MEDICAL POLICY

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REFERENCES
CODING
APPENDIX
HISTORY

Hematopoietic Stem-Cell Transplantation for Breast Cancer

Number 8.01.27

Effective Date March 8, 2013

Revision Date(s) 03/8/13; 03/13/12; 03/08/11; 02/10/09; 04/08/08; 03/13/07; 04/11/06

Replaces 8.01.512

Policy

Single or tandem autologous hematopoietic stem-cell transplantation is considered not medically necessary to treat any stage of breast cancer.

Allogeneic stem-cell transplantation is investigational to treat any stage of breast cancer.

Related Policies

7.01.50

Placental and Umbilical Cord Blood as a Source of Stem Cells

7.01.526

Cryosurgical Ablation of Miscellaneous Solid Tumors Other Than Liver, Prostate, or Dermatologic Tumors

8.01.17

Hematopoietic Stem-Cell Transplantation for Plasma Cell Dyscrasias, Including Multiple Myeloma and POEMS Syndrome

8.01.20

Hematopoietic Stem-Cell Transplantation for Non-Hodgkin Lymphomas

8.01.21

Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms

8.01.22

Allogeneic Hematopoietic Stem-Cell Transplantation for Genetic Diseases and Acquired Anemias

8.01.23

Hematopoietic Stem-Cell Transplantation for Epithelial Ovarian Cancer

8.01.24

Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults

8.01.25

Hematopoietic Stem-Cell Transplantation for Autoimmune Diseases

8.01.26

Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia

8.01.28

Hematopoietic Stem-Cell Transplantation for CNS Embryonal Tumors and Ependymoma

8.01.29

Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma

8.01.30

Hematopoietic Stem-Cell Transplantation for Treatment of Chronic Myelogenous Leukemia

8.01.35

Hematopoietic Stem-Cell Transplantation in the Treatment of Germ Cell Tumors

8.01.42

Hematopoietic Stem-Cell Transplantation for Primary Amyloidosis

8.01.511

Hematopoietic Stem-Cell Transplantation for Solid Tumors of Childhood

8.01.514

Hematopoietic Stem-Cell Support for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

8.01.520

Hematopoietic Stem-Cell Transplantation for Acute Lymphoblastic Leukemia

12.04.36

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

Policy Guidelines

In 2003, CPT centralized codes describing allogeneic and autologous hematopoietic stem-cell transplant services to the hematology section (CPT 38204-38242). Not all codes are applicable to each high-dose chemotherapy/stem-cell support procedure. For explants, it should be determined if cryopreservation is performed. A range of codes describes services associated with cryopreservation, storage, and thawing of cells (38208-38215).

38208 and 38209 describe thawing and washing of cryopreserved cells

38210 – 38214 describe certain cell types being depleted

38215 describes plasma cell concentration

Description

The use of high-dose chemotherapy (HDC) and hematopoietic stem cell transplantation (HSCT), instead of standard dose chemotherapy, has been used in an attempt to prolong survival in women with high-risk nonmetastatic and metastatic breast cancer.

Background

Hematopoietic Stem-Cell Transplantation

Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naive” and thus are associated with a lower incidence of rejection or graft versus host disease. Cord blood is discussed in greater detail in a separate medical policy. (See Related Policies)

Immunologic compatibility between infused 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 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 success of autologous HSCT is predicated on the ability of cytotoxic chemotherapy with our 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.

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 conditions. 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 immune suppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections.

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 meyloablative 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.

HSCT in Solid Tumors in Adults

HSCT is an established treatment for certain hematologic malignancies; however, its use in solid tumors in adults continues to be largely experimental. Initial enthusiasm for the use of autologous transplant with the use of high-dose chemotherapy and stem cells for solid tumors has waned with the realization that dose intensification often fails to improve survival, even in tumors with a linear-dose response to chemotherapy. With the advent of reduced-intensity allogeneic transplant, interest has shifted to exploring the generation of alloreactivity to metastatic solid tumors via a graft-versus-tumor effect of donor-derived T cells.

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application

For indications considered investigational, the following considerations may supersede this policy:

  • State mandates requiring coverage for autologous bone marrow transplantation offered as part of clinical trials of autologous bone marrow transplantation approved by the National Institutes of Health (NIH).
  • Some contracts or certificates of coverage (e.g., FEP) may include specific conditions in which autologous bone marrow transplantation would be considered eligible for coverage.

Rationale

History of Hematopoietic Stem-Cell Transplant for Breast Cancer

In the late 1980s/early 1990s, initial results of Phase II trials for breast cancer and autologous hematopoietic stem-cell transplant (HSCT) were promising, showing high response rates in patients with metastatic disease who underwent high-dose consolidation, with a subset of up to 30% remaining disease-free for prolonged periods. (1) In the early 1990s, larger prospective comparisons of conventional-dose chemotherapy to high-dose therapy with stem-cell transplant (SCT) were initiated but accrued slowly, with up to a decade from initiation to the reporting of results. (1). The first results from randomized trials at a single institution in early stage and metastatic disease showed survival benefits, but were ultimately shown to be based on fraudulent data. (1) In the interim, however, the treatment became almost standard of care, while many patients received high-dose therapy off protocol, further reducing accrual to ongoing randomized trials. (1) The results of the randomized trials were presented beginning in 1999, and showed little survival benefit; subsequently, the number of HSCT procedures performed for breast cancer has fallen from thousands every year to only a few. (1)

Autologous HSCT

The PBT-1 trial randomized patients with a complete response (CR) or partial response (PR) to induction therapy for previously untreated metastatic breast cancer to autologous HSCT (n=101) or to conventional-dose maintenance chemotherapy (n=83) for up to 2 years. (2) Of 553 patients enrolled and given initial induction therapy, only 310 achieved a PR (n=252) or CR (n=58), and only 199 were randomized. Of 72 partial responders assigned to the HSCT arm after initial induction therapy, only 5 (7%) were converted to complete responses. Median survival (24 vs. 26 months) and overall survival at 3 years (32% vs. 38%) did not differ between arms. There also were no statistically significant differences between arms in time to progression (TTP) or progression-free survival (PFS) at 3 years. While treatment duration was substantially shorter for those randomly assigned to HSCT, acute morbidity was markedly more severe than after conventional-dose maintenance.

During 2003 and 2004, 4 trials reported final outcomes analyses from randomized comparisons of autologous HSCT versus conventional dose chemotherapy for adjuvant therapy of high-risk non-metastatic breast cancer. (3-6) Two of the studies involved women with at least 4 positive auxiliary lymph nodes, and the other two at least 10 positive lymph nodes. The four studies pooled included 2,337 patients.

Evidence from these trials did not support the conclusion that autologous HSCT improved outcomes when compared with conventional-dose adjuvant therapy, as no overall survival (OS) difference was seen in any of the studies. An editorial that accompanied one of the trials briefly reviewed and commented on factors contributing to the diffusion of autologous HSCT into routine practice of the treatment of certain breast cancer patients, without adequate testing in randomized clinical trials (RCTs). (7)

A Cochrane systematic review and meta-analysis published in July 2005 pooled data from 6 RCTs on metastatic breast cancer reported through November 2004 (N=438 randomized to autologous HSCT, 412 to conventional dose therapy). (8) The relative risk (RR) for treatment-related mortality was significantly higher in the arm randomly assigned to HSCT (15 vs. 2 deaths; RR=4.07; 95% CI: 1.39–11.88). Treatment-related morbidity also was more severe among those randomly assigned to HSCT. Overall survival did not differ significantly between groups at 1, 3, or 5 years after treatment. Statistically significant differences in event-free survival (EFS) at 1 year (RR=1.76; 95% CI: 1.40–2.21) and 5 years (RR=2.84; 95% CI: 1.07–7.50) favored the HSCT arms. Only 1 of the 6 included trials had followed up all patients for at least 5 years. Reviewers recommended further follow-up for patients randomized in the other 5 trials. They also concluded that, in the interim, patients with metastatic breast cancer should not receive HSCT outside of a clinical trial, since available data showed greater treatment-related mortality and toxicity without improved overall survival.

A second Cochrane systematic review and meta-analysis, also published in July 2005, included data from 13 RCTs on patients with high-risk (poor prognosis) early breast cancer (N=2,535 randomized to HSCT, 2,529 to conventional dose therapy). (9) Treatment-related mortality was significantly greater among those randomly assigned to high-dose chemotherapy/autologous SCT (HDC/AuSCT) (65 vs. 4 deaths; RR=8.58; 95% CI: 4.13, 17.80). Treatment-related morbidity also was more common and more severe in the high-dose arms. There were no significant differences between arms in overall survival rates at any time after treatment. Event-free survival was significantly greater in the HSCT group at 3 years (RR=1.12; 95% CI: 1.06, 1.19) and 4 years (RR=1.30; 95% CI: 1.16, 1.45, respectively) after treatment. However, the 2 groups did not differ significantly with respect to event-free survival at 5 and 6 years after treatment. Quality-of-life scores were significantly worse in the HSCT arms than in controls soon after treatment, but differences were no longer statistically significant by 1 year. Reviewers concluded available data were insufficient to support routine use of HSCT for patients with poor-prognosis early breast cancer.

Hanrahan and colleagues, with a median follow-up of 12 years, demonstrated no recurrence-free or overall survival advantage for patients with high-risk primary breast cancer treated with autologous HSCT after standard dose chemotherapy (n=39) versus standard chemotherapy alone (n=39). (10) Coombes and colleagues reported on autologous HSCT as adjuvant therapy for primary breast cancer in women free of metastatic disease, with a median follow-up of 68 months. (11) A total of 281 patients were randomly assigned to receive standard chemotherapy or high-dose chemotherapy (HDC) with HSCT. They found no significant difference in relapse-free survival or overall survival (overall survival hazard ratio 1.18, 95% CI: 0.80-1.75, p=0.40).

A systematic review and meta-analysis published in 2007 included RCTs comparing autologous HSCT to standard dose chemotherapy in women with early, poor prognosis breast cancer, which included 13 trials to September 2006 with 5,064 patients. (12) Major conclusions were that, at 5 years, event-free survival approached statistical significance for the high-dose group, but no overall survival differences were seen. There were more transplant-related deaths in the high dose group. The end conclusion was that there was insufficient evidence to support routine use of autologous HSCT for treating early, poor prognosis breast cancer.

Crump and colleagues reported the results of a randomized trial of women who had not previously been treated with chemotherapy, and had metastatic breast cancer or locoregional recurrence after mastectomy. (13) After initial response to induction therapy, 112 women were allocated to standard chemotherapy and 112 to autologous HSCT. After a median follow-up of 48 months, 79 deaths were observed in the high-dose group and 77 in the standard chemotherapy group. No difference in overall survival was observed between the two groups after a median follow-up of 48 months, with median overall survival being 24 months in the HSCT group (95% CI: 21-35 months) and 28 months for the standard chemotherapy group (95% CI: 22–33 months; HR: 0.9; 95% CI: 0.6–1.2; p=0.43).

Biron and colleagues reported the results of a Phase III, open, multicenter, prospective trial of women with metastatic breast cancer (and/or local or regional relapse beyond curative treatment by surgery or radiation). (14) After a complete remission (CR) or at least 50% partial response to induction therapy, 88 women were randomly assigned to HSCT, and 91 to no further treatment. No overall survival difference was seen between the 2 groups, with 3-year survival 33.6% in the high-dose group and 27.3% in the observation group (p=0.8).

Zander and colleagues reported survival data after 6 years of follow-up (15) on a trial that had previously been reported after 3.8 years of follow-up. (8) Women with surgically resected breast cancer and axillary lymph node dissection with 10 or more positive axillary lymph nodes but no evidence of metastatic disease were randomly assigned to standard chemotherapy (n=152) or HSCT (n=150). No difference in overall survival was observed, with the estimated 5-year overall survival rate in the standard arm was 62% (95% CI: 54-70%) and 64% (95% CI: 56-72%) in the high-dose/transplant group.

Nieto and Shpall performed a meta-analysis of all randomized trials published or updated since 2006 focusing on those that compared high-dose chemotherapy with standard-dose chemotherapy for high-risk primary breast cancer. (16) The meta-analysis of 15 randomized trials involving patients with high-risk primary breast cancer or metastatic disease (n=6,102) detected an absolute 13% event-free survival benefit in favor of high-dose chemotherapy and autologous HSCT (p=0.0001) at a median follow-up of 6 years. The absolute differences in disease-specific and overall survival did not reach statistical significance (7% and 5%, respectively). Subset analyses suggested that high-dose chemotherapy could be particularly effective in patients with triple negative tumors (hormone receptor and HER2-negative). The authors concluded that high-dose chemotherapy remains a valid research strategy in certain subpopulations with high-risk primary breast cancer, for example those with triple negative tumors.

Berry and colleagues performed a meta-analysis with individual patient data from 15 randomized trials comparing autologous HSCT with HDC (n=3,118) to standard chemotherapy (n= 3,092) for patients with high-risk primary breast cancer. (17) A survival analysis was adjusted for trial, age, number of positive lymph nodes, and hormone receptor status. HSCT was associated with a non-significant 6% reduction in risk of death (HR: 0.94; 95% CI: 0.87-1.02; p=0.13) and a significant reduction in the risk of recurrence (HR: 0.87; 95% CI: 0.81-0.93; p<0.001). Toxic death was higher in the HSCT group with 72 (6%) of 1,207 deaths in these trial arms compared to 17 (1.4%) of 1,261 deaths in the standard therapy arms. In a subgroup analysis, the authors investigated whether age, number of positive lymph nodes, tumor size, histology, hormone receptor status, or HER2 status impacted survival when comparing HSCT versus standard treatment. The authors found that HER2-negative patients receiving HSCT had a 21% reduction in the risk of death and HER2-negative and hormone receptor negative patients receiving HSCT had a 33% reduction in the risk of death. In their discussion, the authors state that this relationship could be spurious due to the amount of missing data on HER2 status and suggest that HSCT is unlikely to show much benefit in these subgroups of patients.

A meta-analysis by Wang et al. included aggregate data from 14 trials (n=5,747) published since March 2010. (18) Clinical trials of patients receiving HSCT as a first-line treatment for primary breast cancer were eligible for inclusion. A higher treatment-related mortality was found among the patients who received HSCT compared to standard chemotherapy (RR=3.42, 95% CI: 1.32-8.86). Overall survival did not differ significantly between groups with a hazard ratio of 0.91 (95% CI: 0.82-1.00) for the HSCT compared to standard treatment. Risk of secondary, non-breast cancer was higher in the HSCT group (RR=1.28, 95% CI: 0.82-1.98). Disease free survival was better in the HSCT group compared to chemotherapy alone (RR=0.89, 95% CI: 0.79-0.99). Patients receiving HSCT had a greater risk of dying during remission than patients treated with nonmyeloablative chemotherapy due to the toxicity of the regimen. This increase in treatment-related mortality may help explain why there was no observed overall survival benefit for patients receiving HSCT when disease-free survival was observed to be superior to standard chemotherapy.

Tandem Autologous Transplantation

Kroger and colleagues reported on the comparison of single versus tandem autologous HSCT in 187 patients with chemotherapy-sensitive metastatic breast cancer. (19) Only 52 of 85 patients completed the second high-dose chemotherapy (HDC) cycle in the tandem arm, mostly due to withdrawal of consent (most common reason), adverse effects, progressive disease or death. The rate of complete remission was 33% in the single-dose arm, versus 37% in the tandem arm (p=.48). Although there was a trend toward improved progression-free survival after tandem HSCT, median overall survival tended to be greater after single versus tandem HDC (29 versus 23.5 months, respectively; p=0.4). The authors concluded that tandem HSCT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HSCT.

Schmid and colleagues published results of 93 patients without prior chemotherapy for metastatic breast cancer who were randomly assigned to standard-dose chemotherapy or double high-dose chemotherapy with autologous HSCT. (18) The primary study objective was to compare complete response (CR) rates. Objective response rates for the patients in the high dose group were 66.7% versus 64.4% for the standard group (p=0.82). There were no significant differences between the two treatments in median time to disease progression, duration of response, or overall survival (overall survival 26.9 months versus 23.4 months for the double high-dose arm versus the standard arm, respectively [p=0.60]).

Allogeneic HSCT

To date, allogeneic HSCT for breast cancer has mostly been used in patients who have failed multiple lines of conventional chemotherapy. (21)

Ueno and colleagues reported the results of allogeneic HSCT in 66 women with poor-risk metastatic breast cancer from 15 centers who received transplantation between 1992 and 2000. (22) Thirty-nine (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. A total of 17 (26%) patients had received a prior autologous HSCT. Median follow-up time for survivors was 40 months (range 3-64 months). Treatment-related mortality was lower in the RIC group (7% versus 29% at 100 days; p=0.03). Progression-free survival at 1 year was 23% in the myeloablative group versus 8% in the RIC group (p=0.09). Overall survival rates after myeloablative conditioning versus the RIC group were 51% (95% CI: 36–67%) versus 26% (95% CI: 11–45%) [p=0.04] at 1 year, 25% (95% CI: 13–40%) versus 15% (95% CI: 3–34%; p=0.33) at 2 years, and 19% (95% CI: 8–33%) versus 7% (95% CI: <1–25%; p=0.21) at 3 years, respectively.

Fleskens and colleagues reported the results of a Phase II study of 15 patients with metastatic breast cancer treated with HLA-matched reduced-intensity allogeneic HSCT. (23) Median patient age was 49.5 years (range: 39.7-60.8 years) and all patients had been extensively pretreated and had undergone at least one palliative chemotherapy regimen for metastatic disease. Treatment-related mortality was 2/15 (13%). Once-year progression-free survival was 20% and 1- and 2-year OS was 40% and 20%, respectively. The authors noted no objective tumor responses, but concluded that the relatively long PFS suggests a graft-versus-tumor effect.

Clinical Trials

The National Cancer Institute clinical trials database (as of December 2012) showed no ongoing Phase III trials for HSCT for breast cancer.

Summary

Randomized trials of autologous hematopoietic stem cell transplantation (HSCT) versus standard dose chemotherapy for patients with high-risk non-metastatic or metastatic breast cancer have not shown a survival advantage with HSCT, with greater treatment-related mortality and toxicity. Therefore, autologous HSCT is considered not medically necessary for this indication.

Nonrandomized studies using reduced-intensity or myeloablative allogeneic HSCT for metastatic breast cancer have suggested a possible graft-versus-tumor effect, but remains investigational for this indication.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) guidelines do not address the use of HSCT in the treatment of breast cancer. (24)

Medicare National Coverage

There is no national coverage determination.

References

  1. Vogl DT, Stadtmauer EA. Editorial: high-dose chemotherapy and autologous hematopoietic stem cell transplantation for metastatic breast cancer: a therapy whoe time has passed. Bone Marrow Transplant 2006; 37(11):985-7.
  2. Stadtmauer EA, O'Neill A, Goldstein LJ et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med 2000; 342(15):1069-76.
  3. Leonard RC, Lind M, Twelves C, et al. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst 2004; 96(14):1076-83.
  4. Rodenhuis S, Bontenbal M, Beex LV, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med 2003; 349(1):7-16.
  5. Tallman MS, Gray R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med 2003; 349(1):17-26.
  6. Zander AR, Kroger N, Schmoor C et al. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol 2004; 22(12):2273-83.
  7. Hortobagyi GN. What is the role of high-dose chemotherapy in the era of targeted therapies? J Clin Oncol 2004; 22(12):2263-6.
  8. Farquhar C, Marjoribanks J, Basser R et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Syst Rev 2005; (3):CD003142.
  9. Farquhar C, Marjoribanks J, Basser R et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer. Cochrane Database Syst Rev 2005; (3):CD003139.
  10. Hanrahan EO, Broglio K, Frye D et al. Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma: follow-up at 12 years. Cancer 2006; 106(11):2327-36.
  11. Coombes RC, Howell A, Emson M et al. High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial. Ann Oncol 2005; 16(5):726-34.
  12. Farquhar CM, Marjoribanks J, Lethaby A, et al. High dose chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis. Cancer Treat Rev 2007; 33(4):325-37.
  13. Crump M, Gluck S, Tu D et al. Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16. J Clin Oncol 2008; 26(1):37-43.
  14. Biron P, Durand M, Roche H et al. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant 2008; 41(6):555-62.
  15. Zander AR, Schmoor C, Kroger N, et al. Randomized trial of high-dose adjuvant chemotherapy with autologous hematopoietic stem-cell support versus standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: overall survival after 6 years of follow-up. Ann Oncol 2008; 19(6):1082-9.
  16. Nieto Y, Shpall EJ. High-dose chemotherapy for high-risk primary and metastatic breast cancer: is another look warranted? Curr Opin Oncol 2009; 21(2):150-7.
  17. Berry DA, Ueno NT, Johnson MM et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 2011; 29(24):3214-23.
  18. Wang J, Zhang Q, Zhou R et al. High-dose chemotherapy followed by autologous stem cell transplantation as a first-line therapy for high-risk primary breast cancer: a meta-analysis. PLoS One 2012; 7(3):e33388.
  19. Kroger N, Frick M, Gluz O et al. Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patient with chemotherapy-sensitive metastatic breast cancer. J Clin Oncol 2006; 24(24):3919-26.
  20. Schmid P, Schippinger W, Nitsch T et al. Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: Results of a randomized trial. J Clin Oncol 2005; 23(3):432-40.
  21. Carella AM, Bregni M. Current role of allogeneic stem cell transplantation in breast cancer. Ann Oncol 2007; 18(10):1591-3.
  22. Ueno NT, Rizzo JD, Demirer T et al. Allogeneic hematopoietic cell transplantation for metastatic breast cancer. Bone Marrow Transplant 2008; 41(6):537-45.
  23. Fleskens AJ, Lalisang RI, Bos GM et al. HLA-matched allo-SCT after reduced intensity conditioning with fludarabine/CY in patients with metastatic breast cancer. Bone Marrow Transplant 2010; 45(3):464-7.
  24. Breast Cancer. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Breast Cancer. V2.2011. Last accessed January 31, 2013.
  25. Reviewed and recommended for adoption by the Oncology Advisory Panel, February 22, 2007; February 21, 2008; February 18, 2010; February 17, 2011.

Coding

Codes

Number

Description

CPT

38205

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogenic

 

38206

autologous

 

38207

Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage

 

38208

Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing

 

38209

thawing of previously frozen harvest, with washing

 

38210

Specific cell depletion within harvest, T-Cell depletion

 

38211

Tumor cell depletion

 

38212

Red blood cell removal

 

38213

Platelet depletion

 

38214

Plasma (volume) depletion

 

38215

Cell concentration in plasma, mononuclear or buffy coat layer.

 

38220

Bone marrow, aspiration only

 

38221

Bone marrow, biopsy, needle or trocar

 

38230

Bone marrow harvesting for transplantation

 

38232

Bone marrow harvesting for transplantation; autologous

 

38240

Bone marrow or blood-derived peripheral stem cell transplantation; allogeneic

 

38241

autologous

 

38242

Allogeneic donor lymphocyte infusions

 

86812

HLA typing; A, B, or C (e.g., A10, B7, B27), single antigen

 

86813

A, B, or C, multiple antigens

 

86816

DR/DQ, single antigen

 

86817

HLA typing; DR/DQ, multiple antigens

 

86821

Lymphocyte culture, mixed (MLC)

 

86822

Lymphocyte culture, primed (PLC)

 

86825

Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); first serum sample or dilution

 

86826

Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); each additional serum sample or sample dilution (List separately in addition to primary procedure)

ICD-9 Procedure

41.01

Autologous bone marrow transplant without purging

 

41.02

Allogeneic bone marrow transplant with purging

 

41.03

Allogeneic bone marrow transplant without purging

 

41.04

Autologous hematopoietic stem cell transplant without purging

 

41.05

Allogeneic hematopoietic stem-cell transplant without purging

 

41.07

Autologous hematopoietic stem cell transplant with purging

 

41.08

Allogeneic hematopoietic stem cell transplant with purging

 

41.09

Autologous bone marrow transplant with purging

 

41.91

Aspiration of bone marrow from donor for transplant

 

99.25

Chemotherapy

 

99.79

Other therapeutic apheresis (includes harvest of stem cells)

ICD-9 Diagnosis

   

ICD-10-CM
(effective 10/1/14)

C50.011 – C50.929

Malignant neoplasm of nipple and breast, code range

 

C79.81

Secondary malignant neoplasm of breast.

ICD-10-PCS
(effective 10/1/14)

30230G,

03233G0

Transfusion of autologous bone marrow into peripheral vein, code by approach

 

30230G1, 30233G1

Transfusion of nonautologous bone marrow into peripheral vein, code by approach

 

30240G0, 30243G0

Transfusion of autologous bone marrow into central vein, code by approach

 

30240G1, 30243G1

Transfusion of nonautologous bone marrow into central vein, code by approach

 

30250G0, 30253G0

Transfusion of autologous bone marrow into peripheral artery, code by approach

 

30250G1, 30253G1

Transfusion of nonautologous bone marrow into peripheral artery, code by approach

 

30260G0, 30263G0

Transfusion of autologous bone marrow into central artery, code by approach

 

30260G1, 30263G1

Transfusion of nonautologous bone marrow into central artery, code by approach

 

3E03005, 3E03305

Introduction of other antineoplastic into peripheral vein, code by approach

 

3E04005, 3E04305

Introduction of other antineoplastic into central vein, code by approach

 

3E05005, 3E05305

Introduction of other antineoplastic into peripheral artery, code by approach

 

3E06005, 3E06305

Introduction of other antineoplastic into central artery, code by approach

 

30230AZ, 30233AZ

Transfusion of stem cells, embryonic into peripheral vein, code by approach

 

30230Y0, 30233YO

Transfusion of autologous stem cells, hematopoietic into peripheral vein, code by approach

 

30240AZ, 30234AZ

Transfusion of stem cells, embryonic into central vein, code by approach

 

30240Y0, 30243YO

Transfusion of autologous stem cells, hematopoietic into peripheral vein, code by approach

 

30250Y0, 30253YO

Transfusion of autologous stem cells, hematopoietic into peripheral artery, code by approach

 

30230Y1, 30233Y1

Transfusion of nonautologous stem cells, hematopoietic into peripheral vein, code by approach

 

30240Y1, 30243Y1

Transfusion of nonautologous stem cells, hematopoietic into central vein, code by approach

 

30250Y1, 30253Y1

Transfusion of nonautologous stem cells, hematopoietic into peripheral artery, code by approach

 

30260Y1, 30263Y1

Transfusion of nonautologous stem cells, hematopoietic into central artery, code by approach

 

079T00Z, 079T30Z, 079T40Z

Drainage of bone marrow with drainage device, code by approach

 

079T0ZZ, 079T4ZZ

Drainage of bone marrow, code by approach

 

07DQ0ZZ, 07DQ3ZZ

Extraction of sternum bone marrow, code by approach

 

07DR0ZZ, 07DR3ZZ

Extraction of iliac bone marrow, code by approach

 

07DS0ZZ, 07DS3ZZ

Extraction of vertebral bone marrow, code by approach

 

6A550ZT, 6A551ZT

Pheresis of cord blood stem cells, code for single or multiple

 

6A550ZV, 6A551ZV

Pheresis of hematopoietic stem cells, code for single or multiple

HCPCS

J8999

Prescription drug, oral, chemotherapeutic, NOS

 

S2140

Cord blood harvesting for transplantation, allogeneic

 

S2142

Cord blood derived stem-cell transplantation, allogenic

 

S2150

Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications including pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition

Type of Service

Therapy / Medical / Oncology

 

Place of Service

Inpatient / Outpatient

 

Appendix

N/A

History

Date

Reason

04/11/06

Add to Therapy Section - New Policy, replaces PR.8.01.512

06/02/06

Disclaimer and Scope update - No other changes

03/13/07

Replace Policy - Policy updated with literature review; references added. Policy statement unchanged. Reviewed and recommended by OAP February 22, 2007.

10/9/07

Cross References Updated - No other changes

11/12/07

Code updated - CPT code 86817 deleted as directed by RPIW.

04/08/08

Replace Policy - Policy updated with literature search; no change to the policy statement. Reviewed and Recommended by OAP on February 21, 2008.

05/13/08

Cross Reference Update - No other changes

02/10/09

Replace Policy - Policy updated with literature review; Description, Rationale, and Reference sections revised extensively. Reference list consolidated; reference numbers 14, 16-17, and 19-23 added. Terminology in policy statements modified; however, intent of policy statements remains unchanged. “High-dose chemotherapy” removed from title.

12/08/09

Code Update – 86817 added back to the policy.

02/09/10

Code Update - New 2010 codes added.

03/09/10

Cross Reference Update - No other changes

03/08/11

Replace Policy - Reviewed and recommended by OAP on February 17, 2011. Policy updated with literature review. Description extensively revised. Policy statement for single or tandem autologous transplant changed to “not medically necessary”. No other changes to policy statements. References added, updated, removed and renumbered. ICD-10 codes added.

01/03/12

Deleted code 96445 removed.

01/24/12

Code 38232 added.

02/09/12

CPT code 38204 was removed from the policy.

03/23/12

Replace policy. Policy updated with literature search; no references added; reference 22 updated. No change to policy statements.

05/24/12

Related Policies updated; 2.04.36 renumbered to 12.04.36.

06/20/12

Minor update: Related Policies updated; 8.01.17 replaced 8.01.507 effective June 12, 2012.

07/30/12

Update Related Policies: Remove 2.01.45, and 2.01.55, as they were archived. Update titles to: 8.01.17, 8.01.21, 8.01.22, 8.01.26, 8.01.29, 8.01.30, 8.01.31, 8.01.35, 8.01.514, 8.01.520

10/08/12

Update Coding Section – ICD-10 codes are now effective 10/01/2014. Remove Related Policy 6.01.510 as it was archived.

03/08/13

Replace policy. Policy updated with literature search, references 17 and 18 added. No change to policy statements. The following codes were removed from the policy, as they were not suspending and just informational: CPT 38204, 96401 – 96450; ICD-9 Diagnosis 174.0 – 175.9; HCPCS J9000-J999 and Q0083 – Q0085.

09/30/13

Update Related Policies. Change title to policy 8.01.31.

10/18/13

Update Related Policies. Change title to policy 8.01.17.

12/06/13

Update Related Policies. Remove 8.01.31 as it was archived.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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