.01
Acute lymphoblastic leukemia, in remission
Remission-state ALL monitoring
ICD-10-CM
C91.02
Acute lymphoblastic leukemia, in relapse
Relapse-state ALL monitoring
ICD-9-CM
20400
Acute lymphoid leukemia, without mention of having achieved remission
Legacy active disease identification
ICD-9-CM
20401
Acute lymphoid leukemia, in remission
Legacy remission-state identification
ICD-9-CM
20402
Acute lymphoid leukemia, in relapse
Legacy relapse-state identification
ICD-9-CM
V1061
Personal history of lymphoid leukemia
Legacy personal-history identification
11
Diagnostic Procedure & Lab Codes
The supplied materials identify HCPCS, CPT, and LOINC concepts related to bone marrow evaluation, flow cytometry, and FISH cytogenetic testing relevant to ALL diagnostic workup and monitoring. Genomic targets referenced in the evidence include BCR/ABL1, KMT2A, ETV6/RUNX1, CRLF2, ABL1, ABL2, PDGFRB, PBX1;TCF3, and CDKN2A.
Diagnostic Footprint
Ready|4 sources|includes web evidence
What this means
Procedure and laboratory utilization can provide observable diagnostic and disease-monitoring signals in claims-linked datasets when direct treatment-intent coding is incomplete. Repeated bone marrow, flow cytometry, and FISH testing may support longitudinal assessment of disease activity and follow-up.
Worth checking: Check whether additional CPT hematopathology or molecular pathology codes are required for the intended claims algorithm.
Flow cytometry study, blast-cell assessment, and lymphocyte/leukocyte quantification
FISH cytogenetic testing
CPT
88237; 88275; 88271
FISH testing for diagnostic, prognostic, and follow-up evaluation
12
Code System Crosswalk
The supplied evidence aligns legacy ICD-9-CM acute lymphoid leukemia concepts with ICD-10-CM Acute Lymphoblastic Leukemia remission-state concepts. ICD-11 stem or extension mappings were not provided.
Diagnostic Footprint
Ready|6 sources|includes web evidence
What this means
Legacy claims data using ICD-9-CM can be aligned to ICD-10-CM remission-state ALL concepts using the supplied wording-based mappings. International harmonization and molecular subtype representation remain limited because ICD-11 mappings were not identified.
Worth checking: Verify whether wording-based ICD-9 to ICD-10 alignment is sufficient without formal GEM or CMS crosswalk references.
Acute lymphoid/leukoblastic leukemia not having achieved remission or without mention of remission
20401
C91.01
Not provided
Acute lymphoid/leukoblastic leukemia, in remission
20402
C91.02
Not provided
Acute lymphoid/leukoblastic leukemia, in relapse
V1061
Not provided
Not provided
Personal history of lymphoid leukemia
13
Claims Observability Limits
The supplied evidence documents multiple claims observability gaps affecting ALL cohort construction and line-of-therapy inference. Key limitations include incomplete procedure coverage, absent ICD-11 subtype coding, and lack of clinical-trial participation markers.
Diagnostic Footprint
Ready|6 sources|includes web evidence
The supplied evidence does not provide ICD-11 stem or extension codes for molecular or lineage-specific ALL subtype representation.
The supplied documents do not provide coding conventions for suspected-versus-confirmed diagnoses, secondary malignancy involvement, or ICD-10-CM personal-history Z85 mappings.
Procedure-code coverage is incomplete because the evidence set does not include comprehensive CPT, HCPCS, or ICD-10-PCS coding for leukapheresis, stem-cell transplantation workflows, conditioning regi
Clinical-trial participation indicators, including HCPCS modifiers Q0 and Q1, investigational service indicators, and revenue-code markers, were not identified in the supplied materials.
Many monitoring signals in ALL claims analytics may therefore require proxy inference from diagnosis-state transitions, laboratory utilization, or repeated bone marrow and flow-cytometry testing rathe
What this means
Claims-based ALL analytics using this evidence set will rely heavily on proxy signals rather than direct treatment coding. Missing subtype, procedure, and trial-participation visibility may limit cohort specificity and treatment-pathway reconstruction.
Worth checking: Assess whether supplemental coding sources are needed to support transplant, CAR-T, and chemotherapy administration observability.
The supplied evidence provides therapy-specific cycle timing and interruption rules for BLINCYTO and BESPONSA that may support line advancement, continuation, and discontinuation logic in ALL claims sequencing. The document does not provide a complete standardized U.S. claims-based line-of-therapy algorithm.
Treatment Logic
Ready|9 sources|includes web evidence
BLINCYTO induction or consolidation consists of 28 days of continuous intravenous infusion followed by a 14-day treatment-free interval.
BLINCYTO continued therapy consists of 28 days of continuous intravenous infusion followed by a 56-day treatment-free interval.
BLINCYTO interruptions due to adverse reactions that are 7 days or less may continue within the same cycle.
BLINCYTO interruptions longer than 7 days require starting a new cycle.
BESPONSA Cycle 1 is 3 weeks in duration and may be extended to 4 weeks for complete remission, complete remission with incomplete hematologic recovery, or toxicity recovery.
BESPONSA interruptions greater than 28 days may require consideration of permanent discontinuation, and HSCT-directed treatment is recommended for 2 cycles in patients proceeding to hematopoietic stem
What this means
These timing and interruption thresholds can support cycle segmentation and treatment continuation logic for relapsed or refractory ALL therapies in claims analyses. Additional governance rules are still required for regimen aggregation, maintenance grouping, and cross-agent line advancement definitions.
Worth checking: Expert review should confirm whether interruption thresholds are operationalized as line breaks or cycle restarts in the target claims framework.
Sources
FDA Drug Labeling (openFDA)DailyMedNLM Clinical Tables (HCPCS)ESMOFDA NDC Directory (openFDA)FDA Drugs@FDA (openFDA)CMS HCPCS Release FilesFDA Purple BookOpen Web (Supplementary)
15
Regimen Library
The evidence identifies several ALL-related therapy constructs and comparator regimens, including subpopulation-specific relapsed/refractory and maintenance settings, but does not provide a comprehensive standardized U.S. regimen library across all treatment phases.
Treatment Logic
Ready|6 sources|includes web evidence
What this means
The evidence supports construction of partial regimen libraries tied to specific ALL subpopulations and treatment phases. Analysts would still need external governance for regimen aliases, induction versus consolidation categorization, and maintenance normalization.
Worth checking: Expert review should verify whether comparator regimens should be classified as distinct lines or pooled chemotherapy backbones.
Sources
ESMOFDA Drug Labeling (openFDA)DailyMedFDA Purple BookCMS HCPCS Release FilesOpen Web (Supplementary)
Regimen
Setting / phase
Components
Population
BESPONSA-based therapy
Relapsed or refractory setting
Inotuzumab ozogamicin
Adult and pediatric patients with relapsed or refractory CD22-positive B-cell precursor ALL
BLINCYTO-based therapy
Relapsed or refractory setting
Blinatumomab
Patients with relapsed or refractory B-cell precursor ALL
Asparaginase-containing pediatric or pediatric-inspired regimens
AYA and adult ALL populations
16
Drug, Administration & NDC Codes
The evidence provides HCPCS/J-code mappings for multiple infused or cellular ALL therapies and representative NDC information for selected oral and injectable agents. The document does not explicitly define pharmacy-benefit versus medical-benefit adjudication rules.
Treatment Logic
Ready|8 sources
What this means
HCPCS-coded therapies can support medical-claim exposure identification, while oral kinase inhibitors and maintenance agents may require pharmacy-claim integration using NDCs. Mixed oral and infused product representation introduces routing and completeness challenges for line-of-therapy reconstruction.
Worth checking: Expert review should confirm whether alternate HCPCS descriptors or retired codes need harmonization across study years.
Sources
FDA NDC Directory (openFDA)CMS HCPCS Release FilesNLM Clinical Tables (HCPCS)FDA Drug Labeling (openFDA)FDA Drugs@FDA (openFDA)FDA Purple BookDailyMedESMO
Agent
HCPCS / J-code
NDC / labeler
Benefit
Note
Blinatumomab
J9039
Not supplied
Medical claim construct inferred from HCPCS coding
HCPCS description states injection, blinatumomab, 1 microgram
Inotuzumab ozogamicin
J9229
Not supplied
Medical claim construct inferred from HCPCS coding
HCPCS description states injection, inotuzumab ozogamicin, 0.1 mg
Rituximab
J9312
Biosimilars include Truxima, Ruxience, and Riabni
Medical claim construct inferred from HCPCS coding
Multiple formulations and manufacturers identified
Both oral and injectable formulations identified
Potential same-drug different-intent ambiguity across maintenance and meningeal prophylaxis contexts
17
Exclusions & Ambiguity Rules
The supplied evidence identifies selected supportive-care examples and multiple ambiguity considerations but does not provide a comprehensive exclusion framework for ALL claims sequencing analyses. Same-drug different-intent ambiguity is specifically noted for methotrexate.
Treatment Logic
Ready|9 sources|includes web evidence
The supplied evidence does not provide a comprehensive exclusion framework for supportive-care, prophylactic, rescue, adjunctive, transfusion-support, tumor-lysis, antiemetic, anti-infective, or non-t
Low-molecular-weight heparins at prophylactic doses are described as a first-line prophylactic anticoagulation strategy in ALL supportive care contexts.
LEUKINE is described as a leukocyte growth factor indicated to shorten neutrophil recovery time and reduce severe infections.
The evidence references transfusion-related endpoints including platelet and RBC transfusion independence.
The supplied evidence identifies oral therapies such as dasatinib and ponatinib and infused therapies such as BLINCYTO, BESPONSA, KYMRIAH, and TECARTUS but does not define pharmacy-benefit versus medi
Same-drug different-intent ambiguity may arise for methotrexate because both injectable and oral formulations are identified along with maintenance-regimen and meningeal leukemia prophylaxis or treatm
What this means
Supportive-care filtering and ambiguity resolution will require analyst-defined governance because the source material does not standardize exclusions or routing conventions. Methotrexate exposure classification may require indication-sensitive logic to distinguish maintenance therapy from prophylactic or other treatment contexts.
Worth checking: Expert review should focus on whether methotrexate prophylaxis exposures should be excluded from regimen-defining logic.
Sources
FDA NDC Directory (openFDA)FDA Drug Labeling (openFDA)DailyMedNLM Clinical Tables (HCPCS)CMS HCPCS Release FilesFDA Drugs@FDA (openFDA)ESMOFDA Purple BookOpen Web (Supplementary)
18
Treatment Journey States
The supplied documents describe ALL as a prolonged multiphase treatment journey with induction, consolidation, maintenance, remission surveillance, relapsed or refractory treatment, and possible HSCT or CAR-T pathways. Response states include CR, CRi, MRD positivity, MRD negativity, relapse, and transplant eligibility.
Patient Journey
Ready|6 sources|includes web evidence
Induction combination chemotherapy
Consolidation phase chemotherapy
Maintenance or continued therapy
CR or CRi assessment
MRD-positive or MRD-negative
Relapsed or refractory treatment
HSCT bridge or transplant
CAR-T pathway in relapsed disease
What this means
Claims-derived line-of-therapy reconstruction can follow transitions between induction, consolidation, maintenance, relapse treatment, HSCT, and CAR-T through encounter and infusion patterns. Laboratory-defined remission and MRD states are clinically central but are not directly observable in administrative claims.
Worth checking: Confirm whether CAR-T positioning applies only to relapsed or refractory B-cell ALL.
Sources
DailyMedNational Cancer Institute (NCI)NLM Clinical Tables (LOINC)CIBMTRASCOOpen Web (Supplementary)
19
Discontinuation & Adverse-Event Signals
Multiple ALL therapy classes include toxicity-driven interruption, discontinuation, or dose-modification signals. Key toxicities include CRS and ICANS with BLINCYTO, hepatotoxicity and VOD with BESPONSA, cardiomyopathy with anthracyclines, and severe toxicities with vincristine-based therapy.
Patient Journey
Ready|6 sources|includes web evidence
What this means
Treatment gaps, hospitalization, transfusions, dose reductions, and infusion interruptions may function as proxy indicators of discontinuation or toxicity-related modification in claims analyses. The supplied evidence does not define validated claims-based discontinuation thresholds or switching algorithms.
Worth checking: Verify whether dose-reduction percentages were regimen-specific or broadly generalized.
Sources
DailyMedFDA Drug Labeling (openFDA)National Cancer Institute (NCI)ASCOAmerican Cancer SocietyOpen Web (Supplementary)
Treatment response assessment includes CR, CRi, bone marrow blast assessment, peripheral blood count recovery, and MRD-related milestones. Monitoring cadence is only partially described, with frequent follow-up exams and tests after therapy and no standardized claims-based cadence framework defined.
Patient Journey
Ready|7 sources|includes web evidence
What this means
Claims can identify biopsy encounters and follow-up utilization patterns, but remission status, MRD results, and marrow blast percentages remain laboratory-based concepts outside direct claims capture. Monitoring cadence definitions are incomplete for standardized line-of-therapy analytics.
Worth checking: Confirm that the monthly follow-up language applies broadly to adult ALL survivorship monitoring.
Sources
DailyMedNLM Clinical Tables (LOINC)National Cancer Institute (NCI)American Cancer SocietyCIBMTRASCOOpen Web (Supplementary)
Assessment
Tool / criteria
Timing
Complete remission (CR)
< 5% blasts in bone marrow and absence of peripheral blood leukemic blasts
During response assessment
Complete remission with incomplete hematologic recovery (CRi)
Bone marrow remission with incomplete platelet and/or ANC recovery
During response assessment
MRD assessment
MRD negativity milestone; MRD greater than or equal to 0.1% referenced in indication
First or second complete remission
Bone marrow assessment
Bone marrow biopsy reporting and pathology assessment
During disease evaluation
Disease response documentation
Disease-specific laboratory results, cytogenetic and molecular markers, staging
At transplantation reporting and disease assessment
Follow-up monitoring
Blood tests, bone marrow exams, and other tests
Every month or so at first, then less often
Toxicity monitoring
Clinical examinations and symptom review
During and after treatment
21
Outcomes & Claims Observability
The supplied evidence describes downstream outcome states including complete remission, MRD negativity, relapse, post-transplant complications, hospitalization, survivorship, and death. Claims observability is strongest for hospitalization, transfusion, bone marrow biopsy encounters, treatment interruption, and transplant-related utilization.
Patient Journey
Ready|8 sources|includes web evidence
What this means
Administrative claims data are more reliable for identifying utilization-based journey events than clinical response states. Cohort definitions requiring CR, CRi, or MRD status would need linkage to laboratory, registry, or chart data.
Worth checking: Check whether home infusion observability differs by medical versus pharmacy benefit capture.
Sources
DailyMedFDA Drug Labeling (openFDA)NLM Clinical Tables (LOINC)National Cancer Institute (NCI)ASCOAmerican Cancer SocietyCIBMTROpen Web (Supplementary)
Journey signal
Observable in claims
How
Hospitalization during induction or toxicity management
DIRECT SIGNAL
Inpatient hospitalization encounters
Transfusion requirement
DIRECT SIGNAL
Transfusion-related claims
Bone marrow biopsy encounter
DIRECT SIGNAL
Procedure or pathology-related claims
Treatment interruption or delayed cycle
PROXY SIGNAL
Treatment gaps or delayed infusion timing
Dose reduction
PROXY SIGNAL
Reduced administered dose intensity
MRD status
NOT OBSERVABLE
Laboratory-defined clinical concept without claims methodology
Complete remission status
NOT OBSERVABLE
Remission definitions depend on marrow and laboratory results
Home infusion and ambulatory monitoring
PROXY SIGNAL
Home infusion therapy and outpatient monitoring encounters
22
Unmet Needs & Evidence Gaps
The supplied evidence indicates that adult ALL treatment complexity, subgroup heterogeneity, and dependence on molecular and MRD testing create major limitations for standardized claims-based line-of-therapy construction. Explicit sequencing evidence is limited to isolated frontline-to-second-line asparaginase switching examples, including 35/154 (22.7%) patients switching from frontline pegaspargase/calaspargase pegol to recombinant Erwinia.
Celestra Synthesis
Ready|5 sources|includes web evidence
What this means
Claims-only ALL analyses will require explicit assumptions for line transitions, remission, relapse, and discontinuation because clinically important disease and response variables depend on molecular and laboratory assessments. Cohort logic must preserve subgroup qualifiers such as Ph+ ALL and Ph- B-ALL to avoid inappropriate generalization.
Worth checking: Confirm whether frontline-to-second-line asparaginase switching should be treated as a true line advancement or toxicity-driven substitution.
Sources
NCI SEERPubMedEurope PMCClinicalTrials.govOpen Web (Supplementary)
Gap area
Description
Impact on modelling
Treatment sequencing standardization
Adult ALL treatment lacks a single standardized regimen approach because “The standard treatment for adults with ALL con
Regimen grouping and line attribution may vary across analyses because treatment sequences are heterogeneous and multi-s
Limited claims-based line definition evidence
The supplied evidence provides only isolated examples of claims-oriented sequencing definitions, including patients who
Claims-based line-of-therapy algorithms may require operational assumptions due to sparse published sequencing rules.
Population heterogeneity
Evidence distinguishes molecular and disease subgroups including “Ph+ ALL,” “Philadelphia (Ph) chromosome-negative B-cel
Subpopulation-specific evidence cannot be generalized across all ALL populations without preserving subgroup qualifiers.
Molecular subtype observability
Clinically relevant disease characterization includes “EP300::ZNF384,” “TCF3::ZNF384,” and kinase/RAS pathway mutations.
Administrative claims data may not capture the molecular features needed for clinically meaningful stratification.
Response and remission ascertainment
Key treatment states rely on specialized assessments including “bone marrow morphologic complete remission,” “flow cytom
Remission and MRD states may require proxy definitions because these assessments are not directly observable in claims.
Relapse characterization limitations
Outcomes literature reports that “nearly half of patients relapsed within 3 years,” but no standardized claims-based rel
Longitudinal relapse detection and post-relapse sequencing may be inconsistently defined across datasets.
23
Guideline, Label & Evidence Divergence
The supplied document contains limited direct evidence on guideline-label divergence in ALL, but identifies tensions between subgroup-specific approval statements, heterogeneous regimen practices, and sparse sequencing definitions. The evidence does not provide detailed NCCN-to-label comparisons or temporal FDA label evolution.
Celestra Synthesis
Ready|3 sources|includes web evidence
What this means
The available evidence supports cautious interpretation of guideline and label applicability because subgroup restrictions and heterogeneous treatment practices are common in ALL. Claims-based sequencing frameworks should therefore include traceable assumptions and explicit subgroup handling.
Worth checking: Verify the exact frontline approval population associated with the blinatumomab statement before using it in downstream materials.
Sources
Europe PMCClinicalTrials.govOpen Web (Supplementary)
Topic
Guideline says
Label / evidence says
Resolution
Frontline targeted therapy approval scope
NCCN-related commentary describes ALL treatment as complex and heterogeneous.
One source states that “Blinatumomab is currently the only targeted agent approved for frontline treatment,” but the sup
Preserve the exact subpopulation scope when interpreting frontline targeted therapy statements and avoid generalizing ac
Standardization of adult ALL regimens
NCCN-related commentary describes ALL treatment as “one of the most complex and difficult” hematologic malignancies.
The evidence states “there is no standard which drugs to give and how to combine them.”
Use transparent regimen grouping logic because no universal adult ALL sequencing standard was identified in the supplied
Claims-based sequencing transitions
No guideline-defined claims-based line-of-therapy algorithm was supplied.
Published evidence identified only isolated transitions such as switching from “frontline (1 L) pegaspargase (PEG)/calas
Document all sequencing assumptions explicitly when constructing retrospective treatment lines.
Subpopulation applicability
Several cited studies are restricted to “adults with Ph- B-ALL.”
The evidence also distinguishes “Ph+ ALL” and fusion-defined subtypes including “EP300::ZNF384” and “TCF3::ZNF384.”
Maintain subgroup-specific attribution because evidence and potential treatment approaches differ across molecularly def
24
Key Insights for Downstream Modelling
The supplied evidence highlights that ALL claims-based modelling is constrained by incomplete observability of molecular subtype, MRD status, remission assessment, and standardized relapse logic. Published sequencing evidence is limited and highly subgroup-specific.
Celestra Synthesis
Ready|5 sources|includes web evidence
Claims-based ALL analyses may require proxy definitions for remission, relapse, treatment discontinuation, and maintenance because key clinical states depend on MRD testing, flow cytometry, RT-qPCR, a
Subgroup qualifiers such as “Ph- B-ALL,” “Ph+ ALL,” and fusion-defined populations including “EP300::ZNF384” and “TCF3::ZNF384” should be preserved throughout cohort construction and treatment sequenc
Adult ALL regimens involve “different combinations and ... several steps,” and the supplied evidence states that “there is no standard which drugs to give and how to combine them,” limiting standardiz
Published claims-oriented sequencing evidence is limited to isolated examples such as switching from frontline pegaspargase/calaspargase pegol to second-line recombinant Erwinia.
No validated claims-based relapse detection algorithm or maintenance therapy definition was identified in the supplied evidence.
What this means
Downstream modelling should emphasize transparent sequencing assumptions, subgroup preservation, and explicit handling of unobservable clinical states. Validation workflows should specifically review remission logic, molecular subgroup attribution, and line-transition traceability.
Worth checking: Check whether the intended modelling framework distinguishes therapy substitution from advancement to a new line of therapy.
Sources
NCI SEERPubMedEurope PMCClinicalTrials.govOpen Web (Supplementary)
Discovery (9 cards)
Reviewed at the gate
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 / OrphadataNCI SEERCDC / NCHSWHO Global Health ObservatoryNational Cancer Institute (NCI)Europe PMCPubMedASH / Blood (American Society of Hematology)Open Web (Supplementary)
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
WHONational Cancer Institute (NCI)Orphanet / OrphadataASH / Blood (American Society of Hematology)Europe PMCPubMedOpen Web (Supplementary)
Segment
Approximate share
Defining feature
Children and adolescents
Most common population
Most frequently diagnosed among people aged <20
Childhood ALL peak incidence
Not quantified
Peak 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 ALL
Not quantified
Adult B-cell ALL molecular subgroup
ZNF384-rearranged B-cell ALL
Rare subtype
EP300::ZNF384 and TCF3::ZNF384 fusion partners
MRD-negative patients
Not quantified
Treatment segmentation by MRD status
Patients in MRD-positive CR1
Not quantified
Higher-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 / OrphadataWHONational Cancer Institute (NCI)NCI SEERCDC / NCHSEurope PMCASH / Blood (American Society of Hematology)PubMedOpen Web (Supplementary)
Classification
Category
Note
Acute lymphoblastic leukemia
Rare Non-Hodgkin lymphoma
Malignant lymphoid proliferation affecting marrow and blood
B-cell acute lymphoblastic leukemia
Lineage subtype
Defined using CD19, CD22, cytoplasmic CD79a
T-cell acute lymphoblastic leukemia
Lineage subtype
Defined using cytoplasmic CD3 and CD5
Philadelphia chromosome-negative B-cell ALL
Molecular subgroup
Adult treatment-linked subgroup
ZNF384-rearranged B-cell ALL
Molecular subgroup
Includes EP300::ZNF384 and TCF3::ZNF384 fusions
MRD-positive CR1 disease
Risk subgroup
Used for treatment stratification
Higher-risk subsets
Risk category
May 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
Bone marrow aspiration
Morphology assessment
Cytochemical analysis
Flow cytometric immunophenotyping
Lineage marker evaluation
Cytogenetics testing
Immunohistochemistry assessment
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
WHOOrphanet / OrphadataEurope PMCASH / Blood (American Society of Hematology)Open Web (Supplementary)
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
Initial symptom presentation
Bone marrow confirmation
Immunophenotypic lineage assignment
Molecular subgroup classification
MRD status assessment
Frontline treatment selection
Response-based risk stratification
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 / OrphadataNational Cancer Institute (NCI)NCI SEERCDC / NCHSEurope PMCPubMedASH / Blood (American Society of Hematology)Open Web (Supplementary)
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)ESMOFDANational Cancer Institute (NCI)FDA Drugs@FDA (openFDA)ASCOClinicalTrials.govASH / Blood (American Society of Hematology)Open Web (Supplementary)
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
ESMOFDA Drug Labeling (openFDA)FDANational Cancer Institute (NCI)FDA Drugs@FDA (openFDA)ASH / Blood (American Society of Hematology)ASCOClinicalTrials.govOpen Web (Supplementary)
Guideline / body
Population
Recommended approach
NCCN Clinical Practice Guidelines in Oncology for Acute Lymphoblastic Leukemia Version 2.2024
Adults with Ph-positive and Ph-negative ALL
Treatment strategies stratified by Philadelphia chromosome status, age, MRD assessment, and supportive care consideratio
NCCN Pediatric Acute Lymphoblastic Leukemia guideline Version 2.2025
Pediatric BCR::ABL1-positive and BCR::ABL1-negative B-cell lineage, T-cell lineage, and infant ALL
Risk assessment and stratification of risk-adapted therapy
American Society of Hematology 2026 frontline management guideline
Adolescents and young adults (AYAs) with B-ALL/T-ALL or T-LBL/LLy receiving frontline therapy
Pediatric-inspired regimens containing asparaginase are recommended as frontline therapy compared with traditional adult
American Society of Hematology 2026 relapsed/refractory guideline
AYAs with relapsed/refractory ALL
Blinatumomab and/or inotuzumab over chemotherapy for reinduction
NCCN and ASH pathway structure
ALL across treatment phases
Pretreatment, 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)ESMOClinicalTrials.govASCOASH / Blood (American Society of Hematology)Open Web (Supplementary)
Therapy
Indication / population
Setting
Approval
Recent label change
Ponatinib (ICLUSIG)
Adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with chemoth
Frontline newly diagnosed adult Ph+ ALL
FDA accelerated approval 2024-03-19
2025-10-10 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 new
Relapsed/refractory adult Ph+ ALL and frontline pediatric Ph+ ALL
Initial U.S. Approval: 2006
2024-07-31 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 Ph
Relapsed/refractory adult Ph+ ALL and frontline pediatric Ph+ ALL
Initial U.S. Approval: 2001
Multiple 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 lymphoblas
Relapsed/refractory T-ALL/T-LBL after at least two regimens
Initial U.S. Approval: 2005
2025-03-11 ARRANON SUPPL 14 labeling action; specific ALL scope not provided
Clofarabine injection
Pediatric patients 1 to 21 years old with relapsed or refractory ALL after at least two prior regimens
Pediatric relapsed/refractory ALL
Initial U.S. Approval: 2004
No recent label change identified in supplied evidence
Methotrexate Injection
Adult and pediatric ALL as part of a combination chemotherapy regimen or maintenance regimen
Combination chemotherapy and maintenance settings
Initial U.S. Approval: 1953
No recent label change identified in supplied evidence
TECARTUS (brexucabtagene autoleucel)
Adult relapsed or refractory B-cell precursor ALL
Relapsed/refractory adult B-cell precursor ALL
Approved; approval date not provided in supplied evidence
No 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
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
Diagnostic classification frameworks rely on bone marrow assessment, morphology, cytochemical testing, immunophenotyping, cytogenetics, and lumbar puncture evaluation, with lineage assignment supporte
Treatment selection pathways are stratified across induction, consolidation, maintenance, transplant, and relapsed/refractory settings by Philadelphia chromosome/BCR::ABL1 status, lineage subtype, age
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.
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,
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 / OrphadataNCI SEERCDC / NCHSWHO Global Health ObservatoryNational Cancer Institute (NCI)Europe PMCPubMedASH / Blood (American Society of Hematology)Open Web (Supplementary)WHOFDA Drug Labeling (openFDA)ESMOFDAFDA Drugs@FDA (openFDA)ASCOClinicalTrials.gov
No findings match that filter
Pick a different filter.
Source conflicts (10)
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-9-CM code 20401 is defined as "Acute lymphoid leukemia, in remission" in the NLM Clinical Tables (ICD-9-CM) ICD-9-CM table.
Possible reason: One claim describes an in-remission leukemia code while the other describes not having achieved remission, which are incompatible disease-status definitions.
Document approved; decisions are final.
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Acknowledged
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-9-CM code 20401 is defined as "Acute lymphoid leukemia, in remission" in the NLM Clinical Tables (ICD-9-CM) ICD-9-CM table.
| C91.00 | Acute lymphoblastic leukemia not having achieved remission | Use for newly diagnosed or active ALL without remission. | - Bone marrow blasts ≥20% - Flow cytometry confirming B/T-cell lineage |
Possible reason: One claim defines an in-remission code whereas the other defines a not-in-remission code, so they assert different remission statuses for the same disease category.
Document approved; decisions are final.
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-9-CM code 20402 is defined as "Acute lymphoid leukemia, in relapse" in the NLM Clinical Tables (ICD-9-CM) ICD-9-CM table.
Possible reason: One claim defines a relapse-state leukemia code while the other describes disease not having achieved remission, which are distinct and conflicting statuses.
Document approved; decisions are final.
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-10-CM code C91.01 is defined as "Acute lymphoblastic leukemia, in remission" in the NLM Clinical Tables (ICD-10-CM) ICD-10-CM table.
Possible reason: One claim specifies acute lymphoblastic leukemia in remission while the other specifies not having achieved remission, which are contradictory statuses.
Document approved; decisions are final.
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-10-CM code C91.01 is defined as "Acute lymphoblastic leukemia, in remission" in the NLM Clinical Tables (ICD-10-CM) ICD-10-CM table.
| C91.00 | Acute lymphoblastic leukemia not having achieved remission | Use for newly diagnosed or active ALL without remission. | - Bone marrow blasts ≥20% - Flow cytometry confirming B/T-cell lineage |
Possible reason: One claim defines relapse disease status while the other defines not having achieved remission, which are different and incompatible statuses.
Document approved; decisions are final.
stage_3
what icd-10-cm diagnosis codes identify acute lymphoblastic leukemia, including status, remission, relapse, secondary neoplasm, and personal-history (e.g., z85) variants
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-10-CM code C91.02 is defined as "Acute lymphoblastic leukemia, in relapse" in the NLM Clinical Tables (ICD-10-CM) ICD-10-CM table.
| C91.00 | Acute lymphoblastic leukemia not having achieved remission | Use for newly diagnosed or active ALL without remission. | - Bone marrow blasts ≥20% - Flow cytometry confirming B/T-cell lineage |
Possible reason: The first claim identifies a relapse code whereas the second identifies a not-in-remission code, so they conflict on disease status.
Document approved; decisions are final.
stage_3
how are icd-9-cm and icd-11 leukemia codes crosswalked to icd-10-cm, and what are each code's effective and retirement dates across annual code-set updates
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-10-CM code C91.01 is defined as "Acute lymphoblastic leukemia, in remission" in the NLM Clinical Tables (ICD-10-CM) ICD-10-CM table.
Possible reason: The claims assign different remission statuses within ICD-10-CM acute lymphoblastic leukemia coding: C91.01 is in remission whereas C91.00 is not having achieved remission.
Document approved; decisions are final.
stage_3
how are icd-9-cm and icd-11 leukemia codes crosswalked to icd-10-cm, and what are each code's effective and retirement dates across annual code-set updates
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-9-CM code 20402 is defined as "Acute lymphoid leukemia, in relapse" in the NLM Clinical Tables (ICD-9-CM) ICD-9-CM table.
Possible reason: The claims describe different disease-status concepts for acute lymphoblastic/lymphoid leukemia: relapse versus not having achieved remission.
Document approved; decisions are final.
stage_3
how are icd-9-cm and icd-11 leukemia codes crosswalked to icd-10-cm, and what are each code's effective and retirement dates across annual code-set updates
Escalated
Source A preferred
Source A
U.S. National Library of Medicine (tier 1)Tier 1
ICD-10-CM code C91.02 is defined as "Acute lymphoblastic leukemia, in relapse" in the NLM Clinical Tables (ICD-10-CM) ICD-10-CM table.
Possible reason: The claims refer to different ICD-10-CM remission-status concepts: C91.02 is in relapse whereas C91.00 is not having achieved remission.