MEDICAL POLICY – 8.01.28

Hematopoietic Cell Transplantation for Central Nervous

System Embryonal Tumors and Ependymoma

BCBSA Ref. Policy: 8.01.28

Effective Date: April 1, 2020

Last Revised: March 19, 2020

Replaces: N/A

RELATED MEDICAL POLICIES:

7.01.50 Placental and Umbilical Cord Blood as a Source of Stem Cells

Select a hyperlink below to be directed to that section.

POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING

RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY

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Introduction

Some tumors form within the brain and spinal cord, which are both part of the central nervous

system (CNS). Treatment for these tumors may include surgery, chemotherapy, and radiation.

High dose chemotherapy may damage the person’s bone marrow, which is important in making

different types of blood cells. In order to restore bone marrow function, a hematopoietic stem

cell transplant may be done.

Hematopoietic stem cells are cells that form within the bone marrow and can become many

different types of blood cells. In a hematopoietic stem cell transplant, stem cells can be taken

from a donor’s bone marrow, peripheral blood, or from a newborn baby’s umbilical cord blood

or placenta shortly after the baby was delivered. The stem cells can also be harvested from the

patient himself before he is given any high dose chemotherapy. In all of these cases, the

harvested stem cells are then given to the patient, just like in a transfusion. It is hoped that these

new stem cells will then settle into the bone marrow and start producing normal blood cells.

If the hematopoietic stem cells are harvested from another person, it is called an allogeneic

transplant. If the cells come from the patient himself before his high dose chemotherapy is

given, it is called an autologous stem cell transplant. This policy discusses when different types

of hematopoietic stem cell transplants might be medically necessary to treat CNS tumors.

https://www.premera.com/medicalpolicies/7.01.50.pdf

Page | 2 of 15 ∞

Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The

rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for

providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can

be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a

service may be covered.

Policy Coverage Criteria

Transplant Medical Necessity Autologous hematopoietic

cell transplantation

Autologous hematopoietic cell transplantation may be

considered medically necessary as consolidation therapy for

previously untreated embryonal tumors of the central nervous

system (CNS) that show partial or complete response to

induction chemotherapy, or stable disease after induction

therapy (see Additional Information below).

Autologous hematopoietic cell transplantation may be

considered medically necessary to treat recurrent embryonal

tumors of the CNS.

Transplant Investigational Tandem autologous

hematopoietic cell

transplantation

Tandem autologous hematopoietic cell transplant is

investigational to treat embryonal tumors of the CNS.

Allogeneic hematopoietic

cell transplantation

Allogeneic hematopoietic cell transplantation is investigational

to treat embryonal tumors of the CNS.

Autologous, tandem

autologous, and allogeneic

hematopoietic cell

transplant

Autologous, tandem autologous, and allogeneic hematopoietic

cell transplant is investigational to treat ependymoma.

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Additional Information In general, use of autologous hematopoietic cell transplantation for previously untreated

medulloblastoma has shown no survival benefit for those patients considered to be at

average risk (ie, patients older than 3 years of age, without metastatic disease, and with

total or near total surgical resection [

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Related Information

Consideration of Age

The age stated in this policy for which autologous HSCT may be considered medically necessary

as consolidation therapy for previously untreated embryonal tumors of the central nervous

system that show partial or complete response to induction chemotherapy, or stable disease

after induction therapy is age 3 or younger. This is based on scientific evidence that has shown

no survival benefit for patients considered to be at average risk (older than 3 years) without

metastatic disease and with total or near total surgical resection when compared with

conventional therapies. The treatment protocols are based on risk stratification as average or

high risk. The average-risk group at 3 years, without metastatic disease, and with tumors that are

totally or near totally resected. The high-risk group includes children aged 3 years or younger, or

with metastatic disease, and/or subtotal resection.

Benefit Application

The following considerations may supersede this policy:

• State mandates requiring coverage for autologous hematopoietic bone marrow

transplantation offered as part of clinical trials of autologous bone marrow transplantation

approved by the National Institutes of Health.

• Some plans may participate in voluntary programs offering coverage for patients

participating in National Institutes of Health-approved clinical trials of cancer

chemotherapies, including autologous hematopoietic bone marrow transplantation.

• Some contracts or certificates of coverage may include specific conditions in which

autologous hematopoietic bone marrow transplantation would be considered eligible for

coverage.

Evidence Review

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Description

High-dose chemotherapy with hematopoietic cell transplantation (HCT) has been investigated

as a possible therapy in pediatric patients with brain tumors, particularly in those with high risk

disease. The use of HCT has allowed for a reduction in the dose of radiation needed to treat

both average and high-risk disease with a goal of preserving the quality of life and intellectual

functioning.

Background

Central Nervous System Embryonal Tumors

Classification of brain tumors is based on both histopathologic characteristics of the tumor and

location in the brain. Central nervous system (CNS) embryonal tumors are more common in

children and are the most common brain tumor in childhood. Medulloblastomas account for

20% of all childhood CNS tumors.

Recurrent childhood CNS embryonal tumor is not uncommon and, depending on which type of

treatment the patient initially received, autologous hematopoietic cell transplantation (HCT) may

be an option. For patients who receive high-dose chemotherapy and autologous HCT for

recurrent embryonal tumors, objective response is 50% to 75%; however, long-term disease

control is obtained in fewer than 30% of patients and is primarily seen in patients in the first

relapse with localized disease at the time of the relapse.1

Ependymoma

Ependymoma is a neuroepithelial tumor that arises from the ependymal lining cell of the

ventricles and is, therefore, usually contiguous with the ventricular system. An ependymoma

tumor typically arises intracranially in children, while in adults a spinal cord location is more

common. Ependymomas have access to the cerebrospinal fluid and may spread throughout the

entire neuroaxis. Ependymomas are distinct from ependymoblastomas due to their more mature

histologic differentiation.

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Hematopoietic Cell Transplantation

HCT is a procedure in which hematopoietic cells are infused to restore bone marrow function in

cancer patients who receive bone marrow ablative doses of cytotoxic drugs with or without

whole-body radiotherapy. Hematopoietic stem cells may be obtained from the transplant

recipient (autologous HCT) or a donor (allogeneic HCT [allo-HCT]). They can be harvested from

bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an

issue in autologous HCT. In allogeneic stem cell transplantation, immunologic compatibility

between donor and patient is a critical factor for achieving a successful outcome. Compatibility

is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or

molecular techniques. HLA refers to the gene complex expressed at the HLA-A, -B, and -DR

(antigen-D related) loci on each arm of chromosome six. An acceptable donor will match the

patient at all or most of the HLA loci.

Conditioning for HCT

Conventional Conditioning

The conventional (“classical”) practice of allo-HCT involves administration of cytotoxic agents

(eg, cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to

cause bone marrow ablation in the recipient. The beneficial treatment effect of this procedure is

due to a combination of the initial eradication of malignant cells and subsequent graft-versus-

malignancy effect mediated by non-self-immunologic effector cells. While the slower graft-

versus-malignancy effect is considered the potentially curative component, it may be

overwhelmed by existing disease in the absence of pretransplant conditioning. Intense

conditioning regimens are limited to patients who are sufficiently medically fit to tolerate

substantial adverse effects. These include opportunistic infections secondary to loss of

endogenous bone marrow function and organ damage or failure caused by cytotoxic drugs.

Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize

graft rejection and graft-versus-host disease, which increases susceptibility to opportunistic

infections.

The success of autologous HCT is predicated on the potential of cytotoxic chemotherapy, with

or without radiotherapy, to eradicate cancerous cells from the blood and bone marrow. This

permits subsequent engraftment and repopulation of the bone marrow with presumably normal

hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation.

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Therefore, autologous HCT is typically performed as consolidation therapy when the patient’s

disease is in complete remission. Patients who undergo autologous HCT are also susceptible to

chemotherapy-related toxicities and opportunistic infections before engraftment, but not graft-

versus-host disease.

Reduced-Intensity Conditioning Allogeneic HCT

RIC refers to the pretransplant use of lower doses of cytotoxic drugs or less intense regimens of

radiotherapy than are used in traditional full-dose myeloablative conditioning treatments.

Although the definition of RIC is variable, with numerous versions employed, all regimens seek

to balance the competing effects of relapse due to residual disease and non-relapse mortality.

The goal of RIC is to reduce disease burden and to minimize associated treatment-related

morbidity and non-relapse mortality in the period during which the beneficial graft-versus-

malignancy effect of allogeneic transplantation develops. RIC regimens range from nearly total

myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific

diseases and patient condition. Patients who undergo RIC with allo-HCT initially demonstrate

donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to

full-donor chimerism. In this review, the term reduced-intensity conditioning will refer to all

conditioning regimens intended to be nonmyeloablative.

Autologous HCT allows for the escalation of chemotherapy doses above those limited by

myeloablation and has been tried in patients with high-risk brain tumors in an attempt to

eradicate residual tumor cells and improve cure rates. The use of allo-HCT for solid tumors does

not rely on the escalation of chemotherapy intensity and tumor reduction but rather on a graft-

versus-tumor effect. Allo-HCT is not commonly used in solid tumors and may be used if an

autologous source cannot be cleared of a tumor or cannot be harvested.

Summary of Evidence

For individuals who have newly diagnosed central nervous system (CNS) embryonal tumors who

receive autologous HCT, the evidence includes prospective and retrospective studies. The

relevant outcomes are overall survival, disease-specific survival, and treatment-related mortality

and morbidity. For pediatric CNS embryonal tumors, an important consideration is whether the

use of HCT may allow for a reduction in radiation dose. Data from single-arm studies using HDC

with autologous HCT to treat newly diagnosed CNS embryonal tumors have shown comparable

or improved survival (both event-free survival and overall survival) compared with historical

controls treated with conventional therapy, with or without radiotherapy, particularly in patients

Page | 8 of 15 ∞

with disease considered high risk. In a retrospective comparative study, survival in patients

receiving HDC with HCT and delayed craniospinal irradiation was comparable with survival in

those receiving upfront craniospinal irradiation. Overall, data from these observational studies

have suggested HCT may allow reduced doses of craniospinal irradiation without worsening

survival outcomes. The evidence is sufficient to determine that the technology results in a

meaningful improvement in the net health outcome.

For individuals who have recurrent or relapsed CNS embryonal tumors who receive autologous

HCT, the evidence includes prospective and retrospective single-arm studies and a systematic

review of these studies. The relevant outcomes are overall survival, disease-specific survival, and

treatment-related mortality and morbidity. For recurrent/relapsed CNS embryonal tumors,

survival outcomes after HCT vary, and survival is generally very poor for tumors other than

medulloblastoma. Data from some single-arm studies using autologous HCT to treat recurrent

CNS embryonal tumors have shown comparable or improved survival compared with historical

controls treated with conventional therapy for certain patients. The results of a 2012 systematic

review of observational studies in patients with relapsed supratentorial primitive

neuroectodermal tumor suggested that a subgroup of infants with chemosensitive disease

might benefit from autologous HCT, achieving survival without the use of radiotherapy, whereas

outcomes in older children and/or in pineal location are poor with this modality. However, a

relatively large prospective multicenter study has reported that HCT was not associated with

improved survival outcomes in patients who had a good response to therapy. Overall, data from

these single-arm studies have suggested HCT may be associated with improved survival

outcomes in select patients, although data for some tumor types are limited (eg, atypical

teratoid/rhabdoid tumors). The evidence is sufficient to determine that the technology results in

a meaningful improvement in the net health outcome.

For individuals who have CNS embryonal tumors who receive tandem autologous HCT, the

evidence includes prospective and retrospective single-arm studies. The relevant outcomes are

overall survival, disease-specific survival, and treatment-related mortality and morbidity. Less

evidence specifically addresses the use of tandem autologous HCT for CNS embryonal tumors.

The available single-arm studies are very small, but appear to report overall survival and event-

free survival rates comparable with single autologous HCT. Tandem transplants might allow

reduced doses of craniospinal irradiation, with the goal of avoiding long-term radiation damage.

However, most studies used standard-dose irradiation, making the relative benefit of tandem

autologous HCT uncertain. The evidence is insufficient to determine the effects of the

technology on health outcomes.

For individuals who have CNS embryonal tumors who receive allogeneic HCT, the evidence

includes case reports. The relevant outcomes are overall survival, disease-specific survival, and

Page | 9 of 15 ∞

treatment-related mortality and morbidity. The available evidence is limited. The evidence is

insufficient to determine the effects of the technology on health outcomes.

For individuals who have ependymoma who receive autologous HCT, the evidence includes

relatively small case series. The relevant outcomes are overall survival, disease-specific survival,

and treatment-related mortality and morbidity. The available case series do not report higher

survival rates for patients with ependymoma treated with HCT compared with standard

therapies. The evidence is insufficient to determine the effects of the technology on health

outcomes.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT No. Trial Name Planned

Enrollment

Completion

Date

Ongoing

NCT00085202 Treatment of Patients With Newly Diagnosed

Medulloblastoma, Supratentorial Primitive Neuroectodermal

Tumor, or Atypical Teratoid Rhabdoid Tumor

416 Jan 2023

Unpublished

NCT00653068 Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of

the Central Nervous System With Surgery, Intensive

Chemotherapy, and 3-D Conformal Radiation

70 Apr 2015

(completed)

NCT00336024 A Phase III Randomized Trial for the Treatment of Newly

Diagnosed Supratentorial PNET and High Risk

Medulloblastoma in Children < 36 Months Old With

Intensive Induction Chemotherapy With Methotrexate

Followed by Consolidation With Stem Cell Rescue Versus

the Same Therapy Without Methotrexate

96 Dec 2016

(completed)

NCT02653196 A Multi-Institutional Phase II Feasibility Study of Allogeneic

Hematopoietic Stem Cell Transplantation for Patients With

Malignant Neuro-Epithelial and Other Solid Tumors

30 Aug 2017

(terminated; the

principal

investigator left

the institution)

https://www.clinicaltrials.gov/ct2/show/NCT00085202?term=NCT00085202&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00653068?term=NCT00653068&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00336024?term=NCT00336024&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02653196?term=NCT02653196&rank=1

Page | 10 of 15 ∞

NCT: national clinical trial.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

Current National Comprehensive Cancer Network (v.3.2019) guidelines on treating central

nervous system tumors make the following recommendations about hematopoietic cell

transplant (HCT)36:

• For medulloblastoma and supratentorial primitive neuroectodermal tumor, autologous HCT

for localized recurrent disease with maximum safe resection is a category 2A

recommendation.

American Society for Blood and Marrow Transplantation

The American Society for Blood and Marrow Transplantation (2015) published consensus

guidelines on the use of HCT to treat specific conditions, in both clinical trial and clinical practice

settings.37 Per this review, clinical evidence is available to support autologous HCT in pediatric

patients (

Page | 11 of 15 ∞

References

1. Mueller S, Chang S. Pediatric brain tumors: current treatment strategies and future therapeutic approaches. Neurotherapeutics.

Jul 2009;6(3):570-586. PMID 19560746

2. Fangusaro J, Finlay J, Sposto R, et al. Intensive chemotherapy followed by consolidative myeloablative chemotherapy with

autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive

neuroectodermal tumors (sPNETs): report of the Head Start I and II experience. Pediatr Blood Cancer. Feb 2008;50(2):312-318.

PMID 17668858

3. National Cancer Institute Physician Data Query (PDQ). Childhood Central Nervous System Embryonal Tumors (last modified

August 1, 2013). http://www.cancer.gov/cancertopics/pdq/treatment/childCNSembryonal/healthprofessional Accessed

March 2020.

4. Odagiri K, Omura M, Hata M, et al. Treatment outcomes and late toxicities in patients with embryonal central nervous system

tumors. Radiat Oncol. Sep 11 2014;9:201. PMID 25209395

5. Alsultan A, Alharbi M, Al-Dandan S, et al. High-dose chemotherapy with autologous stem cell rescue in saudi children less than

3 years of age with embryonal brain tumors. J Pediatr Hematol Oncol. Apr 2015;37(3):204- 208. PMID 25551668

6. Raleigh DR, Tomlin B, Buono BD, et al. Survival after chemotherapy and stem cell transplant followed by delayed craniospinal

irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients. J Neurooncol. Jan

2017;131(2):359-368. PMID 27778212

7. Chintagumpala M, Hassall T, Palmer S, et al. A pilot study of risk-adapted radiotherapy and chemotherapy in patients with

supratentorial PNET. Neuro Oncol. Sep 2009;11(1):33-40. PMID 18796696

8. Massimino M, Gandola L, Biassoni V, et al. Evolving of therapeutic strategies for CNS-PNET. Pediatr Blood Cancer. Dec

2013;60(12):2031-2035. PMID 23852767

9. Lester RA, Brown LC, Eckel LJ, et al. Clinical outcomes of children and adults with central nervous system primitive

neuroectodermal tumor. J Neurooncol. Nov 2014;120(2):371-379. PMID 25115737

10. Dhall G, Grodman H, Ji L, et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma

treated with chemotherapy on the Head Start I and II protocols. Pediatr Blood Cancer. Jun 2008;50(6):1169-1175. PMID

18293379

11. Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and

stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a

prospective, multicentre trial. Lancet Oncol. Oct 2006;7(10):813- 820. PMID 17012043

12. Bergthold G, El Kababri M, Varlet P, et al. High-dose busulfan-thiotepa with autologous stem cell transplantation followed by

posterior fossa irradiation in young children with classical or incompletely resected medulloblastoma. Pediatr Blood Cancer.

May 2014;61(5):907-912. PMID 24470384

13. Lee JY, Kim IK, Phi JH, et al. Atypical teratoid/rhabdoid tumors: the need for more active therapeutic measures in younger

patients. J Neurooncol. Apr 2012;107(2):413-419. PMID 22134767

14. Raghuram CP, Moreno L, Zacharoulis S. Is there a role for high dose chemotherapy with hematopoietic stem cell rescue in

patients with relapsed supratentorial PNET? J Neurooncol. Feb 2012;106(3):441-447. PMID 21850536

15. Dunkel IJ, Gardner SL, Garvin JH, Jr., et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for

patients with previously irradiated recurrent medulloblastoma. Neuro Oncol. Mar 2010;12(3):297- 303. PMID 20167818

16. Dunkel IJ, Boyett JM, Yates A, et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for

patients with recurrent medulloblastoma. Children's Cancer Group. J Clin Oncol. Jan 1998;16(1):222- 228. PMID 9440746

http://www.cancer.gov/cancertopics/pdq/treatment/childCNSembryonal/healthprofessional

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17. Grodman H, Wolfe L, Kretschmar C. Outcome of patients with recurrent medulloblastoma or central nervous system germinoma

treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous

hematopoietic stem cell rescue. Pediatr Blood Cancer. Jul 2009;53(1):33- 36. PMID 19326417

18. Kostaras X, Easaw JC. Management of recurrent medulloblastoma in adult patients: a systematic review and recommendations. J

Neurooncol. Oct 2013;115(1):1-8. PMID 23877361

19. Bode U, Zimmermann M, Moser O, et al. Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and

adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial. J

Neurooncol. Dec 2014;120(3):635-642. PMID 25179451

20. Gill P, Litzow M, Buckner J, et al. High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent

embryonal tumors of the central nervous system. Cancer. Apr 15 2008;112(8):1805-1811. PMID 18300237

21. Kim H, Kang HJ, Lee JW, et al. Irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide for refractory or relapsed

medulloblastoma/PNET in pediatric patients. Childs Nerv Syst. Oct 2013;29(10):1851-1858. PMID 23748464

22. Egan G, Cervone KA, Philips PC, et al. Phase I study of temozolomide in combination with thiotepa and carboplatin with

autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease. Bone Marrow

Transplant. Apr 2016;51(4):542-545. PMID 26726947

23. Sung KW, Lim DH, Yi ES, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for atypical

teratoid/rhabdoid tumor. Cancer Res Treat. Oct 2016;48(4):1408-1419. PMID 27034140

24. Dufour C, Kieffer V, Varlet P, et al. Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly

diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors. Pediatr Blood Cancer. Aug

2014;61(8):1398-1402. PMID 24664937

25. Sung KW, Lim do H, Son MH, et al. Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and

autologous stem cell transplantation in patients with high-risk medulloblastoma. Neuro Oncol. Mar 2013;15(3):352-359. PMID

23258845

26. Friedrich C, von Bueren AO, von Hoff K, et al. Treatment of young children with CNS-primitive neuroectodermal

tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy.

Neuro Oncol. Feb 2013;15(2):224-234. PMID 23223339

27. Park ES, Sung KW, Baek HJ, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation in young children

with atypical teratoid/rhabdoid tumor of the central nervous system. J Korean Med Sci. Feb 2012;27(2):135-140. PMID 22323859

28. Sung KW, Yoo KH, Cho EJ, et al. High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed

high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor. Pediatr Blood Cancer. Apr

2007;48(4):408-415. PMID 17066462

29. Lundberg JH, Weissman DE, Beatty PA, et al. Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy

and allogeneic bone marrow transplantation. J Neurooncol. Jun 1992;13(2):151-155. PMID 1432032

30. Matsuda Y, Hara J, Osugi Y, et al. Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from

HLA-mismatched donors. Bone Marrow Transplant. Feb 1998;21(4):355-360. PMID 9509968

31. Secondino S, Pedrazzoli P, Schiavetto I, et al. Antitumor effect of allogeneic hematopoietic SCT in metastatic medulloblastoma.

Bone Marrow Transplant. Jul 2008;42(2):131-133. PMID 18372908

32. Sung KW, Lim do H, Lee SH, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic

ependymoma in children younger than 3 years of age. J Neurooncol. Apr 2012;107(2):335-342. PMID 22081297

33. Mason WP, Goldman S, Yates AJ, et al. Survival following intensive chemotherapy with bone marrow reconstitution for children

with recurrent intracranial ependymoma--a report of the Children's Cancer Group. J Neurooncol. Apr 1998;37(2):135-143. PMID

9524092

34. Grill J, Kalifa C, Doz F, et al. A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation

in childhood recurrent ependymoma. A phase-II study. Pediatr Neurosurg. Jul 1996;25(1):7-12. PMID 9055328

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35. Zacharoulis S, Levy A, Chi SN, et al. Outcome for young children newly diagnosed with ependymoma, treated with intensive

induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer. Jul

2007;49(1):34-40. PMID 16874765

36. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: central nervous system

cancers. Version 3.2019. http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf Accessed March 2020.

37. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation:

Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov

2015;21(11):1863-1869. PMID 26256941

History

Date Comments 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.

12/11/01 Replace Policy - Policy references updated.

03/11/03 Replace Policy - Policy updated and references added; no change in policy statement.

10/12/04 Replace Policy - Policy updated with literature review; policy statement unchanged

(text updated for clarification only). Approved by OAP 10/29/04, no need to go back to

MPC.

01/10/06 Replace Policy - Policy updated with literature review; no change to policy statement.

Reviewed by OAP 10/27/05.

06/02/06 Disclaimer and Scope update - No other changes

11/14/06 Replace Policy - Policy reviewed and recommended by OAP October 26, 2006; no

changes to policy statement.

12/11/07 Replace Policy - Policy updated with literature review. Policy statement added to

indicate that multi-cycle high-dose chemotherapy (with or without associated

radiotherapy) and autologous stem-cell support (ie, tandem transplants) as

investigational. Policy reviewed and recommended by OAP November 15, 2007.

05/13/08 Cross Reference Update - No other changes

12/16/08 Replace Policy - Policy updated with literature search; no change to the policy

statement. References added. Reviewed and recommended by OAP, August 21, 2008.

01/13/09 Code Updates - Code added, J8705; effective 1/1/09.

01/12/10 Replace Policy - Policy extensively revised with literature search; policy title changed to

remove “high-dose chemotherapy” and to change PNET to embryonal tumors. Policy

statement changed regarding autologous consolidation therapy in patients with

previously untreated embryonal tumors showing complete or partial response to, or

http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf

Page | 14 of 15 ∞

Date Comments stable disease after, induction therapy; now considered medically necessary. Other

policy statements reworded and separated to address ependymoma and embryonal

CNS tumors specifically; however, the intent of the statements remains the same.

References added.

02/09/10 Code Update - New 2010 codes added.

03/08/11 Replace Policy - Policy updated with literature search through October 2010;

references 7, 12-14 added. No change to policy statements.

05/12/11 Reviewed by OAP - No changes recommended to the policy.

01/06/12 Replace Policy – Policy updated with literature search. No references added; no change

in policy statements. ICD-10 codes added.

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.

07/30/12 Related Policy title updates to: 8.01.17, 8.01.22, 8.01.31, 8.01.35 and 8.01.520. Deleted

8.01.38 as it was archived.

10/08/12 Update Coding Section – ICD-10 codes are now effective 10/01/2014.

01/29/13 Replace policy. Policy updated with literature search. References 7, 8, 13 and 18 added;

no change in policy statements. Removed CPT codes 38220 and 38221; they do not

apply to this policy. Change title to Related 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 policy title to 8.01.31.

10/18/13 Update Related Policies. Change title to policy 8.01.17.

01/21/14 Replace policy. Policy updated with literature search through October 8, 2013.

References 13 and 14 added, references 3 and 24 updated; no change in policy

statements. Remove CPT code 38230; it does not apply to this policy.

03/21/14 Update Related Policies. Remove 801.514 as it was deleted.

04/18/14 Update Related Policies. Remove 8.01.20 and replace with 8.01.529.

06/24/14 Update Related Policies. Remove 8.01.35, 8.01.42 and 8.01.54, then add 8.01.530,

8.01.531 and 8.01.532.

12/03/14 Update Related Policies. Remove 8.01.17 and 8.01.26.

01/28/15 Annual Review. Policy updated with literature review through September 30, 2014.

References 5-6, 9, 15, and 17-19 added. Policy statements unchanged. ICD-9 and ICD-

10 diagnosis codes removed; these are not utilized in policy adjudication.

Page | 15 of 15 ∞

Date Comments 05/01/16 Annual Review, approved April 12, 2016. Policy updated with literature review through

October 27, 2015; references 4-6 and 9 added. Policy statements unchanged.

11/04/16 Coding update. Removed codes that are transplant benefit related.

04/01/17 Annual Review, approved March 14, 2017. Policy updated with literature review

through November 7, 2016; references 6, and 22-23 added. Changed “hematopoietic

stem cell transplantation” to “hematopoietic cell transplantation” per NCCN

terminology change. Policy statements unchanged.

11/10/17 Policy moved to new format, no changes to policy statement.

05/01/18 Annual Review, approved April 3, 2018. Policy updated with literature review through

November 2017; reference 37 added; reference 36 updated. Policy statements

unchanged.

09/01/18 Minor update. Re-added Consideration of Age information, which was inadvertently

removed during a previous update.

04/01/19 Annual Review, approved March 19, 2019. Policy updated with literature review

through December 2018; no references added; reference 36 updated. Policy

statements unchanged.

04/01/20 Annual Review, approved March 19, 2020. Policy updated with literature review

through November 2019; no references added. Policy statements unchanged.

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). ©2020 Premera

All Rights Reserved.

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. This medical policy does not apply to Medicare Advantage.

Discrimination is Against the Law

Premera Blue Cross complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. Premera does not exclude people or treat them differently because of race, color, national origin, age, disability or sex.

Premera: • Provides free aids and services to people with disabilities to communicate

effectively with us, such as: • Qualified sign language interpreters • Written information in other formats (large print, audio, accessible

electronic formats, other formats) • Provides free language services to people whose primary language is not

English, such as: • Qualified interpreters• Information written in other languages

If you need these services, contact the Civil Rights Coordinator.

If you believe that Premera has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator - Complaints and Appeals PO Box 91102, Seattle, WA 98111 Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357 Email AppealsDepartmentInquiries@Premera.com

You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights, electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services 200 Independence Avenue SW, Room 509F, HHH Building Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD) Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Getting Help in Other Languages

This Notice has Important Information. This notice may have important information about your application or coverage through Premera Blue Cross. There may be key dates in this notice. You may need to take action by certain deadlines to keep your health coverage or help with costs. You have the right to get this information and help in your language at no cost. Call 800-722-1471 (TTY: 800-842-5357).

አማሪኛ (Amharic): ይህ ማስታወቂያ አስፈላጊ መረጃ ይዟል። ይህ ማስታወቂያ ስለ ማመልከቻዎ ወይም የ Premera Blue Cross ሽፋን አስፈላጊ መረጃ ሊኖረው ይችላል። በዚህ ማስታወቂያ ውስጥ ቁልፍ ቀኖች ሊኖሩ ይችላሉ። የጤናን ሽፋንዎን ለመጠበቅና በአከፋፈል እርዳታ ለማግኘት በተውሰኑ የጊዜ ገደቦች እርምጃ መውሰድ ይገባዎት ይሆናል። ይህን መረጃ እንዲያገኙ እና ያለምንም ክፍያ በቋንቋዎ እርዳታ እንዲያገኙ መብት አለዎት።በስልክ ቁጥር 800-722-1471 (TTY: 800-842-5357) ይደውሉ።

( ةالعربي :(. امةھ ماتولعم اإلشعار ھذا يحوي

خالل من ھاعلي صولحلا تريد لتيا التغطيةلل أو ةصحيلاكطيتتغ لىع اظلحفل نةعيم يخراوت في إجراء خاذتال تحتاج وقد .اإلشعار ھذا في

تكلفة أية بدتك دون بلغتك مساعدةوال تاوملالمع ھذه على ولحصال لك يحق .800-722-1471 (TTY: 800-842-5357)

أو طلبك وصخصب مةمھ ماتوعلم عارشإلا ھذا ويحي قدةمھم يخراوت ھناك تكون قد .Premera Blue Cross

اعدةمس تصلايفكالتال دفع فيبـ

.

Arabic

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Italiano ( ):Questo avviso contiene informazioni importanti. Questo avviso può contenere informazioni importanti sulla tua domanda o copertura attraverso Premera Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe essere necessario un tuo intervento entro una scadenza determinata per consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di ottenere queste informazioni e assistenza nella tua lingua gratuitamente. Chiama 800-722-1471 (TTY: 800-842-5357).

Italian

中文 (Chinese):本通知有重要的訊息。本通知可能有關於您透過 Premera Blue Cross 提交的申請或保險的重要訊息。本通知內可能有重要日期。您可能需要在截止日期

之前採取行動，以保留您的健康保險或者費用補貼。您有權利免費以您的母

語得到本訊息和幫助。請撥電話 800-722-1471 (TTY: 800-842-5357)。

037338 (07-2016)

https://www.hhs.gov/ocr/office/file/index.htmlhttps://ocrportal.hhs.gov/ocr/portal/lobby.jsfmailto:AppealsDepartmentInquiries@Premera.com

日本語 (Japanese):この通知には重要な情報が含まれています。この通知には、 Premera Blue Crossの申請または補償範囲に関する重要な情報が含まれている場合があります。この通知に記載されている可能性がある重要な日付をご確認くだ

さい。健康保険や有料サポートを維持するには、特定の期日までに行動を

取らなければならない場合があります。ご希望の言語による情報とサポー

トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話ください。

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ລາວ (Lao): ແຈ້ງການນີ້ ນສໍ າຄັນ. ແຈ້ງການນີ້ອາດຈະມີ ນສໍ າຄັນກ່ຽວກັບຄໍ າຮ້ອງສະ ກ ຫຼື ຄວາມຄຸ້ມຄອງປະກັນໄພຂອງທ່ານຜ່ານ Premera Blue Cross. ອາດຈະມີ ນທີ າຄັນໃນແຈ້ງການນີ້. ທ່ານອາດຈະຈໍ າເປັ ນຕ້ອງດໍ າເນີ ນການຕາມກໍ ານົດ ເວລາສະເພາະເພື່ອຮັກສາຄວາມຄຸ້ມຄອງປະກັນສຸຂະພາບ ຫຼື ຄວາມຊ່ວຍເຫຼື ອເລື່ອງ າໃຊ້ າຍຂອງທ່ານໄວ້ . ທ່ານມີ ດໄດ້ ບຂໍ້ ນນີ້ ແລະ ຄວາມຊ່ວຍເຫຼື ອເປັ ນພາສາ ຂອງທ່ານໂດຍບ່ໍ ເສຍຄ່າ. ໃຫ້ໂທຫາ 800-722-1471 (TTY: 800-842-5357).

ູຂໍ້

່

ສໍ ັ

ຈ

ໝ

ສິ

ັ

່

ວ

ຄ

ມ

ມູຮັ

ູມີ ມຂໍ້

ភាសាែខមរ ( ): ឹ

រងរបស់

Premera Blue Cross ។ របែហលជាមាន កាលបរ ិ ឆ ំខានេនៅកងេសចក

េសចកតជី ូ

ជាមានព័ ៌ ៉ ងសំ ់អពី ់ ៉ ប់

នដំ ងេនះមានព័ ី

តមានយា ខាន ំ ទរមងែបបបទ ឬការរា

ណ ត៌មានយ៉ា ំ ់ តងសខាន។ េសចក

េចទស ់ ន ុ ត

ណងេនះ។ អ វការបេញញសមតភាព ដលកណតៃថ ចបាស

កតាមរយៈ

ដំ ឹ នករបែហលជារតូ ច ថ ់ ំ ់ ងជាក់ ់

នដ

ន

ី ន

ូ

អ

ូ

ជ

ជ

ំណឹងេនះរបែហល

នានា េដើ ីនងរកសាទុ ៉ បរងស់ ុ ់ ក ឬរបាក់ ំ

អ

មប ឹ កការធានារា ខភាពរបស ជ

ធនកមានសិ ទទលព័ មានេនះ និ ំ យេនៅកុងភាសារបសទិ ួ ត៌ ងជ ននួ

ន

់ កេដាយម

អ

នអ

យេចញៃថល។ ួ

នអស

ន

ិ

លុ ើ ូ ូយេឡយ។ សមទ ទ រស័ព 800-722-1471 (TTY: 800-842-5357)។

Khmer

ਕਵਰਜ ਅਤ ਅਰਜੀ ਬਾਰ ਮਹ ਤਵਪਰਨ ਜਾਣਕਾਰੀ ਹ ਸਕਦੀ ਹ . ਇਸ ਨ ਿਜਸ ਜਵਚ ਖਾਸ

ਤਾਰੀਖਾ ਹ ਸਕਦੀਆ ਹਨ. ਜੇਕਰ ਤਸੀ ਜਸਹਤ ਕਵਰਜ ਿਰਖਣੀ ਹਵ ਜਾ ਓਸ ਦੀ ਲਾਗਤ ਜਿਵਚ ਮਦਦ ਦ ੇਇਛ ੁਕ ਹ ਤਾਂ ਤਹਾਨ ਅ ਤਮ ਤਾਰੀਖ਼ ਤ ਪਿਹਲਾਂ ਕੁ ਝ ਖਾਸ ਕਦਮ ਚ ਕਣ ਦੀ ਲੜ ਹ ਸਕਦੀ ਹ ,ਤਹੁਾਨ ਮਫ਼ਤ ਿਵਚ ਤ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵ ਚ ਜਾਣਕਾਰੀ ਅਤ ਮਦਦ ਪਾਪਤ ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹ ,ਕਾਲ 800-722-1471 (TTY: 800-842-5357).

ਪ ਜਾਬੀ (Punjabi): ਇਸ ਨ ਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹ. ਇਸ ਨ ਿਟਸ ਿਵਚ Premera Blue Cross ਵਲ ਤੁਹਾਡੀ

ੰ

ੰ

ੇ ੇ ੇ ੱ ੂ ੋ ੈ ੋੋ ਂ ੁ ੇ ੱ ੋ ੇ ੱੱ ੁ ੱ ੂੁ ੱ ੇ ੱ ੇ ੍ਰ ੈ

ੋ ੰ ੂ ੱ ੁ ੋ ੋ ੈ ੰ

ੋ ੈ ੋ

(Farsi): فارسی فرم بارهدر ھمم اطالعات حاوی است ممکن يهمالعا اين. ميباشد ھمم اطالعات یوحا يهمالعا اين

در ھمم ھای خيتار به باشد.پ رایبستاکنممماش زينهھ اختدپر در مککيا تان بيمهوشش حقظ

Premera Blue Cross طريق از ماش مهبيوشش يا و تقاضا ای پ. يدماين جهتو يهمالعا اين

حق شما. يدشاب داشته اجتياح صیاخ کارھای امانج برای صیمشخ ایھ خيتار به تان، انیمدر ھای کسب برای .نماييد دريافت گانيرا ورط به ودخ زبان به را کمک و اطالعات اين که داريد را اين

استم ) 5357-842-800 مارهباش ماست TTY انکاربر(800-722-1471 مارهش با اطالعات .اييدنم برقرار

้

Polskie (Polish): To ogłoszenie może zawierać ważne informacje. To ogłoszenie może

zawierać ważne informacje odnośnie Państwa wniosku lub zakresu świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej lub pomocy związanej z kosztami. Macie Państwo prawo do bezpłatnej informacji we własnym języku. Zadzwońcie pod 800-722-1471 (TTY: 800-842-5357).

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Spanish

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้ี ี ้ ู ํ ั ้ี ี ้ ู ่ี ํ ั ่ี ั ั ื ัุ ุ ่ ี ํ ี ุ ้ํ ิ ํ ่ี ่ ่ื ั ั ุ ุ ื ่ ื ่ีี ่ ้ ่ ุ ี ิ ิ ่ี ้ ั ้ ู ่ ื ้ี ุ ี ่ ้ ่

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