DESCRIPTION
High-dose (myeloablative) chemotherapy involves the administration of cytotoxic agents at doses several times greater than the standard therapeutic dose. In some cases, whole body or localized radiotherapy is also given. The rationale for high-dose chemotherapy (HDC) is the belief that many cytotoxic agents act according to a steep dose-response curve. Thus, small increases in the dosage will result in relatively large increases in tumor cell kill. However, increasing the dose also increases the incidence and severity of adverse effects (e.g., opportunistic infections, hemorrhage, and organ failure). Since the probability of life-threatening toxicity is so high, individuals are usually hospitalized for an extended period in order to undergo HDC. They also require hospitalization beyond the period of drug administration. HDC typically requires treatment with one or more support measures specifically developed to combat adverse effects.
The standard follow-up to treatment with HDC includes the transplantation of bone marrow, peripheral stem cells or cord blood. This is a technique involving the collection of donor marrow or stem cells and preparation for infusion to rescue hematopoiesis in a recipient previously treated with a cytoreductive regimen. Treatment for certain cancers has also included infusion of allogeneic bone marrow or stem cells. However, unlike treatment of primary marrow diseases in which allogeneic bone marrow infusion is the treatment, bone marrow / stem cell infusion in the treatment of cancers is used solely to support high-dose chemotherapy.
Hematopoietic stem cells are those cells found within the bone marrow. These cells facilitate continuous blood cell production. In certain malignant or nonmalignant disease processes, these necessary building cells are damaged or destroyed. Infusion of transplanted hematopoietic stem cells is done to restore normal hematopoiesis or immune function.
There are several methods used to obtain stem cells for transplant. Autologous bone marrow transplantation refers to harvesting of bone marrow, usually from the iliac crest, or from the peripheral blood using a pheresis procedure. The harvested cells are then re-administered to the same individual. Allogeneic bone marrow transplantation involves harvesting of hematopoietic stem cells from a healthy donor (related or unrelated) for infusion into an individual whose bone marrow is compromised. This procedure can be used as a treatment for certain congenital, hereditary or acquired disease defects / processes or as an intentional or unintentional consequence of the treatment of medical conditions. There are three potential sources for obtaining allogeneic stem cells: bone marrow, peripheral blood and placental or umbilical cord blood. The use of allogeneic peripheral stem cells and bone marrow is viewed as essentially equivalent for malignant disease and myeloplastic syndromes. Direct bone marrow may be the only appropriate treatment for some nonmalignant diseases.
Immunologic compatibility between donor and individual is a critical factor for achieving a good outcome with allogeneic bone marrow transplantation due to the risks of graft rejection and graft-versus-host disease. Serologic typing of tissue of human leukocyte antigens (HLA) and mixed leukocyte cultures are used to determine compatibility. HLA antigens refer to the tissue type expressed at the HLA A, B and DR loci on each leg of chromosome 6. Depending upon the age of the recipient and the specific disease being treated, an acceptable donor may be required to have a perfect match of all six loci, or may be allowed to have one, two or rarely three mismatches. In all cases, donor and recipient tissue must be non-reactive in mixed leukocyte culture or molecular DNA typing.
POLICY
High dose chemotherapy followed by bone marrow / stem cell transplantation for the treatment of certain disease processes is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
High dose chemotherapy and/or other marrow ablative treatments followed by hematopoietic stem cell transplantation are considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
High dose chemotherapy followed by transplantation with umbilical cord or placental blood stem cells from unrelated or related donors with an appropriate indication for allogeneic stem cell transplant, but without a hematopoietic stem cell donor is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Collection and storage of cord blood from a neonate when an allogeneic transplant is imminent in an identified recipient with a diagnosis that is consistent with the possible need for allogeneic transplant is considered medically necessary.
Repeated labs and procedures to address changes in condition and for continued transplant listing are considered medically necessary.
High dose chemotherapy followed by stem cell / bone marrow transplantation for the treatment of all stages of breast cancer is considered investigational. This applies to all contracts.
Prophylactic collection and storage of cord blood from a neonate when proposed for some unspecified future use as an autologous stem-cell transplant in the original donor or for some unspecified future use as an allogeneic stem-cell transplant in a related or unrelated donor is considered not medically necessary.
Multiple labs and work-up procedures for the sole purpose of repeat evaluation at multiple transplant centers are considered not medically necessary.
Any chemotherapeutic agent utilized for this procedure
must have FDA approval specific to the indication or for some off-label
indication, otherwise it will be considered
investigational.
Note: off-label indication must be supported by published, clinical
data that supports its efficacy; and regimens utilized must be standardized
by the institution, and the protocol approved by the institution's Internal
Review Board (IRB).
See also:
MEDICAL APPROPRIATENESS
BCBST approval is required prior to transplantation
High dose chemotherapy is considered medically appropriate if ALL of the following are met:
ANY ONE of the following:
Followed by bone marrow / stem cell transplantation for the treatment of certain disease processes
And/or other marrow ablative treatments followed by hematopoietic stem cell transplantation
Followed by transplantation with umbilical cord or placental blood stem cells from unrelated or related donors with an appropriate indication for allogeneic stem cell transplant, but without a hematopoietic stem cell donor
ALL of the following:
The Clinical information submitted for determination of medical appropriateness must be dated within the last seven months
ANY ONE of the following to determine the criteria for specific diseases:
Refer to Milliman Care Guidelines - Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplants
Refer to Milliman Care Guidelines - Autologous Bone Marrow and Peripheral Blood Stem Cell Transplants
The individual has a disease or condition where hematopoietic stem cell transplant will provide an improved outcome over standard therapy
The individual must have a good Daily Activity performance status based on the Karnofsky Performance Scale or equivalent measurement scale
Have a FULL psychosocial evaluation including evaluation of support systems, etc.
Have documentation of their current status for the following: Hepatitis, Cytomegalovirus (CMV), Herpes Simplex Virus (HSV) profiling
Have Pulmonary function tests: FVC, FEV1, DLco with results that must all be greater than or equal to 60% of the predicted values. (Young children may be unable to comply and may be evaluated using age appropriate testing)
Have a left ventricular (LV) ejection fraction must be greater than or equal to 50% of the institutional lower limit of normal
Have an estimated creatinine clearance that is greater than or equal to 60 ml/min
Have a serum bilirubin and SGOT less than or equal to 1.5 times the institutional upper limit of normal
Have a willingness and ability by the individual or legal guardian to give signed consent and to comply with regular follow-up requirements
ABSENCE of ALL of the following:
Serious, uncontrolled psychiatric illness that would hinder compliance with any stage of the transplant process
Neurologic illness independent of the disease process being treated
Active infection (must be afebrile for greater than 48 hours and off antibiotics)
Elevated liver function tests if has a Positive hepatitis C RNA
Active drug or alcohol abuse (Individual will provide documentation of at least a six month abstinence from drug or alcohol use and ongoing participation in a formal treatment program.)
ADDITIONAL INFORMATION
There is a lack of evidence to show the efficacy of high dose chemotherapy followed by hematopoietic transplantation for the treatment of breast cancer as compared to other standard treatments.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2008). High-dose chemotherapy with hematopoietic stem-cell support for breast cancer (8.01.27). Retrieved May 20, 2009 from BlueWeb.
BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2003). Placental and umbilical cord blood as a source of stem cells (7.01.50). Retrieved May 20, 2009 from BlueWeb.
BlueCross BlueShield of Tennessee network physicians. August 2005.
Complete Guide to Medicare Coverage Issues [Computer software]. (2009, April). Stem cell transplantation (NCD 110.8.1, p. 2-53, 2-55). The Ingenix Complete Guide to Medicare Coverage Issues.
Farquhar C, Marjoribanks J, Basser R, Hetrick S, Lethaby A. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD003142. DOI: 10.1002/14651858.CD003142.pub2.
Farquhar, C., Marjoribanks, J., Basser, R., Lethaby, A. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer. The Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD003139. DOI: 10.1002/14651858.CD003139.pub2.
Hoodin, F., & Kalbfleisch, K. R. (2003). Factor analysis and validity of the transplant evaluation rating scale in a large bone marrow transplant sample. Journal of Psychosomatic Research, 54 (5), 465-473. Abstract retrieved April 24, 2007 from PubMed database.
Keller, C., & Karanes, C. (2006). Evaluating adult patients prior to hematopoietic cell transplant. National Marrow Donor Program. Retrived May 20, 2009 from http://www.marrow.org/PHYSICIAN/Tx_Indications_Timing_Referral/Evaluating_Adult_Patients_Prio/index.html.
Laughlin, M. J., Barker, J., Bambach, B., Koc, O. N., Rizzieri, D. A., Wagner, J. E., et al. (2001). Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. New England Journal of Medicine, 344 (24), 1815-1822.
National Cancer Institute. (2008, October). Bone marrow transplantation and peripheral blood stem cell transplantation: Questions and answers. Retrieved May 20, 2009 from http://cis.nci.nih.gov/fact/7_41.htm.
National Institutes of Health. (2009, April). Hematopoietic stem cells. Retrieved May 20, 2009 from http://stemcells.nih.gov/info/scireport/chapter5.
ORIGINAL EFFECTIVE DATE: 6/1986
MOST RECENT REVIEW DATE: 7/9/2009
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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