Donor Lymphocyte Infusion
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Medical necessity criteria and coding guidance for donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation for relapsed or high-risk hematologic malignancies; applies to non-Medicare Arizona Complete Health plans adopting this Centene policy.
No material clinical or coverage changes in this revision.
Coverage Criteria for Donor Lymphocyte Infusion (DLI)
Medically necessary indications (non-Medicare plans)
Covered when ANY of the following is met for non-Medicare plans affiliated with Centene:
sourced to policy statement I.
Not recommended/contraindicated uses
Not covered for the following (evidence does not support):
sourced to policy statement II and Description.
Genetic modification or other ex vivo manipulation of donor lymphocytes (for example, enrichment, depletion, activation, or other graft engineering techniques) is not supported for routine clinical use outside of an approved clinical trial. The policy states that these techniques are still investigational because benefits have not been established to outweigh risks and require further study before routine adoption.
This exclusion is sourced from the policy statement disallowing genetic modification or ex vivo manipulation and the Description noting such techniques are under investigation and not recommended outside clinical trials.
Donor lymphocyte infusion should not be administered in the presence of grade 2 or higher acute graft-versus-host disease (GvHD). The policy explicitly lists active significant acute GvHD (grade ≥2) as a contraindication and may be a basis for denial.
This restriction is stated in the policy criteria and reinforced in the background/description as a situation where DLI is not supported.
DLI is not recommended solely to increase donor chimerism in patients who do not have relapse or a clear risk of relapse. The Description explains that DLI offers no additional benefit in the setting of full chimerism and that using DLI solely to convert mixed chimerism to full chimerism, absent relapse risk, may unnecessarily expose patients to the risk of exacerbating graft-versus-host disease.
The policy note reiterates that DLI should not be used for the sole purpose of increasing donor chimerism without relapse risk.
Use of donor lymphocyte infusion for indications other than following an allogeneic HSCT for relapsed or refractory hematologic malignancy, or to decrease the risk of relapse, is not supported by current evidence and is considered not medically necessary. The policy explicitly states that evidence does not support other indications and lists this stance as the overall coverage position.
Providers requesting authorization for DLI should document the prior allogeneic HSCT and the specific indication (relapse, refractory disease, or high relapse risk) because other indications may be denied.
Clinical Use and Regimens
| Indication | Regimen / Role of DLI | Coverage |
|---|---|---|
| Relapsed chronic myeloid leukemia (CML) after allogeneic HSCT | Donor lymphocyte infusion — often effective as a single modality; can establish complete remissions in 70–80% of patients and responses are frequently durable. | Covered |
| Indication | Regimen / Role of DLI | Coverage |
|---|---|---|
| Relapsed acute myeloid leukemia (AML) after allogeneic HSCT | DLI often combined with chemotherapy; response rates lower than CML with approximately 15–20% chance of remission when DLI is used for relapsed AML. | Covered |
| Indication | Regimen / Role of DLI | Coverage |
|---|---|---|
| Relapsed multiple myeloma after allogeneic HSCT | DLI may be used to stimulate a graft‑versus‑myeloma effect per NCCN guidance; reported response rates vary (~22–52%) and DLI has been used to induce conversion to full chimerism in some reports. | Covered |
Coding and Dose Information
| 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
Prior authorization is required per payer policy for donor lymphocyte infusion (DLI) and associated procedures. When requesting authorization, include relevant CPT/HCPCS codes and clinical documentation that supports the indication (see documentation callout).
Step Therapy
DLI is indicated after allogeneic HSCT for relapsed or refractory hematologic malignancy or to decrease risk of relapse in high‑risk patients. There is no step‑therapy algorithm requiring prior failure of other specific treatments before DLI; however, DLI should be used appropriately as therapeutic or pre‑emptive therapy per clinical criteria (e.g., relapse, mixed chimerism with high relapse risk, or detectable minimal residual disease).
Active Significant Acute GvHD
Do not administer DLI in the presence of active significant acute graft‑versus‑host disease (GvHD). DLI is contraindicated for patients with grade 2 or higher acute GvHD and such requests may be denied.
- Active grade ≥2 acute GvHD is a contraindication to DLI and a basis for denial
Line of Therapy Guidance
salvage
effectiveness varies by disease (highest in CML).
Definitions and Key Terms
Background
Donor lymphocyte infusion (DLI) is the infusion of lymphocytes derived from the original hematopoietic stem cell donor into a patient who previously underwent allogeneic HSCT. The intended therapeutic mechanism is a graft-versus-tumor (GvT) immune effect that can treat overt relapse or be used pre-emptively in patients at high risk of relapse (for example, with mixed chimerism or detectable minimal residual disease).
Effectiveness of DLI varies by disease: it tends to be highest in chronic myeloid leukemia and lower in diseases such as acute myeloid leukemia or ALL. Major risks associated with DLI include graft-versus-host disease and bone marrow aplasia; the policy notes these complications (GvHD incidence and 2–5% risk of marrow aplasia) and advises careful patient selection and documentation when DLI is considered.
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