ModifiedCignaPolicy 0533

Hematopoietic Stem Cell Transplantation (HSCT) for Blood Cancers

Defines medical necessity, contraindications, and coverage stance for autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for various hematologic malignancies and related disorders for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyHematopoietic Stem Cell Transplantation (HSCT) for Blood Cancers

Policy CodePolicy 0533

Change TypeFocused review moved PCNSL content from CP 0534annual review no clinical statement changes

Effective DateAug 15, 2024

Next Review DateAug 15, 2025

Key ActionObtain prior authorization and document disease-specific indication, remission status, risk category, and donor HLA matching for planned transplant.

SourceLink

POLICY UPDATE CHANGES

Content addressing primary central nervous system lymphoma (PCNSL) was removed from CP 0534 and added to this Coverage Policy.

No clinical policy statement changes during the annual review on 8/15/2024.

10disease categories referenced

YesASTCT/NCCN recommendations cited

physiologic cutoffseligibility thresholds noted

01/15/2024focused review date

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

08/15/2024annual review date

Coverage Criteria for Hematopoietic Stem Cell Transplantation

Chronic lymphocytic leukemia (CLL), chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) — Hematopoietic Stem Cell Transplantation (HSCT) coverage criteria. All allogeneic transplantations must be from an appropriately matched human leukocyte antigen (HLA) donor.

CLL and CMML — Allogeneic HSCT coverage criteria

Chronic Lymphocytic Leukemia (CLL): Allogeneic HSCT is considered medically necessary for individuals with high-risk disease (eg, del(17p) or TP53 mutation) in first or greater remission, or for those with transformation to a higher-grade lymphoma or other indications per guidelines when alternative therapies (including targeted agents and CAR T where appropriate) are not suitable or have failed. Clinical factors to document include prior lines of therapy, molecular/cytogenetic status (eg, del(17p)/TP53), response to covalent BTK inhibitors, and candidacy for autologous HSCT or CAR T-cell therapy. Autologous HSCT for CLL is not generally recommended (considered not medically necessary).
Chronic Myelomonocytic Leukemia (CMML): Allogeneic HSCT is considered medically necessary for the treatment of CMML when the patient is an appropriate transplant candidate. Document disease risk features, prior therapies, performance status and comorbidities. Autologous HSCT for CMML is considered experimental, investigational, or unproven.

Acute Myeloid Leukemia (AML) — HCT indications

Allogeneic HSCT is considered medically necessary for AML when ANY of the following apply: first complete remission (CR1) for adverse-risk or intermediate-risk disease (per ELN/ASTCT guidance), second or subsequent remission, induction failure, secondary or therapy-related AML, or other high-risk features (including presence of measurable residual disease [MRD] after induction).
A second allogeneic HSCT is considered medically necessary when relapse occurs more than six months after the first allogeneic HSCT and the patient achieves a second or subsequent remission.
Autologous HSCT may be considered medically necessary when allogeneic HSCT is not available or not appropriate and for selected favorable/intermediate-risk patients as consolidation (per guideline-specified scenarios). Tandem HSCT is considered experimental, investigational or unproven for AML.
See ASTCT 2020/2021 guidance and ELN risk stratification for pediatric and adult distinctions, MRD implications, and select exceptions (eg, CBF-AML with KIT mutation may be considered for allo-HCT in CR1).

CML — Allogeneic HSCT indications

Allogeneic HSCT is considered medically necessary for chronic myeloid leukemia (CML) in any of the following situations: failure to achieve hematologic remission after approximately 3 months of tyrosine kinase inhibitor (TKI) therapy; lack of cytogenetic response or cytogenetic relapse at 6, 12, or 18 months after initial response; failure to achieve molecular remission by ~12 months of appropriate TKI therapy; disease progression on TKI therapy to accelerated phase or blast crisis; intolerance to or contraindication for TKI therapy; or other advanced-phase disease where transplant is the only curative option.
Autologous HSCT for CML is considered experimental, investigational or unproven.
Refer to NCCN and ASTCT guidance for pediatric vs adult recommendations and for donor selection and timing considerations.

Billing and Coding

Considered Medically Necessary CPT CodesCPTCovered

38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic.
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous.
38207	Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage.
38208	Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing, per donor.
38209	Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, with washing, per donor.
38210	Transplant preparation of hematopoietic progenitor cells; specific cell depletion within harvest, T-cell depletion.
38211	Transplant preparation of hematopoietic progenitor cells; tumor cell depletion.
38212	Transplant preparation of hematopoietic progenitor cells; red blood cell removal.
38213	Transplant preparation of hematopoietic progenitor cells; platelet depletion.
38214	Transplant preparation of hematopoietic progenitor cells; plasma (volume) depletion.

1–10 of 16

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Considered Medically Necessary HCPCS/S-codesHCPCSCovered

S2140	Cord blood harvesting for transplantation, allogeneic.
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 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.

inv-46: Cardiac ejection fraction — physiologic contraindication threshold

Cardiac ejection fractionContraindication: ejection fraction less than 35%

Source contextListed as a relative contraindication to HSCT when EF <35%

Actionable notePatients with EF <35% should be considered ineligible for transplant authorization unless compelling justification and specialty evaluation are documented

inv-47: Bilirubin — physiologic contraindication threshold

BilirubinContraindication: total bilirubin greater than 2.0 mg/dL

TransaminasesContraindication: transaminases greater than two times normal (may represent significant hepatic dysfunction)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required per member's benefit plan. Coverage varies by benefit document; verify eligibility and any plan-specific prior authorization steps before scheduling HCT.

Coverage varies by plan — refer to member benefit document
Prior authorization required when billing listed CPT/HCPCS (see coding block in policy)

Documentation Required

HCT Indication and Documentation

Document the HCT indication with guideline-aligned rationale (for example NCCN, ASTCT or ELN where applicable), including disease-specific risk stratification and why HCT is indicated versus alternative therapies.

State specific disease indication (e.g., ALL, AML, MDS, MM, CLL) and whether autologous or allogeneic HCT is planned
Cite guideline source and version supporting the indication

Conditioning Regimens and Covered Transplant Approaches

Regimen	Indication / Notes	Coverage Stance
Autologous hematopoietic cell transplantation after eligibility assessment
Selected patients with systemic light chain amyloidosis after assessment of organ function and comorbidity; low tumor burden patients may proceed to HCT immediately; patients with high tumor burden may receive systemic therapy first and be reassessed
Covered when eligibility criteria (adequate organ function and absence of severe/multiple comorbidities) are met

Conditioning Intensity	Patient Factors	Coverage Stance
High-dose (myeloablative) conditioning
Typically used for younger patients with sufficient physiologic reserve
Recommended option for eligible younger patients where appropriate per society guidance

Conditioning Type	Age Consideration	Policy Note
Myeloablative (high-dose) conditioning
Preferred for younger patients who can tolerate intensive regimens
Coverage aligned with guideline-based selection of conditioning intensity by age and fitness

Regimen	Context / Response Required	Coverage Stance
DA-R-EPOCH, R-CHOP or similar high-intensity regimens
Used as frontline or salvage chemo; autologous HCT consolidation is not routinely recommended in PET-negative complete remission after first-line R-CHOP or similar
Neutral/mixed — panel does not recommend routine autologous HCT consolidation in PET-negative CR1; HCT may be considered in specific high-risk or relapsed scenarios per guideline

Regimen	Setting	Coverage Stance
High-dose chemotherapy (eg, cytarabine/thiotepa followed by carmustine/thiotepa; or thiotepa/busulfan/cyclophosphamide) with stem cell rescue
Consolidation for primary CNS lymphoma patients who achieve complete or partial response after induction high‑dose methotrexate–based therapy; thiotepa‑containing conditioning preferred per guideline
Covered as a recommended consolidation option for eligible PCNSL patients when criteria met

Regimen	Indication	Coverage Stance
High-dose chemotherapy followed by autologous stem cell transplant (HDCT+ASCT)
Consolidation for relapsed/refractory Hodgkin lymphoma and as standard consolidation for eligible multiple myeloma patients to improve response and overall survival
Covered when disease-specific criteria and transplant eligibility are met

Transplant Type	Typical Indications	Coverage Stance
Myeloablative allogeneic HSCT
Selected high‑risk myeloid diseases such as CMML and JMML where curative intent is sought
Covered for selected patients meeting guideline-based indications and eligibility criteria

Transplant Type	Typical Use	Coverage Stance
Reduced‑intensity / non‑myeloablative allogeneic HSCT
Acceptable option for selected adults with NHL and other diseases when reduced toxicity is preferred or donor/graft‑versus‑tumor effect is desired
Covered when consistent with disease indication, patient fitness, and guideline recommendations

Topic	Summary from Evidence	Policy Relevance
Comparisons of reduced‑intensity vs myeloablative conditioning
Meta-analyses and trials report outcomes comparing RIC and myeloablative regimens, often favoring RIC in older or higher‑comorbidity patients while myeloablative approaches may be used in younger, fit patients
Informational — conditioning intensity selection should be individualized and documented per guideline recommendations

Regimen Components	Clinical Context	Coverage Stance
Thiotepa + Busulfan + Cyclophosphamide (TBC) with autologous stem cell transplant
Used as a thiotepa‑containing conditioning option for consolidation in primary CNS lymphoma patients in first complete remission per cited series/trials
Covered as an evidence‑supported conditioning regimen for eligible PCNSL patients when clinical criteria are met

Transplant Indications by Line of Therapy

Line of therapy categories — first-line | second-line | salvage

Line‑of‑therapy categories used in policy determinations:

Lines of therapy: first‑line OR second‑line OR salvage (line of therapy specified per disease‑specific criteria)

Policy organizes indications by first‑line, second‑line and salvage contexts as applicable.

Biomarker and Molecular Test Requirements

inv-129: MRD — MRD positive at end of induction (ALL/AML guidance)

MRD at end of inductionPresence of measurable residual disease (MRD) positive at end of induction is cited as an indication to offer allogeneic HCT (ASTCT guidance)

PopulationReferenced in ASTCT recommendations for AML and pediatric ALL contexts — MRD+ at end of induction supports HCT consideration

Authorization noteDocument MRD testing method, timing (end of induction), and positive result when submitting for transplant authorization

inv-130: FLT3-ITD biomarker (reference)

FLT3-ITD biomarkerFLT3-ITD is noted by ASTCT as a biomarker prompting consideration of HCT in pediatric AML CR1

UseFLT3-ITD presence influences recommendations for HCT in select pediatric AML patients per ASTCT guidance

Background and Definitions

Hematopoietic stem cell transplantation (HSCT) replaces hematopoietic stem cells that are destroyed by high‑dose chemotherapy or radiation and is used to treat a range of hematologic malignancies and selected nonmalignant disorders. Autologous HCT uses the patient’s own collected stem cells, reinfused after high‑dose therapy, while allogeneic HCT uses donor cells (matched sibling, unrelated donor, haploidentical relative, or cord blood) and requires appropriate HLA matching.

Conditioning regimens vary in intensity from myeloablative (very high‑dose chemotherapy/radiation) to reduced‑intensity/non‑myeloablative approaches that lower toxicity and are often used in older or comorbid patients; transplant type and conditioning selection are driven by disease indication, patient age, comorbidity, and guideline recommendations.

inv-96: Definition — Autologous transplant

Autologous transplant — definitionTransplant using the individual's own hematopoietic stem cells collected prior to high‑dose therapy and reinfused after treatment

Key pointUsed commonly as consolidation for eligible multiple myeloma and certain lymphoma settings

DocumentationEligibility assessment and stem cell collection plan should be documented prior to authorization

Policy Revision History and Changes

Policy Summary

PayerCigna

PolicyHematopoietic Stem Cell Transplantation (HSCT) for Blood Cancers

Policy CodePolicy 0533

Change TypeFocused review moved PCNSL content from CP 0534annual review no clinical statement changes

Effective DateAug 15, 2024

Next Review DateAug 15, 2025

Key ActionObtain prior authorization and document disease-specific indication, remission status, risk category, and donor HLA matching for planned transplant.

SourceLink

On This Page

Clinical implicationSignificant hepatic dysfunction (bilirubin >2.0 mg/dL or transaminases >2x normal) may preclude HSCT unless related to underlying disease and reversible

inv-48: Transaminases — physiologic contraindication threshold

Transaminases thresholdGreater than two times normal is listed as a relative contraindication to HSCT

Associated contextHepatic dysfunction criteria are listed together with bilirubin >2.0 mg/dL as reasons to consider ineligibility

Documentation recommendationRecord liver enzyme levels and etiology; reversible causes should be treated and reassessed prior to authorization

inv-49: Creatinine clearance — physiologic contraindication threshold

Creatinine clearanceContraindication: creatinine clearance less than 50 mL/min (not applicable for most autologous transplants)

ContextRenal dysfunction is noted as a relative contraindication; NCCN notes renal dysfunction is not an absolute contraindication to transplant

Actionable noteDocument measured creatinine clearance and any plan for renal optimization or dialysis support prior to authorization

inv-50: Pulmonary diffusion capacity (DLCO) — physiologic contraindication threshold

Pulmonary diffusion capacity (DLCO)Contraindication: DLCO less than 50% of predicted

Clinical implicationPoor pulmonary function (DLCO <50% predicted) may preclude HSCT eligibility

Documentation recommendationProvide formal pulmonary function testing results and any interventions or optimization plans

inv-51: Karnofsky/ECOG performance status thresholds

Karnofsky performance statusContraindication: Karnofsky score less than 60%

ECOG performance statusContraindication: ECOG performance status greater than 2

Clinical implicationPoor performance status (Karnofsky <60% or ECOG >2) is cited as a contraindication to HSCT and should be documented for authorization decisions

inv-52: WBC threshold for ALL high-risk (B-ALL/T-ALL)

WBC threshold — B-ALLHigh-risk criterion: white blood cell count >30 x 10^9/L for B-ALL

WBC threshold — T-ALLHigh-risk criterion: white blood cell count >100 x 10^9/L for T-ALL

UseThese WBC thresholds are listed in NCCN ALL high-risk features and inform risk stratification for transplant consideration

inv-53: Age threshold for ALL high-risk (>35 years)

Age threshold>35 years for both B-ALL and T-ALL (listed as a high-risk feature)

UseAge >35 years is included in NCCN high-risk features that inform consideration for allo-HCT

DocumentationRecord patient age and reference to NCCN ALL high-risk criteria when seeking authorization

Prior Authorization

Prior Authorization: Document Risk, Remission, and Guideline Alignment

For prior authorization include documentation of disease risk, remission status, prior treatment history (including duration and response), and explicit alignment with guideline criteria (e.g., ELN 2017 risk groups for AML; NCCN MRD guidance). Lack of this documentation may affect coverage determination.

Document risk group (e.g., favorable/intermediate/adverse per guideline)
Remission status (CR1, CR2, relapse, refractory, sensitive vs resistant relapse)
Prior therapies and response (including trials of standard therapies where required e.g., TKI duration for CML)

Prior Authorization

Prior Authorization for HCT Type and Indication

Specify the type of HCT planned (autologous, allogeneic, tandem, reduced-intensity vs myeloablative) and the indication. Include donor search/selection plan and stem-cell collection strategy for prior authorization.

Planned HCT type: autologous, allogeneic, tandem, reduced-intensity conditioning (RIC) or myeloablative
Donor type planned (matched related, matched unrelated, cord blood, haploidentical) and HLA testing plan
Stem-cell collection plan (peripheral blood vs marrow) and intent to collect enough cells for intended number of transplants

Note

Reference NCCN Transplant Guidance

Reference NCCN transplant guidance for supportive-care and transplant-related recommendations; cite specific disease guideline pages (e.g., NCCN HCT principles, HCT sections within disease-specific guidelines).

Use NCCN HCT supportive care guidance and disease-specific HCT sections to guide documentation and planning
Include citation/version in authorization request

Documentation Required

Disease Status Required for Prior Authorization

Prior authorization requires documentation of disease status: specify complete remission (CR1), CR2, relapse timing (sensitive vs resistant), refractory disease, or not in remission as applicable to the indication.

Document CR1/CR2 or later remission status or refractory/relapsed state
If relapse, document time from prior transplant or prior remission and sensitivity to therapy

Documentation Required

Disease-Specific Candidate Documentation

Include disease-specific candidate documentation: risk group (e.g., AML ELN risk), cytogenetics/molecular markers, MRD status where relevant, prior transplant history, and rationale for transplant candidacy.

AML: ELN risk group, presence of adverse cytogenetics/mutations, MRD status
MDS: IPSS-R risk category
MM: cytogenetic high-risk features and prior response to induction therapy
CLL: prior targeted therapy exposure and indications for allo-HCT

Note

Prior Authorization: Literature Cited Only

Citations in the literature section provide supporting evidence for coverage decisions but do not replace required prior authorization documentation. Include relevant literature citations when supporting non-standard indications.

Attach pertinent literature only to supplement guideline-based indications — literature alone does not establish coverage

Denial Risk

Triggers for Denial / Not Medically Necessary Examples

Triggers for denial / examples of not medically necessary determinations: active CNS disease, significant uncontrolled comorbidities, poor performance status, or clinical contraindications listed below.

Active CNS involvement (unless specific guideline-supported autologous HCT indication exists and disease is controlled)
Significant comorbid medical or psychiatric illness that compromises survival or clinical care
Advanced age alone is not always a contraindication — decisions individualized

Denial Risk

Physiologic Contraindications

Physiologic contraindications that should be documented and may preclude HCT include: EF <35%, bilirubin >2.0 mg/dL or transaminases >2x normal (unless disease-related), CrCl <50 mL/min (not absolute for some autologous transplants), DLCO <50% predicted, uncontrolled HIV/hepatitis, and poor performance status (Karnofsky <60% or ECOG >2).

Cardiac: EF <35%
Hepatic: Bilirubin >2.0 mg/dL or transaminases >2x normal (unless disease-related)
Renal: Creatinine clearance <50 mL/min (note exceptions for autologous HCT)
Pulmonary: DLCO <50% predicted
Performance status: Karnofsky <60% or ECOG >2
Active uncontrolled infections (HIV if uncontrolled; active hepatitis B/C; HTLV-1)

Documentation Required

Referral and HLA Typing Recommendation

Consider early referral for HCT center evaluation and perform HLA typing early to facilitate timely donor identification for patients who may be candidates for allogeneic transplant.

Recommend HLA typing at diagnosis for patients with diseases where HCT may be considered
Refer to transplant center for formal evaluation when guideline criteria are met or when high-risk features present

Prior Authorization

Coverage Decisions May Be Guided by Risk

Coverage decisions may be guided by validated risk stratification systems (ELN for AML, IPSS-R for MDS, disease-specific cytogenetic/molecular risk) and guideline recommendations; absence of documented risk assessment may affect authorization.

Include documented risk stratification used to justify transplant (e.g., ELN, IPSS-R)
Note how risk assessment influenced the decision to pursue HCT

Documentation Required

Eligibility Organ-Function Requirement

Eligible candidates must have sufficient hepatic, renal, pulmonary, and cardiac function as documented in the medical record; renal dysfunction is not always an absolute contraindication for autologous HCT per guidelines.

Document specific organ function test results (EF, bilirubin/AST/ALT, CrCl, DLCO) and any compensatory measures
If using dose-adjusted conditioning for renal impairment or older age, document rationale

Note

Not Applicable / Excerpt Limitations

The excerpt does not specify payer-level prior authorization timing, nor does it replace plan benefit determinations; use the policy criteria in combination with member-specific benefit documents.

Not applicable content: this excerpt does not define plan-specific authorization workflows or explicit denial appeals processes

Documentation Required

Autologous HCT Consolidation Guidance

Autologous HCT consolidation guidance: not routinely recommended as consolidation in PET-negative CR1 DLBCL; in multiple myeloma early autologous transplant is recommended after induction for eligible patients and repeat autologous HCT may be considered at relapse per guideline criteria.

DLBCL: autologous HCT not recommended as consolidation in PET-negative CR1
MM: early autologous HCT after 4-6 cycles is recommended for eligible patients; maintenance recommendations differ by risk

Documentation Required

Evaluation for Allogeneic HCT

Evaluation for allogeneic HCT should be considered after adequate response to prior treatment; lack of adequate response or poor fitness may preclude transplant candidacy. For some diseases (e.g., systemic mastocytosis) consideration may follow re-staging or in context of AHN component.

Document prior treatment response and restaging before referring for allogeneic HCT
Note that allogeneic HCT evaluation is often driven by disease indication and response

Billing Rule

Medicare Coverage Alignment

Ensure Medicare coverage alignment by reviewing the National Coverage Determination (NCD) for stem cell transplantation and applicable Local Coverage Determinations (LCDs) when members are Medicare beneficiaries.

Check NCD 110.8.1 (or current NCD number) and relevant LCDs for Medicare members
Document compliance with Medicare requirements in authorization request

Note

None Specified in Literature Citations

Some literature citations are provided in the policy for evidence support, but no explicit additional documentation or prior authorization steps are defined in those citation-only lists.

Literature lists support clinical rationale but do not alter prior authorization requirements

Documentation Required

Pre-Transplant Assessment

Pre-transplant assessment should include HCT-CI, organ function testing, performance status, chromosomal and somatic mutation assessment where indicated, and documentation of symptom burden and quality-of-life considerations for diseases like myelofibrosis.

Use HCT-CI for comorbidity assessment in older adults
Assess chromosomal anomalies and somatic mutations prior to HCT when relevant (e.g., MDS, AML)

Documentation Required

Assessment of Autologous HCT Eligibility

Assessment of autologous HCT eligibility in systemic light-chain amyloidosis should document tumor burden, organ involvement, and consideration of immediate HCT versus initial systemic therapy to improve transplant candidacy.

Document organ involvement and functional status
If high tumor burden, document systemic therapy plan and reassessment for HCT eligibility

Documentation Required

Essential Pre-HCT Documentation

Essential pre-HCT documentation for prior authorization includes eligibility, planned stem-cell collection, donor search and consent, HLA typing results, organ function tests, performance status, and disease-specific risk/remission documentation.

HLA typing and donor search plan
Stem-cell mobilization/collection plan and storage intent
Informed consent and transplant center evaluation notes

Documentation Required

Transplant Planning Should Be Driven By

Transplant planning should be driven by the underlying disease indication, donor selection, preparative regimen, and the preparative evaluation checklist; include these elements in authorization requests.

State how disease indication influences tempo and donor selection
Include planned conditioning intensity and rationale

Billing Rule

Clinical and Coding Documentation

Clinical and coding documentation must support that the transplant meets policy clinical criteria and that billed services correspond to listed CPT/HCPCS codes (e.g., 38230–38241, S2140/S2142, S2150).

Ensure clinical notes justify billed transplant procedure codes
Include code-specific documentation such as allogeneic vs autologous designation and related cell-processing services

Note

No Explicit Documentation or Prior Authorization Steps Present

No explicit documentation or prior authorization steps are defined in some literature citation lists; use guideline and policy clinical criteria to determine required authorization documents.

When literature is cited without operational steps, rely on policy criteria and plan benefit rules for authorization

Note

Policy Administrative Notes

Administrative notes: annual review (8/15/2024) made no clinical policy statement changes; content addressing primary central nervous system lymphoma (PCNSL) was migrated into this coverage policy — providers should reference this policy for PCNSL transplant guidance.

Annual review date: 2024-08-15
PCNSL content moved into this policy (focused review 01/15/2024)

Documentation Required

Therapy Trials Prior to HSCT and Post-Remission Sequencing

Document prior therapy trials where required (for example, duration of TKI therapy in CML before considering allo-HCT) and sequencing rationale when HCT is chosen over prolonged maintenance.

CML: document TKI duration and cytogenetic/molecular response timelines
When HCT is chosen post-remission, document rationale versus maintenance approaches

Documentation Required

CLL: Targeted Therapies and HCT Sequencing

For CLL, document use of available targeted therapies (e.g., BTK inhibitors, venetoclax) as first-line and that allogeneic HCT is generally reserved for relapsed/refractory disease after these agents when appropriate.

Document prior BTKi and venetoclax exposure and response
Allogeneic HCT may be considered after failure of targeted therapies in eligible patients

Documentation Required

Therapy Sequencing and Conditioning Intensity Considerations

Therapy sequencing considerations and conditioning intensity: document induction and consolidation sequencing (e.g., induction then early autologous HCT for MM), rationale for CAR-T versus HCT timing, and choice of myeloablative vs reduced-intensity conditioning based on age and comorbidity.

Conditioning intensity: myeloablative for younger/fit patients; RIC for older/comorbid patients
CAR-T: document number of prior lines when used (e.g., CAR-T after ≥4 prior lines in MM per recommendations) and sequencing relative to HCT

Documentation Required

Therapy Sequence Documentation

When guidelines list alternative stepwise treatments, document the sequence of therapies actually used and the rationale for selecting HCT at the documented point in the treatment course.

Provide stepwise treatment history and why HCT was selected at this juncture

Documentation Required

Sequencing Relative to CAR-T and BTK Inhibitors

Sequencing relative to CAR T and BTK inhibitors: for mantle cell lymphoma and other indications, document prior BTK inhibitor exposure and the role/timing of CAR-T; include guideline recommendations about when to consider CAR-T versus HCT.

For relapsed MCL, CAR-T is recommended after relapse following BTKi in many settings; allogeneic HCT may be considered in selected scenarios per guidelines

Step Therapy

Step Therapy Not Detailed

Step therapy requirements are not detailed in this excerpt; follow plan-specific utilization management rules where applicable.

Policy does not define step therapy lists — check member benefit document

DocumentationReport FLT3-ITD testing results in pre-transplant assessment and authorization materials

inv-131: MRD presence at end of induction per ASTCT guidance

MRD presence at end of inductionASTCT recommends that presence of MRD at the end of induction should be considered an indication to offer allo-HCT

ContextStatement appears in ASTCT evidence-based review of AML HCT decision-making

Authorization implicationInclude MRD status (EOI) in documentation for HCT authorization when applicable

inv-132: KIT mutation (reference for AML/CBF exceptions)

KIT mutation — AML/CBF exceptionCBF-AML with KIT mutation may be considered for allo-HCT in CR1 despite otherwise favorable-risk cytogenetics (ASTCT guidance)

UseKIT mutation presence modifies usual ASTCT recommendation against allo-HCT in favorable-risk CR1 AML

DocumentationReport KIT mutation testing and cite guideline rationale when pursuing HCT in favorable-risk CBF-AML

inv-133: cytogenetic and somatic mutation assessment prior to HCT

Cytogenetic and somatic mutation assessmentSociety guidelines recommend assessing chromosomal anomalies and somatic mutations prior to HCT for risk stratification (MDS and other diseases)

UsePre-transplant molecular/cytogenetic assessment informs eligibility and HCT recommendations (ASTCT/NCCN guidance)

DocumentationInclude results of cytogenetic and somatic mutation testing in pre-transplant authorization materials

inv-134: chromosomal anomalies and somatic mutations — assessment recommended prior to HCT

Chromosomal anomalies & somatic mutations assessmentRecommendation: patients should be assessed for chromosomal anomalies and somatic mutations prior to HCT (ASTCT/NCCN)

PurposeUsed for risk stratification and to determine candidacy for allogeneic HCT, particularly in MDS and AML

Authorization noteAttach cytogenetic and molecular testing reports when requesting HCT authorization

inv-135: TK fusion genes (PDGFRA, PDGFRB, FGFR1, JAK2, ABL1, FLT3) — testing noted for select neoplasms

TK fusion genes to testTesting noted for PDGFRA, PDGFRB, FGFR1, JAK2, ABL1, and FLT3 rearrangements in MLN‑Eo and select neoplasms

Clinical implicationPresence of certain TK fusion rearrangements (eg, FGFR1, JAK2, ABL1, FLT3) indicates aggressive disease where allogeneic HCT may be the only curative option

Documentation recommendationReport fusion testing results when MLN‑Eo or related neoplasm is indication for HCT

inv-136: TP53 mutation (or biallelic deletion) — relevant biomarker in MCL and other diseases

TP53 mutation (or biallelic deletion)Recognized as a high-risk biomarker (eg, in mantle cell lymphoma) that alters transplant and CAR T recommendations

UsePresence of TP53 mutation/biallelic deletion may lead to consideration of alternate consolidation strategies (CAR T, allo‑HCT) and affects autologous HCT recommendations

DocumentationInclude TP53 mutation testing results when relevant to transplant decision-making or authorization

inv-137: KIT mutation (imatinib-sensitive) — systemic mastocytosis testing reference

KIT mutation (imatinib‑sensitive)Imatinib has therapeutic role only in rare patients with imatinib‑sensitive KIT mutation; testing identifies these rare responders

Clinical implicationIn systemic mastocytosis, imatinib sensitivity is limited to rare KIT mutations and transplant is reserved for advanced disease or AMN components

DocumentationProvide KIT mutation testing results when considering non‑transplant targeted therapy versus HCT

inv-138: cytogenetic/molecular risk markers (TP53, NPM1, FLT3-ITD, KMT2A, etc.) — assessment prior to HCT

Cytogenetic/molecular risk markersAssess markers such as TP53, NPM1, FLT3‑ITD, KMT2A and others prior to HCT for risk stratification

UseThese markers inform AML/ALL risk groups and can change HCT recommendations (ASTCT/ELN/NCCN guidance)

Authorization noteAttach cytogenetic and molecular risk reports with transplant authorization requests

inv-97: Definition — Allogeneic transplant

Allogeneic transplant — definitionTransplant using hematopoietic stem cells from a donor (matched sibling, unrelated donor, haploidentical relative, or umbilical cord blood)

Key pointAll allogeneic transplantations must be from an appropriately matched HLA donor as noted in coverage criteria

DocumentationDonor type and HLA matching status should be included in authorization materials

inv-98: Definition — Myeloablative vs Non-myeloablative conditioning

Myeloablative vs Non‑myeloablativeMyeloablative uses very high dose chemo/radiation; non‑myeloablative (reduced intensity) uses lower doses to reduce toxicity while preserving graft‑versus‑tumor effect

UseConditioning intensity is selected based on age and comorbidity (myeloablative in younger patients; RIC in older patients)

Authorization noteSpecify conditioning intensity planned (myeloablative vs RIC) in transplant authorization documentation

inv-99: Definition — Leukemia

Leukemia — definitionCancer of blood and bone marrow caused by rapid production of abnormal white blood cells; classified as acute vs chronic and lymphoblastic vs myeloid

UseLeukemia subtypes (ALL, AML, CML, CMML, JMML) are referenced throughout HCT indications

DocumentationSpecify leukemia subtype and risk classification when requesting HCT authorization

inv-100: Definition — Multiple myeloma and related plasma cell disorders

Multiple myeloma & related disorders — definitionPlasma cell malignancy producing monoclonal protein (M‑protein); includes smoldering myeloma, light chain amyloidosis, and POEMS syndrome

UseAutologous HCT is standard consolidation for eligible newly diagnosed MM patients after induction

DocumentationDocument MM disease status, prior induction cycles, and stem cell collection plan when seeking authorization

inv-101: Definition — Primary CNS Lymphoma (PCNSL)

Primary CNS Lymphoma (PCNSL) — definitionAggressive extranodal non‑Hodgkin lymphoma localized to CNS structures, mostly diffuse large B‑cell (ABC subtype >90%)

Clinical implicationPCNSL may be considered for autologous HCT consolidation in relapsed/refractory settings per NCCN/NORD summaries

DocumentationReport CNS‑localized disease status and prior induction response when requesting HCT for PCNSL

inv-102: Definition — CR1 (first complete remission)

CR1 — definitionFirst complete remission; used as a decision point for offering allo‑HCT in several diseases including AML and Hodgkin lymphoma

UseCR1 status should be documented for transplant decisions and authorization

DocumentationInclude date and evidence of CR1 (imaging, marrow biopsy) in pre‑transplant materials

inv-103: Definition — MRD (measurable residual disease)

MRD — definitionMeasurable residual disease; presence at end of induction in AML and certain ALL contexts is considered an indication to offer allo‑HCT per ASTCT

UseReport MRD methodology, timing (end of induction), and results when considering HCT

Authorization noteMRD+ status at EOI should be explicitly documented to support allogeneic HCT authorization where guideline‑based

inv-104: Definition — Low tumor burden (SLCA)

Low tumor burden (SLCA) — definitionIn systemic light chain amyloidosis, patients with low tumor burden may proceed to autologous HCT immediately; high‑burden patients may require systemic therapy first

UseAssess tumor burden and organ function to determine timing of autologous HCT in SLCA

DocumentationProvide tumor burden assessment and organ function testing when requesting SLCA autologous HCT authorization

inv-105: Definition — Tandem HCT

Tandem HCT — definitionA planned second course of high‑dose therapy and HCT within 6 months of the first course

UseTandem HCT may be considered in MM for those not achieving ≥VGPR after first autologous HCT or with high‑risk features

DocumentationIndicate planned tandem approach and timing (within 6 months) when requesting authorization

inv-106: Definition — Autologous HCT (additional reference)

Autologous HCT (additional) — noteTransplant using the patient's own harvested hematopoietic stem cells; standard of care after primary therapy for eligible MM patients

PlanningCollect stem cells for at least one HCT and consider collecting for two in younger patients per NCCN/ASTCT guidance

DocumentationInclude stem cell collection plan and number of collections in authorization materials

inv-107: Definition — Higher-risk MDS categories (IPSS/IPSS-R/WPSS)

Higher‑risk MDS categories — definitionHigher‑risk MDS includes IPSS intermediate‑2/high and equivalent IPSS‑R intermediate/high/very high or WPSS high/very high strata used to guide HCT recommendations

UseAllogeneic HCT is recommended for eligible patients in these higher‑risk categories (ASTCT recommendations)

DocumentationProvide prognostic scoring (IPSS/IPSS‑R/WPSS) and cytogenetic/molecular results when requesting HCT authorization for MDS

inv-108: Definition — MLN-Eo (myeloid/lymphoid neoplasms with eosinophilia and TK fusions)

MLN‑Eo — definitionMyeloid/lymphoid neoplasms with eosinophilia and TK fusions: neoplasms with PDGFRA, PDGFRB, FGFR1, JAK2, ABL1, or FLT3 rearrangements; some subtypes are aggressive and may require HCT

Clinical implicationSpecific fusion rearrangements (FGFR1, JAK2, ABL1, FLT3) generally predict aggressive course where allo‑HCT may be the only curative option

DocumentationInclude fusion testing results when considering HCT for MLN‑Eo patients

inv-109: Definition — Allogeneic HCT as curative option for myelofibrosis

Allogeneic HCT as curative option for myelofibrosisAllogeneic HCT is described as the only potentially curative treatment option for myelofibrosis and is recommended for eligible higher‑risk patients

UseTransplant candidacy assessment should include symptoms, age, comorbidities, donor availability, and functional status

DocumentationProvide disease‑specific risk assessment and rationale when requesting HCT for myelofibrosis

inv-110: Definition — Autologous HCT (panel nuance for lymphoma)

Autologous HCT — panel nuance for lymphomaAutologous HCT is standard in selected lymphoma settings but recommendations vary by subtype, remission status, and guideline grading

UsePanel does not recommend routine autologous consolidation in PET‑negative CR1 DLBCL

DocumentationProvide lymphoma histology, remission status, and prior therapies when requesting authorization for autologous HCT

inv-111: Definition — TP53 mutation/biallelic deletion as biomarker in MCL

TP53 mutation/biallelic deletion — definition for MCLTP53 mutation (or biallelic deletion) is a biomarker in mantle cell lymphoma associated with poor outcomes that alters transplant and CAR‑T recommendations

UsePresence of TP53 mutation influences consideration of autologous transplant, CAR‑T, or allo‑HCT and is referenced in ASTCT MCL guidance

DocumentationReport TP53 mutation status and consider clinical trial context for recommendations when seeking authorization

inv-112: Definition — Systemic mastocytosis (SM)

Systemic mastocytosis (SM) — definitionClonal proliferation of abnormal mast cells in extracutaneous organs; categorized as indolent/smoldering or advanced (ASM, SM‑AMN, mast cell leukemia)

UseAllogeneic HCT is considered for advanced SM, particularly when an aggressive associated myeloid neoplasm is present

Testing noteKIT mutation testing guides targeted therapy selection; imatinib utility limited to imatinib‑sensitive KIT mutations

inv-113: Definition — POEMS syndrome

POEMS syndrome — definitionPOEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy (M‑protein), Skin changes; a rare plasma cell disorder

UseAutologous HCT is considered a standard option alongside systemic therapy for newly diagnosed POEMS patients per registry data

DocumentationProvide diagnostic criteria and registry/supporting data when requesting HCT for POEMS

inv-114: Definition — Reduced-intensity conditioning

Reduced‑intensity conditioning — definitionConditioning regimens less myeloablative than conventional preparative regimens, used to reduce toxicity while preserving graft‑versus‑tumor effect

UseRIC is generally used in older patients or those with comorbidities; specify RIC vs myeloablative when planning HCT

DocumentationInclude planned conditioning regimen intensity in transplant authorization requests

inv-115: Definition — POEMS Syndrome (repeated entry)

POEMS Syndrome — repeated definitionPolyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS)

UseRegistry and literature support autologous HCT as a component of frontline management in selected patients

DocumentationProvide POEMS diagnostic evidence and treatment history when requesting HCT authorization