Donor Lymphocyte Infusion
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Medical necessity and coverage criteria for donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation for relapsed or high-risk hematologic malignancies; applies to non-Medicare health plans affiliated with the payer.
No material clinical or coverage changes in this revision.
Coverage Criteria for Donor Lymphocyte Infusion (DLI)
Initial and prophylactic DLI
Covered when ALL of the following are met:
Contraindications / Not supported
Not supported / contraindicated when ANY of the following are present:
Genetic modification or other ex vivo manipulation of donor lymphocytes for use in donor lymphocyte infusion (DLI) is not supported outside of an appropriate clinical trial setting and is not considered a covered indication under this policy.
When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers should consult the applicable state Medicaid manual for any specific coverage requirements or variations.
Use of DLI solely to increase donor chimerism in a patient with no risk of relapse is not recommended and is considered not medically necessary. DLI should be reserved for treatment of relapsed or refractory hematologic malignancy or to decrease relapse risk when there is a clinical indication.
Regimens and Indications Covered
| Indication | Regimen / Rationale | Coverage Label |
|---|---|---|
| Relapsed chronic myeloid leukemia (CML) after allogeneic HSCT | ||
| DLI — high remission rates reported (complete remissions in 70–80% of patients); may be definitive therapy for relapsed CML | ||
| Criteria: prior allogeneic HSCT and documented relapse; absence of contraindications such as grade ≥2 acute GvHD |
| Indication | Regimen / Rationale | Coverage Label |
|---|---|---|
| Relapsed acute myeloid leukemia (AML) after allogeneic HSCT | ||
| DLI often combined with chemotherapy to achieve an anti-tumor effect; remission induction probability with DLI alone ~15–20% | ||
| Criteria: prior allogeneic HSCT and documented relapse; documentation of adjunct/prior chemotherapy may be relevant; absence of grade ≥2 acute GvHD |
| Indication | Regimen / Rationale | Coverage Label |
|---|---|---|
| Relapsed multiple myeloma after allogeneic HSCT | ||
| DLI may be used to stimulate a graft‑versus‑myeloma effect; reported response rates ~22–52%; NCCN notes DLI may be used to stimulate beneficial graft‑versus‑myeloma effect | ||
| Criteria: prior allogeneic HSCT and relapsed disease; consider clinical trial status and absence of contraindications such as grade ≥2 acute GvHD |
| Indication | Regimen / Rationale | Coverage Label |
|---|---|---|
| Conversion of mixed chimerism to full chimerism when there is risk of relapse | ||
| DLI to convert mixed chimerism to full donor chimerism when clinically warranted; examples report conversion with clinical response in some patients | ||
| Criteria: mixed chimerism (<90% donor cells) with clinical risk of relapse or evidence of impending relapse; prior allogeneic HSCT and no contraindicating active grade ≥2 acute GvHD |
Procedure and Billing Codes
| 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; drugs, 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 |
Provider Actions, Authorization, and Documentation
Prior authorization required for DLI and listed procedure codes
Prior authorization is required for donor lymphocyte infusion (DLI) procedures and related billing codes. Providers must submit clinical rationale and supporting documentation demonstrating prior allogeneic HSCT and evidence of relapse risk or active relapse when requesting authorization for codes such as 38242 (Allogeneic lymphocyte infusions), 38215, 86950, and S2150.
- Submit documentation of prior allogeneic HSCT and indication (relapsed/refractory hematologic malignancy or risk of relapse).
- Include relevant chimerism data and evidence of mixed chimerism when applicable.
Coverage subject to member contract and regulatory requirements
Coverage and authorization decisions are determined by the member's coverage documents and applicable state and federal requirements. Providers should review applicable NCDs/LCDs and state Medicaid manuals before applying criteria.
- Coverage is subject to terms, conditions, exclusions, and limitations of the member's evidence of coverage or policy.
- State Medicaid provisions take precedence where they conflict with this clinical policy; review the state Medicaid manual for specific guidance.
Document prior/adjunct chemotherapy when DLI is used for relapsed AML
When DLI is used for relapsed AML, it is often combined with chemotherapy; documentation of prior or concurrent adjunct therapies may be relevant to authorization decisions.
- Provide records of recent or planned chemotherapy regimens when DLI is proposed for relapsed AML.
- Detail timing and rationale for combining DLI with adjunct systemic therapy.
No additional provider action noted
(No additional provider-action specified in the source.)
Required clinical documentation to support authorization
Prior authorization requests and claims should include documentation supporting prior allogeneic HSCT, the clinical indication (relapsed/refractory hematologic malignancy or high risk of relapse/mixed chimerism with relapse risk), chimerism status, and absence of contraindications such as grade ≥2 acute GvHD.
- Include prior HSCT records, pathology/hematology reports, and chimerism testing results.
- Explicitly document absence of grade 2 or higher acute graft-versus-host disease prior to DLI.
Follow Health Plan administrative policies and coverage terms
Follow the Health Plan's administrative policies, procedures, and the terms of the member's coverage documents when submitting claims; this clinical policy is a guide to medical necessity and is not a guarantee of payment.
- Ensure claim submission follows Health Plan-level administrative rules and coding guidance.
- Review the clinical policy for medical necessity criteria but verify payment under the member's contract.
Unsupported indications may be denied
Do not request authorization or perform DLI for indications not supported by this policy; use of DLI for indications other than post-allogeneic HSCT to treat relapsed/refractory hematologic malignancy or to decrease relapse risk (including genetic modification or ex vivo manipulation of donor lymphocytes) is not supported and may be denied.
- Genetic modification or ex vivo manipulation of donor lymphocytes is not supported outside of a clinical trial.
- Requests for DLI outside the post-allogeneic HSCT indications may be denied.
Do not perform DLI for active grade ≥2 acute GvHD
DLI performed in the presence of grade 2 or higher acute graft-versus-host disease (GvHD) is a contraindication and is not supported; such requests may be denied.
- Document absence of grade ≥2 acute GvHD before authorization; presence of grade ≥2 acute GvHD should preclude DLI.
- Grade 2 or higher acute GvHD at the time of proposed infusion is a basis for denial.
State Medicaid provisions take precedence when conflicting
If state Medicaid provisions conflict with this clinical policy, the state Medicaid manual governs; providers must follow applicable state Medicaid requirements when treating Medicaid members.
- Review the state Medicaid manual for any provisions that supersede this clinical policy.
- Ensure compliance with Medicaid-specific coverage rules when they differ from this policy.
Definitions and Key Terms
Background on Donor Lymphocyte Infusion (DLI)
Donor lymphocyte infusion (DLI) is the infusion of donor mononuclear lymphocytes after allogeneic hematopoietic stem cell transplantation (HSCT) intended to induce a graft‑versus‑tumor effect, reduce relapse risk, or convert mixed donor chimerism to full donor chimerism when clinically warranted. DLI has demonstrated high remission rates in chronic myeloid leukemia (CML), more limited effectiveness in acute leukemias, and potential activity in other hematologic malignancies. Major complications include graft‑versus‑host disease (GvHD) and, less commonly, bone marrow aplasia; these risks should be weighed against potential benefit when considering DLI.
Key Statistics
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