BlueCross and BlueShield of Montana Medical Policy/Codes
Stem-Cell Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information)
Chapter: Surgery: Procedures
Current Effective Date: December 27, 2013
Original Effective Date: December 27, 2013
Publish Date: September 27, 2013

Human blood contains a remarkable variety of cells, each precisely tailored to its own vital function.  Erythrocytes, or red blood cells, transport life-sustaining oxygen throughout the body.  Tiny platelets stop bleeding by promoting clotting.  White blood cells (eg., lymphocytes, monocytes, and neutrophils) form the immune system that guards against attack by foreign tissue, viruses, and various other microorganisms. 

All of these cells develop from master cells or blood cell progenitors, which are known as hematopoietic blood-forming or blood-parent stem-cells and reside primarily in bone marrow.  Injury to the stem-cells, from chemotherapy, radiation, or disease, can cripple the immune and blood production systems.

The most appropriate stem-cell source for a particular patient depends upon his or her disease, treatment history, and the availability of a compatible donor.  The most appropriate source of stem-cells for each patient must be balanced by the risks of graft failure, the reinfusion of defective or diseased cells in the autologous procedure, the risks of graft rejections and graft-versus-host disease in allogeneic procedures.  This becomes especially critical with the use of a mismatched or unrelated donor.

Stem-cell Harvesting Followed by Infusion:

Stem-cells can be harvested from the following sources:

  • Bone marrow, or
  • Peripheral blood, or
  • Umbilical cord blood.

Stem-cells can be harvested from the donor’s bone marrow prior to the recipient’s marrow ablative therapy or from a donor’s marrow after verifying the donor and recipient are well-matched with respect to human leukocyte antigens.

Types of stem-cells harvesting followed by infusion procedures are:

  • Autologous – Stem-cells are harvested prior to any ablative therapy and infused back (reinfusion) into the same individual, the procedure is referred to as autologous). 
  • Allogeneic – Stem-cells from a healthy antigen compatible (histocompatible) donor are harvested and then infused into a different recipient.
  • Syngeneic  – Stem-cells refer to genetically identical bone marrow or peripheral stem-cells harvested from an identical twin.  Syngeneic bone marrow transplants are obviously limited by the rarity of identical twins.   

Infusion of stem-cells to the recipient procedures are also known as:

  • Hematopoietic stem-cell support or Hematopoietic stem-cell transplant,
  • Peripheral blood stem-cell support or Peripheral blood stem-cell transplant,
  • Stem-cell support (previously referred to as Stem-cell transplant or Stem-cell rescue),
  • Bone marrow transplant, Allogeneic stem-cell support, Autologous stem-cell support, Syngeneic stem-cell support, and
  • Umbilical cord blood stem-cell support.

Stem-cells are the main ingredient in bone marrow transplantations.  The stem-cells in the transplanted marrow can reestablish the patient's blood-producing and immune systems, which have been devastated by leukemia, cancer, chemotherapy, radiation therapy, or unknown causes.  The objective of all types of stem-cell support is to provide the healthy stem-cell population that will differentiate into blood cells to replace the deficient or pathologic cells of the host.  Improvement of stem-cell grafting and long-term, disease-free survival is accomplished by:

  • Intensive preparative regimens, and
  • Effective graft-versus-host disease treatment, and
  • Improvements in supportive care.

Conventional Preparative Conditioning (High-Dose Chemotherapy):

The conventional (“classical”) practice of allogeneic stem-cell transplantation involves administration of myelotoxic agents (e.g., cyclophosphamide, busulfan; also known as high-dose chemotherapy) with or without total body or localized irradiation (known as chemoradiotherapy) at doses sufficient to cause bone marrow failure.  High-dose chemotherapy may be given as one type of myelotoxic agent only, known as monotherapy, or several types of agents sequentially, known as sequential high-dose chemotherapy.  The rationale for this type of therapy is that many cytotoxic agents act according to a steep dose-response curve.  The beneficial treatment effect in this procedure results from chemotherapeutic eradication of malignant cells with an associated immune-mediated graft-versus-malignancy effect.  While such treatment may eliminate the malignant cells, patients are as likely to die from opportunistic infections, graft-versus-host disease, hemorrhage, or organ failure as from the underlying malignancy.  Since the life-threatening toxicity is so high, patients are usually hospitalized for the high-dose chemotherapy regimen and may require further hospitalization to treat the drug toxicity effects.  Autologous stem-cell transplantation necessitates myeloablative chemotherapy to eradicate cancerous cells from the blood and bone marrow, thus permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells.  As a consequence, autologous stem-cell transplantation is typically performed as consolidation therapy when the patient’s disease is in complete remission.  Patients who undergo autologous stem-cell transplantation are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not graft-versus-host disease.

Reduced-Intensity Conditioning:

Reduced-intensity conditioning (previously known as nonmyeloablative or non-marrow-ablative chemotherapy or mini-transplant) refers to chemotherapy regimens that seek to reduce adverse effects secondary to toxicity while retaining the beneficial graft-versus-malignancy effect of allogeneic stem-cell transplantation.  These regimens do not eradicate the patient’s hematopoietic ability, thereby allowing for relatively prompt hematopoietic recovery (e.g., 28 days or less) even without a transplantation.  Patients who undergo reduced-intensity conditioning with allogeneic stem-cell support initially demonstrate donor cell engraftment and bone marrow mixed chimerism.  Most will subsequently convert to full-donor chimerism, which may be supplemented with donor leukocyte infusion to eradicate residual malignant cells.  A number of different cytotoxic regimens, with or without radiotherapy, may be used for reduced-intensity conditioning allogeneic stem-cell support.  They represent a continuum in their effects, from nearly totally myeloablative, to minimally myeloablative with lymphoablation.  

Bone Marrow Transplantation:

The transplantation procedure itself is simple.  If the patient is not self-donating his/her bone marrow, it is obtained from a donor individual and is known as allogeneic stem-cell transplant.  The bone marrow is aspirated, under local or general anesthesia, over several sessions from the iliac crests of the pelvis of:

  • A related or unrelated donor who is human leukocyte antigen compatible (known as allogeneic);
  • A related donor who is human leukocyte antigen-identical (known as syngeneic).

If the patient is self-donating his/her bone marrow, known as autologous stem-cell transplantation, the bone marrow is removed from the iliac crests of the pelvis when a complete remission has been induced.  The patient is then given high-dose chemotherapy with the hope of destroying any residual tumor. 

Bone marrow transplantations present numerous medical hurdles.  The patient must receive a steady supply of fresh red cells, platelets, and antibiotics for several weeks until the transplanted stem-cells begin producing large quantities of mature blood elements. 

In an allogeneic stem-cell transplant, the patient's immune system must be sufficiently suppressed so that it will not reject the transplanted stem-cells.  At the same time, the immune system produced by the donor stem-cells may recognize their new host as foreign, a reaction known as graft-versus-host disease, in which case they may cause organ damage and/or death.  Allogeneic stem-cell transplantation is an established treatment for certain marrow dysplasias and aplasias and genetic diseases (such as immunodeficiencies and inborn errors of metabolism).

Immunologic compatibility between the donor and patient is a critical factor for achieving a good outcome of allogeneic stem-cell transplantation.  In general, the more compatible the donor and recipient tissue types are, the greater the chances for a successful outcome.  Compatibility is established by the typing (testing) of six human leukocyte antigen and the outcome of mixed leukocyte (white blood cell types) cultures.  An acceptable donor will match the patient's six human leukocyte antigens.  A mismatch of one or more antigens may not be considered an acceptable donor.  In all cases, the donor and recipient tissue/cells must be non-reactive (no reaction) in the mixed leukocyte culture.

Autologous stem-cell transplantation eliminates the need to find a compatible marrow donor and bypasses the risk of graft-versus-host disease.  The limitation to this approach is the possibility of reinfusing contaminated marrow.  Even if the marrow is truly uninvolved, a significant amount of blood is also collected at the time of the harvest.  Thus, circulating disease cells could also be a source of contamination.

Peripheral Blood Transplantation:

Patients treated with high-dose chemotherapy regimens that ablate their own bone marrow function are increasingly being reinfused with autologous stem-cells rather than with bone marrow cells.  Small numbers of stem-cells circulate in the peripheral blood and can be harvested via a pheresis procedure.  After several cycles of conventional doses of chemotherapy and stimulation with colony stimulating factors, the number of hematopoietic stem-cells in the peripheral circulation rises.  The patient may be subjected to a leukapheresis process several times where peripheral blood is removed and undergoes repeated selective separation and removal of leukocytes (white blood cells), progenitor cells, and platelets. The red blood cells and plasma are returned to the donor.  After the patient receives high-dose chemotherapy, the patient's bone marrow is reconstituted by the reinfusion of the stem-cell population.  Peripheral blood stem-cells are now used for nearly all autologous stem-cell transplantations and nearly half of allogeneic stem-cell transplantations.

Colony stimulating factor are hematopoietic growth factors that stimulate the growth and maturation of bone marrow stem-cells.  Two of these colony stimulating factors are currently available: 

  • Granulocyte Colony Stimulating Factor or
  • Granulocyte Macrophage Colony Stimulating Factor.

Umbilical Cord Blood Transplantation:

Blood from the umbilical cord, previously disposed of after birth, today provides umbilical cord blood stem-cells that can be cryopreserved and stored for later use.  Research has shown that umbilical cord blood stem-cell transplant offers a viable alternative to bone marrow transplant or peripheral blood stem-cell transplant in patients with select malignant and nonmalignant hematologic disorders, perhaps at a lower cost and with fewer complications.  Besides the lower cost and reduced risk of collecting, purifying, and cryo-processing umbilical cord blood stem-cells, it eliminates the need for hospitalization, general anesthesia, and subsequent blood replacement that is associated with bone marrow transplant or peripheral blood stem-cell transplant.  In addition, collecting umbilical cord blood stem-cells causes no discomfort to the donor.  Umbilical cord blood is being used for many of the allogeneic stem-cell transplantation indications whenever a suitable human leukocyte antigen-matched donor is unavailable or whenever time for identifying, typing, and harvesting from an unrelated donor is limited.

The U.S. Food and Drug Administration (FDA) is collecting data to develop product standards and criteria for a biologics license for UCB storage, known as cord blood banks.  At the present time, cord blood banks are not regulated. 

Currently, cord blood banks offer the expectant parents the opportunity to cryogenically store their baby's umbilical cord blood stem-cells in case of future need.  This service is being offered to the newborn's parents for use by a family member, such as a sibling, in whom an allogeneic stem-cell transplant is anticipated due to a history of leukemia or other conditions (i.e., cancer or blood/immune system disorders) requiring allogeneic stem-cell transplantation.

Donor Leukocyte Infusions:

Donor leukocyte infusions or buffy coat transfusions have been used for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia, but also acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin's, and non-Hodgkin's lymphoma.

Patients who relapse following treatment with chemotherapy and allogeneic stem-cell transplant for various hematologic malignancies have limited additional treatment options.  A clinical observation has been made that these select patients may benefit from an additional infusion of stem-cells from the original donor.  The source of the donor cells can be from a previously collected and cryopreserved reserve or can be freshly harvested, provided from the original stem-cell donor.  Collection of donor leukocytes requires that the original donor undergo a leukapheresis procedure. This additional donor leukocyte infusion, which is a form of adoptive immunotherapy, induces a graft-versus-tumor response, without the need for additional peripheral blood stem-cell harvest from the donor, or further high-dose chemotherpay for the recipient.  These patients do not receive immunosuppressive medication.

There is also research interest in the genetic modification of donor leukocytes.  For example, donor leukocytes can be modified by insertion of a thymidine kinase gene, rendering the cells susceptible to ganciclovir therapy.  If the infusion of donor leukocytes results in severe graft-versus-host disease, the patients can be treated with ganciclovir to selectively destroy the donor leukocytes. 

Donor leukocyte infusion may also be a component of a nonmyeloablative or reduced-intensity conditioning allogeneic stem-cell transplantation.  In the nonmyeloablative therapy setting, donor leukocyte infusion may be considered as part of the primary treatment.  For example, the intent of a mini-transplant is to establish a mixed donor-host hematopoietic chimerism using an infusion of allogeneic allogeneic stem-cells.  Once established, a donor leukocyte infusion may be used to induce a graft-versus-tumor effect to eradicate malignant cells.  In contrast, in the setting of a prior myeloablative allogeneic stem-cell support, a donor leukocyte infusion is not part of the initial therapy but is considered a salvage therapy at the time of relapse.

One of the reasons that cancer cells can grow, multiply, and spread is that the body does not recognize them as diseased, but accepts them as “self”.  Immune system-cells transplanted from a normal donor can often recognize cancer cells, particularly those of leukemia patients, as diseased cells and go to work eliminating them.  This phenomenon is called the graft-versus-leukemia or graft-versus-tumor effect, and it is one of the reasons that allogeneic stem-cell support may be curative.

Tandem Transplantation (Including Triple Transplantation):

Tandem high-dose chemotherapy with autologous stem-cell support or allogeneic stem-cell support is a planned process of bone marrow ablation performed alone or with total body irradiation followed by stem-cells by using the patient's or donor’s harvested stem-cells.  This process is repeated without regard to response and following recovery of the earlier infusion or transplant.  The patient can expect two planned cycles of bone marrow ablation, sequential high-dose chemotherapy, followed by stem-cell support. The second (or subsequent) cycle(s) is intended to further tumor cell reduction and eliminate any possibility of tumor progression or relapse.  Tandem high-dose chemotherapy with stem-cell support are generally administered at intervals of two- to six-months, contingent on the recovery from the early stem-cell support.  A third (or subsequent) cycle(s) is considered a “triple transplantation”.  Tandem high-dose chemotherapy with stem-cell support has also been described as the patient is being given the “second” or “final” dose of stem-cells following the first stem-cell support at an interval of approximately two-months.

Functional Status of Cancer Patients:

Oncologists have identified that the functional status of the patient can be correlated with the outcome of the underlying disease.  The following Karnofsky Performance Status Index (Scale) has been the most widely used measure of the functional status of cancer patients.




Able to carry on normal activity, no special care needed


Normal, no complaints, no evidence of disease

(same as above) 


Able to carry on normal activity, minor signs or symptoms of disease

(same as above) 


Normal activity with effort, some signs or symptoms of disease

Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed


Cares for self, unable to carry on normal activity or to do work 

(same as above) 


Requires occasional assistance from others, but able to care for most needs

(same as above)


Requires considerable assistance from others and frequent medical care

Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing



Disabled, requires special care and assistance


(same as above) 


Severely disabled, hospitalization indicated, death not imminent

(same as above)


Very sick, hospitalization necessary, active supportive treatment necessary

(same as above)


Moribund (a dying state)




Additional Definitions:

Listed below are several definitions not included in the above description. 

  • Chemosensitive disease is defined as a tumor, showing at least a 50% reduction in tumor burden in response to chemotherapy, typically measured by serial computed tomography scans.
  • Complete remission or response is the disappearance or absence of the signs and symptoms of the disease.
  • Malignancy refers to a harmful uncontrolled growth that can spread throughout the body and eventually lead to death.
  • Minimal response is defined as AT LEAST a 25% reduction in tumor burden, such as multiple myeloma being typically measured in terms of serum levels of beta-2 microglobulin or monoclonal immunoglobulins.
  • Monotherapy refers to a therapy that uses only one drug.
  • “No change” represents cases that do meet the response classifications of partial or minimal response.
  • Non-Malignancy refers to a benign growth or condition, such as dysplasias.
  • Partial response or partial remission is defined as AT LEAST a 50% reduction in tumor burden, such as multiple myeloma being typically measured in terms of serum levels of beta-2 microglobulin or monoclonal immunoglobulins.
  • Plateau indicates stable values or response for at least three months.
  • Primary progressive disease is progression that occurs during or immediately after the first conventional-dose induction regimen given to a newly diagnosed myeloma patient, such as before any stem-cell transplant, even before the first transplant cycle in a planned tandem transplant.  Patients with primary progressive disease can be categorized as high risk or standard risk.  One approach to identifying high-risk patients (other patients are standard risk) is the detection of t(4:14), t(14:16), or 17p deletion by FISH assay, chromosome 13 deletion or hypodiploidy by karyotyping, or plasma cell labeling index greater than 3%; finding one abnormality identifies a patient at high risk.  Patients with beta-2-microglobulin levels greater than 5.5 mg per liter are also often considered high risk. 
  • Primary refractory is defined as a tumor that fails to achieve a CR after initial standard dose chemotherapy.
  • The term refractory is defined as a LESS THAN 50% reduction in tumor burden.  Therefore, even those tumors that exhibited a 30% reduction, for example, would be considered refractory.  The terms refractory and resistant are synonymous.  Tumor response can be measured using serial computed tomography scans, or levels of circulating tumor markers, such as alpha fetoprotein in the case of germ cell tumors.
  • Relapsed is defined as tumor recurrence after a prior complete response.
  • Responsive is defined as a tumor showing either a complete, partial, or minimal response/remission.
  • The term "salvage therapy" describes chemotherapy given to patients who have:
    1. Failed to achieve complete response after initial treatment for newly diagnosed malignancy; or
    2. Relapsed after an initial complete response.
  • Staging refers to the extent of the disease, based on the Ann Arbor system of stages I through IV, indicating the number and site of involved lymph nodes and the involvement of extralymphatic organs.
  • Stem-cell purging is a technique to attempt removing any remaining tumor or cancer cells in the patient’s autologous harvested stem-cell donation from bone marrow or peripheral blood to minimize the chance that the malignancy will return.  Purging can be done by using protein antigens (i.e., CD34, CD20, CD90, or CD133), monoclonal antibodies (i.e., Rituxan), magnetic attraction, photodynamic techniques, oncolytic viruses (i.e., DNA or RNA), or electroporation (pulsed electric field application).  Purging is part of the stem-cell process in preparation for infusion to the autologous donor-recipient minimizing tumor contamination.
  • Tumor response can be measured by using serial computed tomography scans or by levels of circulating tumor markers.

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.


Stem-cells, using bone marrow or peripheral blood, for autologous or allogeneic reinfusion (infusion) or transplantation following a chemotherapy regimen may be considered medically necessary if the recipient patient has a condition or disorder for which the planned transplant is considered medically necessary and has met the transplant selection criteria; refer to the appropriate, individual transplant policy for description and coverage information.

Umbilical cord blood stem-cell transplant, following a chemotherapy regimen, from related or unrelated donors may be considered medically necessary in patients who have met the transplant selection criteria, and who have an appropriate indication for allogeneic stem-cell support but without an hematopoietic stem-cell donor; refer to the appropriate, individual transplant policy for description and coverage information.

Collection and storage of umbilical cord blood stem-cell from a newborn may be considered medically necessary when an allogeneic stem-cell support is imminent (less than one year) in an identified recipient, such as a sibling, with a diagnosis that is consistent with the possible need for allogeneic stem-cell support.

Prophylactic collection and storage of umbilical cord blood stem-cells from a newborn AND/OR speculative collection and storage of stem-cells from donor-recipient (autologous) or from related or unrelated donor (allogeneic) is considered not medically necessary and therefore not eligible for coverage when proposed for potential and unspecified future use, such as but not limited to:

  • a potential and unspecified future use as an autologous stem-cell support in the original donor; OR
  • a potential and unspecified future use as an allogeneic stem-cell support in a related or unrelated recipient.

Stem-cell purging is an integral part of the autologous stem-cell preparation after harvesting and is not eligible for additional reimbursement beyond the standard stem-cell donation preparation prior to recipient infusion.

Stem-cell purging as part of the allogeneic stem-cell preparation after harvesting is considered not medically necessary and therefore not eligible for coverage as an allogeneic stem-cell donation should be cancer free prior to recipient infusion.

CAREFULLY REVIEW the member’s benefit plan, summary plan description or contract for transplant coverage provisions.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, then the benefit plan, summary plan description or contract will govern.

Policy Guidelines

Charges for the acquisition of CB through a CB bank will be submitted as part of the hospital bill or claim.  Cryopreservation process and storage may be billed separately from other vendors.


Hematopoietic stem-cell transplantation has been used for treatment for approximately 50 years.  The earliest use was for congenital immunodeficiency disorders and end-stage leukemias.  Subsequent research focused on designing the preparatory conditioning regimens, decreasing transplant related morbidity and mortality, improving survival and the understanding of the immune responses of the transplanted graft.  The list of diseases for which hematopoietic stem-cell supports have been used to treat patients has rapidly increased.  More than 30,000 autologous stem-cell support and 15,000 allogeneic stem-cell support procedures are performed every year worldwide. 

Stem-cells have been damaged by disease or treatment of a disease.  Stem-cell support may benefit patients with a variety of both cancerous (malignant) and noncancerous (nonmalignant) diseases by:

  • Replacing dysfunctional bone marrow.  For instance, in aplastic anemia, a noncancerous condition, the bone marrow doesn't make enough new blood cells.  A stem-cell support procedure destroys the dysfunctional marrow, and healthy stem-cells are infused.  If all goes well, the new stem-cells migrate to the marrow and begin working normally.
  • Destroy unhealthy bone marrow that may contain cancer cells.  In the case of cancer, such as leukemia, a stem-cell support procedure may help rid the bone marrow of cancer cells.  When healthy stem-cells are transplanted, normal cell production can resume.  In addition, immune factors in the transplanted cells may help destroy any cancer cells that remain in the bone marrow.

For years, the traditional source for hematopoietic stem-cells for use in autologous stem-cell transplantation and allogeneic stem-cell transplantation was bone marrow.  Use of peripheral blood as a source of stem-cells later replaced bone marrow for nearly all autologous stem-cell tranplantations and most allogeneic stem-cell transplantations.  Utilization of umbilical cord blood has started to surpass the use of peripheral blood. 

The following grid displays the sources of stem-cells and their differences of composition in critical types of cells as well as contamination risk:

Cellular Characteristics

Stem-Cell Source

Bone Marrow

Peripheral Blood

Cord Blood

Stem-cell content




Progenitor-cell content




T-cell content




Risk of tumor cell contamination



Not Applicable

* Studies have show that the cord blood progenitor cells have greater proliferative potential than that of peripheral blood or bone marrow progenitor – cells.

** cord blood progenitor cells may be functionally immature, thus their T-cell content is low.

The following grid shows the sources of stem-cells and their clinical application in pre-matching compatibility, post-outcome rate of engraftment, and risk of graft-versus-host disease.

Cellular Characteristics

Stem-Cell Source

Bone Marrow

Peripheral Blood

Cord Blood

Human leukocyte antigen  matching between donor and recipient

Close matching required

Close matching required

Less restrictive than bone marrow or peripheral blood

Engraftment into recipient marrow

Faster than cord blood, but slower than peripheral blood



Risk of acute graft-versus-host disease

Same as in peripheral blood

Same as in bone marrow


Risk of chronic graft-versus-host disease

Lower than peripheral blood



Reduced-Intensity (Nonmyeloablative) Conditioning:

For Coverage and Rationale regarding tandem stem-cell support treatments following high-dose chemotherapy or reduced-intensity conditioning, refer to the Medical Policy targeting the specific condition and/or disorder.

Umbilical Cord Blood:

Literature concludes that umbilical cord blood stem-cell transplant improves health outcomes for children, adolescents, or adults, when a suitable bone marrow donor is not available. The available data show that hematopoietic recovery, as measured by neutrophil and platelet engraftment is somewhat slower and less frequent among adults than younger patients when placental or umbilical cord blood stem-cells are used.  Nevertheless, neutrophil counts are restored in the majority (74% to 91%) of adult patients.  Acute and chronic graft-versus-host disease and early mortality also are somewhat more frequent among adults than among younger patients given placental or umbilical cord blood stem-cells.  However, for adult patients who require urgent transplantation and are unable to wait for a protracted donor search, the available data show survival one year after umbilical cord blood stem-cell transplant is not worse than survival one year after allogeneic stem-cell support from an unrelated donor.

Donor Leukocyte Infusion:

The role of donor leukocyte infusion is based on the presence of a beneficial graft-versus leukemia effect.  While there have not been additional controlled studies examining the role of donor leukocyte infusion as a salvage therapy in patients with hematologic malignancies followed by post-allogeneic stem-cell support, there have been studies suggesting that a graft-versus-leukemia effect is present in a broader group of hematologic malignancies, including non-Hodgkin’s lymphoma, multiple myeloma, and Hodgkin’s disease. 

In addition, donor leukocyte infusion is a planned component of reduced-intensity conditioning transplantations, and this conditioning regimen with allogeneic stem-cell support would be considered an acceptable option for hematologic malignancies in patients otherwise considered candidates for high-dose chemotherapy with allogeneic stem-cell support.  Taken together, this evidence suggests that donor leukocyte infusion would be an effective salvage therapy in patients with hematologic malignancies after allogeneic stem-cell support. 

There are inadequate data to permit conclusions regarding the use of genetic modification of donor leukocytes as an adjunct to donor leukocyte infusion.

Tandem/Triple Stem-cell Transplant:

No studies in published literature were identified that described “triple transplantation”.  Therefore, the experience with “triple transplantation” so far is too limited to allow any conclusions to be made.


Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

042, 41.00, 41.01, 41.02, 41.03, 41.04, 41.05, 41.91, 99.25, 99.74, 99.79, 155.0, 158.0, 158.8, 159.0 to 159.9, 162.0 to 162.9, 164.0, 164.2 to 164.9, 170.0 to 170.9, 171.0 to 171.9, 172.0 to 172.9, 174.0 to 174.9, 175.0 to 175.9, 179, 180 to 180.9, 182.0 to 182.8, 183.0 to 183.9, 185, 186.0, 186.9, 189.0 to 189.9, 190.5, 191.6, 191.9, 193, 194.0, 199.1, 200.00 to 200.88, 201.00 to 201.98, 202.00 to 202.08, 202.80 to 202.88, 203.00 to 203.01, 204.00, 204.01, 204.10, 204.11, 205.00, 205.01, 205.10, 205.11, 208.90, 208.91, 238.4, 238.7, 238.9, 239.0, 239.5, 239.6, 239.7, 239.8, 239.9, 272.7, 277.2, 277.5, 279.12, 279.2, 281.3, 282.4, 282.60 to 282.69, 284.0 to 284.9, 285.0, 287.3 to 287.5, 288.0, 288.2, 288.3, 288.9, 289.8, 289.9, 330.0, 340, 413.9, 710.0, 710.1, 714.0, 756.52, 758.9

Procedural Codes: 36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86849, 86950, 86985, 88240, 88241, S2140, S2142, S2150
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  22. Placental and Umbilical Cord Blood as a Source of Stem-cells for Hematopoietic Support. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1996 November) 11(17):1-27.
  23. Sugarman, J., et al., Ethical Issues in Umbilical Cord Blood Banking: Consensus Statement. Journal of the American Medical Association (1997 September 17) 278(11):938-43.
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  27. Laughlin, M.J., Barker, J., et al. Hematopoietic engraftment and survival adult recipients of umbilical-cord blood from unrelated donors. New England Journal of Medicine (2001 June 14) 344(24):1815-22.
  28. Barker, J.N., Krepski, T.P., et al. Searching for unrelated donor hematopoietic Stem-cells: Availability and speed of umbilical cord blood versus bone marrow. Biology Blood Marrow Transplant (2002) 8(5):257-60.
  29. Wagner, J.E., Barker, J.N., et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: Influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood (2002 September 1) 100(5):1611-8.
  30. Transplanting Adult Patients with Hematopoietic Stem-cells from Placental and Umbilical Cord Blood.  Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2002 April) 16(17):1-25.
  31. Placental and Umbilical Cord Blood as a Source of Stem-cells.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2003 January) Surgery 7.01.50.
  32. Placental and Umbilical Cord Blood as a Source of Stem-Cells.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2003 April) Therapy 8.01.17.
  33. Barker, J.N., Weisdorf, D.J., et al. Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood. (2003 September 1) 102(5):1915-9.
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  35. Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem-Cell Transplant.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2005 September) Medicine 2.03.03.
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  37. Nonmyeloablative Allogeneic Transplants of Hematopoietic Stem-Cells for Treatment of Malignancy.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 May) Therapy 8.01.38.
  38. Single or Tandem Courses of Hematopoietic Stem-Cell Transplantation for Multiple Myeloma.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 July) Therapy 8.01.17.
September 2013  New 2013 BCBSMT medical policy.
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Stem-Cell Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information)