CurrentCentenePolicy CP.MP.101

Donor Lymphocyte Infusion

Medical necessity criteria for donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation for management of relapsed or high-risk hematologic malignancies; applies to non‑Medicare Centene-affiliated health plans and notes a separate Medicare criteria reference.

Policy Summary

PayerCentene

PolicyDonor Lymphocyte Infusion

Policy CodePolicy CP.MP.101

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionObtain prior authorization and document prior allogeneic HSCT, diagnosis, and rationale for DLI (relapse, mixed chimerism, or MRD).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

40-60%GvHD rate after DLI

70-80%CR rate in relapsed CML

15-20%Remission rate in relapsed AML

22-52%Response range in relapsed MM

2-5%Bone marrow aplasia rate

Medical Necessity / Coverage Criteria

Initial coverage criteria (non‑Medicare plans)

Covered when ALL of the following are met

Primary indication: Patient has had an allogeneic hematopoietic stem cell transplantation (HSCT) and now has relapsed or refractory hematologic malignancy, or is at high risk of relapse and DLI is intended to decrease relapse risk or convert mixed to full donor chimerism when there is risk of relapse.

Applies to diseases including but not limited to CML, AML, ALL, lymphoma, multiple myeloma, and MDS.

Unsupported indications / Contraindications

Not covered / current evidence does not support when ANY of the following are present

Contraindications and unsupported uses: Active acute graft‑versus‑host disease (GvHD) grade 2 or higher; full donor chimerism where DLI is being used solely to increase donor chimerism without risk of relapse; genetically modified or ex vivo manipulated donor lymphocytes; other indications where current evidence does not support use.

Policy states current evidence does not support use for these indications.

Policy Summary

PayerCentene

PolicyDonor Lymphocyte Infusion

Policy CodePolicy CP.MP.101

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionObtain prior authorization and document prior allogeneic HSCT, diagnosis, and rationale for DLI (relapse, mixed chimerism, or MRD).

SourceLink

On This Page

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DLI is intended to provide an immune-mediated graft‑versus‑tumor effect after an allogeneic HSCT for patients with relapsed or refractory hematologic malignancy or to reduce relapse risk in high‑risk patients by converting mixed to full donor chimerism. The policy explicitly states that DLI should not be used for the sole purpose of increasing donor chimerism in the absence of relapse risk because doing so exposes the patient to the risk of exacerbating graft‑versus‑host disease without clear clinical benefit. (See separate Medicare criteria reference MC.CP.MP.101 for Medicare members.)

Current evidence does not support the use of DLI when acute graft‑versus‑host disease (GvHD) grade 2 or higher is present; use in this setting is listed as a contraindication and may lead to denial. Additionally, the policy states that genetic modification or ex vivo manipulation of donor lymphocytes for DLI is not supported outside of a clinical trial because benefits have not been established to outweigh risks.

Provider Requirements and Operational Considerations

Prior Authorization

Prior Authorization and Coding References

Prior authorization is required for donor lymphocyte infusion (DLI). Submit claims using the applicable procedure and billing codes and include prior authorization approval number on the claim.

Prior authorization required prior to scheduling DLI
Ensure authorization number is documented on all claims

Denial Risk

Contraindication: Active Significant GvHD

Do not administer DLI in the presence of active, clinically significant graft-versus-host disease (GvHD). Specifically, DLI is contraindicated when the patient has acute GvHD grade 2 or higher due to increased risk of worsening GvHD and associated morbidity.

Assess and document current GvHD status prior to authorization request
If acute GvHD grade ≥2 is present, DLI is not supported by current evidence

Documentation Required

Required Clinical Documentation

Clinical documentation must demonstrate the following prior to approval: evidence of a prior allogeneic HSCT from the original donor, a qualifying diagnosis of relapsed or refractory hematologic malignancy (examples: CML, AML, ALL, lymphoma, multiple myeloma, MDS), and rationale for DLI (therapeutic for proven relapse or pre-emptive for high relapse risk such as mixed chimerism or detectable minimal residual disease). Include relevant diagnostic test results, prior treatment history, and transplant/chimerism reports.

Operative/transplant report or transplant center records documenting original donor and HSCT date
Laboratory or molecular data showing mixed chimerism or MRD when DLI is requested for pre-emptive use
Clinical notes documenting relapse or refractory disease and prior therapies
Documentation of prior or current GvHD assessment

Note

Concurrent Therapy Consideration

When DLI is requested for relapsed acute leukemias (for example, relapsed AML), document any planned or prior concurrent chemotherapy or other cytoreductive therapy, as DLI is frequently combined with chemotherapy to improve response in these settings. Include timing of chemotherapy relative to planned DLI and rationale for combination therapy.

Document prior or concurrent chemotherapy regimens and schedule relative to DLI
Indicate whether DLI is being used as salvage, therapeutic, or pre-emptive strategy

Procedure / Billing Codes (Informational)

Referenced procedure codes (informational)mixed

38215	Transplant preparation of hematopoietic progenitor cells; cell concentration in plasma, mononuclear or buffy coat layer.
38242	Allogeneic lymphocyte infusions.
86950	Leukocyte transfusion.
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; supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre-and posttransplant care in the global definition.

Indications and Reported Outcomes for DLI

Regimen	Indication	Notes / Reported outcomes
DLI	Relapsed chronic myeloid leukemia (CML) after allogeneic HSCT	Multiple studies report complete remission in 70–80% of patients; remissions are durable in the majority of cases.

Regimen	Indication	Notes / Reported outcomes
DLI (often combined with chemotherapy)	Relapsed acute myeloid leukemia (AML) after allogeneic HSCT	Lower single‑agent efficacy; reported remission induction approximately 15–20%; often necessary to combine DLI with chemotherapy to elicit anti‑tumor effect.

Regimen	Indication	Notes / Reported outcomes
DLI	Relapsed multiple myeloma after allogeneic HSCT	May be used to stimulate a graft‑versus‑myeloma effect; reported response rates vary (approximately 22–52%); some reports show clinical response with conversion to full chimerism without GvHD.

Treatment Setting and Line of Therapy

salvage

Salvage/line of therapy: DLI may be used post‑allogeneic HSCT as a salvage therapy for relapse or as pre‑emptive/prophylactic therapy in high‑risk patients; effectiveness varies by disease (high in relapsed CML; lower in AML/ALL) and may be combined with other therapies such as chemotherapy when clinically indicated.

No explicit line numbering provided; clinical context guides use.

Background and Rationale

Donor lymphocyte infusion (DLI) is adoptive immunotherapy in which donor T lymphocytes from the original HSCT donor are infused into a recipient to induce an immune‑mediated graft‑versus‑tumor effect or to convert mixed chimerism to full donor chimerism. DLI may be used for a range of hematologic malignancies including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), lymphomas, multiple myeloma, and myelodysplastic syndromes. The procedure can reduce relapse risk after allogeneic HSCT but has variable efficacy by disease and carries significant risks, including graft‑versus‑host disease and bone marrow aplasia; therefore its use should be guided by the policy’s specified medical necessity criteria.

Key Definitions

Chimerism

Mixed chimerismDefined as <90% donor cells detected.

Full (complete) chimerismDefined as 100% donor cells detected (complete hematopoietic replacement).

Clinical relevanceConversion from mixed to full chimerism may be an intended goal of DLI to induce graft‑versus‑tumor effects.