Donor Lymphocyte Infusion for Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant

POLICY NUMBER

L.2.03.402

DESCRIPTION

Donor lymphocyte infusion (DLI), also called donor leukocyte or buffy-coat infusion, is a type of therapy in which T lymphocytes from the blood of a donor are given to a patient who has already received a hematopoietic stem cell transplant (HSCT) from the same donor. The DLI therapeutic effect results from a graft-versus-leukemic or graft-versus-tumor effect due to the recognition of certain antigens on the cancer cells by the donor lymphocytes and the resultant elimination of the tumor cells.

Approximately 40-60% of patients who receive a DLI develop graft-versus-host disease (GVHD), and the development of GVHD predicts a response to the DLI. Treatment-related mortality after DLI is 5-20%. There does not seem to be a correlation between the type of hematologic malignancy for which the DLI was given and the development of GVHD. The risk of development of GVHD is related, in part, to DLI dose and therapy prior to DLI.

DLI may be usedfor various indications such as relapse after allogeneic HSCT, to prevent disease relapse in the setting of T cell-depleted grafts or non-myeloablative conditioning regimens, or to convert mixed to full donor chimerism. Management of relapse, which occurs in approximately 40% of all hematologic malignancy patients, is the most common indication for DLI.

The literature is heterogeneous for reporting methods of cell collection, indication (e.g., planned after chemotherapy, in early relapse), cell dose infused, and cell subtype used. In addition, many studies include multiple diseases with little information regarding disease-specific outcomes; however, DLI is used in nearly all hematologic malignancies for which allogeneic HSCT is performed, including chronic myeloid leukemia, acute myeloid and lymphoblastic leukemias, myelodysplastic syndromes, multiple myeloma, and Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL).  

POLICY

No benefits will be provided for a covered transplant procedure or a transplant evaluation unless the Member receives prior authorization through case management from Blue Cross & Blue Shield of Mississippi.

Donor lymphocyte infusion may be considered medically necessary following allogeneic-hematopoietic stem cell transplantation (HSCT) that was originally considered medically necessary for the treatment of a hematologic malignancy that has relapsed or is refractory, to prevent relapse in the setting of a high risk of relapse (see Policy Guidelines), or to convert a patient from mixed to full donor chimerism.

Donor lymphocyte infusion is considered investigational following allogeneic-hematopoietic stem cell transplantation (HSCT) that was originally considered investigational for the treatment of a hematologic malignancy.

Donor lymphocyte infusion is considered investigational as a treatment of nonhematologic malignancies following a prior allogeneic HSCT. 

Genetic or other modification of donor leukocytes is considered investigational.

POLICY EXCEPTIONS

For Federal Employee Program (FEP) subscribers, the Service Benefit Plan includes specific conditions in which autologous or allogeneic blood or marrow stem cell transplants would be considered eligible for coverage.

For State and School Employee subscribers, all bone marrow/stem cell transplants must be certified as medically necessary by the Plan’s Utilization Review Vendor. No benefits will be provided for any transplant procedure unless prior approval for the transplant is obtained.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Settings considered high risk for relapse include T cell-depleted grafts or nonmyeloablative (reduced-intensity conditioning) allogeneic HSCT.

In patients undergoing allogeneic stem-cell transplant for chronic myelogenous leukemia or acute myelogenous leukemia, donor leukocytes may be collected and stored at the time of the original collection of stem-cells from the donor.

Charges for the leukapheresis procedure for the donor should be considered as recipient expenses and the claims administered accordingly.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

8/1998: Approved by Medical Policy Advisory Committee (MPAC)

2/14/2002: Investigational definition added

4/26/2002: Type of Service and Place of Service deleted

3/25/2004: Policy reviewed and revised to be consistent with BCBSA policy # 2.03.03, policy title “Donor Leukocyte Infusion” renamed “Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem-Cell Transplant,” Sources updated

9/2/2004: Code Reference section updated, CPT code 36511, 86812, 86813, 86817 added, CPT 36520 deletion date added, ICD-9 diagnosis code 205.10-205.11, V59.09 deleted

1/10/2005: Code Reference section updated, CPT code 36511, 36520 deleted, CPT code 38242 added, ICD-9 procedure code 99.72 deleted

08/11/2011: Policy title changed from "Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem-Cell Transplant" to “Donor Lymphocyte Infusion for Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant.”  Policy description re-written. Policy statement revised to indicate that donor lymphocyte infusion would be considered medically necessary following an allogeneic-hematopoietic stem cell transplantation (HSCT) that was considered medically necessary for the treatment of a hematologic malignancy that has relapsed or is refractory, to prevent relapse in the setting of a high risk of relapse, or to convert a patient from mixed to full donor chimerism. Deleted outdated references from Sources section.

06/06/2012: Policy reviewed; no changes.

08/09/2013: Policy reviewed; no changes.

07/10/2014: Policy reviewed; no changes.

08/25/2015: Code Reference section updated to add ICD-10 codes. Updated the code description for 38242.

09/18/2015: Policy reviewed; policy statements unchanged. Policy Guidelines section updated to add medically necessary and investigative definitions.

03/08/2016: Policy description updated. Policy statement updated to state that genetic or other modification of donor leukocytes is considered investigational.

06/06/2016: Policy number A.2.03.03 added.

09/30/2019: Code Reference section updated regarding deleted ICD-10 procedure codes.

12/27/2021: Code Reference section updated to make note of deleted ICD-10 procedure codes and to remove deleted ICD-10 procedure codes 30253Q1 and 30263Q1.

04/04/2023: Policy number changed from "A.2.03.03" to "L.2.03.402." Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

04/29/2024: Policy Exceptions updated regarding Federal Employee Program and State and School Employee subscribers.

03/28/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association policy # 2.03.03

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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