CurrentAetnaPolicy 0627

Hematopoietic Cell Transplantation for Aplastic Anemia and other Bone Marrow Failure Syndromes

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Defines Aetna's coverage stance for hematopoietic cell transplantation in aplastic anemia and related bone marrow failure syndromes, including medical necessity criteria for allogeneic transplantation, investigational designation for autologous transplantation, and related coding. Applies to Aetna members and providers submitting transplant requests.

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CurrentAetnaPolicy 0627

Hematopoietic Cell Transplantation for Aplastic Anemia and other Bone Marrow Failure Syndromes

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Policy Summary

PayerAetna

PolicyHematopoietic Cell Transplantation for Aplastic Anemia and other Bone Marrow Failure Syndromes

Policy CodePolicy 0627

Change TypeNo material clinical or coverage changes

Effective DateJun 28, 2002

Last ReviewSep 12, 2023

Next Review DateJul 11, 2024

Key ActionObtain prior authorization and document diagnostic confirmation, donor availability, and required clinical testing when requesting allogeneic hematopoietic cell transplantation.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

06/28/2002policy origin

09/12/2023last review

97.3%haplo HSCT engraftment

6.7%/yrhaplo TRM

Coverage Criteria

Allogeneic transplantation — medical necessity criteria

Covered when ALL of the following are met (either transplanting institution selection criteria or, if absent, the policy's criteria):

Primary rule: Allogeneic hematopoietic cell transplantation is medically necessary for the treatment of severe aplastic anemia, Diamond-Blackfan anemia, Fanconi's anemia, paroxysmal nocturnal hemoglobinuria, and pure red cell aplasia when members meet the transplanting institution's selection criteria.

Institution-level criteria take precedence if present

Severe aplastic anemia — policy criteria: When institutional selection criteria are absent, allogeneic transplantation is medically necessary for severe aplastic anemia when the member has at least 3 of the following 4 features: bone marrow cellularity <25% (markedly hypocellular); neutrophil count <0.5 x 10^9/L; reticulocyte count <1% or <20 x 10^9/L (corrected for hematocrit); untransfused platelet count <20 x 10^9/L.3_of_4

Pure red cell aplasia: Allogeneic transplantation is medically necessary for pure red cell aplasia when bone marrow cellularity <25% (markedly hypocellular) AND reticulocyte count <1% or <20 x 10^9/L (corrected for hematocrit).both

Diamond-Blackfan anemia: Covered when patient is corticosteroid-refractory.

Fanconi's anemia: Covered when patient has severe bone marrow failure, myelodysplastic syndrome, or acute myelogenous leukemia.

Paroxysmal nocturnal hemoglobinuria: Covered when there are ongoing transfusion requirements and a suitable HLA-matched donor.

Congenital dyserythropoietic anemia: Covered when transfusion-dependent and has failed interferon alfa and splenectomy.

Repeat allogeneic transplant: Repeat allogeneic stem cell transplantation is medically necessary for primary graft failure, failure to engraft, or rejection in the listed conditions.

Autologous transplantation — investigational

Not covered / investigational:

Autologous HCT: Autologous hematopoietic cell transplantation is considered experimental and investigational for the treatment of severe aplastic anemia, Diamond-Blackfan anemia, Fanconi's anemia, paroxysmal nocturnal hemoglobinuria, and pure red cell aplasia because its effectiveness for these indications has not been established.

Covered clinical indications

Evidence-based contexts in which allogeneic HSCT is considered

Indications summarized from sources: Allogeneic hematopoietic cell transplantation may be considered for: idiopathic severe aplastic anemia (particularly when an HLA-identical sibling donor is available), inherited marrow failure syndromes (Fanconi anemia, Diamond-Blackfan anemia), paroxysmal nocturnal hemoglobinuria, pure red cell aplasia, congenital dyserythropoietic anemia, refractory cases after immunosuppressive therapy, and selected nonmalignant marrow disorders.

Taken from UpToDate reviews and multiple studies cited in the policy background.

Second transplant after graft failure: For adult patients with severe AA experiencing graft failure after initial HSCT, a second HLA-matched sibling donor HSCT with reconditioning (eg, TNI-750/ATG) achieved high engraftment and 5-year OS in reported series.

Yahng et al. reported neutrophil and platelet engraftment in most patients and 5-year OS 95.7%.

Haploidentical donor use: Haploidentical HSCT is an option when matched donors are unavailable; systematic review/meta-analysis reported successful engraftment in ~97.3% with pooled transplant-related mortality ~6.7%/yr; outcomes influenced by conditioning intensity and GVHD prophylaxis.

Autologous hematopoietic cell transplantation is designated experimental/investigational for treatment of severe aplastic anemia, Diamond‑Blackfan anemia, Fanconi’s anemia, paroxysmal nocturnal hemoglobinuria, and pure red cell aplasia because its effectiveness for these indications has not been established. Requests for autologous HCT for these conditions are therefore subject to denial or noncoverage in this Clinical Policy Bulletin; specific autologous procedure codes are listed as not covered for the indications in this bulletin (for example, CPT 38232, 38241).

The provided document portion does not list explicit policy exclusions beyond the investigational designation for autologous hematopoietic cell transplantation. The Clinical Policy Bulletin excerpt is a summary reference and does not enumerate plan‑specific exclusion clauses in this section; providers should consult the full policy bulletin or plan documents for any additional exclusion language.

This Clinical Policy Bulletin is intended to summarize Aetna’s medical policy and administrative guidance for hematopoietic cell transplantation in aplastic anemia and related marrow failure syndromes. It contains only a partial, general description of plan or program benefits and does not constitute a contract or guarantee of coverage. Participating providers remain independent contractors and treating clinicians are responsible for medical advice and treatment decisions; the bulletin may be updated and is subject to change.

Autologous hematopoietic cell transplantation is not considered medically necessary (investigational) for severe aplastic anemia and the listed bone marrow failure syndromes because effectiveness has not been established. For patients older than 40 years, immunosuppressive therapy (IST) is generally the preferred initial treatment, and allogeneic transplantation is reserved for IST failures or other specific indications.

The document portion does not provide a list of distinct not medically necessary conditions beyond stating that autologous HCT for the listed marrow failure syndromes is investigational due to unestablished effectiveness. The background and evidence review emphasize limited and heterogeneous comparative data (for example, on first‑line matched sibling HSCT versus first‑line IST), supporting individualized clinical decision‑making and conservative coverage determinations where evidence is insufficient.

Coding

Covered CPT Codes (if selection criteria met)CPTCovered

38230	Bone marrow harvesting for transplantation; allogeneic.
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor.
86813	HLA typing; A, B or C multiple antigens.
86817	DR/DQ, multiple antigens.
86821	Lymphocyte culture, mixed (MCL).

CPT codes not covered for indications listedCPTNot Covered

38232	Bone marrow harvesting for transplantation; autologous.
38241	Hematopoietic progenitor cell (HPC); autologous transplantation.

Covered HCPCSHCPCSCovered

S2150

Bone marrow or blood-derived stem-cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; includes comprehensive services.

Related HCPCS/J-codesHCPCS

J9212	Injection, interferon alfacon-1, recombinant, 1 microgram.
J9213	Injection, interferon, alfa-2a, recombinant, 3 million units.
J9214	Injection, interferon, alfa-2b, recombinant, 1 million units.
J9215	Injection, interferon, alfa-n3, (human leukocyte derived), 250,000 iu.
S0145	Injection, pegylated interferon alfa-2a, 180 mcg per ml.
S0148	Injection, pegylated interferon alfa-2b, 10 mcg.

ICD-10 diagnosis codes referencedICD-10

D59.5	Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli].
D60.0 - D61.9	Aplastic anemia [severe].
D64.4	Congenital dyserythropoietic anemia.
T86.5	Complications of stem cell transplant.
Z94.84	Stem cells transplant status.

Other related CPT codesCPT

38100	Splenectomy; total (separate procedure).
38101	Splenectomy; partial (separate procedure).
38102	Splenectomy; total, en bloc for extensive disease.
38120	Laparoscopy, surgical, splenectomy.
38204 - 38215	Bone marrow or stem cell services/procedures.
85004 - 85049	Blood count.
85055	Reticulated platelet assay.
85060	Blood smear, peripheral, interpretation by physician with written report.
85097	Bone marrow, smear interpretation.
86920 - 86923	Compatibility test each unit.

Severe aplastic anemia diagnostic thresholds — inv-15

Neutrophil thresholdNeutrophil count < 0.5 x 10^9/L

Platelet thresholdUntransfused platelet count < 20 x 10^9/L

Reticulocyte thresholdReticulocyte count < 1% or < 20 x 10^9/L (corrected for hematocrit)

Marrow cellularityBone marrow cellularity < 25% (markedly hypocellular) — policy notes <20% in background as severe definition

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for allogeneic hematopoietic cell transplantation (HCT) procedures and associated transplant services. Requests must document that the member meets the transplanting institution's selection criteria; if the institution has no published criteria, documentation must demonstrate that the member meets Aetna's medical necessity criteria for allogeneic HCT.

Prior authorization required for allogeneic HCT and related CPT/HCPCS codes (see CPT/HCPCS lists).
Autologous HCT requests for indications listed in this policy are considered investigational and require denial documentation if submitted for those indications.

Documentation Required

Prior Authorization: Diagnostic and Donor Documentation

Documentation submitted with prior authorization requests should include diagnostic confirmation, donor availability and HLA status, and other clinically relevant donor information. Where applicable, include telomere length testing and genetic testing to exclude inherited marrow-failure syndromes.

Transplant Candidate Criteria

Transplant candidate criteria

Candidates for allogeneic HCT:

Institutional selection criteria: Members who meet the transplanting institution's selection criteria are candidates for allogeneic HCT for the listed disorders.

Institution criteria take precedence

Severe AA candidates when no institutional criteria: Patients meeting policy-defined severe AA criteria (≥3 of 4 findings: marrow cellularity <25%; neutrophils <0.5 x 10^9/L; reticulocytes <1% or <20 x 10^9/L; untransfused platelets <20 x 10^9/L) are candidates for allogeneic HCT.3_of_4

Pediatric with matched sibling: Young patients (<20 years) with an HLA-matched related donor are generally accepted as initial transplant candidates.age<20

Contraindications

For patients older than 40 years, the policy and supporting background indicate that immunosuppressive therapy (anti‑thymocyte globulin plus cyclosporine A) is generally the accepted initial treatment of choice. Consequently, allogeneic transplantation may be relatively contraindicated as first‑line therapy in this age group and is typically reserved for those who fail IST or have other specific indications.

Within the provided document portion there are no explicit absolute or relative contraindications listed that would universally preclude transplant coverage. The policy instead describes treatment preferences by age and designates autologous HCT as investigational for the listed indications; individual transplanting institution selection criteria and full policy materials should be consulted for patient‑level contraindication determinations.

Evaluation and Pre-Transplant Requirements

Note

Center and Program Requirements

Note

Post-Transplant Coverage and Services

Comprehensive transplant service — inv-44

HCPCS S2150 descriptionBone marrow or blood-derived stem-cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; includes comprehensive services (pre- and post-transplant care).

Scope of bundleIncludes harvesting, transplantation, related complications, and pre- and post-transplant care within its global definition.

Applicable settingsUsed to represent comprehensive transplant services for billing and coverage consideration.

Post-transplant monitoring and management — inv-45

Outcomes reportedAcute and chronic GVHD incidence, engraftment timing, graft failure rates, and long-term overall survival (OS) / event-free survival (EFS).

Specific metrics — engraftment

Background

Aplastic anemia is a disorder of bone marrow failure resulting in pancytopenia and a markedly hypocellular marrow. Severe aplastic anemia is defined by specific cytopenia and marrow criteria: for example, neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, reticulocyte count <1% (or <20 x 10^9/L), and markedly reduced bone marrow cellularity (eg, <20–25%); the policy indicates that the presence of 3 of these 4 findings defines severe disease and informs transplant candidacy. Definitive therapeutic options include immunosuppressive therapy (IST) and allogeneic hematopoietic cell transplantation, with allogeneic HCT from an HLA‑matched sibling generally preferred in younger patients when criteria are met.

Definitions

Severe aplastic anemia — diagnostic thresholds (inv-29)

Neutrophil thresholdNeutrophils < 0.5 x 10^9/L

Platelet thresholdPlatelets < 20 x 10^9/L (untransfused)

Reticulocyte thresholdReticulocytes < 1% or < 20 x 10^9/L (corrected for hematocrit)

Marrow cellularityBone marrow cellularity markedly hypocellular — policy uses <25% (background notes <20% as severe definition)

Transplant status code — inv-30

ICD-10 codeZ94.84 — Stem cells transplant status

Use

Revision History & References

2023-09-12policy_reviewLatest

Policy last reviewed; references and evidence base (including recent systematic reviews and cohort reports on haploidentical HSCT and outcomes after second transplants) were updated in the review history.

2022-06evidence_update

Publication of a multicenter report on HCT for congenital dyserythropoietic anemia (Rangarajan et al., 2022) incorporated into evidence supporting transplant indications and pre-HCT management considerations.

2020-06

Policy Summary

PayerAetna

PolicyHematopoietic Cell Transplantation for Aplastic Anemia and other Bone Marrow Failure Syndromes

Policy CodePolicy 0627

Change TypeNo material clinical or coverage changes

Effective DateJun 28, 2002

Last ReviewSep 12, 2023

Next Review DateJul 11, 2024

Key ActionObtain prior authorization and document diagnostic confirmation, donor availability, and required clinical testing when requesting allogeneic hematopoietic cell transplantation.

SourceLink

On This Page

Multiple studies and a systematic review/meta-analysis summarized in the background.

Transplant for congenital dyserythropoietic anemia (CDA): HCT is considered the sole curative option for CDA; multicenter series report favorable 2-year OS and EFS but notable risks (VOD, viral reactivation, graft failure), and pre-HCT chelation for iron overload is often used.

Rangarajan et al. multicenter retrospective series.

Documented donor HLA typing (e.g., 86813, 86817, 86920-86923).
Evidence of donor availability and relationship (matched sibling, unrelated, haploidentical) and graft source (bone marrow, peripheral blood, cord blood).
Telomere length and genetic testing results when inherited marrow-failure syndromes are suspected.

Documentation Required

Diagnostic Workup Expectations

Expected diagnostic workup prior to authorization includes a bone marrow evaluation with cellularity assessment, cytogenetics and FISH to exclude genetic etiologies, complete blood counts and reticulocyte count, and other tests as clinically indicated (e.g., compatibility testing). Results of these studies are often required before initiation of therapy or approval of transplant.

Bone marrow biopsy/report with cellularity.
Cytogenetics and specific FISH assays to exclude genetic causes.
Complete blood count with neutrophil, platelet, and reticulocyte counts (document thresholds when applicable).
Compatibility and crossmatch testing as appropriate.

Denial Risk

Autologous Transplant Considered Investigational

Autologous hematopoietic cell transplantation for severe aplastic anemia and the specified inherited marrow-failure syndromes is considered experimental and investigational; prior authorization submissions for autologous HCT for these indications should be evaluated against this policy and will generally not be approved.

Autologous transplantation CPT codes (e.g., 38232, 38241) are not covered for indications listed in this CPB.
Denial rationale should reference lack of established effectiveness for these indications.

Note

Preferred Initial Therapy and Sequence Considerations

Clinical decision-making should reflect age-based and evidence considerations: allogeneic HCT from an HLA-matched sibling donor is generally preferred as initial therapy in younger patients (typically <20 years); for patients >40 years, immunosuppressive therapy (IST) is generally the preferred initial approach and allogeneic transplant is reserved for IST failure, relapse, or other appropriate indications. Comparative effectiveness of first-line matched-sibling HSCT versus first-line IST is uncertain; individual patient factors, donor availability, and institutional expertise should guide sequencing.

Preferred initial therapy: <20 yrs — allogeneic HCT from HLA-matched related donor.
Preferred initial therapy: >40 yrs — IST (e.g., ATG + cyclosporine); reserve allogeneic HCT for IST failure or relapse.
Uncertainty exists comparing first-line matched sibling HSCT vs first-line IST; document rationale for chosen sequence.

Step Therapy

There are no formal step-therapy requirements or sequencing rules imposed by this policy beyond the clinical recommendations above; authorization decisions are based on documented medical necessity, diagnostic workup, donor status, and institutional selection criteria.

No mandated step-therapy protocols in policy; do not require prior IST trial for young patients when allogeneic HCT with matched sibling donor is clinically indicated.
Authorization guided by member-specific clinical data rather than automatic sequencing rules.

Documentation Required

Required Documentation

Required documentation must show that the member meets the transplanting institution's selection criteria or, if institutional criteria are unavailable, that the member meets Aetna's listed medical necessity criteria for allogeneic HCT. Include prior treatment history, response to IST when relevant, and indication-specific clinical details.

Transplant center selection criteria or statement that institutional criteria were applied.
Clinical history including prior therapies (e.g., IST), response or failure, transfusion dependence, and complications.
Specific indication documentation (e.g., diagnostic thresholds for severe aplastic anemia: marrow cellularity, neutrophil, platelet, reticulocyte counts).

Documentation Required

Required Clinical Documentation

Required clinical documentation includes bone marrow evaluation reports, cytogenetic/FISH results, telomere length or genetic testing when relevant, donor HLA status and compatibility testing, and transplant candidacy assessments (age, comorbidities, prior therapies). These items support medical necessity determinations.

Bone marrow biopsy and cellularity report.
Cytogenetics and FISH assay results.
Telomere length testing when inherited syndromes suspected.
Donor HLA typing and compatibility tests (e.g., 86813, 86817, 86920-86923).
Documentation of graft source and donor type.

Denial Risk

No Explicit Denial Triggers Specified

This policy does not enumerate specific denial triggers beyond the investigational status of autologous HCT for the listed indications and failure to meet medical necessity or documentation requirements. Denials should be based on absence of required clinical criteria, investigational status where applicable, or lack of necessary diagnostic/donor documentation.

No other explicit automatic denial triggers are listed in the policy.
Common denial reasons: insufficient diagnostic data, missing donor/HLA information, autologous HCT requested for investigational indications.

Note

Supplemental Documentation Links

Supplemental resources and links that should accompany authorization and clinical review processes include the policy review history, definitions, and Clinical Policy Bulletin Notes. Use these resources for administrative guidance and definitions relevant to coverage determinations.

Include links or references to: Review History, Definitions, and Clinical Policy Bulletin Notes when submitting or adjudicating requests.
Reference policy effective date and last review (Effective: 06/28/2002; Last Review: 09/12/2023) as needed.

Candidate selection

Candidate selection considerations drawn from reviews and consortium survey

Diagnostic confirmation: Bone marrow evaluation with cytogenetics and specific FISH assays to establish diagnosis and exclude genetic etiologies is generally required prior to initiating immunosuppressive therapy or proceeding to HSCT.

Many institutions require results before IST.

Donor considerations: Uniform referral for HSCT as first-line therapy if an HLA-identical sibling is identified; when an identical sibling is not available, first-line IST is commonly used and haploidentical related donors may be considered when HSCT is indicated and matched donors are unavailable.

Neutrophil engraftment timing reported (median ~12 days in second transplant series); platelet engraftment timing also reported.

Complications trackedVeno-occlusive disease, viral reactivation, and chronic GVHD rates reported in congenital dyserythropoietic anemia series.

Performance outcomesReported 5-year OS after 2nd MSD HSCT 95.7% (Yahng et al.) and 2-year OS for CDA 88% (Rangarajan et al.).

Denotes transplant status for members in medical records and coding contexts.

Aplastic anemia (AA) — inv-31

DefinitionAplastic anemia (AA) — a disorder characterized by peripheral blood pancytopenia and a hypocellular bone marrow.

EtiologiesCan be idiopathic, secondary to infections, drugs/toxins, or hereditary causes (e.g., Fanconi's anemia, Diamond-Blackfan syndrome).

Clinical relevanceSevere AA defined by specific cytopenia and marrow cellularity thresholds used to guide treatment decisions (IST vs allogeneic HCT).

Pure red cell aplasia (PRCA) — inv-32

DefinitionPure red cell aplasia (PRCA) — a rare form of profound anemia characterized by absence of reticulocytes and virtual absence of erythroid precursors in the bone marrow.

Relation to AAConsidered a unique form of aplastic anemia affecting erythroid lineage; may be an indication for allogeneic transplantation when criteria met.

Clinical Policy Bulletin resources — inv-33

Review history linkClinical Policy Bulletin: Review history and prior review dates available via policy history links.

Definitions linkDefinitions page accessible from Clinical Policy Bulletin for term clarification.

Supplemental notesClinical Policy Bulletin notes provided for administrative and interpretive guidance (e.g., prior authorization instructions).

EBMT Severe Aplastic Anemia Working Party report on haploidentical transplantation and post-transplant cyclophosphamide (Prata et al., 2020) cited to support haploidentical donor approaches and conditioning considerations.

2018-10evidence_update

Series reporting successful outcomes of second HSCT with total nodal irradiation and ATG conditioning for graft failure (Yahng et al., 2018) added to references informing reconditioning strategies for repeat transplantation.

2002-06-28policy_effective_date

Policy effective date (policy origin), establishing coverage framework and linking to the references and review process for future updates.

Administrative notes: this Clinical Policy Bulletin lists an effective date of 06/28/2002, last review date 09/12/2023, and next scheduled review 07/11/2024. The bulletin also includes standard disclaimers that it provides a partial summary of plan benefits, may be updated, and that providers should refer to the full Clinical Policy Bulletin and supplemental materials for specific prior‑authorization and documentation procedures.