I'm a member

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HSCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HSCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the Class I and Class II loci on each arm of chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci (with the exception of umbilical cord blood).

Conventional Preparative Conditioning for HSCT
The conventional (“classical”) practice of allogeneic HSCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to destroy endogenous hematopoietic capability in the recipient. The beneficial treatment effect in this procedure is due to a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy (GVM) effect mediated by non-self immunologic effector cells that develop after engraftment of allogeneic stem cells within the patient’s bone marrow space. While the slower GVM effect is considered to be the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to patients who are sufficiently fit medically to tolerate substantial adverse effects that include pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allogeneic HSCT, immunosuppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections.

The success of autologous HSCT is predicated on the ability of cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient prior to undergoing bone marrow ablation. As a consequence, autologous HSCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HSCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not GVHD.

Reduced-Intensity Conditioning for Allogeneic HSCT
Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less-intense regimens of cytotoxic drugs or radiation than are used in traditional full-dose myeloablative conditioning treatments. The goal of RIC is to reduce disease burden, but also to minimize as much as possible associated treatment-related morbidity and non-relapse mortality (NRM) in the period during which the beneficial GVM effect of allogeneic transplantation develops. Although the definition of RIC remains arbitrary, with numerous versions employed, all seek to balance the competing effects of NRM and relapse due to residual disease. RIC regimens can be viewed as a continuum in effects, from nearly totally myeloablative, to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allogeneic HSCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism, which may be supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For the purposes of this Policy, the term “reduced-intensity conditioning” will refer to all conditioning regimens intended to be non-myeloablative, as opposed to fully myeloablative (traditional) regimens.

Multiple Myeloma
Multiple myeloma is a systemic malignancy of plasma cells that represents approximately 10% of all hematologic cancers. It is treatable but rarely curable, with estimated new cases and deaths in 2008 in the United States 19,920 and 10,690, respectively. At the time of diagnosis most patients have generalized disease, and, the selection of treatment is influenced by patient age, general health, prior therapy, and the presence of complications of the disease. The disease is staged by estimating tumor mass, based on various clinical parameters like hemoglobin, serum calcium, number of lytic bone lesions, and the presence or absence of renal failure.  Multiple myeloma usually evolves from an asymptomatic premalignant stage (termed “monoclonal gammopathy of undetermined significance” or MGUS). Treatment is usually reserved for patients with symptomatic disease (usually progressive myeloma), whereas asymptomatic patients are observed, as there is little evidence that early treatment of asymptomatic multiple myeloma prolongs survival when compared to therapy delivered at the time of symptoms or end-organ damage.  In some patients, an intermediate asymptomatic but more advanced premalignant stage is recognized, and referred to as smoldering multiple myeloma. The overall risk of disease progression from smoldering to symptomatic multiple myeloma is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% for the next 10 years.

A single or second (salvage) autologous hematopoietic stem-cell transplantation may be considered medically necessary to treat multiple myeloma.

Tandem autologous-autologous hematopoietic stem-cell transplantation may be considered medically necessary to treat multiple myeloma in patients who fail to achieve at least a near-complete or very good partial response after the first transplant in the tandem sequence. (For definitions of near-complete response and very good partial response, see Policy Guidelines).

Tandem transplantation with an initial round of autologous hematopoietic stem-cell transplantation followed by a non-marrow-ablative conditioning regimen and allogeneic hematopoietic stem-cell transplantation (i.e., reduced-intensity conditioning transplant) may be considered medically necessary to treat newly diagnosed multiple myeloma patients.

Allogeneic hematopoietic stem-cell transplantation, myeloablative or nonmyeloablative, as upfront therapy of newly diagnosed multiple myeloma or as salvage therapy, is considered investigational. 

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

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

2/11/2002: Investigational definition added

5/8/2002: Type of Service and Place of Service deleted

3/18/2003: HCPCS G0266, G0267 added covered codes, CPT code 38242 added non-covered codes

1/27/2004: Policy reviewed, policy title "Tandem High Dose Chemoradiotherapy with Autologous Stem Cell Support for Multiple Myeloma" renamed "Single or Tandem Courses of High-Dose Chemotherapy plus Hematopoietic Stem-Cell Support to Treat Multiple Myeloma", Description, Policy, and Policy Guidelines sections aligned with BCBSA policy # 8.01.17, See "High-Dose Chemotherapy with Hematopoietic Stem-Cell Support for Malignancies" medical policy for dates of service prior to 1-27-2004

3/25/2004:  Reviewed by MPAC, "Tandem high-dose chemotherapy with autologous stem-cell support is considered investigational to treat multiple myeloma." changed to "Tandem high-dose chemoradiotherapy with autologous stem-cell support may be considered medically necessary to treat newly diagnosed or responsive multiple myeloma.", "An initial course of high-dose chemotherapy with autologous stem-cell support followed by non marrow-ablative chemotherapy and allogeneic stem-cell support (i.e. "mini transplant") is considered investigational to treat multiple myeloma" added

7/19/2004: Code Reference section updated

11/18/2004: Reviewed by MPAC, “An intial course of high-dose chemotherapy with autologous stem-cell support followed by non marrow-ablative chemotherapy and allogeneic stem-cell support (i.e. “mini transplant”) is considered investigational to treat multiple myeloma.” changed to medically necessary

7/11/2005: Code Reference section updated, CPT code 38204, 86812, 86813, 86816, 86817, 86821, 86822 moved from covered codes to non-covered codes, CPT code 38230 added covered codes, HCPCS G0355, G0356, G0357, G0358, G0359, G0360, G0361, G0362, G0363, G0364 added covered codes, HCPCS J9000-J9999 statement added to HCPCS and all separately listed codes deleted

10/21/2005: Code reference section updated, ICD9 code 41.01, 41.09 added to the covered table, 41.02, 41.03 added to the non-covered table, ICD9 procedure code 41.04, 99.79 description revised

03/17/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy.

12/20/2007: Coding updated per 2008 CPT/HCPCS revisions

9/11/2008: Annual ICD-9 updates applied

04/27/2010: Policy title changed from “Single or Tandem Courses of High Dose Chemotherapy plus Hematopoietic Stem Cell Support to Treat Multiple Myeloma” to “Hematopoietic Stem-Cell Transplantation for Multiple Myeloma.” Changed “Stem-Cell Support” to “Stem-Cell Transplantation” throughout policy. Policy description updated regarding prevalence of disease and treatment approaches. Added the prior authorization requirement to the policy statement. Policy statement updated regarding situations when autologous SCT may be indicated for patients with primary progressive myeloma, and statement regarding allogeneic HSCT being investigational as initial or salvage therapy was reworded. FEP and State and School Employees verbiage added to the Policy Exceptions section. Added new CPT codes 86825 and 86826 to the non-covered table.  Deleted CPT codes 96400, 96414, 96520, 96530, and 96545 from the code section as these codes were deleted on 12/31/2005. Deleted HCPCS G0355, G0356, G0357, G0358, G0359, G0360, G0361, and G0362 from the code section as these codes were deleted on 12/31/2005. Deleted HCPCS G0265, G0266, and G0267 from the code section as these codes were deleted on 12/31/2007. Updated policy source section.

06/21/2011: Added "in the tandem sequence" to the medically necessary tandem autologous-autologous policy statement.

05/09/2012: Policy reviewed; no changes.

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

Covered Codes

Non-Covered Codes

Top