MEDICAL POLICY

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APPENDIX
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Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults

Number 8.01.24

Effective Date December 9, 2013

Revision Date(s) 12/09/13; 12/11/12; 10/11/11; 12/14/10; 12/08/09; 11/11/08; 11/13/07; 11/14/06; 10/11/05; 10/12/04; 8/12/03; 05/13/03; 03/11/03; 02/01/00

Replaces N/A

Policy

Autologous or allogeneic hematopoietic stem-cell transplant is considered investigational for the following malignancies in adults:

  • Lung cancer, any histology
  • Colon cancer
  • Rectal cancer
  • Pancreas cancer
  • Stomach cancer
  • Esophageal cancer
  • Gall bladder cancer
  • Cancer of the bile duct
  • Renal cell cancer
  • Cervical cancer
  • Uterine cancer
  • Cancer of the fallopian tubes
  • Prostate cancer
  • Nasopharyngeal cancer
  • Paranasal sinus cancer
  • Neuroendocrine tumors
  • Soft tissue sarcomas
  • Thyroid tumors
  • Tumors of the thymus
  • Tumors of unknown primary origin
  • Malignant melanoma

Related Policies

7.01.50

Placental and Umbilical Cord Blood as a Source of Stem Cells

7.01.95

Radiofrequency Ablation of Miscellaneous Solid Tumors Excluding Liver Tumors

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 Hematopoietic 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

8.01.25

Hematopoietic Stem-Cell Transplantation for Autoimmune Diseases

8.01.26

Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

8.01.27

Hematopoietic Stem-Cell Transplantation for Breast Cancer

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

Policy Guidelines

N/A

Description

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 from umbilical cord blood shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naïve” and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD). 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 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 a result of a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy (GVM) effect mediated by non-selfimmunologic 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, immune suppressant 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.

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 HSCT 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. (1) With the advent of nonmyeloablative 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. (2)

Miscellaneous Solid Tumors in Adults

Hematopoietic SCT as a treatment either of breast, ovarian, or testicular cancer, ependymoma, or malignant glioma is addressed in separate policies, No. 8.01.27, 8.01.23, 8.01.15, 8.01.28, or 8.01.31, respectively. This policy collectively addresses other solid tumors of adults for which SCT has been investigated, including lung cancer; malignant melanoma; tumors of the gastrointestinal tract (include colon, rectum, pancreas, stomach, esophagus, gallbladder, and bile duct); male and female genitourinary systems (e.g., renal cell carcinoma, cervical carcinoma, cancer of the uterus, fallopian tubes, and prostate gland); tumors of the head and neck; soft tissue sarcoma; thyroid tumors; tumors of the thymus; and tumors of unknown primary origin.

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

N/A

Rationale

Literature Review

This policy has been updated annually, with the most recent MEDLINE literature search performed through September 26, 2013.

This policy was initially based on a 1995 TEC assessment that focused on the malignancies listed in the Policy section. (3) The assessment offered the following conclusions:

  • While 125 articles were identified that reported on the results of HSCT in a variety of solid tumors, only 17 included survival data from groups of patients with the same cancer. These studies reported on 4 indications: advanced small -cell lung cancer, advanced colorectal cancer, malignant melanomas, and inoperable gastric cancer.
  • The evidence did not permit conclusions as to the effect of HSCT on patient survival.

A 1999 TEC Assessment evaluated the use of allogeneic hematopoietic stem-cell transplantation (HSCT) as a salvage therapy after a failed prior autologous HSCT for solid tumors. (4) Data were inadequate to permit conclusions.

Autologous HSCT in Solid Tumors of Adults

Data on the use of autologous HSCT for the solid tumors of adults addressed in this policy consist mainly of anecdotal reports and small series, and the number of randomized trials is limited.

Adult Soft Tissue Sarcomas

The prognosis of patients with unresectable or metastatic soft tissue sarcomas is poor, with a median survival of approximately 1 year and less than a 10% 5-year survival. (5) In general, dose-intensive doxorubicin and ifosfamide-based regimens have yielded higher response rates and prolonged disease-free survival but not overall survival (OS). (5) However, as it was shown that patients who achieved complete remission (CR) had longer survival; several Phase I and II trials using autologous HSCT were conducted in the 1990s in an attempt to improve outcomes. (5) These trials were composed of small numbers of patients (ranging from 2–55), yielding overall response rates from 2065%, with CR from 1043%. The longest reported 5-year progression-free survival (PFS) rate was 21%, and 5-year OS was 32%. (5) One study of 21 patients with soft tissue sarcoma showed a PFS and OS benefit only in patients with no evidence of disease before undergoing HSCT. (6) The data from these small trials are insufficient to support the use of autologous HSCT in adult patients with soft tissue sarcoma. In one additional Phase ll study, 21 of 55 (38%) patients responded to doxorubicin-based induction chemotherapy (14% vs. 3%; p=0.003), but estimated OS was not statistically different between those who received an autologous SCT and those who did not. The authors felt that their results warranted a Phase lll trial examining the role of HSCT as consolidation therapy in these patients. (7) No Phase lll trials involving HSCT for first-line therapy of advanced or metastatic adult soft tissue sarcoma compared to conventional standard-dose chemotherapy were found in a systematic review. (8)

Kasper and colleagues reported the results of a prospective, single institution Phase II study that enrolled 34 patients with advanced and/or metastatic soft tissue sarcoma. (9) After 4 courses of chemotherapy, patients with at least a partial response underwent high-dose chemotherapy and autologous HSCT (n=9). All other patients continued chemotherapy for 2 more cycles. The median PFS for patients treated with HSCT was 11.6 months (range 8-15 months) versus 5.6 months for patients treated with standard chemotherapy (p=0.047) and median OS for the 2 groups was 23.7 months (range 12-34 months) versus 10.8 months (range 0-39 months) (p=0.027), respectively. The improved PFS and OS observed in the HSCT group probably reflected chemoresponse; however, this would need to be addressed in a randomized study.

Small-cell Lung Carcinoma

The interest in treating small-cell lung carcinoma (SCLC) with HSCT stems from the extremely high chemosensitivity and poor prognosis of this tumor type. A Phase III trial of 318 patients with SCLC randomly assigned patients to standard chemotherapy or HSCT. (10) No statistically significant difference in response rates was seen between the two groups (80% response rate in the standard arm vs. 88% in the HSCT group [difference: 8%, 95% confidence interval (CI): -1% to 17%; p=0.09]). There was no statistically significant difference in OS between the two groups, with a median OS of 13.9 months in the standard arm (95% CI: 12.1 to 15.7 months) versus 14.4 months in the HSCT arm (95% CI: 13.1 to 15.4); p=0.76. One smaller, randomized study and several single-arm studies of HSCT and autologous HSCT for SCLC are summarized in a review article. (11) Overall, the majority of the data from these studies, including the randomized study, showed no increased OS with autologous HSCT.

Jiang and colleagues performed a meta-analysis of the medical literature through October 2008 of English language studies using intensified chemotherapy with autologous hematopoietic progenitors to treat SCLC. (12) The meta-analysis consisted of 5 randomized, controlled trials (RCTs; 3 were Phase III trials and 2 were Phase II), for a total of 641 patients. They found no significant increase in the odds ratio for response rate with autologous transplant versus control chemotherapy (odds ratio [OR]: 1.29; 95% CI: 0.87–1.93; p=0.206). No statistically significant increase in OS was seen among the autologous transplant patients compared to control regimens (hazard ratio [HR]: 0.94; 95% CI: 0.80–1.10; p=0.432). The authors concluded that current evidence does not support the use of intensified chemotherapy and autologous HSCT for treating SCLC.

Miscellaneous

Uncontrolled pilot studies of HSCT for patients with refractory urothelial carcinoma (13) and recurrent or advanced nasopharyngeal carcinoma (14) failed to provide adequate evidence of improved outcomes to alter previous conclusions.

A review article summarizes the data from studies of autologous HSCT for solid tumors in adults. (15)

Allogeneic HSCT in Solid Tumors of Adults

Single-case reports and small series of patients with various types of solid tumors have been treated with allogeneic HSCT, including some of the tumor types addressed in this policy. (1, 2, 16)

Renal Cell Carcinoma

Metastatic renal cell carcinoma (RCC) has an extremely poor prognosis, with a median survival of less than 1 year and a five-year survival of less than 5%. (17) RCC is relatively resistant to chemotherapy but is susceptible to immune therapy, and interleukin-2 (IL-2) and/or interferon alpha have induced responses and long-term PFS in 415% of patients. (16) Therefore, the immune-based strategy of a graft-versus-tumor effect possible with an allogeneic transplant has led to an interest in its use in RCC. In 2000, Childs and coworkers published the first series of patients with RCC treated with nonmyeloablative allogeneic HSCT. (17) The investigators showed regression of the tumor in 10 of 19 (53%) patients with cytokine-refractory, metastatic RCC who received an HLA-identical sibling allogeneic HSCT. Three patients had a CR and remained in remission 16, 25, and 27 months after transplant. Four of 7 patients with a partial response were alive without disease progression 9 to 19 months after transplantation. Other pilot trials have demonstrated the graft-versus-tumor effect of allogeneic transplant in metastatic RCC, but most have not shown as high a response rate as the Childs’ et al. study. Overall response rates in these pilot trials have been approximately 25%, with CR rates of approximately 8%. (1) Prospective, randomized trials are needed to assess the net impact of this technique on the survival of patients with cytokine-refractory RCC. (1)

Bregni and colleagues assessed the long-term benefit of allografting in 25 patients with cytokine-refractory metastatic RCC who received an RIC allograft from a sibling who is human leukocyte antigen (HLA) identical. (18) All patients received the same conditioning regimens. Response to allograft was available in 24 patients, with a CR in 1 patient and partial response in 4 patients. Twelve patients had minor response or stable disease, and 7 reported progressive disease. Overall response rate (complete plus partial) was 20%. Six patients died because of transplant-related mortality. Median survival was 336 days (12–2,332+). One-year OS was 48% (95% CI: 28–68), and 5-year OS was 20% (95% CI: 4–36). The authors concluded that allografting is able to induce long-term disease control in a small fraction of cytokine-resistant patients with RCC but that with the availability of novel targeted therapies for RCC, future treatment strategies should consider the incorporation of these therapies into the transplant regimen.

Colorectal Carcinoma

Aglietta and colleagues reported their experience with 39 patients with metastatic colorectal cancer who underwent reduced-intensity conditioning (RIC) allogeneic HSCT between 1999 and 2004 at 9 European Group for Blood and Marrow Transplantation (EBMT) centers. (19) Patients were treated with 1 of 5 different RIC regimens. Endpoints that were assessed were achievement of mixed chimerism, incidence of graft-versus-host disease (GVH), treatment-related mortality and toxicities, OS, and time to treatment failure (in patients who responded to the therapy). Patient population characteristics were heterogeneous; pretransplant disease status was partial response in 2 patients, stable disease in 6 patients, and progressive disease in 31. Thirty-eight patients (97%) had been previously treated, some with only chemotherapy and others with surgery and/or chemotherapy. After transplant, tumor responses were complete in 2% of patients, partial in 18%, and 26% of patients had stable disease, for overall disease control in 46% of patients. Transplant-related mortality was 10%. Median overall follow-up was 202 days (range: 6–1,020 days), after which time 33 patients had died and 6 were still alive. Tumor progression was the cause of death in 74% of patients. A comparison of OS of patients was performed after stratifying by some potential prognostic factors. Achievement of response after transplantation was associated with a difference in OS, with the 18 patients who had a response having a median OS of approximately 400 days versus approximately 120 days for those who had no response (p=0.00018). The authors concluded that the HSCT approach should probably be reserved for patients with a partial response or stable disease after second-line therapy for metastatic colorectal cancer and second-generation clinical trials in these patients are warranted.

Pancreatic Cancer

Kanda and colleagues reported on the efficacy of RIC allogeneic HSCT against advanced pancreatic cancer in 22 patients from 3 transplantation centers in Japan. (20) The RIC regimens differed among the centers, and the patient population was fairly heterogeneous, with 15 patients having metastatic disease and 7 locally advanced disease. All but 1 patient received chemotherapy of various combinations before transplant, and 10 patients received local radiation. After HSCT, 1 patient achieved complete response, 2 patients had partial response, 2 had minor response, and 8 had stable disease, with an overall response rate of 23%. Median survival was 139 days, and the major cause of death was tumor progression (median duration of survival in advanced pancreatic cancer in the nontransplant setting is less than 6 months, even in patients treated with gemcitabine). Only 1 patient survived longer than 1 year after transplantation. The authors concluded that a tumor response was observed in one fourth of patients with advanced pancreatic cancer who underwent HSCT and that the response was not durable. However, they felt that their observation of a relationship between longer survival and the infusion of a higher number of CD34-positive cells or the development of chronic graft-versus-host disease (GVHD) warrant future studies to enhance the immunologic effect against pancreatic cancer.

Abe and colleagues reported the outcomes for 5 patients with chemotherapy-resistant, unresectable pancreatic adenocarcinoma who received a nonmyeloablative allogeneic peripheral blood HSCT. (21) The conditioning regimen consisted of fludarabine and low-dose total-body irradiation. The median patient age was 54 years (range: 44–62 years). All patients had advanced disease, either with metastases or peritonitis, and had received at least 1 course of chemotherapy including gemcitabine. After HSCT, tumor response was only observed in 2 patients—1 had complete disappearance of the primary tumor and 1 had a 20% reduction in tumor size; the remaining patients had progressive disease (n=2) or stable disease (n=1). Four patients died of progressive disease, ranging from post-transplant day 28 to day 209 (median: 96 days). One patient died at day 57 secondary to rupture of the common bile duct from rapid tumor regression. The authors concluded that their study showed a graft-versus-tumor effect but that in order to obtain durable responses, an improved conditioning regimen and new strategies to control tumor growth after nonmyeloablative allogeneic HSCT are needed.

Nasopharyngeal Carcinoma

Toh and colleagues reported the outcomes of a Phase II trial of 21 patients with pretreated metastatic nasopharyngeal carcinoma. (22) Median patient age was 48 years (range: 34-57 years), and patients had received a median of 2 previous chemotherapy regimens (range; 1-8). All patients had extensive metastases. Patients underwent a nonmyeloablative allogeneic HSCT with sibling allografts. Seven patients (33%) showed a partial response and 3 (14%) achieved stable disease. Four patients were alive at 2 years, and 3 showed prolonged disease control of 344, 525, and 550 days. After a median follow-up of 209 days (range: 4-1,147 days), the median PFS was 100 days (95% CI: 66-128 days), and median OS was 209 days (95% CI: 128-236 days). One- and 2-year OS rates were 29% and 19%, respectively, comparable to the median 7-14 months OS for metastatic nasopharyngeal patients in the literature treated with salvage chemotherapy without HSCT.

Ongoing Clinical Trials

A September 2013 search of the online site Clinicaltrials.gov showed a Phase III trial of sequential, high-dose chemotherapy followed by peripheral stem-cell or bone marrow transplant compared with chemotherapy alone in treating patients with SCLC (NCT00011921); the recruitment status is unknown. No additional ongoing Phase III clinical trials of chemotherapy followed by HSCT in treating adults with miscellaneous solid tumors listed in this policy were identified.

Summary

Hematopoietic stem-cell transplantation (HSCT) is an established treatment for certain hematologic malignancies. The use of autologous HSCT in solid tumors in adults continues to be largely experimental, as most studies have failed to show an improvement in health outcomes. Interest continues in exploring non-myeloablative allogeneic HSCT for a graft-versus-tumor effect of donor-derived T cells in metastatic solid tumors.

In summary, as of September 2013, no trials have been published that would alter the current policy statement; this is considered investigational.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

As of September 2013, National Comprehensive Cancer Network (NCCN) guidelines on the tumors addressed in this policy do not indicate HSCT as a treatment option. (23)

References

  1. Imanguli MM, Childs RW. Hematopoietic stem cell transplantation for solid tumors. Update Cancer Ther 2006; 1(3):343-52.
  2. Carnevale-Schianca F, Ricchiardi A, Capaldi A et al. Allogeneic hemopoietic stem cell transplantation in solid tumors. Transplant Proc 2005; 37(6):2664-6.
  3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). High-dose chemotherapy with autologous stem-cell support for miscellaneous solid tumors in adults. TEC Assessments 1995; Volume 10, Tab 4.
  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Salvage HDC/AlloSCS for Relapse following HDC/AuSCS for Non-lymphoid Solid Tumors. TEC Assessments 1999; Volume 14, Tab 11.
  5. Pedrazzoli P, Ledermann JA, Lotz JP et al. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol 2006; 17(10):1479-88.
  6. Kasper B, Dietrich S, Mechtersheimer G et al. Large institutional experience with dose-intensive chemotherapy and stem cell support in the management of sarcoma patients. Oncology 2007; 73(1-2):58-64.
  7. Schlemmer M, Wendtner CM, Falk M et al. Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas. Oncology 2006; 71(1-2):32-9.
  8. Verma S, Younus J, Stys-Norman D et al. Dose-intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma: a systematic review. Cancer 2008; 112(6):1197-205.
  9. Kasper B, Scharrenbroich I, Schmitt T et al. Consolidation with high-dose chemotherapy and stem cell support for responding patients with metastatic soft tissue sarcomas: prospective, singleinstitutional phase II study. Bone Marrow Transplant 2010; 45(7):1234-8.
  10. Lorigan P, Woll PJ, O’Brien ME et al. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst 2005; 97(9):666-74.
  11. Crivellari G, Monfardini S, Stragliotto S et al. Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses. Oncologist 2007; 112(1):79-89.
  12. Jiang J, Shi HZ, Deng JM et al. Efficacy of intensified chemotherapy with hematopoietic progenitors in small-cell lung cancer: a meta-analysis of the published literature. Lung Cancer 2009; 65(2):214-8.
  13. Nishimura M, Nasu K, Ohta H et al. Highdose chemotherapy for refractory urothelial carcinoma supported by peripheral blood stem cell transplantation. Cancer 1999; 86(9):1827-31.
  14. Airoldi M, De Crescenzo A, Pedani F et al. Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma. Head Neck 2001; 23(9):799-803.
  15. Pedrazzoli P, Rosti G, Secondino S et al. High-dose chemotherapy with autologous hematopoietic stem cell support for solid tumors in adults. Semin Hematol 2007; 44(4):286-95.
  16. Demirer T, Barkholt L, Blaise D et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol 2008; 5(5):256-67.
  17. Childs R, Chernoff A, Contentin N et al. Regression of metastatic renal cell carcinoma after nonmyeloablative allogeneic peripheral blood stem cell transplantation. N Engl J Med 2000; 343(11):750-8.
  18. Bregni M, Bernardi M, Servida P et al. Long-term follow-up of metastatic renal cancer patients undergoing reduced-intensity allografting. Bone Marrow Transplant 2009; 44(4):237-42.
  19. Aglietta M, Barkholt L, Schianca FC et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adaptive cell therapy approach. The European Group for Blood and Marrow Transplantation experience. Biol Blood Marrow Transplant 2009; 15(3):326-35.
  20. Kanda Y, Omuro Y, Baba E et al. Allo-SCT using reduced-intensity conditioning against advanced pancreatic cancer: a Japanese survey. Bone Marrow Transplant 2008; 42(2):99-103.
  21. Abe Y, Ito T, Baba E et al. Nonmyeloablative allogeneic hematopoietic stemcell transplantation as immunotherapy for pancreatic cancer. Pancreas 2009; 38(7):815-9.
  22. Toh HC, Chia WK, Sun L et al. Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation. Bone Marrow Transplant 2011; 46(4):573-9.
  23. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. 2013. Available online at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Last accessed November 13, 2013
  24. Policy reviewed and recommended for adoption by Oncology Advisory Panel on February 22, 2007; May 22, 2008; November 19, 2009; November 20, 2010.
  25. Blue Cross and Blue Shield Association. Medical Policy Manual. Hematopoietic Stem-Cell Transplant for Miscellaneous Solid Tumor in Adults. Policy No. 8.01.24, 2013.

Coding

Codes

Number

Description

CPT

38205

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

 

38206

;autologous

 

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 with 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

 

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

 

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

 

41.06

Cord blood stem cell transplant

 

41.07

Autologous hematopoietic stem cell transplant with purging

 

41.09

Autologous bone marrow transplant with purging

 

41.91

Aspiration of bone marrow from donor for transplant

 

99.79

Other therapeutic apheresis (includes harvest of stem cells)

ICD-9 Diagnosis

159.0

Malignant neoplasm of intestinal tract, part unspecified

 

162.0

Malignant neoplasm of trachea

 

162.2

Malignant neoplasm of main bronchus

 

162.3

Malignant neoplasm of upper lobe, bronchus or lung

 

162.4

Malignant neoplasm of middle lobe, bronchus or lung

 

162.5

Malignant neoplasm of lower lobe, bronchus or lung

 

162.8

Malignant neoplasm of other parts of bronchus or lung

 

162.9

Malignant neoplasm of bronchus and lung, unspecified

 

171.0

Malignant neoplasm of connective and other soft tissue of head, face and neck

 

171.2

Malignant neoplasm of connective and other soft tissue of upper limb, including shoulder

 

171.3

Malignant neoplasm of connective and other soft tissue of lower limb, including hip

 

171.4

Malignant neoplasm of connective and other soft tissue of thorax

 

171.5

Malignant neoplasm of connective and other soft tissue of abdomen

 

171.6

Malignant neoplasm of connective and other soft tissue of pelvis

 

171.7

Malignant neoplasm of connective and other soft tissue of trunk, unspecified

 

171.8

Malignant neoplasm of connective and other soft tissue of other specified sites

 

171.9

Malignant neoplasm of connective and other soft tissue of unspecified site(s)

ICD-10-CM (effective 10/01/14)

C11.0 - C11.9

Malignant neoplasm of nasopharynx code range

 

C15.30 - C15.9

Malignant neoplasm of esophagus code range

 

C16.0 – C16.9

Malignant neoplasm of stomach code range

 

C18.0 - C18.9

Malignant neoplasm of colon code range

 

C20

Malignant neoplasm of rectum

 

C23

Malignant neoplasm of gallbladder

 

C24.0 – C24.9

Malignant neoplasm of other and unspecified parts of biliary tract code range

 

C25.0 – C25.9

Malignant neoplasm of pancreas code range

 

C31.0 – C31.9

Malignant neoplasm of accessory sinuses code range

 

C34.00 – C34.92

Malignant neoplasm of bronchus and lung code range

 

C37

Malignant neoplasm of thymus

 

C43.0 – C43.9

Malignant melanoma of skin code range

 

C46.1

Kaposi's sarcoma of soft tissue

 

C53.0 – C53.9

Malignant neoplasm of cervix uteri code range

 

C54.0 – C54.9

Malignant neoplasm of corpus uteri code range

 

C55

Malignant neoplasm of uterus, part unspecified

 

C57.00 – C57.02

Malignant neoplasm of fallopian tube code range

 

C61

Malignant neoplasm of prostate

 

C64.0 – C64.9

Malignant neoplasm of kidney, except renal pelvis code range

 

C65.0 – C65.9

Malignant neoplasm of renal pelvis code range

 

C73

Malignant neoplasm of thyroid gland

 

C7a.00 – C7b.8

Malignant neuroendocrine tumors code range

 

C80.1

Malignant (primary) neoplasm, unspecified

ICD-10-PCS (effective 10/01/14)

30243G0, 30243X0, 30243Y0

Percutaneous transfusion, central vein, bone marrow or stem cells, autologous, code list

 

30243G1, 30243X1, 30243Y1

Percutaneous transfusion, central vein, bone marrow or stem cells, nonautologous, code list

 

07DQ0ZZ, 07DQ3ZZ, 07DR0ZZ, 07DR3ZZ, 07DS0ZZ, 07DS3ZZ

Surgical, lymphatic and hemic systems, extraction, bone marrow, code list

HCPCS

S2140

Cord blood harvesting for transplantation, allogeneic

 

S2142

Cord blood derived stem cell transplantation, allogeneic

 

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

 

Place of Service

Inpatient
Outpatient

 

Appendix

N/A

History

Date

Reason

02/01/00

Add to Therapy Section - New Policy — replaces 8.01.15, original master policy on high-dose chemotherapy for miscellaneous malignancies. However, policy statement is unchanged.

03/11/03

Replace policy - Policy updated; new references; no change in policy statement.

05/13/03

Replace policy - Update CPT codes only.

08/12/03

Replace policy - Reviewed by OAP on 7/22/03. Recommended that investigational statement be more inclusive.

10/12/04

Replace policy - Policy updated with literature review; no change to policy statement. Approved by OAP 10/29/04, no need to back to MPC.

10/11/05

Replace policy - Policy updated with literature review; no clinical trial publications found. No change to policy statement.

06/02/06

Disclaimer and Scope updates - No other changes.

11/14/06

Replace policy - Policy updated with literature review; policy statement unchanged.

02/22/07

Update References - Policy reviewed and recommended by OAP on February 22, 2007.

11/13/07

Replace policy - Policy updated with literature review; policy statement unchanged. References added.

11/11/08

Replace policy - Policy updated with literature search; no change to the policy statement. Description and rationale updated. Title changed to delete “HDC” and added “Transplant” after “Stem Cell”. References and codes added. Policy reviewed and recommended by OAP on May 22, 2008.

12/08/09

Replace policy - Policy updated with literature search; no change to the policy statement. References added. Policy reviewed and recommended by OAP on November 19, 2009.

02/09/10

Code Update - New 2010 codes added.

12/14/10

Replace policy - Policy updated with literature review using MEDLINE through July 2010; reference number 22 added and number 23 updated. Policy statements remain unchanged. Reviewed and recommended by OAP in November 2010.

10/11/11

Replace policy – Policy updated with literature review using MEDLINE through July 2011; reference numbers 9 and 22 added; reference 6 removed; references renumbered. Policy statements unchanged. ICD-10 codes added. Codes 38220 and 38221 removed from policy.

01/24/12

Code 38232 added.

02/10/12

The CPT code 38204 was removed from the policy.

06/20/12

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

07/31/12

Update Related Policy titles: 8.01.17, 8.01.21, 8.01.26, 8.01.27, 8.01.29, 8.01.30, 8.01.31, and 8.01.35. Removed Policy 8.01.507 as it was renamed to 8.01.17.

12/19/12

Replace policy. Policy updated with literature review using MEDLINE through September 2012; no references added. Policy statement unchanged. Updated Related Policy 7.01.540, now replaced with 7.01.95.

02/01/13

Update Related Policies, change title of policy 8.01.21.

03/20/13

The following codes were removed from the policy, as they were not suspending and just informational: HCPCS J9000-J9999 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.

12/09/13

Replace policy. Policy updated with literature review using MEDLINE through September 26 2013; no references added. Policy statement unchanged.

01/20/14

Update Related Policies. Change title to 8.01.21.


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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