CurrentPremera BluecrossPolicy 8.01.42

Hematopoietic Cell Transplantation for Primary Amyloidosis

Defines coverage and medical necessity criteria for autologous and allogeneic hematopoietic cell transplantation (HCT) in primary systemic (AL) amyloidosis for Premera Blue Cross members and informs providers about documentation, coding, and supporting evidence.

Policy Summary

PayerPremera Bluecross

PolicyHematopoietic Cell Transplantation for Primary Amyloidosis

Policy CodePolicy 8.01.42

Change TypeNo material change

Effective DateApr 1, 2026

Next Review Date

Key ActionObtain prior authorization and include documentation of diagnosis, organ involvement assessment, and cardiac function (LVEF) to support transplant candidacy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

coveredAutologous HCT

investigationalAllogeneic HCT

77%5‑yr survival (responders)

38232,38241,S2142,S2150Key codes listed

≤2 organs; LVEF>45%CMS thresholds cited

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Coverage stance by transplant type

Covered when specific transplant modality criteria are met:

Autologous HCT - covered: Autologous hematopoietic cell transplantation may be considered medically necessary to treat primary systemic (AL) amyloidosis.

Autologous HCT is considered an important treatment option for eligible individuals based on evidence of improved survival and society guidance.

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

Evidence is sparse with high treatment-related mortality; not established as improving net health outcome.

Autologous hematopoietic cell transplantation (covered_with_criteria)

Covered when CMS-like selection criteria and society guidance are satisfied

Auto-HCT coverage criteria

Organ involvement: Amyloid deposition is limited to 2 or fewer organs (≤ 2 organs).≤ 2 organs
Per CMS National Coverage Determination 110.23; documented organ assessment per amyloidosis consensus criteria is required.
Cardiac function: Left ventricular ejection fraction (LVEF) is greater than 45%.> 45%
Per CMS NCD selection thresholds; document cardiac assessment.
Transplant intent and regimen: Autologous HCT is being used to effect hematopoietic reconstitution following high‑dose melphalan (myeloablative therapy).
Autologous HCT must be used for hematopoietic rescue after severely myelotoxic chemotherapy per CMS NCD.
Society and guideline alignment: Clinical decision aligns with ASTCT guidance supporting autologous HCT as standard of care and with NCCN evaluation recommendations.
Supports candidate selection and timing of transplant relative to systemic therapy.

Allogeneic hematopoietic cell transplantation (not_covered/ investigational)

Not routinely recommended

Allogeneic HCT stance: Allogeneic hematopoietic cell transplantation is not generally recommended for primary amyloidosis and is considered investigational/unsupported for routine use.

ASTCT rated allogeneic HCT as N (not generally recommended) due to limited evidence and high treatment‑related mortality.

Use of allogeneic hematopoietic cell transplantation (HCT) for primary systemic (AL) amyloidosis is considered investigational. The published evidence is sparse and limited largely to case reports, and available data demonstrate high treatment-related mortality, so there is insufficient evidence to conclude that allogeneic HCT improves net health outcomes for this indication.

The American Society for Transplantation and Cellular Therapy (ASTCT) rates allogeneic HCT as “N” (not generally recommended) for treatment of primary amyloidosis in adults, indicating that neither evidence nor routine clinical practice supports its routine use.

Allogeneic HCT is not generally recommended as routine therapy for primary (AL) amyloidosis. Society guidance (ASTCT) and the limited clinical evidence—characterized by few reports and elevated transplant‑related mortality—do not support adoption of allogeneic HCT as a standard therapeutic approach.

Transplant Candidate Evaluation and Selection

Candidate evaluation — pre-transplant considerations and candidacy evaluation mentioned in evidence and guidelines

Pre-transplant considerations and candidacy evaluation mentioned in evidence and guidelines:

Organ assessment: Assess organ involvement based on amyloidosis consensus criteria (document number and sites of organ deposition).

NCCN recommends organ involvement assessment in newly diagnosed disease; documentation supports selection per CMS thresholds.

Evaluate transplant candidacy: Evaluate individuals for stem cell transplant candidacy including overall fitness for myeloablative therapy and expected tolerance of high‑dose chemotherapy.

Fitness for transplant should consider organ dysfunction and comorbidities; candidacy evaluation referenced by NCCN.

Consider induction therapy: Consider initial systemic therapy (preferred regimen: daratumumab plus bortezomib/cyclophosphamide/dexamethasone) before or alongside transplant evaluation as clinically indicated.

NCCN prefers daratumumab‑based induction; induction may optimize disease control prior to autologous HCT.

Transplant candidate evaluation — follow consensus and guideline-recommended assessments

Evaluation and selection for transplant candidacy should follow consensus and guideline-recommended assessments

Consensus-based selection: Assess organ involvement per amyloidosis consensus criteria and document the number of organs involved; document cardiac function including LVEF.see thresholds module (≤ 2 organs; LVEF >45%)

Selection thresholds mirror CMS NCD and NCCN evaluation steps; documentation should be included in authorization requests.

Eligibility determination: Patient meets selection criteria consistent with CMS NCD: amyloid deposition in 2 or fewer organs AND cardiac LVEF greater than 45%.amyloid deposition ≤ 2 organs; LVEF >45%

These criteria are used to identify individuals likely to benefit from autologous HCT per Medicare national coverage.

Contraindications

Individuals who are not medically fit to tolerate myeloablative conditioning or who have significant organ dysfunction face substantially increased risks with full‑intensity allogeneic HCT. Myeloablative regimens can cause organ damage, profound cytopenias with susceptibility to opportunistic infections, and require prolonged immunosuppression to prevent graft rejection and graft‑versus‑host disease; such toxicities make allogeneic HCT contraindicated in patients lacking sufficient physiologic reserve.

The policy does not list additional specific contraindications beyond established selection thresholds. Practical non‑eligibility is implied when patients fail to meet CMS‑style criteria such as a left ventricular ejection fraction ≤45% or involvement of more than 2 organs, or when overall organ dysfunction renders the patient unfit for transplant conditioning.

Pre-approval Evaluation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Submit clinical documentation with the prior authorization request demonstrating that medical necessity criteria are met.

A complete diagnosis/condition description
History and physical examination documenting severity of the condition
Severity and prognosis, including prognostic index scores when applicable

Documentation Required

Evaluation per NCCN and Amyloidosis Consensus Criteria

Assess organ involvement using the amyloidosis consensus criteria for newly diagnosed systemic light‑chain (AL) amyloidosis and perform a formal evaluation of hematopoietic stem cell transplant candidacy (per NCCN systemic AL amyloidosis v1.2026). Document the organ involvement assessment and the transplant candidacy evaluation in the medical record and include these findings in the prior authorization submission.

Provider Actions, Prior Authorization and Documentation

Prior Authorization

Prior authorization required for HCT — include procedure codes

Prior authorization is required for hematopoietic cell transplantation services; include the relevant CPT and HCPCS procedure codes in authorization requests.

Include applicable codes such as 38230, 38232, 38240, 38241, S2142, S2150 when submitting authorization requests

Prior Authorization

Prior authorization must reflect documented candidacy, organ involvement, and cardiac assessment

Approval of prior authorization should be based on documented transplant candidacy including organ involvement assessment and cardiac function consistent with CMS selection criteria and NCCN evaluation steps.

Documentation should demonstrate amyloid deposition in ≤2 organs and cardiac LVEF >45% when applicable

Step Therapy

Pre-transplant systemic therapy: use of induction regimens (e.g., daratumumab + VCD)

Clinical guidance notes that induction systemic therapies (for example, daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone) are preferred initial systemic regimens and may be used prior to consideration of autologous HCT.

Daratumumab + bortezomib/cyclophosphamide/dexamethasone cited as preferred initial systemic therapy

Step Therapy

Initial systemic therapy consideration per NCCN (daratumumab‑based regimen)

NCCN recommends assessing daratumumab plus bortezomib/cyclophosphamide/dexamethasone as preferred initial systemic therapy in most patients before or alongside evaluation for transplant candidacy.

Consider daratumumab + bortezomib/cyclophosphamide/dexamethasone as initial therapy per NCCN v1.2026

Documentation Required

Required clinical documentation: diagnosis, history & physical, severity and prognosis

Medical records submitted for review must document the diagnosis/condition, history and physical examination documenting severity, and the severity/prognosis (including prognostic index scores when applicable).

Diagnosis/condition
History and physical with severity
Severity and prognosis; include prognostic scores when applicable

Documentation Required

Required documentation: organ involvement assessment and stem cell transplant candidacy evaluation

Documentation should explicitly include an assessment of organ involvement using amyloidosis consensus criteria and a formal evaluation of stem cell transplant candidacy, including cardiac function (LVEF) and the number of organs involved.

Organ involvement assessment per amyloidosis consensus criteria
Evaluation for stem cell transplant candidacy (NCCN)
Cardiac function (LVEF) and count of organs involved

Denial Risk

Insufficient documentation may result in denial

Failure to document that medical necessity criteria are met — including diagnosis, history and physical documenting severity, and prognosis — may trigger denial of the request.

Omissions in diagnosis, severity, or prognosis documentation may result in denial

Denial Risk

Selection criteria-related denial risk: CMS-like thresholds (organs involved, LVEF)

Transplant authorization may be denied if patient selection criteria similar to the CMS NCD are not met, for example when more than two organs have amyloid deposition or cardiac LVEF is ≤45%.

Amyloid deposition in >2 organs is inconsistent with CMS selection criteria
Cardiac left ventricular ejection fraction ≤45% may make the patient ineligible

Procedure, HCPCS and Billing Codes

Procedure and HCPCS codesmixed

38230	Bone marrow harvesting for transplantation; allogeneic
38232	Bone marrow harvesting for transplantation; autologous
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
38241	Hematopoietic progenitor cell (HPC); autologous transplantation
S2142	Cord blood-derived stem-cell transplantation, allogeneic
S2150	Bone marrow or blood-derived stem-cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with out-patient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services

Historically removed codesmixed

38242	CPT code 38242 (previously removed from policy)
S2140	HCPCS S2140 (removed Oct 2022)

inv-09: Left ventricular ejection fraction — selection threshold value (> 45%)

Selection threshold> 45% left ventricular ejection fraction (LVEF)

ContextCMS NCD requires cardiac LVEF greater than 45% for autologous HCT eligibility

Use in evaluationDocument cardiac function (LVEF) in pre-transplant assessment and prior authorization records

inv-10: Number of organs with amyloid deposition — selection threshold (≤ 2 organs)

Selection thresholdAmyloid deposition in ≤ 2 organs

ContextCriterion is specified by CMS NCD for autologous HCT candidacy

Use in evaluationDocument number and sites of organ involvement per amyloidosis consensus criteria for authorization

Post-Transplant Services and Stem Cell Rescue

inv-33: Transplant global services and related post-transplant care — coding notes including global definitions and days of care

Global service noteListed HCPCS/CPT codes include global definitions and associated numbers of days of pre- and post-transplant care

Codes referenced38230, 38232, 38240, 38241, S2142, S2150

Documentation implicationInclude services within global period when submitting claims or prior authorization

inv-34: Hematopoietic stem cell rescue after high-dose melphalan — autologous HCT must be used to effect hematopoietic reconstitution per CMS NCD

CMS NCD requirementAutologous HCT must be used to effect hematopoietic reconstitution following severely myelotoxic doses of chemotherapy (e.g., high‑dose melphalan)

ContextThis requirement is part of Medicare National Coverage determination 110.23

Implication for requestsPrior authorization and clinical documentation should state intent to provide hematopoietic reconstitution after high‑dose melphalan

Definitions and Terminology

inv-20: Autologous HCT — definition

DefinitionAutologous HCT: collection of a patient’s own hematopoietic stem cells with reinfusion after high‑dose chemotherapy to permit marrow recovery

Therapeutic roleTypically performed as consolidation when disease is in response to cytotoxic therapy; avoids graft‑versus‑host disease

RisksSusceptible to chemotherapy‑related toxicities and opportunistic infections during aplastic period

inv-21: Allogeneic HCT — definition

DefinitionAllogeneic HCT: transplantation of hematopoietic stem cells obtained from a donor with HLA matching

Therapeutic effectMay provide graft‑versus‑malignancy effect but requires immunosuppression to prevent rejection and GVHD

RisksHigher treatment‑related mortality and risks of graft‑versus‑host disease and opportunistic infections

inv-22: Reduced-intensity conditioning (RIC) — definition

DefinitionReduced‑intensity conditioning (RIC): pretransplant regimens using lower doses or less intense cytotoxic therapy than full myeloablative conditioning

PurposeIntended to reduce treatment‑related morbidity and non‑relapse mortality while permitting donor engraftment and graft‑versus‑malignancy effects

ScopeTerm refers to conditioning regimens intended to be nonmyeloablative as opposed to fully myeloablative

inv-23: Autologous hematopoietic cell transplantation (auto-HCT) — definition specific to AL amyloidosis

Definition specific to AL amyloidosisAutologous HCT for AL amyloidosis: high‑dose melphalan with autologous stem cell rescue used to provide hematopoietic reconstitution following myeloablative therapy

Coverage/stanceConsidered standard of care by ASTCT and covered by CMS when selection criteria (≤2 organs; LVEF >45%) are met

Clinical aimEradicate clonal plasma cells to reduce light‑chain production and improve organ function/outcomes

inv-24: Allogeneic hematopoietic cell transplantation (allo-HCT) — definition and ASTCT stance

DefinitionAllogeneic HCT: transplantation using donor hematopoietic cells

ASTCT stanceASTCT rating N (not generally recommended) for allogeneic HCT in primary amyloidosis in adults

Clinical implicationRoutine use is considered investigational/unsupported due to sparse evidence and high treatment‑related mortality

Background and Evidence Summary

Primary (AL) amyloidosis is a systemic clonal plasma cell disorder in which misfolded immunoglobulin light chains form insoluble fibrils that deposit in tissues and organs, most commonly the kidneys, heart, and liver. Organ deposition leads to progressive organ dysfunction. Treatment focuses on rapidly reducing light‑chain production by the clonal plasma cell population. Autologous HCT following high‑dose chemotherapy can eradicate the pathogenic clone and provide hematopoietic reconstitution; evidence shows meaningful survival benefit in selected, eligible patients. Allogeneic HCT uses donor cells and carries additional risks (graft‑versus‑host disease and higher treatment‑related mortality), and is considered investigational for this condition.

Center and Program Requirements

Note

Center input: academic transplant centers consulted; no specific accreditation stated

Clinical input for the policy was solicited from academic medical centers, including transplant centers, and their feedback informed the policy statements; specific center accreditation or volume requirements are not stated.

Input received from five academic medical centers, including three transplant centers
No specific accreditation or volume requirements specified in the document

Note

Center requirements: not specified in the document

The policy does not specify additional center requirements or accreditation expectations beyond the documented input from transplant centers.

No explicit center accreditation or volume requirements provided in this section

OpenPayer

Hematopoietic Cell Transplantation for Primary Amyloidosis

Coverage Criteria for Hematopoietic Cell Transplantation

Transplant Candidate Evaluation and Selection

Contraindications

Pre-approval Evaluation Requirements

Provider Actions, Prior Authorization and Documentation

Procedure, HCPCS and Billing Codes

Post-Transplant Services and Stem Cell Rescue

Definitions and Terminology

Background and Evidence Summary

Center and Program Requirements