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Clinical Policy Bulletin:
Hematopoietic Cell Transplantation for Solid Tumors in Adults
Number: 0811


Policy

Aetna considers autologous or allogeneic hematopoietic stem cell transplant (ablative and non-myeloablative) for the treatment of any of the following solid tumors in adults experimental and investigational because its effectiveness for these indications has not been established:

  • Bile duct
  • Breast
  • Central nervous system tumors (e.g., astrocytoma, choroid plexus tumors, ependymoma, germ cell tumors, gliomas, medulloblastoma, oligodendroglioma, and primitive neuroectodermal tumors; not an all-inclusive list)
  • Cervix
  • Colon
  • Esophagus
  • Fallopian tube
  • Gallbladder
  • Kidney
  • Lung
  • Melanoma
  • Nasopharynx
  • Pancreas
  • Paranasal sinus
  • Prostate
  • Rectum
  • Soft tissue sarcomas
  • Stomach
  • Thymus 
  • Thyroid
  • Uterus.

See also CPB 0496 - High Dose Chemotherapy and Bone Marrow or Peripheral Stem Cell Transplant for Selected Childhood Solid TumorsCPB 0507 - High-Dose Chemotherapy with Hematopoietic Stem Cell Support for Breast CancerCPB 0617 - High Dose Chemotherapy with Bone Marrow or Peripheral Stem Cell Transplant for Testicular CancerCPB 0634 - Non-myeloablative Bone Marrow/Peripheral Stem Cell Transplantation (Mini-Allograft / Reduced Intensity Conditioning Transplant), and CPB 0635 - High Dose Chemotherapy with Bone Marrow or Peripheral Stem Cell Transplant for Ovarian Cancer.



Background

Solid tumors (also known as solid neoplasms) in adults represent a heterogeneous group of malignancies that encompass various body systems.  While some solid tumors are very chemo-radiosensitive (e.g., Ewing’s sarcoma and gonadal tumors); as a whole they are not curable by chemotherapy.  The use of hematopoietic stem cell transplant (HSCT) has been investigated for the treatment of selected solid tumors.  This approach arose from studies that allogeneic HSCT has been successfully employed for patients with aplastic anemia and hemoglobinopathies.  Storb et al (2003) stated that the allogeneic graft-versus-tumor (GVT) effects observed in patients who received HSCT for hematological malignancies have stimulated trials of allogeneic HSCT in patients with refractory metastatic solid tumors.  The graft-versus-leukemia (GVL) effect is an important component of the therapeutic effect of allogeneic HSCT.  Data from experimental animal models as well as from preliminary clinical trials suggested that a GVT effect, analogous to the GVL effect, may be generated against solid tumors such as breast cancer, renal cell cancer, and other malignancies.  The use of non-myeloablative, immunosuppressive conditioning regimens, also known as reduced-intensity conditioning (RIC) regimens, offers the opportunity to achieve full-donor engraftment with reduced transplant-related complications and mortality, thus, enabling also patients of advanced age and with co-morbidities to receive allografting.  Bregni and colleagues (2004) stated that advanced renal cell cancer has emerged from pilot studies as a disease susceptible to the GVT effect; and future studies will show if tumor responses observed after allografting will translate into a clinically meaningful survival advantage.  Other tumors in which tumor responses have been demonstrated include breast cancer, colorectal cancer, ovarian cancer, soft-tissue sarcoma, and others.  In contrast, advanced melanoma may not be amenable to GVT effect.

Non-myeloablative HSCT provides a safer approach to explore the effectiveness of allogeneic HSCT in patients with solid tumors.  Initial reports have demonstrated that GVT may occur against several different solid tumors, including  breast cancer, ovarian cancer, renal cell carcinoma, and others (Espinoza-Delgado and Childs, 2004).  Busca et al (2006) evaluated the feasibility and effectiveness of RIC regimen to achieve complete donor chimerism following allogeneic HSCT in patients with metastatic solid tumors.  Seven patients with renal cell carcinoma, 3 with colorectal carcinoma, and 1 with soft tissue sarcoma received allogeneic HSCT after fludarabine (90 mg/m2) and total body irradiation (200 cGy).  At day 30, median donor chimerism was 94 %.  Regression of tumor metastases was observed in 1 patient with renal cell carcinoma.  Eight patients (73 %) died from progressive disease (median progression-free survival of 3.7 months) and 1 (9 %) from treatment-related complications; 2 patients were alive 152 and 862 days after transplantation, respectively.  The authors concluded that these preliminary results suggested that allogeneic HSCT with RIC regimen for metastatic solid tumors is feasible, although it may lead to durable responses in only a minority of patients.

Demirer et al (2008) noted that allogeneic transplantation of hematopoietic cells from an HLA-compatible donor has been used to treat hematological malignancies.  Allogeneic transplantation not only replaces the marrow affected by the disease, but exerts an immune GVT effect mediated by donor lymphocytes.  The development of RIC before allogeneic transplantation has allowed this therapy to be used in elderly and disabled patients.  An allogeneic GVT effect is observed in a proportion of patients with breast, colorectal, ovarian, pancreatic, and renal cancer treated with allogeneic transplantation.  In general, the tumor response is associated with the development of acute and chronic graft-versus-host disease (aGVHD and cGVHD).  The authors stated that further improvements will depend on the identification of the antigen targets of GVT, and on reduction of the toxicity of the procedure.

In a multi-center clinical trial, Aglietta and co-workers (2009) examined RIC regimens for allogeneic HSCT in patients with metastatic colorectal cancer (mCRC).  A total of 39 participants with progressing mCRC were treated with different RIC regimens.  At the time of transplant, disease status was partial response (PR) in 2 (5 %) patients, stable disease (SD) in 6 (15 %), and progressive disease (PD) in 31 (80 %).  All patients engrafted (median donor T cell chimerism of 90 % at day +60).  Transplant-related morbidities were limited.  Grades II to IV aGVHD occurred in 14 patients (35 %) and cGVHD in 9 (23 %) patients.  Transplant-related mortality occurred in 4 patients (10 %).  The best tumor responses were 1 complete response (CR) (2 %), 7 PR (18 %), and 10 SD (26 %), giving an overall disease control in 18 of 39 patients (46 %).  The authors concluded that allogeneic HSCT after RIC regimen is feasible; the collected results compared favorably in terms of tumor response with those observed using conventional approaches beyond second-line therapies.  They stated that investigation of an allogeneic cell-based therapy in less advanced patients is warranted.

A recent review on allogeneic and autologous transplantation for hematological diseases, immune disorders, and solid tumors by the European Group for Blood and Marrow Transplantation (Ljungman et al, 2010) stated that allogeneic HSCT is considered (i) a clinical option (can be performed after careful assessment of risks and benefits) for renal cancer relapsed/resistant to cytokine therapy, (ii) a developmental therapy (further trials are needed) for breast and ovarian cancer, and (iii) a developmental therapy that is not recommended for other solid tumors with the possible exception of colorectal cancer.  The authors stated that currently allogeneic HSCT should only be considered in the context of prospective clinical trials.

Autologous HSCT pursuing an immune GVT effect has also been evaluated for patients with advanced and refractory solid malignancies.  Neito et al (2004) noted that over the past 20 years, high-dose chemotherapy (HDC) with autologous HSCT has been explored for a variety of solid tumors in adults, especially breast cancer, ovarian cancer, and non-seminomatous germ-cell tumors.  The findings of prospective phase II studies seemed superior in many cases to the outcome expected with standard-dose chemotherapy.  The authors stated that the value of HDC for adult solid tumors remains, in most instances, a controversial issue; and is currently under the scrutiny of randomized phase III trial evaluation.  Pedrazzoli et al (2006) stated that since the early 1980s HDC with autologous HSCT was adopted by many oncologists as a potentially curative option for solid tumors, supported by a strong rationale from laboratory studies and apparently convincing results of early phase II studies.  As a result, the number and size of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) to prove or disprove its value was largely insufficient.  In fact, with the possible exception of breast cancer, the benefit of a greater escalation of dose of chemotherapy with stem cell support in solid tumors is still unsettled and many oncologists believe that this approach should cease.  In this regard, the Centers for Medicare and Medicaid Services (2006) noted that there are insufficient data to establish definite conclusions regarding the effectiveness of autologous HSCT for solid tumors (other than neuroblastoma).

Available clinical practice guidelines have not recommended HSCT for the treatment of solid tumors in adults.  The Dutch Urological Tumors National Working Group (2006) did not mention autologous or allogeneic HSCT as a therapeutic option for patients with renal cell carcinoma.  The Dutch Thyroid Carcinoma Working Group (2007) did not discuss autologous or allogeneic HSCT as a therapeutic option for patients with thyroid carcinoma.  Furthermore, the Cancer Care Ontario Program in Evidence-based Care's clinical guideline on stem cell transplantation in adults (Imrie et al, 2009) stated that (i) HDC with autologous HSCT has no proven efficacy in advanced epithelial ovarian cancer, germ-cell tumors, primary breast cancer, or small-cell lung cancer, and (ii) there is also no benefit for HDC with autologous bone marrow transplantation in patients with breast cancer compared with standard-dose chemotherapy alone.

The National Cancer Institute's Physician Data Query on treatment for cervical cancer (2010), colon cancer (2010), endometrial cancer (2010), esophageal cancer (2010), extra-hepatic bile duct (2010), gallbladder cancer (2010), gastric cancer (2010), melanoma (2010), nasopharygeal cancer (2010), non-small cell lung cancer (2010), pancreatic cancer (2010), paranasal sinus and nasal cavity cancer (2008), prostate cancer (2010), rectal cancer (2010), small cell lung cancer (2010), soft tissue sarcoma treatment (2010), thymoma and thymic carcinoma (2010), thyroid cancer (2010), and uterine cancer (2008) do not mention autologous or allogeneic HSCT as a therapeutic option.

Kasper et al (2010) noted that prognosis of patients with metastatic soft tissue sarcoma (STS) remains poor.  Whether high-dose chemotherapy (HDCT) with stem cell support improves the long-term outcome for these patients is debatable.  These investigators presented a prospective, single-institutional, phase II study that enrolled 34 STS patients with advanced and/or metastatic disease.  After 4 courses of chemotherapy consisting of doxorubicin and ifosfamide, responding patients in at least partial response (PR) were treated with HDCT (n = 9); all other patients continued chemotherapy for 2 more cycles.  After standard chemotherapy, PR (n = 10), stable disease (SD, n = 6) and progressive disease (PD, n = 14) were attained for the evaluable patients.  A total of 29 patients died and 5 are alive with the disease.  Median progression free survival (PFS) was 11.6 months (range of 8 to 15) for patients treated with HDCT (n = 9) versus 5.6 months (range of 0 to 19) for patients treated with standard chemotherapy.  Median overall survival (OS) was 23.7 months (range of 12 to 34) versus 10.8 months (range of 0 to 39), respectively.  The subgroup of patients treated with HDCT gained significant survival benefit.  Nevertheless, HDCT as a possible consolidation strategy remains highly investigational.

In a Cochrane review, Peinemann and colleagues (2011) evaluated the effectiveness and safety of HDCT followed by autologous HSCT for all stages of STS in children and adults.  These investigators searched the electronic databases CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE and EMBASE (February 2010).  Online trial registers, congress abstracts and reference lists of reviews were searched and expert panels and authors were contacted.  Terms representing STS and autologous HSCT were required in the title, abstract or keywords.  In studies with aggregated data, participants with non-rhabdomyosarcoma STS (NRSTS) and autologous HSCT had to constitute at least 80 % of the data.  Comparative non-randomized studies were included because randomized controlled trials (RCTs) were not expected.  Case series and case reports were considered for an additional descriptive analysis.  Study data were recorded by 2 review authors independently.  For studies with no comparator group, the authors synthesised results for studies reporting aggregate data and conducted a pooled analysis of individual participant data using the Kaplan-Meyer method.  The primary outcomes were OS and treatment-related mortality (TRM).  These researchers included 54 studies, from 467 full texts articles screened (11.5%), reporting on 177 subjects that received HSCT and 69 subjects that received standard care.  Only 1 study reported comparative data.  In the 1 comparative study, OS at 2 years after HSCT was estimated as statistically significantly higher (62.3 %) compared with subjects that received standard care (23.2 %).  In a single-arm study, the OS 2 years after HSCT was reported as 20 %.  In a pooled analysis of the individual data of 54 subjects, OS at 2 years was estimated as 49 % (95 % confidence interval: 34 % to 64 %).  Data on TRM, secondary neoplasia and severe toxicity grade 3 to 4 after transplantation were sparse.  All 54 studies had a high risk of bias.  The authors concluded that due to a lack of comparative studies, it is unclear whether subjects with NRSTS have improved survival from autologous HSCT following HDCT.  Owing to this current gap in knowledge, at present HDCT and autologous HSCT for NRSTS should only be used within controlled trials.

There is insufficient evidence regarding the safety and effectiveness of autologous/allogeneic HSCT for the treatment of central nervous system (CNS) tumors (e.g., astrocytoma, choroid plexus tumors, ependymoma, germ cell tumors, gliomas, medulloblastoma, oligodendroglioma, and primitive neuroectodermal tumors).

Baek and colleagues (2013) evaluated the feasibility and effectiveness of myeloablative HDC and autologous SCT (autoSCT) in patients with relapsed or progressed CNS-germ cell tumors (CNS-GCTs).  A total of 11 patients with non-germinomatous GCTs (NGGCTs) and 9 patients with germinomas were enrolled.  Patients received between 2 and 8 cycles of conventional chemotherapy prior to HDCT/autoSCT with or without radiotherapy (RT).  Overall, 16 patients proceeded to the first HDCT/autoSCT, and 9 proceeded to the second HDCT/autoSCT.  CTE (carboplatin-thiotepa-etoposide) and cyclophosphamide-melphalan (CM) regimens were used for the first and second HDCT, respectively.  Toxicities during HDCT/autoSCT were acceptable, and there were no treatment-related deaths.  Twelve patients experienced relapse or progression; however, 4patients with germinomas remain alive after subsequent RT.  Therefore, a total of 12 patients (4 NGGCTs and 8 germinomas) remained alive with a median follow-up of 47 months (range of 22 to 90) after relapse or progression.  The probability of 3-year OS was 59.1 ± 11.2 % (36.4 ± 14.5 % for NGGCTs versus 88.9 ± 10.5 % for germinomas, p = 0.028).  Radiotherapy, particularly craniospinal RT, was associated with a better tumor response prior to HDCT/autoSCT and a better final outcome.  The authors concluded that HDCT/autoSCT was feasible, and survival rates were encouraging.  Moreover, they stated that further study with a larger cohort of patients is needed to ascertain the role of HDCT/autoSCT in the treatment of relapsed or progressed CNS-GCTs.

Samuel et al (2013) noted that choroid plexus carcinomas (CPCs) are rare epithelial CNS tumors.  Choroid plexus carcinomas occur mainly in infants and young children, comprising approximately 1 to 4 % of all pediatric brain neoplasms.  There is very limited information available regarding tumor biology and CPC treatment due to its rarity.  There have been various case reports and meta-analyses of reported cases with CPC.  Surgical resection is often challenging but remains a well-established treatment option.  Chemotherapy is often reserved for recurrent or refractory cases, but the goal of treatment is usually palliative.  These investigators presented a case of recurrent, adult CPC with disseminated lepto-meningeal involvement treated with salvage chemotherapy including high-dose ifosfamide, carboplatin, and etoposide; once a remission was achieved, this response was consolidated with a syngeneic stem cell (bone marrow) transplant after a preparative regimen of HDC with carboplatin, etoposide, and thiotepa.  Although the patient tolerated the transplant well and remained disease-free for 12 months, she subsequently succumbed to relapsed disease 18 months post-transplant.  The authors believed that this was the first report of using syngeneic stem cell transplant in CPC to consolidate a remission achieved by salvage chemotherapy.

Kostaras and Easaw (2013) stated that medulloblastoma accounts for almost 1/3 of pediatric CNS cancers, but is very rare in the adult population.  As a result, adult patients with medulloblastoma are often treated according to therapies developed for children with similarly staged disease at diagnosis, based on the assumption that adult and pediatric tumors have similar properties.  These researchers summarized the evidence and made recommendations for the management of recurrent disease in adult patients with medulloblastoma.  These investigators conducted a systematic literature search to find publications addressing treatment of recurrent medulloblastoma in adults.  Current treatment strategies for adult patients with relapsed medulloblastoma are based on the results of retrospective case series and published consensus recommendations, and include maximal safe re-resection where possible, combined with chemotherapy and/or re-irradiation.  They described the results of 13 publications involving 66 adult patients treated with HDC plus SCT for recurrent medulloblastoma.  The authors concluded that HDC with SCT may be a treatment option for a small proportion of adult patients who are unlikely to benefit from conventional chemotherapy and who are fit and have their disease recurrence contained within the CNS.  Moreover, they stated that potential cases in which SCT is being considered should be discussed at a multi-disciplinary tumor board that includes involvement by hematologic oncologists and transplant specialists.

An UpToDate review on “Overview of the management of central nervous system tumors in children” (Lau and Teo, 2013) does not mention the use of stem cell transplant as a therapeutic option.  Furthermore, the National Comprehensive Cancer Network’s clinical practice guideline on “Central nervous system cancers” (Version 2.2013) states that although evidence of its advantage over conventional treatment is lacking, the panel included HDC-autoSCT as a category 2B option for progressive or recurrent primary CNS lymphomas.  Moreover, there is no recommendation regarding HDC-SCT for other types of CNS tumors.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes not covered for indications listed in the CPB:
38204
38205
38206
38207-38215
38230
38232
38240
38241
38242
Other CPT codes related to the CPB:
86813
86817
86821
86822
HCPCS codes not covered for indications listed in the CPB:
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 preparations/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
ICD-9 codes not covered for indications listed in the CPB:
147.0 - 147.9 Malignant neoplasm of nasopharynx
150.0 - 150.9 Malignant neoplasm of esophagus
151.0 - 151.9 Malignant neoplasm of stomach
153.0 - 153.9 Malignant neoplasm of colon
154.0 - 154.8 Malignant neoplasm of rectum, rectosigmoid junction, and anus
155.1 Malignant neoplasm of intrahepatic bile duct
156.0 - 156.9 Malignant neoplasm of gall bladder and extrahepatic bile duct
157.0 - 157.9 Malignant neoplasm of pancreas
160.2 - 160.9 Malignant neoplasm of accessory sinuses (paranasal)
162.0 - 162.9 Malignant neoplasm trachea, bronchus, and lung
164.0 Malignant neoplasm of thymus
171.0 - 171.9 Malignant neoplasm of connective and other soft tissue
172.0 - 172.9 Malignant neoplasm of skin
174.0 - 174.9 Malignant neoplasm of female breast
175.0 - 175.9 Malignant neoplasm of male breast
176.1 Kaposi's sarcoma, soft tissue
180.0 - 180.9 Malignant neoplasm of cervix uteri
182.0 - 182.8 Malignant neoplasm of body of uterus
183.2 Malignant neoplasm of fallopian tube
185 Malignant neoplasm of prostate
189.0 - 189.9 Malignant neoplasm of kidney and other and unspecified urinary organs
191.0 - 191.9 Malignant neoplasm of brain
192.0 - 192.9 Malignant neoplasm of other and unspecified parts of nervous system
193 Malignant neoplasm of thyroid gland
230.0 - 234.9 Carcinoma in situ


The above policy is based on the following references:
  1. Swedish Council on Technology Assessment in Health Care (SBU). Stem cell transplantation for metastasized kidney cancer - early assessment briefs (Alert). Stockholm, Sweden: Swedish Council on Technology Assessment in Health Care (SBU); 2001.
  2. Storb RF, Lucarelli G, McSweeney PA, Childs RW. Hematopoietic cell transplantation for benign hematologic disorders and solid tumors. Hematology Am Soc Hematol Educ Program. Hematology. 2003;372-397.
  3. Bregni M, Bernardi M, Ciceri F, Peccatori J. Allogeneic stem cell transplantation for the treatment of advanced solid tumors. Springer Semin Immunopathol. 2004;26(1-2):95-108.
  4. Espinoza-Delgado I, Childs RW. Nonmyeloablative transplantation for solid tumors: A new frontier for allogeneic immunotherapy. Expert Rev Anticancer Ther. 2004;4(5):865-875.
  5. Nieto Y, Jones RB, Shpall EJ. Stem-cell transplantation for the treatment of advanced solid tumors. Springer Semin Immunopathol. 2004;26(1-2):31-56.
  6. Centers for Medicare and Medicaid Services. National coverage determination for stem cell transplantation (110.8.1). Effective November 28, 2005. Available at: http://www.cms.gov/mcd/viewncd.asp?ncd_id=110.8.1&ncd_version=4&basket=ncd%3A110%2E8%2E1%3A4%3AStem+Cell+Transplantation. Accessed October 5, 2010.
  7. Busca A, Novarino A, de Fabritiis P, et al. Nonmyeloablative allogeneic blood stem cell transplantation in patients with metastatic solid tumors. Hematology. 2006;11(3):171-177.
  8. 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):1479-1488.
  9. Urological Tumours National Working Group. Renal cell carcinoma. Utrecht, The Netherlands: Association of Comprehensive Cancer Centres (ACCC); October 23, 2006. Available at: http://www.guidelines.gov/content.aspx?id=11791&search=solid+tumors. Accessed October 5, 2010.
  10. Working Group Thyroid Carcinoma. Thyroid carcinoma. Utrecht, The Netherlands: Association of Comprehensive Cancer Centres (ACCC); June 1, 2007. Available at: http://www.guidelines.gov/content.aspx?id=11788&search=solid+tumors. Accessed October 5, 2010.
  11. Farquhar CM, Marjoribanks J, Lethaby A, Basser R. High dose chemotherapy for poor prognosis breast cancer: Systematic review and meta-analysis. Cancer Treat Rev. 2007;33(4):325-337.
  12. Demirer T, Barkholt L, Blaise D, et al; EBMT Solid Tumors Working Party. Transplantation of allogeneic hematopoietic stem cells: An emerging treatment modality for solid tumors. Nat Clin Pract Oncol. 2008;5(5):256-267.
  13. National Cancer Institute. Paranasal sinus and nasal cavity cancer treatment (PDQ). Health professional version. Updated July 11, 2008. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/paranasalsinus/
    HealthProfessional
     
    Accessed October 5, 2010.
  14. National Cancer Institute. Uterine sarcoma treatment (PDQ). Health professional version. Updated May 22, 2008. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/uterinesarcoma/
    healthprofessional
    . Accessed October 5, 2010.
  15. Aglietta M, Barkholt L, Schianca FC, et al; EBMT Solid Tumor Working Party. Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. The European group for blood and marrow transplantation experience. Biol Blood Marrow Transplant. 2009;15(3):326-335.
  16. Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: Recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; January 30, 2009. Available at: http://www.guidelines.gov/content.aspx?id=14435&search=solid+tumors+and+stem+cell+transplant. Accessed October 5, 2010.
  17. 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):214-218.
  18. National Cancer Institute. Cervical cancer treatment (PDQ). Health professional version. Updated July 22, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/cervical/HealthProfessional/page1. Accessed October 5, 2010.
  19. National Cancer Institute. Colon cancer treatment (PDQ). Health professional version. Updated August 19, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional/page4. Accessed October 5, 2010.
  20. National Cancer Institute. Endometrial cancer treatment (PDQ). Health professional version. Updated July 28, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/endometrial/healthprofessional. Accessed October 5, 2010.
  21. National Cancer Institute. Esophaegal cancer treatment (PDQ). Health professional version. Updated July 20, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/esophageal/HealthProfessional/page4. Accessed October 5, 2010.
  22. National Cancer Institute. Extrahepatic bile duct cancer treatment (PDQ). Health professional version. Updated July 20, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/bileduct/HealthProfessional. Accessed October 5, 2010.
  23. National Cancer Institute. Gallbladder cancer treatment (PDQ). Health professional version. Updated July 20, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/gallbladder/healthprofessional. Accessed October 5, 2010.
  24. National Cancer Institute. Gastric cancer treatment (PDQ). Health professional version. Updated July 8, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/gastric/HealthProfessional/page4. Accessed October 5, 2010.
  25. National Cancer Institute. Melanoma treatment (PDQ). Health professional version. Updated August 25, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/melanoma/healthprofessional. Accessed October 5, 2010.
  26. National Cancer Institute. Nasopharygeal cancer treatment (PDQ). Health professional version. Updated May 6, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/nasopharyngeal/healthprofessional. Accessed October 5, 2010.
  27. National Cancer Institute. Non-small cell lung cancer treatment (PDQ). Health professional version. Updated August 13, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/healthprofessional Accessed October 5, 2010.
  28. National Cancer Institute. Pancreatic cancer treatment (PDQ). Health professional version. Updated August 13, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/healthprofessional. Accessed October 5, 2010.
  29. National Cancer Institute. Prostate cancer treatment (PDQ). Health professional version. Updated September 7, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/prostate/healthprofessional. Accessed October 5, 2010.
  30. National Cancer Institute. Rectal cancer treatment (PDQ). Health professional version. Updated August 23, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/rectal/healthprofessional. Accessed October 5, 2010.
  31. National Cancer Institute. Small cell lung cancer treatment (PDQ). Health professional version. Updated July 8, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/HealthProfessional/page4. Accessed October 5, 2010.
  32. National Cancer Institute. Adult soft tissue sarcoma treatment (PDQ). Health professional version. Updated July 9, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/healthprofessional/allpages. Accessed October 5, 2010.
  33. National Cancer Institute. Thymoma and thymic carcinoma treatment (PDQ). Health professional version. Updated April 30, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thymoma/healthprofessional. Accessed October 5, 2010.
  34. National Cancer Institute. Thyroid cancer treatment (PDQ). Health professional version. Updated August 13, 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/healthprofessional. Accessed October 5, 2010.
  35. Ljungman P, Bregni M, Brune M, et al; European Group for Blood and Marrow Transplantation. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: Current practice in Europe 2009. Bone Marrow Transplant. 2010;45(2):219-234.
  36. IQWiG. Autologous stem cell transplantation for breast cancer. Cologne, Germany: Institut fuer Qualitaet und Wirtschaftlichkeit im Gesundheitswesen (IQWiG); 2009.
  37. IQWiG. Autologous stem cell transplantation for soft tissue sarcoma. Cologne, Germany: Institut fuer Qualitaet und Wirtschaftlichkeit im Gesundheitswesen (IQWiG); 2009.
  38. 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, single-institutional phase II study. Bone Marrow Transplant. 2010;45(7):1234-1238.
  39. Peinemann F, Smith LA, Kromp M, et al. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas. Cochrane Database Syst Rev. 2011;(2):CD008216.
  40. Peinemann F, Kroger N, Bartel C, et al. High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma -- a systematic review. PLoS One. 2011;6(2):e17127.
  41. Thiel U, Wawer A, Wolf P, et al; Solid Tumor Working Party (STWP) and the Pediatric DiseaseWorking Party (PDWP) of the European Group for Blood and Marrow Transplantation (EBMT); Asia Pacific Blood and Marrow Transplantation (APBMT); Pediatric Registry for Stem Cell Transplantations (PRST); MetaEICESS Study Group. No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients. Ann Oncol. 2011;22(7):1614-1621.


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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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