Donor Lymphocyte Infusion (DLI) and Hematopoietic Progenitor Cell (HPC) Boost
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Defines medical necessity and investigational indications for donor lymphocyte infusion and hematopoietic progenitor cell boost following hematopoietic stem cell transplantation; applies to members receiving or planning allogeneic or autologous HSCT for hematologic malignancy.
No material clinical or coverage changes in this revision.
Coverage Criteria for DLI and HPC Boost
Coding and Place-of-Service
| No codes listed |
Provider Actions, Authorization, and Billing
Prior Approval
Prior Approval — Not applicable.
Prior authorization for DLI
Prior authorization is required for donor lymphocyte infusion (DLI) when used after an allogeneic HSCT that was originally medically necessary for a hematologic malignancy. Indications that may warrant authorization include: treatment of relapse/refractory disease, prophylaxis to prevent relapse in the setting of T-cell–depleted grafts or nonmyeloablative conditioning, and conversion from mixed to full donor chimerism. DLI is investigational for nonhematologic malignancies and for use following transplants that were originally investigational.
- Confirm original HSCT was medically necessary for a hematologic malignancy
- DLI donor must be the original HSCT donor
- DLI investigational for listed indications
Authorization requirements for HPC/SCB
Authorization for hematopoietic progenitor cell (HPC) boost or CD34-selected stem cell boost (SCB) requires documentation of the original HSCT details and the clinical indication. HPC/SCB is considered medically necessary to promote engraftment or to enhance chimerism (<100% donor cells). HPC/SCB is investigational for other indications.
- Document original HSCT date, donor identity, and that original transplant was medically necessary
- Specify indication: promote engraftment or enhance chimerism (<100% donor cells)
- If using previously cryopreserved product, document provenance and chain-of-custody
- If new donor harvest required, document evaluation, mobilization, and collection plans
Prior authorization for HPC boost
Prior authorization for an HPC boost must include objective measures of poor graft function and exclusion of alternative causes. Provide laboratory thresholds and timing, and donor availability/ product details.
- Define poor graft function (e.g., persistent cytopenias and/or transfusion dependence) with objective values when available (ANC, platelet count, RBC transfusion dependence)
- Document timing from allo‑HSCT to proposed boost and prior therapies (e.g., recent chemotherapy for relapse)
- Exclude relapse/persistent disease, incomplete donor chimerism (if specified), active infection, or drug-related myelosuppression where applicable
- Confirm availability of original donor or backup stem cell product; note if product is cryopreserved and cell counts (CD34+, CD3+) are known
Code reporting requirement
Code reporting requirement — use the appropriate procedure and diagnosis codes when submitting authorization requests and claims.
Evidence limitations may affect coverage
Evidence limitations may affect coverage determinations. Many studies are observational, single‑arm, retrospective, or small prospective cohorts; randomized controlled trials are largely lacking. Overlapping/duplicative populations and variable follow‑up limit certainty about optimal dosing, manipulation (e.g., CD34‑selection), and long‑term outcomes.
- Systematic reviews/meta‑analyses include primarily retrospective and nonrandomized studies
- Limitations: small sample sizes, heterogeneity in populations and interventions, and lack of high‑quality RCTs
Clinical indication for HPC boost
Clinical indication for HPC boost — typically considered to restore hematopoiesis or augment poor graft function after HSCT (e.g., persistent cytopenias, transfusion dependence) or to enhance donor chimerism when donor fraction is suboptimal.
- Typical timing: median reported intervals range weeks to months post‑allo‑HSCT (examples: ~4–138 days reported depending on series)
- HPC boost may use cryopreserved product or require new donor mobilization/harvest
Exclusion-related denial risk
Exclusion‑related denial risk — be aware of common exclusion criteria used in studies that may lead to denial if present: active relapse/persistent hematologic disease as the cause of cytopenias, significant incomplete donor chimerism when not an intended indication, active infection, or drug‑induced myelosuppression.
- PGF secondary to relapse/persistent disease was commonly excluded in studies
- Incomplete (<90–100%) donor chimerism and active infection were exclusion criteria in many trials
- Document that cytopenias are not explained by relapse, infection, or medication effect
No explicit denial triggers provided
No explicit denial triggers beyond documented exclusion criteria are provided in the evidence summary; use clinical judgment and payer policy for final determinations.
- Absence of clear objective documentation of poor graft function or missing transplant history may result in authorization delay or denial
- When study limitations exist, consider supplemental documentation to support medical necessity
Required clinical documentation
Required clinical documentation — provide complete transplant and clinical records to support authorization and billing.
- Indication for DLI or HPC/SCB (relapse, prophylaxis, pre‑emptive MRD, engraftment failure, poor graft function)
- Original HSCT details: date, conditioning regimen (myeloablative vs nonmyeloablative), donor identity and relationship, graft manipulation (T‑cell depletion)
- Prior transplant outcomes: engraftment history, prior GVHD (type, grade), prior relapses and treatments including recent chemotherapy, immunotherapy, or TKIs
- Objective laboratory data demonstrating poor graft function (ANC, platelet count, transfusion dependence), chimerism studies, infectious workup to exclude active infection
- Details of proposed product: cryopreserved versus fresh, CD34+ and CD3+ cell counts if available, provenance and chain-of-custody, plan for donor mobilization/harvest if needed
Comparative/step considerations
Comparative and step considerations — consider alternative or complementary therapies and that no specific mandated step therapy sequences are defined by the evidence summary.
- Comparators include chemotherapy, immunotherapy, and targeted agents such as TKIs (e.g., in CML)
- Some evidence suggests TKIs (with or without DLI) may offer survival advantages in CML relapse; combination strategies may be used case‑by‑case
- No formal step therapy sequences are required by the evidence; document rationale when a non‑DLI/HPC strategy is chosen
Therapy sequencing considerations
Therapy sequencing considerations — document sequencing decisions and backup stem cell use rationale.
- Backup stem cells are typically collected during autologous transplant planning for potential later use (e.g., after ASCT relapse or graft failure)
- HPC boost is usually not preceded by a preparative regimen; boosts may follow reinduction chemotherapy when prolonged cytopenias persist
- Describe prior and planned therapies, and why boost or DLI is preferred given prior responses and GVHD history
Candidate and Transplant Recipient Criteria
inv-63: Transplant candidate criteria — Populations eligible for DLI/HPC boost
Populations eligible for DLI/HPC boost are transplant recipients following allogeneic (or for HPC boost, autologous) HSCT for hematologic malignancy with indications including:
Derived from Populations and Description sections.
inv-64: DLI candidate criteria — Candidate population for DLI
Candidate population for DLI
From Populations and Interventions descriptions.
inv-65: Candidate criteria for HPC boost / DLI — Candidates
Candidates
Population specified in PICO and clinical context sections.
inv-66: Allo-HSCT HPC boost candidate criteria — based on cited studies
Candidate criteria for HPC boost after allo-HSCT (based on cited studies):
Washington University cohort requirement.
Used to define PGF in prospective trial.
Requirement in prospective and retrospective cohorts.
Contraindications and Clinical Cautions
The policy reiterates that genetically modified donor lymphocytes are investigational and therefore not standard of care. While the document does not enumerate absolute contraindications tied specifically to genetic modification, the investigational status itself precludes routine coverage and clinical use outside research settings.
This document segment does not list detailed contraindications; however, clinical practice and the reported series support exercising caution and typically excluding patients with recent or ongoing severe acute or chronic GVHD from receiving DLI.
Contraindications are not explicitly enumerated in the policy text, but the reported observational studies excluded patients with active GVHD, indicating that active GVHD functions as a practical contraindication to DLI in the evidence base.
The policy excerpts do not provide a formal list of relative contraindications; nonetheless, the evidence and clinical practice imply that active GVHD and similar immunologic contraindications are reasons to withhold DLI.
No explicit absolute or relative contraindications for DLI or HPC boost are listed in the reference and coding sections cited; readers should refer to the clinical-exclusion statements and study eligibility criteria elsewhere in the policy for operational contraindication guidance.
Evaluation and Documentation Requirements
Confirm product provenance and that boost needs no preparative regimen
For HPC boost evaluation, confirm whether the product is cryopreserved or if donor re‑evaluation, mobilization, and harvest will be required; document that a boost is not preceded by a preparative regimen.
Assess disease status, tumor burden, GVHD history, and timing
Assess and document disease status (molecular/cytogenetic/hematologic relapse), tumor burden, prior GVHD history, and timing from transplant when evaluating DLI or HPC boost candidacy.
Document cytopenias, transfusion dependence, chimerism, and prior therapies
Document persistent cytopenias, transfusion dependence, MRD status or mixed chimerism, prior transplant details, and prior therapies (including any reinduction chemotherapy) in the authorization record.
Include MRD/chimerism and prior transplant details in evaluation
Include documentation of persistent cytopenias/transfusion dependence, MRD or mixed chimerism assessments, prior HSCT details, and prior therapies as part of standard evaluation prior to authorization.
Reference guideline-supported evaluation steps in authorization package
References and guidelines cited in the policy support specific evaluation steps for prophylactic, pre‑emptive, and therapeutic use of DLI and HPC boost; include relevant guideline citations as applicable.
Center and Institutional Requirements
Document HSC collection practices and backup stem cell availability
Document adherence to institutional/consensus guidance recommending collection of enough HSCs for two transplants at the time of first HSCT where applicable and note availability of backup stem cells.
Document center expertise and donor relationship; no specific accreditation required
Transplant center expertise and clear documentation of indication and donor relationship are recommended though no specific center accreditation or volume requirements are specified in this policy.
Ensure center documents expertise and indication
Not specified in these document segments; ensure transplant center documents expertise and indication when submitting authorization requests.
Include transplant center experience when relevant
Not specified in these chunks; include transplant center clinical experience and supporting documentation when relevant to authorization.
No center accreditation/volume requirements specified
No accreditation or minimum volume requirements are specified in the policy; reference society guidelines (for example ASTCT) may be included to support institutional capability.
Post-Transplant Use, Monitoring, and Follow-up
Background and Rationale
Background: Donor lymphocyte infusion (DLI) is an adoptive immunotherapy in which lymphocytes from the original HSCT donor are infused to induce a graft‑versus‑tumor effect. DLI is used to treat relapse or refractory disease after allogeneic HSCT, to convert mixed to full donor chimerism, or as prophylaxis in select high‑risk graft settings. The policy notes that collection and cryopreservation of donor lymphocytes in association with an otherwise medically necessary HSCT is considered medically necessary.
Key Definitions
Policy Revision History
Annual review completed and policy renewed (most recent policy action: Annual Review / Renewed).
Policy effective date established for donor lymphocyte infusion (DLI) and hematopoietic progenitor cell (HPC) boost coverage criteria.
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