CurrentCapital BluecrossPolicy MP 9.041

Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia

Clinical coverage criteria for autologous and allogeneic hematopoietic cell transplantation (HCT) to treat childhood and adult acute lymphoblastic leukemia (ALL), including reduced-intensity conditioning and donor considerations; intended for providers and utilization review for Capital BlueCross products.

Policy Summary

PayerCapital Bluecross

PolicyHematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia

Policy CodePolicy MP 9.041

Change TypeNo material change

Effective DateMay 1, 2026

Next Review Date

Key ActionObtain prior authorization to confirm the patient meets medical necessity criteria including age group, remission status, relapse risk factors, and planned conditioning intensity.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

multiple RCTsevidence types

up to 85%pediatric long-term survival

35-40%adult 2-yr survival

25-30%Ph chromosome freq

Medical Necessity and Coverage Criteria

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Childhood ALL — Covered Indications

Covered when ANY of the following apply for childhood ALL:

Childhood ALL HCT indications: 1) Autologous or allogeneic HCT may be considered medically necessary in first complete remission (CR1) for children at high risk of relapse (see Policy Guidelines for high-risk factors). 2) Autologous or allogeneic HCT may be considered medically necessary for children in second or greater remission or with refractory ALL. 3) Allogeneic HCT may be considered medically necessary to treat relapsing ALL after a prior autologous HCT in children.

High-risk factors include age <1 year or >9 years, male sex, WBC >50,000/µL at presentation, hypodiploidy, t(9;22)/BCR-ABL1, t(4;11)/MLL-AF4, ProB or T-lineage immunophenotype, poor prednisone response or ≥1% MRD at 6 weeks.

Adult ALL — Covered Indications

Covered when ANY of the following apply for adult ALL:

Adult ALL HCT indications: 1) Autologous HCT may be considered medically necessary in first complete remission (CR1) for adults at high risk of relapse. 2) Allogeneic HCT may be considered medically necessary in CR1 for adults of any risk level. 3) Allogeneic HCT may be considered medically necessary in second or greater remission, or for adults with relapsed or refractory ALL. 4) Reduced-intensity conditioning allogeneic HCT may be considered medically necessary for patients in complete marrow and extramedullary first or second remission who cannot tolerate myeloablative conditioning due to age or comorbidities.

Autologous HCT is investigational (not covered) for adult ALL in second or greater remission or for refractory disease due to insufficient evidence.

Medical Necessity and Indications

Covered when evidence and clinical criteria are met as described below:

Pediatric ALL - Autologous HCT: For children with high-risk ALL in first complete remission (CR1) or with relapsed ALL, autologous HCT may be a treatment option; studies suggest fewer relapses but higher treatment-related mortality. Autologous HCT may be appropriate for a subset of high-risk patients in second complete remission or beyond or with relapsed disease.

Conclusion supported by randomized trials, systematic reviews, and ASBMT position statement.

Pediatric ALL - Allogeneic HCT: For childhood ALL in CR1 at high risk of relapse, or in refractory or relapsed disease, allogeneic HCT is associated with fewer relapses but higher treatment-related mortality; it may be an appropriate treatment option for high-risk pediatric patients.

Supported by randomized trials and systematic reviews.

Adult ALL - Autologous HCT: For adults with high-risk ALL in CR1 whose health status allows tolerance of the procedure, autologous HCT is supported by randomized trials and systematic reviews and may be used.

Evidence deemed sufficient to demonstrate meaningful improvement in net health outcome for this population.

Autologous hematopoietic cell transplantation (autologous HCT) is investigational (not covered) to treat adult acute lymphoblastic leukemia (ALL) when the disease is in second or greater remission or is refractory. The policy states that available evidence is insufficient to support a general conclusion about health outcomes or benefits for autologous HCT in these adult settings, and therefore it is not covered for those indications.

For individuals who relapse after a prior autologous HCT for ALL and are considered for an allogeneic HCT (allo‑HCT), the evidence base is limited to small case series with short-term follow-up. The policy concludes that this evidence is inadequate to determine benefit; accordingly, there is insufficient evidence to establish that allo‑HCT after relapse post‑autologous HCT improves health outcomes.

Regimen	Indication / Patient selection	Notes on intensity or tailoring
Reduced‑intensity conditioning (RIC) allogeneic HCT
Candidates who could benefit from allo‑HCT but cannot tolerate conventional myeloablative conditioning due to age (typically >60 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky performance status)
Pretransplant regimens use lower doses of cytotoxic drugs or less intense radiotherapy than traditional myeloablative regimens; intensity is variable and tailored to disease and patient condition, balancing relapse risk and nonrelapse mortality

Coverage label	Patient population / remission status	Rationale / supporting policy text
Considered
Patients in complete marrow and extramedullary first or second remission who cannot tolerate myeloablative conditioning due to age or comorbidities
Reduced‑intensity conditioning allo‑HCT may be considered for these patients when they would otherwise be expected to benefit from myeloablative allo‑HCT but are medically unable to tolerate full‑intensity conditioning

Coverage label	Patient population	Policy statement
Covered
Adults with acute lymphoblastic leukemia (ALL) of any risk level whose health status is sufficient to tolerate myeloablative conditioning
Current evidence supports use of myeloablative allogeneic HCT for adults with any risk level ALL if the patient can tolerate the procedure; outcomes include overall survival and treatment‑related morbidity considerations

Diagnosis and Procedure Codes

Covered Procedure Codes (when medically necessary)CPTCovered

S2140	Listed in policy coding section
S2142	Listed in policy coding section
S2150	Listed in policy coding section
38204	Procedure code listed
38205	Procedure code listed
38206	Procedure code listed
38208	Procedure code listed
38209	Procedure code listed
38210	Procedure code listed
38211	Procedure code listed

1–10 of 17

1/2

Diagnosis Codes referencedICD-10

C91.00	Acute lymphoblastic leukemia not having achieved remission
C91.01	Acute lymphoblastic leukemia, in remission
C91.02	Acute lymphoblastic leukemia, in relapse

inv-08: Leukocyte count thresholds — Children/adult WBC thresholds and specifics

Children — leukocyte thresholdWhite blood cell (WBC) count at presentation >50,000/µL defines leukocytosis associated with higher relapse risk in pediatric ALL.

Adults — B‑cell lineageLeukocytosis defined as WBC >30,000/µL for B‑cell lineage in adults.

Adults — T‑cell lineageLeukocytosis defined as WBC >100,000/µL for T‑cell lineage in adults.

inv-09: Minimal residual disease (MRD) — High risk defined threshold (e.g., ≥1% by flow cytometry at 6 weeks)

High‑risk MRD definitionMinimal residual disease (MRD) measured by flow cytometry ≥1% at 6 weeks denotes high risk of relapse.

Timing of assessmentMRD assessment noted specifically at the 6‑week post‑induction timepoint for risk stratification.

Use in pediatric risk stratification≥1% MRD at 6 weeks is listed among findings that help define children at high risk of relapse.

Authorization, Documentation, and Billing Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required for hematopoietic cell transplantation (HCT). Requests must be submitted and approved prior to scheduling to confirm medical necessity for the member’s specific clinical situation (including age group, remission status, and presence of high‑risk features as defined in the Policy Guidelines).

Prior authorization required for both autologous and allogeneic HCT when requested for treatment of ALL.
Authorization reviewers will evaluate age (pediatric vs adult), remission status (first CR with high‑risk features, second or greater remission, refractory or relapsed disease), prior transplants, and conditioning intensity (myeloablative vs reduced‑intensity).

Prior Authorization

Verify Benefits and Medical Necessity Prior to Authorization

Prior authorization must be obtained when HCT is being requested and is believed to be medically necessary. Before authorizing, verify member benefits and that the proposed HCT meets the policy’s medical‑necessity criteria (see policy sections on pediatric and adult ALL, donor suitability, and conditioning).

Verify member benefits, eligibility on the date of service, and any plan‑specific transplant coverage limitations.
Authorization is not a coverage guarantee — final payment is subject to member benefit terms and claim adjudication.

Denial Risk

Denial Triggers

Requests that do not meet documented medical‑necessity criteria may be denied. Common denial triggers include requests for HCT in patients who are not in an appropriate remission status, lack documented high‑risk features when required, or lack evidence of prior required lines of therapy.

Autologous HCT requested outside its indicated timing (e.g., not performed as consolidation during complete remission when indicated) may be denied.
Requests lacking documentation of remission status, high‑risk factors, prior treatments, or prior transplant history are subject to denial.

Note

Benefit / Eligibility Verification Required

Coverage and payment are subject to the member’s benefit program, eligibility on the date of service, and a determination that the service is medically necessary. The policy and authorization determinations do not guarantee payment; final claim adjudication follows the member’s contract terms.

Confirm eligibility and benefit limits (including transplant network or facility requirements) before scheduling.
Authorization approvals should be verified against the member’s plan to confirm services are payable.

Documentation Required

Required Clinical Documentation

Provide complete clinical documentation to support medical necessity at the time of authorization and with claim submission. Documentation should clearly demonstrate disease status, prior treatments, donor compatibility assessment, and conditioning plan.

Required documentation includes: HLA typing/donor compatibility results, current remission status (e.g., first CR with high‑risk features, second or greater CR, refractory/relapsed), prior lines of therapy and response, and intent of the conditioning regimen (myeloablative vs reduced‑intensity).
Include rationale for autologous versus allogeneic HCT, history of prior transplants, and any comorbidities affecting conditioning tolerance (e.g., age, organ dysfunction).

Note

Autologous HCT Timing and Indications

Autologous HCT is typically performed as consolidation therapy when the patient’s disease is in complete remission; timing and indication must be documented. For adult ALL, autologous HCT is medically indicated in first CR only for high‑risk patients and is investigational for adult patients in second or later remission or with refractory disease.

Document that autologous HCT is being performed as consolidation in complete remission when claimed.
If autologous HCT is requested for adult patients in ≥ second remission or refractory disease, note that it is considered investigational per policy and may not meet medical necessity.

Billing Rule

Coding and Coverage Notes

Coding information is provided for billing reference only. Identification of codes does not imply coverage; coverage is determined by member benefit information and medical‑necessity determinations.

The code list in the policy may not be all‑inclusive and is subject to change.
Not all billed services are eligible for separate reimbursement — verify coding and bundling rules with the payer prior to claim submission.

Indication by Line of Therapy

first-line | second-line | salvage

Line of therapy: Autologous HCT is typically performed as consolidation therapy when disease is in complete remission; allogeneic HCT may be utilized in CR1, subsequent remissions (CR2+), relapse, or refractory disease depending on patient age, risk profile, donor availability, and ability to tolerate the procedure.

Autologous HCT is investigational for adult ALL in second or greater remission or refractory disease.

first-line | salvage

First-line and salvage settings: Reduced-intensity conditioning (RIC) allogeneic HCT may be considered for patients who cannot tolerate myeloablative conditioning (e.g., older age, comorbidities, low performance status); RIC may be appropriate in patients in complete marrow and extramedullary first or second remission who would otherwise benefit from allo-HCT but are unable to tolerate standard myeloablative regimens.

Choice of myeloablative versus reduced-intensity conditioning should be individualized based on age, comorbidities, and performance status.

Conditioning Regimens and Transplant Types

Term	Description	Clinical implication
Reduced‑intensity conditioning (RIC)
Pretransplant regimens that use lower doses of cytotoxic drugs or less intense radiotherapy than traditional myeloablative conditioning; intended to reduce treatment‑related morbidity and nonrelapse mortality while allowing graft‑versus‑malignancy effects
Intensity is tailored to specific disease and patient condition (range from near‑myeloablative to minimally myeloablative); appropriate for older or comorbid patients who would not tolerate standard myeloablative regimens

Coverage label	Population / remission status	Policy detail
Considered
Patients in complete marrow and extramedullary first or second remission who cannot tolerate myeloablative conditioning due to age or comorbidities
RIC allo‑HCT may be considered when the patient could otherwise benefit from allo‑HCT but medical factors (age, organ dysfunction, low performance status, prior intensive therapy) preclude myeloablative conditioning

Coverage label	Population	Policy summary
Covered
Adult patients with ALL of any risk level who are medically fit to tolerate myeloablative conditioning
Myeloablative allogeneic HCT is supported for adults with any risk level ALL if the patient's health status permits toleration of the procedure; decisions should weigh benefits against treatment‑related morbidity and mortality

Key Terms and Definitions

inv-19: Reduced-intensity conditioning (RIC) — Definition of RIC

RIC definitionReduced‑intensity conditioning (RIC) refers to pretransplant regimens using lower doses of cytotoxic drugs or less intense radiotherapy than traditional myeloablative conditioning, intended to balance relapse risk and nonrelapse mortality.

PurposeGoal is to reduce disease burden and minimize treatment‑related morbidity and nonrelapse mortality while allowing graft‑versus‑malignancy effect to develop.

Intensity spectrumRIC regimens range from nearly myeloablative to minimally myeloablative with lymphoablation; intensity is tailored to disease and patient condition.

inv-20: Hematopoietic cell transplantation (HCT) — Definition of HCT (autologous vs allogeneic)

HCT — general definitionHematopoietic cell transplantation (HCT) is the intravenous infusion of hematopoietic stem cells to restore bone marrow and immune function after marrow‑ablative therapy.

Autologous vs allogeneic sourceStem cells may be obtained from the patient (autologous HCT) or from a donor (allogeneic HCT).

Sources of stem cellsCells can be harvested from bone marrow, peripheral blood, or umbilical cord blood.

inv-21: Allogeneic — Definition and advantages (graft-versus-leukemia)

Allogeneic — definitionAllogeneic transplantation involves donor‑derived stem cells from another person with HLA matching between donor and recipient.

AdvantagesAllogeneic cells avoid tumor contamination present in autologous grafts and confer a graft‑versus‑tumor (graft‑versus‑leukemia) effect.

ConsiderationsAllo‑HCT requires HLA compatibility testing; disadvantage includes risk of graft‑versus‑host disease (GVHD), which increases with HLA disparity and recipient age.

inv-22: Autologous — Definition (patient-derived stem cells)

Autologous — definitionAutologous transplantation uses the patient’s own hematopoietic stem cells harvested before myeloablative therapy.

Immunologic compatibilityImmunologic compatibility is not an issue with autologous HCT because the patient is both donor and recipient.

Clinical roleAutologous HCT is typically used as consolidation therapy in selected patients in complete remission.

inv-23: Karnofsky Index — Performance-status scale definition

Karnofsky Index — purposeKarnofsky Index is a performance‑status scale ranging from 100% (fully active) to 0% (dead) used to estimate physical state, prognosis, and treatment tolerance.

InterpretationLower Karnofsky scores are generally associated with poorer treatment response and prognosis.

Use in HCT assessmentKarnofsky/performance status is used to assess tolerance for conditioning intensity (RIC vs myeloablative).

inv-24: Reduced-intensity conditioning (RIC) allogeneic HCT — Definition/notes

RIC allogeneic HCT — definition/notesReduced‑intensity allogeneic HCT uses lower chemotherapy doses than standard myeloablative transplant, does not completely ablate the patient’s immune system, and is intended for older or sicker patients who may benefit from graft‑versus‑malignancy effects with lower nonrelapse mortality.

Patient selectionMay be appropriate for patients unable to tolerate myeloablative conditioning due to age or comorbidities; intensity is tailored to disease and patient condition.

Expected engraftmentPatients initially show donor cell engraftment and mixed chimerism and most later convert to full donor chimerism.

inv-25: Relapsed — Definition

Relapsed — definitionRelapsed refers to disease that returns after a prior remission (patients who had achieved remission but later have recurrence of leukemia in the bone marrow).

Clinical implicationRelapsed disease is an indication considered in policy for HCT in subsequent remissions or salvage settings.

DocumentationRemission status (CR1, CR2, relapsed) should be documented when considering HCT.

inv-26: Refractory — Definition

Refractory — definitionRefractory refers to persistent disease despite intensive treatment (residual leukemia cells in bone marrow after therapy).

Clinical implicationRefractory disease is included among indications for HCT consideration in the policy for both children and adults.

DocumentationDocumentation of refractory status is required when evaluating HCT medical necessity.

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