CurrentBlue Cross Blue Shield - MassachusettsPolicy 181

Hematopoietic stem-cell transplantation for primary (light-chain) systemic amyloidosis — coverage criteria

This policy governs coverage and prior authorization requirements for autologous and allogeneic hematopoietic stem-cell transplantation to treat primary (light-chain) systemic amyloidosis for Blue Cross Blue Shield Massachusetts commercial members.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyHematopoietic stem-cell transplantation for primary (light-chain) systemic amyloidosis — coverage criteria

Policy CodePolicy 181

Change TypeAnnual reviewno material clinical changes

Effective Date

Next Review Date

Key ActionSubmit prior authorization requests via Authorization Manager including facility and servicing provider NPIs.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

medically necessaryautologous HCT stance

investigationalallogeneic HCT stance

prior auth requiredauthorization

38241example CPT

S2150example HCPCS

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annualreview cadence

Coverage Determinations and Criteria

Coverage determinations

Coverage stance as stated in policy statements

Autologous HCT: Autologous hematopoietic stem-cell transplantation to treat primary systemic (light-chain) amyloidosis is considered medically necessary for Commercial Members.

Allogeneic HCT: Allogeneic hematopoietic stem-cell transplantation to treat primary systemic amyloidosis is considered investigational.

Evidence is insufficient and shows high treatment-related mortality.

Allogeneic hematopoietic stem-cell transplantation (HCT) to treat primary (light-chain) systemic amyloidosis is considered investigational and is therefore not covered under this policy. Evidence on allogeneic HCT for this indication is sparse and is derived largely from case reports; available data have shown high treatment‑related mortality, and the literature is insufficient to demonstrate an improvement in net health outcomes for affected patients.

Policy history reflects coding and authorization changes over time. Notably, on 4/2020 the policy record indicates that bone marrow harvesting codes were removed and that outpatient prior authorization was at that time not required. Subsequent entries clarify that outpatient prior authorization is required for all commercial products (including Medicare Advantage) effective 1/1/2019, and other updates include clarification of coding information (10/2020) and multiple annual reviews. Providers should refer to the current Coding and Authorization sections for the operative requirements and code lists.

Covered Treatment Regimens

Regimen	Indication	Coverage status
Autologous hematopoietic cell transplantation following myeloablative chemotherapy	Patients with primary systemic (light-chain) amyloidosis eligible for consolidation treatment to reduce production of amyloidogenic light chains	Medically necessary for Commercial Members

Regimen	Description / evidence cited	Coverage status
High-dose melphalan with autologous hematopoietic stem-cell transplantation	Described in cited clinical literature showing responses and long-term outcomes (eg, Comenzo et al.; Sanchorawala et al.; Cibeira et al.; D'Souza et al.). References include dose-intensive melphalan with stem-cell support and long-term series of patients treated with high-dose melphalan and autologous SCT.	Informational

Relevant Procedure and Billing Codes

CPT CodesCPT

38241

Hematopoietic progenitor cell (HPC); autologous transplantation

HCPCS CodesHCPCS

S2150

Bone marrow or blood-derived peripheral stem-cell (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications including pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post- transplant care in the global definition.

Coding history and updatesmixed

No codes listed

Authorization, Submission, and Billing Requirements

Prior Authorization

Prior Authorization Required

For services described in this policy, precertification/preauthorization is required for all products when the procedure is performed inpatient. Failure to obtain required precertification/preauthorization may result in denial of coverage or payment.

Applies to all products when services are performed inpatient.
Failure to obtain required precertification/preauthorization may result in denial of benefits or payment.

Prior Authorization

Outpatient Prior Authorization

For services described in this policy performed outpatient, prior authorization is required for commercial products. This includes Commercial Managed Care (HMO and POS), Commercial PPO and Indemnity. Effective 1/1/2019, outpatient prior authorization is required for all commercial products including Medicare Advantage.

Commercial Managed Care (HMO and POS), Outpatient = Prior authorization required.
Commercial PPO and Indemnity, Outpatient = Prior authorization required.
Effective 1/1/2019: Outpatient prior authorization required for all commercial products including Medicare Advantage.

Clinical Background

Primary (light‑chain) systemic amyloidosis (AL amyloidosis) is a clonal plasma cell disorder in which abnormal plasma cells produce amyloidogenic immunoglobulin light chains that misfold and deposit extracellularly as fibrils, leading to progressive organ dysfunction (commonly kidney, heart, and liver). The disease has historically been associated with poor prognosis, and treatment is aimed at rapidly reducing production of the pathogenic light chains. For eligible patients, autologous hematopoietic cell transplantation following myeloablative chemotherapy can markedly reduce amyloidogenic light‑chain production and has been associated with improved survival in selected cohorts.

Key Terms and Definitions

Primary (light-chain) amyloidosis — definition and clinical features

DefinitionA systemic disease caused by a clonal plasma cell producing amyloidogenic immunoglobulin light chains that deposit extracellularly as insoluble beta‑pleated fibrils (primary or light‑chain amyloidosis).

Epidemiology & ageIncidence ~9–14 cases per million person‑years; typical age at diagnosis ~50–65 years.

Pathology & organs affectedAmyloid light chains form Congo red–positive, birefringent beta‑pleated fibrils that deposit in organs — most commonly kidneys, heart, and liver — causing organ dysfunction.

Clinical goal of treatmentRapidly reduce production of amyloidogenic monoclonal light chains by suppressing the underlying plasma cell dyscrasia to preserve organ function.

Therapeutic contextTreatment options include combination chemotherapy (eg, alkylators), autologous HCT after myeloablative chemotherapy, and newer agents (eg, proteasome inhibitors, immunomodulators, anti‑CD38 antibody daratumumab approved in 2021 in combination regimens).

Policy Revision History

2026-02annual_reviewLatest

Annual policy review; references updated; policy statements unchanged.

2025-10coding_clarification

Clarified coding information.

2024-03annual_review

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyHematopoietic stem-cell transplantation for primary (light-chain) systemic amyloidosis — coverage criteria

Policy CodePolicy 181

Change TypeAnnual reviewno material clinical changes

Effective Date

Next Review Date

Key ActionSubmit prior authorization requests via Authorization Manager including facility and servicing provider NPIs.

SourceLink

On This Page

Prior Authorization

Submit via Authorization Manager

Providers must submit initial authorization requests using Authorization Manager. Authorization Manager is available 24/7 and is the preferred method to review requirements, request authorizations, submit clinical documentation, check case status, and view/print decision letters.

Enter the facility's NPI or provider ID for the location where services will be performed.
Enter the servicing surgeon's NPI or provider ID (not the billing group).
Authorization Manager is the quickest way to submit and track authorization requests.

Note

Authorization Manager and Outpatient Prior Authorization

Authorization Manager and prior authorization for outpatient services: providers should use Authorization Manager for all outpatient prior authorization requests for commercial members. Historical policy updates clarified and reinforced the requirement to use Authorization Manager for submitting prior authorization requests.

Use Authorization Manager to submit clinical documentation and check existing case status.
Requests for commercial members must meet medical policy guidelines.

Hematopoietic cell transplantation (HCT) — definition, sources, autologous vs allogeneic

DefinitionInfusion of hematopoietic stem cells to restore bone‑marrow function after bone‑marrow‑toxic cytotoxic therapy; stem cells may be autologous (from the patient) or allogeneic (from a donor).

Sources of stem cellsCells can be harvested from bone marrow, peripheral blood, or umbilical cord blood; cord blood is allogeneic but antigenically naive with lower GVHD risk.

Autologous vs Allogeneic — key immunologyAutologous HCT does not require immunologic compatibility and avoids GVHD; allogeneic HCT requires HLA matching and immunosuppression to prevent graft rejection and GVHD.

Conditioning intensityConditioning ranges from myeloablative regimens (high‑dose cytotoxic therapy) to reduced‑intensity conditioning (RIC) aiming to reduce morbidity and nonrelapse mortality while permitting graft‑versus‑malignancy effects.

Clinical rationale in amyloidosisAutologous HCT can rapidly eradicate amyloidogenic plasma cells and has evidence of improved survival; evidence for allogeneic HCT is sparse with high treatment‑related mortality.

AL amyloidosis — definition

TermAL (amyloid light‑chain) amyloidosis — systemic light‑chain amyloidosis caused by a plasma cell dyscrasia that produces amyloidogenic immunoglobulin light chains.

Pathognomonic featureExtracellular deposition of insoluble beta‑pleated light‑chain fibrils that stain with Congo red and show red‑green birefringence under polarized light.

Clinical significanceDeposits cause organ dysfunction (commonly kidney, heart, liver); management is guided by NCCN guidelines and aims to suppress the underlying plasma cell clone.

Supporting sourcesDefinition and clinical characterization supported by NCCN guidelines and cited literature (eg, Gertz et al., Mayo Clin Proc.; Gertz, Lacy, Dispenzieri publications).

Annual policy review; references updated; policy statements unchanged.

2023-09administrative_update

Policy clarified to include prior authorization requests using Authorization Manager.

2023-03annual_review

Annual policy review; description, summary, and references updated; policy statements unchanged.

2020-04coding_authorization_change

Bone marrow harvesting codes were removed and outpatient prior authorization was noted as not required (historical entry).

2020-10coding_clarification

Clarified coding information.

2019-01-01authorization_requirement

Outpatient prior authorization required for all commercial products including Medicare Advantage effective 1/1/2019.

2026-02annual_reviewLatest

Annual policy review; references updated (including NCCN Version 1.2026) and policy statements unchanged.

2025-10coding_clarification

Clarified coding information.

2025-03annual_review

Annual policy review; references updated; policy statements unchanged.