CurrentCignaPolicy 0261

Donor Lymphocyte Infusion and Hematopoietic Progenitor Cell (HPC) Boost

This policy governs medical necessity and coding for DLI and HPC boost following hematopoietic stem cell transplantation (HSCT) for Cigna-administered health benefit plans; it applies to adult and pediatric patients receiving these therapies from the original HSCT donor.

Policy Summary

PayerCigna

PolicyDonor Lymphocyte Infusion and Hematopoietic Progenitor Cell (HPC) Boost

Policy CodePolicy 0261

Change TypeNo material change

Effective DateMay 15, 2026

Next Review DateMay 15, 2027

Key ActionInclude product source, donor relationship, and intent to use CD34+-selected peripheral blood stem cells in prior authorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

72%CR rate (pooled)

80%ORR (pooled)

17-18%GVHD rate

27%NRM

209Patients pooled

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Coverage Criteria for DLI and HPC Boost

Donor Lymphocyte Infusion (DLI) — Initial

Covered when the following conditions are met

DLI coverage: DLI is medically necessary following an allogeneic HSCT for the treatment of a relapsed, persistent or refractory hematologic malignancy or when there is high risk of relapse of a hematologic malignancy.

Donor source must be the same as the original HSCT donor; applies to adult and pediatric patients.

Hematopoietic Progenitor Cell (HPC) Boost — Initial

Covered when ALL of the following are met

HPC boost indications: Hematopoietic progenitor cell (HPC) boost is medically necessary following autologous or allogeneic HSCT for EITHER: (1) to promote engraftment OR (2) to enhance donor chimerism when studies reveal <100% donor cells.<100% donor cells for chimerism indication

The cell product may be previously cryopreserved or require donor re‑mobilization and harvest; a boost is not preceded by a preparative regimen and is intended to restore hematopoiesis or augment poor graft function.

Not Medically Necessary (Other Indications)

Not medically necessary: DLI and HPC boost are considered not medically necessary for any indication other than those specified above.

Any other use outside the listed indications is excluded.

DLI and HPC boost are covered only for the specific indications listed in this policy. DLI is medically necessary following an allogeneic HSCT for treatment of a relapsed, persistent, or refractory hematologic malignancy or when there is a high risk of relapse. HPC boost is medically necessary following autologous or allogeneic HSCT to either promote engraftment or to enhance donor chimerism when studies reveal <100% donor cells. Use of DLI or HPC boost for any other indication is considered not medically necessary.

The literature supporting HPC (stem cell) boost for poor graft function (PGF) selected studies that excluded patients with active infection, active graft-versus-host disease (GVHD), or significant mixed donor chimerism (<95% donor cells). Reported series of CD34-selected stem cell boost describe a median time from allo‑HSCT to boost of 138 days (range reported in pooled studies). These study inclusion criteria should be considered when applying evidence from the literature to individual authorization decisions.

Providers should exercise caution when considering DLI or HPC boost outside the policy-specified indications (i.e., DLI for relapse/persistent/refractory hematologic malignancy or high relapse risk; HPC boost to promote engraftment or enhance donor chimerism). The pooled literature and study designs informing HPC boost efficacy mainly addressed CD34-selected stem cell boost for poor graft function and excluded patients with active infection, active GVHD, or significant mixed chimerism, so outcomes and risks may not generalize to other clinical scenarios.

Patient Selection and Candidate Criteria

Candidate selection — candidates for therapy

Candidates for therapy

DLI candidate: Patients who have undergone allogeneic HSCT from a donor and have relapsed, persistent, or refractory hematologic malignancy or are at high risk of relapse.

Donor source must be the same as the original HSCT donor.

HPC boost candidate: Patients after autologous or allogeneic HSCT with poor graft function requiring promotion of engraftment or patients requiring enhancement of donor chimerism when studies reveal <100% donor cells.<100% donor cells for chimerism indication

Product may be previously cryopreserved or may require donor evaluation, mobilization, and harvest; boost is not preceded by a preparative regimen.

Candidate criteria from studies — literature-based attributes for SCB in PGF

Literature-based candidate attributes for stem cell boost in poor graft function (PGF)

Contraindications and Exclusion Criteria

DLI and HPC boost are associated with significant procedure-related risks, including acute and chronic graft-versus-host disease (GVHD), anemia, and infection. Although these therapies carry meaningful complication rates, the policy does not list any absolute contraindications; rather, potential harms should be weighed against expected benefit on an individual basis.

In the cited studies of stem cell boost for poor graft function, active infection, active GVHD, or mixed donor chimerism (<95% donor cells) were exclusionary criteria. These factors therefore function as relative contraindications in the evidence base and should be considered when evaluating suitability for HPC boost or when extrapolating study outcomes to a given patient.

Pre‑Boost Evaluation and Donor/Product Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for HPC (stem cell) boost procedures. Submit PA requests before scheduling collection or infusion to avoid denials. Include billing and coding intent (anticipated CPT/HCPCS, NDC if applicable), anticipated facility and provider claims, and expected service dates.

Anticipated CPT/HCPCS codes and modifiers
Original transplant date and donor identifier (if using cryopreserved product)
Requested service date range

Documentation Required

Product and Donor Details Required on Submission

The product for boost may be a previously cryopreserved aliquot from the original donor or require new donor mobilization and harvest. For new collections, document donor eligibility (medical history, infectious disease testing per FDA/AABB), mobilization regimen used (e.g., G-CSF dose), collection method (apheresis vs marrow), cell dose (CD34+ count), and whether product is irradiated or manipulated. If using cryopreserved product, include repository accession number, cryopreservation date, cell viability and CD34+ enumeration, and chain-of-custody documentation.

Provider Actions, Documentation, and Prior Authorization

Covered CPT CodesCPTCovered

38242	Allogeneic lymphocyte infusions.
38243	Hematopoietic progenitor cell (HPC); HPC boost

Prior Authorization

Use CPT 38242 and 38243 for PA and billing

Submit prior authorization using the procedure codes listed as considered medically necessary when policy criteria are met: CPT 38242 (Allogeneic lymphocyte infusions) and CPT 38243 (Hematopoietic progenitor cell (HPC) boost).

38242 — Allogeneic lymphocyte infusions
38243 — Hematopoietic progenitor cell (HPC); HPC boost

Prior Authorization

Provide product source, donor relationship, and CD34+ selection intent in PA

Include product source (fresh vs cryopreserved), donor relationship to recipient, and the intent to use CD34+-selected peripheral blood stem cells (if applicable) when requesting prior authorization for an HPC boost.

Step Therapy

No step therapy required — coverage tied to meeting criteria

Coding Details and Key Values

Donor chimerism threshold for HPC boost indication

Donor chimerism threshold<100% donor cells

ContextUsed as an indication for HPC boost to enhance chimerism after autologous or allogeneic HSCT

Source requirementDocumented donor chimerism testing prior to boost is implied by criteria for chimerism-based indication

Definitions

Donor Lymphocyte Infusion (DLI) — definition

DefinitionInfusion of donor lymphocytes (from the original HSCT donor) given after allogeneic HSCT to treat relapsed, persistent, or refractory hematologic malignancy via graft‑versus‑leukemia/tumor effect.

IntentTherapy is intended to treat malignancy or prevent relapse; not used to restore hematopoiesis.

Preparative regimenRecipient does not receive a preparative regimen prior to DLI, though concomitant therapy may be required.

Hematopoietic Progenitor Cell (HPC) Boost — definition

DefinitionInfusion of hematopoietic progenitor/stem cells from the original HSCT donor given after autologous or allogeneic HSCT to restore hematopoiesis or augment poor graft function/chimerism.

Product source

Post‑Transplant Coverage Notes

HPC boost (CPT 38243) — timing and context post reinduction chemotherapy

Typical timingHPC boost is typically given days to weeks after reinduction chemotherapy when prolonged cytopenias and immunosuppression require additional support.

Indication contextUsed following reinduction chemotherapy to reestablish hematopoiesis after relapse treatment when cytopenias persist.

Procedure codeAssociated service: HPC boost (CPT 38243).

CD34+-selected stem cell boost — conditioning and post‑boost immunosuppression

Observation from seriesSome pediatric series of CD34+-selected stem cell boost reported no conditioning performed prior and no immunosuppressive therapy administered post‑boost.

Variable outcomes

Background

Donor lymphocyte infusion (DLI) is an infusion of donor lymphocytes given after allogeneic HSCT intended to produce a graft‑versus‑leukemia/tumor effect to treat relapse or prevent recurrence. The therapy relies on donor lymphocytes recognizing and eliminating malignant recipient cells but is not intended to restore hematopoiesis. DLI is administered without a preparative conditioning regimen and can result in meaningful benefits for selected patients as well as significant complications such as acute and chronic GVHD and infection.

Center and Program Requirements

Note

Policy applies to Cigna-administered plans; delegated vendor rules may apply

This Coverage Policy applies to health benefit plans administered by Cigna Companies; specific delegated vendor guidelines may be used in certain markets and supersede local processes where applicable.

Note

No center-specific requirements specified in this policy

No specific center accreditation, FACT requirements, or procedural volume requirements are specified in this document.

Policy Summary

PayerCigna

PolicyDonor Lymphocyte Infusion and Hematopoietic Progenitor Cell (HPC) Boost

Policy CodePolicy 0261

Change TypeNo material change

Effective DateMay 15, 2026

Next Review DateMay 15, 2027

Key ActionInclude product source, donor relationship, and intent to use CD34+-selected peripheral blood stem cells in prior authorization.

SourceLink

On This Page

SCB candidate criteria: Adult allo‑HSCT recipients with poor graft function who are generally more than ~60 days post‑transplant (median 138 days in pooled studies), lack active infection and active GVHD, and have predominantly donor chimerism (studies excluded mixed chimerism <95% donor cells).time since transplant approximately >60 days (median 138 days); donor chimerism >95% in included studies

Based on inclusion/exclusion criteria of pooled studies of CD34+-selected stem cell boost; these attributes informed the study populations and eligibility for SCB interventions.

Cryopreserved product: repository accession number, original donor ID, cryopreservation date, CD34+ dose and viability
New donor harvest: donor evaluation notes, infectious disease testing results, mobilization regimen, harvest method, CD34+ yield

Note

Eligibility and Consideration of Alternatives

Evaluate patient eligibility considering cause of cytopenias and alternative therapies. Literature supports use of HPC boost for poor graft function or prolonged severe cytopenias after HSCT; however, reversible causes (drug toxicity, infection, nutritional deficiency) should be addressed first. Consider growth factor support (G-CSF), transfusion support, infection management, and reduction of immunosuppression where appropriate prior to boost.

Confirm indication: persistent cytopenias and/or transfusion dependence attributed to poor graft function
Document trials of alternative/adjunctive therapies (G-CSF, transfusions, infection treatment, immunosuppression adjustment) and rationale for proceeding to boost

Documentation Required

Submission Documentation

Submit documentation with the PA request and at time of service: clinical indication and history, current blood counts, prior transplant summary (donor, graft type, conditioning), pre-boost assessment including donor chimerism (if available), infectious disease status, active graft-versus-host disease (GVHD) evaluation, prior therapies tried, and product/donor details as above. For planned new donor harvest include informed consent and donor eligibility forms.

Clinical note with indication and hematologic trends
Prior HSCT operative/transplant summary
Pre-boost labs: CBC, marrow assessment (if done), donor chimerism, infection testing
Donor/product documentation: repository numbers or donor evaluation and consent forms

Step Therapy

Step Therapy Requirement

Step therapy: when clinically appropriate, members should receive and fail or have contraindications to less invasive measures (e.g., G-CSF, transfusion support, treatable infection correction, immunosuppression modification) before authorization for HPC boost is approved. Document response to these measures and why boost is necessary.

Documented trial and inadequate response to G-CSF or other supportive care
Rationale if step therapies were bypassed (e.g., contraindication or urgent clinical need)

Note

Consideration of Alternative Therapies

Consider alternative therapies and expected outcomes prior to approval. Alternatives include ongoing supportive care (growth factors, transfusions), donor lymphocyte infusion (if relapse is immune-responsive), or second allogeneic transplant in select cases. Provide clinical rationale comparing expected benefits and risks of an HPC boost versus alternatives.

If alternative such as donor lymphocyte infusion or second transplant is being considered, include comparative rationale
Document why boost is preferred over continued supportive care

There is no step therapy sequence specified; coverage is contingent on meeting the medical necessity criteria for DLI or HPC boost as described in the policy.

Note

Consider alternative/adjunct approaches (e.g., DLI, immunosuppression modulation)

Guidance and referenced guidelines discuss alternative or adjunct approaches (for example, DLI or modulation of immunosuppression); documentation of prior or concurrent strategies may be relevant to the clinical rationale.

Documentation Required

Attach benefit terms, diagnosis, codes, and clinical rationale to PA

Requests for coverage or prior authorization should be accompanied by documentation supporting applicable benefit terms, the covered diagnosis and procedure code(s), and the clinical rationale for DLI or HPC boost per the policy criteria.

Documentation Required

Document poor graft function, time since transplant, infection/GVHD/chimerism status

Clinical documentation should demonstrate poor graft function after allo‑HSCT, timing since transplant consistent with the literature (median 138 days reported), and absence or control of active infection, active GVHD, or significant mixed donor chimerism as applicable.

Evidence of persistent cytopenias and/or transfusion dependence (poor graft function)
Time since transplant (median 138 days reported in pooled studies)
Documentation of infection and GVHD status and donor chimerism

Denial Risk

Claims without covered CPT code(s) will be denied

Claims for services billed without a covered code under this Coverage Policy will be denied as not covered; use the most appropriate current CPT codes when submitting claims.

Denial Risk

Study-based eligibility emphasized absence of infection, GVHD, and near-complete donor chimerism

Eligibility criteria in the cited studies required poor graft function in the absence of active infection, active GVHD, and largely full donor chimerism (studies excluded mixed donor chimerism <95% donor cells); absence of these conditions in a patient may affect alignment with the published evidence base.

Studies included allo‑HSCT recipients with PGF in the absence of infection and GVHD
Excluded patients with mixed donor chimerism <95% donor cells

Product may be previously cryopreserved or require donor re‑evaluation, mobilization, and harvest.

Preparative regimenA boost is not preceded by a preparative regimen.

CR (complete response) — definition

DefinitionComplete response (CR): hematologic improvement in all three cell lineages without transfusion dependence.

Use in outcomesCR reported as 72% in pooled CD34‑selected SCB studies (Shahzad et al., 2021).

MeasurementAssessed as part of overall response rate (ORR) in SCB literature for poor graft function.

PR (partial response) — definition

DefinitionPartial response (PR): hematologic improvement in one or two cell lineages.

Use in outcomesPR is combined with CR to calculate overall response rate (ORR) in SCB studies.

TimingHematologic improvement after SCB may be observed within a median of ~30 days in some series.

ORR — definition

DefinitionOverall response rate (ORR): proportion of patients achieving either CR or PR.

Reported valueORR pooled in SCB studies reported in literature review context (used to summarize efficacy).

ComponentsORR includes both complete responses (CR) and partial responses (PR) as defined in studies.

Other series report variable GVHD rates and note need for evaluation of optimal GVHD prophylaxis and timing.

Product selectionCD34+-selected SCB may be administered without preparative regimen in selected patients, per cited studies.