CurrentCommunity Health Plan WashingtonPolicy MC.CP.MP.101

Donor Lymphocyte Infusion

Defines medical necessity criteria for donor lymphocyte infusion (DLI) following allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory hematologic malignancy or to decrease risk of relapse; disallows use for other indications including ex vivo manipulation or in presence of > grade 2 acute GvHD.

Policy Summary

PayerCommunity Health Plan Washington

PolicyDonor Lymphocyte Infusion

Policy CodePolicy MC.CP.MP.101

Change TypeRevision / Clarification

Effective Date

Next Review Date

Key ActionProvider must document prior allogeneic HSCT and that the indication is relapsed/refractory hematologic malignancy or intent to decrease relapse risk, and document absence of higher than grade 2 acute GvHD.

SourceLink

POLICY UPDATE CHANGES

Added clarifying language to Criteria II regarding indications not supported (e.g., genetic modification/ex vivo manipulation and presence of > grade 2 acute GvHD).

Updated description to note the absence of coverage criteria from CMS.

Annual background and reference updates and minor rewording with no impact to criteria.

1Primary covered indication group (post-allogeneic HSCT relapse/pre-emptive)

2Not supported indications listed

4Informational codes provided

Coverage Summary

Overview: This policy (policy_number MC.CP.MP.101) defines medical necessity for Donor Lymphocyte Infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory hematologic malignancy or to decrease the risk of relapse (including pre-emptive use for mixed chimerism or molecular/minimal residual disease). Status: CURRENT. Coverage stance: covered_with_criteria. Last review: 2025-02-25.

Thresholds and key definitions

Mixed chimerism threshold< 90% donor cells

Full/complete chimerism threshold100% donor cells

DLI definitionInfusion of donor mononuclear lymphocytes from the original stem cell donor to induce a graft-versus-tumor effect

DLI primary intentUsed post-allogeneic HSCT to decrease relapse risk or convert mixed to full donor chimerism

GvHD grading notePolicy disallows DLI in presence of higher than grade 2 acute GvHD

Medical Necessity Criteria

Medically Necessary

DLI is medically necessary when ALL of the following are met:

ALL of the following

Post-allogeneic HSCT: DLI is performed following an allogeneic hematopoietic stem cell transplantation (HSCT)
Indication is treatment of relapsed or refractory hematologic malignancy OR to decrease the risk of relapse of a hematologic malignancy
Includes therapeutic (proven relapse/progression) or pre-emptive/prophylactic therapy in high-risk patients (e.g., mixed chimerism, detection of minimal residual disease)
Chimerism restriction: Not performed for the sole purpose of increasing donor chimerism without risk of relapse
DLI not recommended solely to increase donor chimerism due to GvHD risk

Not Medically Necessary / Not Supported

DLI is not supported for the following (any of):

ANY of the following

Genetic/ex vivo manipulation: Genetic modification or ex vivo manipulation of donor lymphocytes
Techniques to manipulate the donor lymphocyte graft (e.g., enrichment, depletion, activation) are investigational and not recommended outside clinical trials
Acute GvHD: Use in the presence of higher than grade 2 acute graft-versus-host-disease (GvHD)
Policy disallows DLI in presence of > grade 2 acute GvHD
Other unsupported indications: Any other indication not specified in the medically necessary criteria

Provider Actions

Documentation Required

Document HSCT and indication

Document prior allogeneic hematopoietic stem cell transplantation (HSCT) and the indication for DLI. Indication must be relapsed or refractory hematologic malignancy or intent to decrease risk of relapse (therapeutic or pre-emptive/prophylactic). When DLI is used pre-emptively, include supporting evidence such as mixed chimerism (<90% donor cells) or detection of molecular/minimal residual disease.

Prior allogeneic HSCT documented
Indication: relapsed/refractory hematologic malignancy OR intent to decrease relapse risk (therapeutic or pre-emptive/prophylactic)
If pre-emptive, provide evidence (e.g., mixed chimerism < 90% donor cells, MRD detection)

Documentation Required

Document absence of contraindications

Document that the patient does not have contraindications to DLI: specifically, absence of higher than grade 2 acute graft-versus-host disease (GvHD). Also document that DLI is not being performed solely to increase donor chimerism without an associated risk of relapse.

Record absence of > grade 2 acute GvHD
Confirm DLI is not solely to increase donor chimerism without relapse risk

Billing Rule

Use informational codes

When billing, reference applicable CPT/HCPCS codes for informational purposes only: 38215, 38242, 86950, S2150. Inclusion of these codes in the policy is informational and does not guarantee coverage; follow current coding guidance and payer policies.

38215
38242
86950
S2150

Coding

Relevant CPT / HCPCS / Other codes (informational only)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; 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

Background & Evidence

Background: DLI is an adoptive immunotherapy in which donor T lymphocytes from the original HSCT donor are infused to induce a graft-versus-tumor response, used therapeutically for proven relapse/progression or pre-emptively in high-risk patients (e.g., mixed chimerism or detectable MRD). Effectiveness varies by disease — high response rates reported in relapsed CML (complete remissions ~70–80%), lower response in AML (~15–20%), variable responses in multiple myeloma (~22–52%) and limited durable benefit reported in ALL. Major risks include graft-versus-host disease (GvHD) (reported in approximately 40–60% of patients, with some studies ~60%), and bone marrow aplasia (occurring in ~2–5%), along with associated infection and bleeding; infusion of subsequent donor stem cells can reverse aplasia. Techniques to manipulate the donor graft (e.g., enrichment, depletion, activation, genetic/ex vivo modification) are investigational and not recommended outside clinical trials.

Reported evidence metrics

Reported GvHD incidence after DLIApproximately 40-60% across published reports; one retrospective reported ~60%

Complete remission in relapsed CML with DLIReported 70-80% in multiple studies

Remission induction in relapsed AML with DLIApproximately 15-20%

Response rate in relapsed multiple myeloma to DLIApproximately 22-52% across reports

Definitions / Glossary: Mixed chimerism — <90% donor cells detected after HSCT. Full/complete chimerism — 100% donor cells detected after HSCT. DLI (Donor Lymphocyte Infusion) — infusion of donor mononuclear lymphocytes from the original stem cell donor to induce a graft-versus-tumor effect. GvHD grading — acute graft-versus-host disease is graded, and DLI is not supported in the presence of acute GvHD higher than grade 2.

Revision History

08/23revised

Policy developed; annual review. Minor rewording in Description with no impact on criteria. Background updated with no impact on criteria. References reviewed and updated.

04/24revised

Annual review. Minor rewording in Description with no impact on criteria. Background updated with no impact on criteria. References reviewed and updated. Reviewed by external specialist.

04/24clarified

Annual review. Added clarifying language to Criteria II regarding indications not supported (e.g., genetic modification/ex vivo manipulation and use in the presence of > grade 2 acute GvHD). References reviewed and updated. Reviewed by internal specialist.

02/25clarified

12/25revisedLatest