0635 Hematopoietic Cell Transplantation for Ovarian Cancer - Aetna€¦ · 01/03/2019 · and the 4th leading cause of cancer death in American women. Each year about 25,400 new

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Hematopoietic Cell Transplantation for Ovarian Cancer

Clinical Policy Bulletins Medical Clinical Policy Bulletins

Policy History

Last

Review

03/01/2019

Effective: 08/16/200

Next Review:

06/27/2019

Review History

Definitions

Additional

Number: 0635

Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.

I. Aetna considers autologous hematopoietic cell transplantation medically

necessary for the treatment of persons with relapsed germ cell tumors of

the ovary that were responsive to standard chemotherapy.

II. Aetna considers autologous hematopoietic cell transplantation medically

necessary as consolidation therapy for persons with germ cell tumors of the

ovary that is in complete remission.

III. Aetna considers tandem autologous hematopoietic cell

transplantation medically necessary for persons with germ cell tumors of

the ovary that is in relapse.

IV. Aetna considers autologous hematopoietic cell

transplantation experimental and investigational when used as initial

treatment (i.e., instead of an initial course of standard-dose chemotherapy

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with Food and D rug Administration (FDA)-approved drugs) of persons with

germ cell tumors of the ovary because its effectiveness for this indication

has not been established.

V. Aetna considers allogeneic hematopoietic cell transplantation experimental

and investigational for the treatment of persons with germ cell tumors of

the ovary because its effectiveness for this indication has not been

established.

VI. Aetna considers hematopoietic cell transplantation (autologous or

allogeneic) experimental and investigational for the treatment of persons

with epithelial ovarian cancers because its effectiveness for this indication

has not been established.

Background

Ovarian cancer is the leading cause of death among gynecological malignancies

and the 4th leading cause of cancer death in American women. Each year about

25,400 new cases of ovarian cancer are diagnosed and 14,500 women die from the

disease. Approximately 90 % of all ovarian cancers are epithelial ovarian

carcinomas arising from the germinal epithelium of the ovary. The remaining 10 %

of ovarian malignancies consist of germ cell origin, stromal and sex cord tumors.

Epithelial ovarian cancer accounts for 4 % of all cancers in women. Germ cell

tumors of the ovary are uncommon but aggressive tumors seen most often in

young women or adolescent girls. About 50 % of germ cell malignancies are pure

dysgerminomas; and about 70 % of dysgerminomas are confined to the ovary at

diagnosis.

The most important risk factor for ovarian cancer is a family history of a 1st-degree

relative with the disease. Approximately 5 to 10 % of ovarian cancers are familial

and there is increasing evidence that there are a small number of families at

particularly high-risk for developing epithelial ovarian cancer. Three distinct

hereditary syndromes associated with the occurrence of familial ovarian cancer

have been identified: (i) ovarian cancer syndrome, (ii) hereditary breast-ovarian

cancer syndrome, and (iii) Lynch II syndrome, which includes a predisposition

to ovarian, endometrial, and colon cancers. All 3 syndromes exhibit an

autosomal dominant pattern of transmission with variable penetrance.

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Since early stage ovarian cancer has no major associated symptoms and there are

no reliable screening tests, the majority of patients present with metastatic disease

throughout the peritoneal cavity. In the United States, nearly 70 % of the 23,000

patients diagnosed annually with epithelial ovarian cancer present with advanced

disease -- International Federation of Gynecology and Obstetrics (FIGO) stages III

to IV. The FIGO staging for primary ovarian carcinoma is as follows:

Table: Stages of Primary Ovarian Carcinoma

The prognosis of ovarian cancer is influenced by several factors including stage at

presentation, size of residual tumor following initial surgery, histologic grade, patient

performance status and age. The 5-year survival rate for patients with advanced

ovarian cancer treated with conventional therapy were only 15 to 25 % for stage III

disease and less than 5 % for stage IV disease.

All stages of ovarian cancer are first treated with cytoreductive surgery, including

oophorectomy and total abdominal hysterectomy. Unilateral oophorectomy is

adequate treatment for most patients with stage I and stage II diseases. The

objective of surgery in disease stages later than stage I is to reduce the bulk of the

largest residual tumor deposit to less than 1 or 2 cm for optimal disease prognosis.

While this may be sufficient treatment for cases confined to the ovary, typically intra-

peritoneal spread is identified; thus, surgery is commonly followed by chemotherapy.

Paclitaxel/platinum combinations are the standard 1st-line chemotherapy. The extent

of chemotherapy treatment varies with the stage of disease. Ovarian cancers are

responsive to chemotherapy in 80 to 90 % of cases, and the success of

chemotherapy is dependent on the volume of disease that remains after

cytoreductive surgery. Salvage chemotherapy with several single

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agents has only modest activity and does not extend survival of patients with

relapsed ovarian carcinoma. Sex cord-stromal tumors can occur at any point in a

woman's life. Because of the rarity of sex cord-stromal tumors, there is no

established chemotherapeutic regimen.

Multiple uncontrolled studies have examined the effectiveness of single and

multiple cycles of high-dose chemotherapy (HDC) with stem cell support (peripheral

stem cells or autologous bone marrow transplantation) in patients with advanced

and chemo-resistant epithelial ovarian cancer. High-dose chemotherapy with

autologous stem cell transplantation is still investigational for patients with epithelial

ovarian cancer.

In a review on HDC for the management of patients with ovarian cancer, McGuire

(2000) noted that the effect of HDC (including stem cell-supported HDC) on the

survival of women with ovarian cancer has been examined in numerous clinical

studies. The data demonstrated increased response rates with high-dose

regimens, but any survival advantages observed have been limited. Patients with

the most favorable outcome were those with low tumor burden and chemotherapy-

sensitive tumors. An attempt to study this group of patients in a randomized trial in

the United States (Gynecologic Oncology Group Protocol 164) was unsuccessful

because of low accrual. European randomized trials are under way to evaluate

HDC and stem cell transplantation as part of initial therapy or as consolidation after

initial response to therapy and to compare HDC with standard-dose chemotherapy.

Until results from these studies become available, HDC remains limited to the

clinical trial setting.

In a phase I clinical trial, Donato and associates (2001) examined the effectiveness

of HDC with autologous stem cell support for the treatment of women with

advanced ovarian cancer (n = 53). All patients had refractory and/or recurrent

ovarian cancer and had been previously treated with paclitaxel and platinum. The

overall response rate in the 30 patients with measurable or evaluable disease was

93 %. It was reported that toxicity was acceptable and there were no treatment-

related deaths. The authors concluded that in the setting of ovarian cancer, high-

dose regimens should be administered only as part of a well-designed clinical trial.

In a retrospective study, Ledermann and colleagues (2001) analyzed the outcome

of patients with advanced or recurrent epithelial ovarian cancer (n = 254) treated

with HDC -- 105 received HDC in complete or very good partial remission, 27 in

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second remission and 122 in the presence of residual disease. Most received

melphalan or carboplatin, or a combination (86 %) supported by autologous bone

marrow or peripheral blood stem cells. The survival of patients treated in remission

was significantly better than in other groups (median 33 versus 14 months). The

durability of remission was longer after transplantation in first remission than in

second remission (median disease-free survival 18 versus 9 months). With a

median follow-up of 76 months from diagnosis, the median disease-free and overall

survival (OS) in stage III disease transplanted in remission is 42 and 59 months and

for stage IV disease 26 and 40 months, respectively. The authors concluded that

HDC has a potential benefit for patients in remission. The results support the

conduct of randomized studies to determine whether there is a real value from this

treatment.

In a review on 2nd-line and subsequent therapy for ovarian carcinoma,

Peethambaram and Long (2002) stated that HDC with autologous stem cell

transplantation is still investigational. Women with advanced ovarian carcinoma

should continue to be encouraged to participate in well-designed clinical trials.

The European Group for Blood and Marrow Transplantation (Urbano-Ispizua et al,

2002) recently stated that for ovarian cancer with minimal residue disease,

allogeneic transplantation is not generally recommended; while autologous

transplantation may be undertaken in approved clinical protocols -- the value of

transplants for patients included in this category needs further investigation. For

refractory ovarian cancer, allogeneic transplantation using sibling donor is

developmental (there is very little experience with this particular type of transplant);

while allogeneic transplantation using alternative donor or autologous

transplantation is not generally recommended. For relapsed germ cell tumors that

were sensitive to chemotherapy, allogeneic transplantation is not generally

recommended, while autologous transplantation is standard use in selected

patients. For refractory germ cell tumors, allogeneic transplantation is not generally

recommended; while autologous transplantation may be undertaken in approved

clinical protocols.

Schilder et al (2003) stated that HDC (supported by hematopoietic stem cells) as 1st-

line treatment for epithelial ovarian cancer remains experimental and should be

restricted to clinical trials.

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Bengala et al (2005) reported that HDC with autologous hemopoietic support does

not benefit patients with advanced epithelial ovarian cancer in first complete

remission.

In a phase II multi-center study, Goncalves and colleagues (2006) assessed the

feasibility, toxicity and effectiveness of post-operative front-line sequential HDC with

hematopoietic stem cell (HSC) support in patients with advanced ovarian cancer

(AOC). A total of 34 patients with stage IIIC/IV epithelial ovarian cancer received a

post-operative sequential combination of high-dose cyclophosphamide/epirubicin

(D1, D21) with HSC harvesting, high-dose carboplatin (D42, D98) followed by HSC

infusion, and dose-dense paclitaxel (D63, D77, D119, D133). Rh-G-CSF (filgrastim)

was administered following all cycles. Primary endpoint was pathological complete

response rate (pCR). A total of 30 patients received at least 7 of the scheduled 8

cycles. Hematological toxicity was significant but manageable. Grade 3/4 extra-

hematopoietic toxicities were relatively uncommon and reversible. No toxicity-

related death was observed. The observed pCR was 37 % and did not reach the

initial endpoint. Post-operative front-line sequential HDC in AOC is feasible and

safe in a multi-center setting. The observed pCR does not support a clear

advantage over conventional treatment. The authors concluded that regarding the

high level of toxicity encountered, this approach should not be performed outside

clinical trials, and remains an experimental strategy to further optimize and validate.

In a multi-center phase I/II clinical study, Frickhofen and colleagues (2006)

assessed the effectiveness of multi-cycle (also known as sequential) HDC with

autologous peripheral blood stem cell support for the treatment of patients with

advanced ovarian cancer. A total of 48 subjects with untreated ovarian cancer

were enrolled in this trial. Median age was 46 (19 to 59 years); International FIGO-

stage was III in 79 % and IV in 21 %; 31 % had residual disease greater than 1 cm

after surgery. Two courses of induction/mobilization therapy with

cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect

peripheral blood stem cells. High-dose chemotherapy consisted of 2 courses of

carboplatin (area under curve (AUC) 18-22) and paclitaxel followed by 1 course of

carboplatin and melphalan (140 mg/m2) with or without etoposide (1,600 mg/m2).

Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating

etoposide resulted in manageable toxicity (69 % without grade 3/4 toxicity). One

patient died from treatment-related pneumonitis. At 8 years median follow-up,

median progression-free-survival (PFS) and OS is 13.3 and 37.0 months. Five-

years PFS and OS are 18 and 33 %, respectively. The authors noted that multi-

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cycle HDC is feasible in a multi-center setting, and a European phase III trial based

on this regimen examining the effectiveness of multi-cycle HDC has been

completed. Preliminary findings do not suggest an improvement of OS or PFS with

multi-cycle HDC compared to standard dose chemotherapy. They stated that multi-

cycle HDC should thus be considered experimental in ovarian cancer.

Mobus and colleagues (2007) compared sequential HDC with peripheral blood

stem cell (PBSC) support with platinum-based combination chemotherapy to

ascertain if dose-intensification improves outcome. A total of 149 patients with

untreated ovarian cancer were randomly assigned after debulking surgery to

receive standard combination chemotherapy or sequential HDC with 2 cycles of

cyclophosphamide and paclitaxel followed by 3 cycles of high-dose carboplatin and

paclitaxel with PBSC support. High-dose melphalan was added to the final cycle.

The median age was 50 years (range of 20 to 65) and International Federation of

Gynecology and Obstetrics stage was IIb/IIc in 4 %, III in 78 %, and IV in 17 %.

Seventy-six percent of patients received all 5 cycles in the high-dose arm and the

main toxicities were neurotoxicity/ototoxicity, gastrointestinal toxicity, and infection

and 1 death from hemorrhagic shock. After a median follow-up of 38 months, the

PFS was 20.5 months in the standard arm and 29.6 months in the high-dose arm

(hazard ratio [HR], 0.84; 95 % confidence interval [CI]: 0.56 to 1.26; p, 0.40).

Median OS was 62.8 months in the standard-arm and 54.4 months in the HD-arm

(HR, 1.17; 95 % CI: 0.71 to 1.94; p, 0.54). The authors stated that this is the first

randomized trial comparing sequential HDC versus standard-dose chemotherapy in

1st-line treatment of patients with advanced ovarian cancer. They observed no

statistically significant difference in PFS or OS and concluded that HDC does not

appear to be superior to conventional dose chemotherapy.

Bay and colleagues (2010) stated that although preliminary results suggested that

allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer

(OC) is a feasible procedure, the low patient number in previous studies had limited

ability to evaluate the true benefit of allo HCT in OC. This retrospective multi-center

study included 30 patients with OC allografted between 1995 and 2005 to

determine the outcome of patients with OC treated with allo HCT. Prior to allo

HCT, patients were in complete response (n = 1), partial response (n = 7), stable

disease (n = 11) or had progressive disease (n = 13). An objective response (OR)

was observed in 50 % (95 % CI: 33 to 67) of patients. Three patients of responding

patients had an OR following the development of acute graft-versus-host disease

(aGVHD). The cumulative incidence of chronic GVHD (cGVHD) was 34 % (95 %

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CI: 18 to 50). Transplant relative mortality rates were 7 and 20 % on day 100 and 1

year, respectively. With a median follow-up of 74.5 months (range of 16 to 148),

median PFS was 6 months and median OS was 10.4 months. Patients who

developed cGVHD following allo HCT had a significant OS improvement compared

to those who did not (17.6 months versus 6.5 months, p = 0.042). However, PFS

was n ot similarly s ignificantly improved in patients who developed cGVHD (12

months versus 3.7 months, p = 0.81). The authors concluded that Allo HCT in OC

may lead to graft-versus-OC effects. Their clinical relevance remains to be shown.

In a phase II clinical trial, Geller et al (2010) evaluated the tumor response and in-

vivo expansion of allogeneic natural killer (NK) cells in recurrent ovarian and breast

cancer. Patients underwent a lympho-depleting preparative regimen: fludarabine

25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in 7 patients,

200 cGy total body irradiation (TBI) to increase host immune suppression. An NK

cell product, from a haplo-identical related donor, was incubated over-night in 1,000

U/ml interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given 3

times/week × 6 doses after NK cell infusion to promote expansion, defined as

detection of greater than or equal to 100 donor-derived NK cells/μL blood 14 days

after infusion, based on molecular chimerism and flow cytometry. A total of 20

patients (14 ovarian cancer, 6 breast cancer) were enrolled. The median age was

52 (range of 30 to 65) years. Mean NK cell dose was 2.16 × 10(7)cells/kg. Donor

DNA was detected 7 days after NK cell infusion in 9/13 (69 %) patients without TBI

and 6/7 (85 %) with TBI. T-regulatory cells (Treg) were elevated at day +14

compared with pre-chemotherapy (p = 0.03). Serum IL-15 levels increased after

the preparative regimen (p < 0.001). Patients receiving TBI had delayed

hematologic recovery (p = 0.014). One patient who was not evaluable had

successful in-vivo NK cell expansion. The authors concluded that adoptive transfer

of haplo-identical NK cells after lympho-depleting chemotherapy is associated with

transient donor chimerism and may be limited by reconstituting recipient Treg cells.

They stated that strategies to augment in-vivo NK cell persistence and expansion

are needed.

De Giorgi and colleagues (2017) noted that a few small retrospective series

reported results with salvage chemotherapy for malignant ovarian adult-type

granulosa cell tumors (GCTs), whereas no data are available on the use of HDC

with hematopoietic progenitor cell support (HSCS) in these patients. These

researchers analyzed the available data of HDC for adult-type GCTs. They

conducted a retrospective analysis of ovarian cancer treated with salvage HDC

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registered with the European Society for Blood and Marrow Transplantation. Of

203 adult female patients with a diagnosis of non-epithelial ovarian cancer treated

with salvage HDC with HSCS and registered with the European Society for Blood

and Marrow Transplantation, 4 (2 %) patients were affected by GCTs. All 4

patients had ovarian adult-type GCTs that relapsed/progressed after 1st-line

chemotherapy. The conditioning regimens included a platinum agent in all 4

patients. Bone marrow recovery was promptly achieved; neither treatment-related

deaths or life-threatening toxicities occurred. At a median follow-up of 8.5 months,

all patients reported a progressive disease. The patient who underwent multi-cycle

HDC enjoyed a long-term remission of 84 months before progression and was the

only one alive after 94+ months. The authors concluded that these findings

showed for the first time a case with long-lasting response to salvage treatment in

adult-type GCTs using multi-cycle HDC and HSCS. These findings need to be

validated by well-designed studies.

Furthermore, an UpToDate review on “Medical treatment for relapsed epithelial

ovarian, fallopian tubal, or peritoneal cancer: Platinum-resistant disease” (Birrer and

Fujiwara, 2017) does not mention hematopoietic cell transplantation as a

therapeutic option.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

CPT codes covered if selection criteria are met:

CPT codes not covered for indications in the CPB:

38205 Blood-derived hematopoietic progenitor cell harvesting for

transplantation, per collection; allogenic

38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per

donor

Other CPT codes related to the CPB:

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HCPCS codes covered if selection criteria are met:

ICD-10 codes covered if selection criteria are met:

C57.4

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The above policy is based on the following references:

1. Droz JP, Pico JL, Ghosn M, et al. Long-term survivors after salvage high dose

chemotherapy with bone marrow rescue in refractory germ cell cancer. Eur J

Cancer. 1991;27(7):831-835.

2. Broun ER, Nichols CR, Kneebone P, et al. Long-term outcome of patients

with relapsed and refractory germ cell tumors treated with high-dose

chemotherapy and autologous bone marrow rescue. Ann Intern Med.

1992;117(2):124-128.

3. Cannistra SA. Cancer of the ovary. N Engl J Med. 1993;329(21):1550-1559.

4. Lotz JP, Andre T, Donsimoni R, et al. High dose chemotherapy with

ifosfamide, carboplatin, and etoposide combined with autologous bone

marrow transplantation for the treatment of poor-prognosis germ cell

tumors and metastatic trophoblastic disease in adults. Cancer. 1995;75

(3):874-885.

5. Margolin BK, Doroshow JH, Ahn C, et al. Treatment of germ cell cancer with

two cycles of high-dose ifosfamide, carboplatin, and etoposide with

autologous stem-cell support. J Clin Oncol. 1996;14(10):2631-2637.

6. Weaver CH, Greco FA, Hainsworth JD, et al. A phase I-II study of high-dose

melphalan, mitoxantrone and carboplatin with peripheral blood stem cell

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support in patients with advanced ovarian or breast carcinoma. Bone

Marrow Transplant. 1997;20(10):847-853.

7. Stiff PJ, Bayer R, Kerger C, et al. High-dose chemotherapy with autologous

transplantation for persistent/relapsed ovarian cancer: A multivariate

analysis of survival for 100 consecutively treated patients. J Clin Oncol.

1997;15(4):1309-1317.

8. Legros M, Dauplat J, Fleury J, et al. High-dose chemotherapy with

hematopoietic rescue in patients with stage III to IV ovarian cancer: Long

term results. J Clin Oncol. 1997;15(4):1302-1308.

9. Fennelly DW, Aghajanian C, Shapiro F, et al. Dose escalation of paclitaxel

with high-dose carboplatin using peripheral blood progenitor cell support

in patients with advanced ovarian cancer. Semin Oncol. 1997;24(1 Suppl

2):S2-26-S2-30.

10. Pecorelli S, Odicini F, Maisonneuve P et al. FIGO annual report of the

results of treatment in gynaecological cancer: Carcinoma of the ovary. J

Epidemiol Biosta. 1998;3:75-102.

11. Holmberg LA, Demirer T, Rowley S, et al. High-dose busulfan, melphalan

and thiotepa followed by autologous peripheral blood stem cell (PBSC)

rescue in patients with advanced stage III/IV ovarian cancer. Bone Marrow

Transplant. 1998;22(7):651-659.

12. Aghajanian C, Fennelly D, Shapiro F, et al. Phase II study of “dose-dense”

high-dose chemotherapy treatment with peripheral-blood progenitor-cell

support as primary treatment for patients with advanced ovarian cancer. J

Clin Oncol. 1998;16(5):1852-1860.

13. Mandanas RA, Saez RA, Epstein RB, et al. Long-term results of autologous

marrow transplantation for relapsed or refractory male or female germ

cell tumors. Bone Marrow Transplant. 1998;21(6):569-576.

14. McGuire WP. High-dose chemotherapy and autologous bone marrow or

stem cell reconstitution for solid tumors. Curr Probl Cancer. 1998;22

(3):135-177.

15. Bonnefoi H, A'Hern RP, Fisher C, et al. Natural history of stage IV epithelial

ovarian cancer. J Clin Oncol. 1999;17(3):767-775.

16. Sobecks RM, Vogelzang N J. High dose chemotherapy with autologous

stem-cell support for germ cell tumors. A critical review. Semin Oncol.

1999;26:106-118.

17. McGuire WP 3rd. High-dose chemotherapeutic approaches to ovarian

cancer management. Semin Oncol. 2000;27(3 Suppl 7):41-46.

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18. Donato ML, Gershenson DM, Wharton JT, et al. High-dose topotecan,

melphalan, and cyclophosphamide (TMC) with stem cell support: A new

regimen for the treatment of advanced ovarian cancer. Gynecol Oncol.

2001;82:420-426.

19. Ledermann JA, Herd R, Maraninchi D, et al. High-dose chemotherapy for

ovarian carcinoma: Long-term results from the Solid Tumour Registry of

the European Group for Blood and Marrow Transplantation (EBMT). Ann

Oncol. 2001;12(5):693-699.

20. Trimble EL, Wright J, Christian MC. Treatment of platinum-resistant ovarian

cancer. Expert Opin Pharmacothe. 2001;2(8):1299-1306.

21. Peethambaram PP, Long HJ. Second-line and subsequent therapy for

ovarian carcinoma. Curr Oncol Rep. 2002;4(2):159-164.

22. Ozols RF. Future directions in the treatment of ovarian cancer. Semin

Oncol. 2002;29(1 Suppl 1):32-42.

23. De Giorgi U, Rosti G, Papiani G, et al. The status of high-dose

chemotherapy with hematopoietic stem cell transplantation in germ cell

tumor patients. Haematologica. 2002;87(1):95-104.

24. Urbano-Ispizua A, Schmitz N, de Witte et al. Allogeneic and autologous

transplantation for haematological diseases, solid tumors and immune

disorders: Definitions and current practice in Europe. Bone Marrow

Transplantation. 2002;29:639-646.

25. Schilder RJ, Brady MF, Spriggs D, Shea T. Pilot evaluation of high-dose

carboplatin and paclitaxel followed by high-dose melphalan supported by

peripheral blood stem cells in previously untreated advanced ovarian

cancer: A gynecologic oncology group study. Gynecol Oncol. 2003;88

(1):3-8.

26. Australian Cancer Network and National Breast Cancer Centre. Clinical

practice guidelines for the management of women with epithelial ovarian

cancer. Camperdown, VIC: National Breast Cancer Centre; March 18, 2004.

27. Stiff PJ, Shpall EJ, Liu PY, et al. Randomized Phase II trial of two high-dose

chemotherapy regimens with stem cell transplantation for the treatment

of advanced ovarian cancer in first remission or chemosensitive relapse: A

Southwest Oncology Group study. Gynecol Oncol. 2004;94(1):98-106.

28. Bengala C, Guarneri V, Ledermann J, et al. High-dose chemotherapy with

autologous haemopoietic support for advanced ovarian cancer in first

complete remission: Retrospective analysis from the Solid Tumour

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Rergistry of the European Group for Blood and Marrow Transplantation

(EBMT). Bone Marrow Transplantation. 2005;36(1):25-31.

29. Tiersten A, Selleck M, Smith DH, et al. Phase I/II study of tandem cycles of

high-dose chemotherapy followed by autologous hematopoietic stem cell

support in women with advanced ovarian cancer. Int J Gynecol Cancer.

2006;16(1):57-64.

30. Goncalves A, Delva R, Fabbro M, et al. Post-operative sequential high-dose

chemotherapy with haematopoietic stem cell support as front-line

treatment in advanced ovarian cancer: A phase II multicentre study. Bone

Marrow Transplant. 2006;37(7):651-659.

31. Frickhofen N, Berdel WE, Opri F, et al; German Study Groups

Arbeitsgemeinschaft Internistische Onkologie (AIO); Arbeitsgemeinschaft

Gynakologische Onkologie (AGO). Phase I/II trial of multicycle high-dose

chemotherapy with peripheral blood stem cell support for treatment of

advanced ovarian cancer. Bone Marrow Transplant. 2006;38(7):493-499.

32. Motzer RJ, Nichols CJ, Margolin KA, et al. Phase III randomized trial of

conventional-dose chemotherapy with or without high-dose

chemotherapy and autologous hematopoietic stem-cell rescue as first-line

treatment for patients with poor-prognosis metastatic germ cell tumors. J

Clin Oncol. 2007;25(3):247-256.

33. Pedrazzoli P, Rosti G, Secondino S, et al; European Group for Blood and

Marrow Transplantation; Solid Tumors Working Party; Gruppo Italiano per

il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia

Cellulare. High-dose chemotherapy with autologous hematopoietic stem

cell support for solid tumors in adults. Semin Hematol. 2007;44(4):286

295.

34. Möbus V, Wandt H, Frickhofen N, et al. Phase III trial of high-dose

sequential chemotherapy with peripheral blood stem cell support

compared with standard dose chemotherapy for first-line treatment of

advanced ovarian cancer: Intergroup trial of the AGO-Ovar/AIO and EBMT.

J Clin Oncol. 2007;25(27):4187-4193.

35. Papadimitriou C, Dafni U, Anagnostopoulos A, et al. High-dose melphalan

and autologous stem cell transplantation as consolidation treatment in

patients with chemosensitive ovarian cancer: Results of a single-institution

randomized trial. Bone Marrow Transplant. 2008;41(6):547-554.

36. Nayl B, Cabrespine-Faugeras A, Maliki Y, Bay JO. Place of autologous and

allogeneic hematopoietic stem cell transplantation in ovarian cancer. Bull

Cancer. 2009;96(12):1225-1232.

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37. Imrie K, Rumble RB, Crump M; Advisory Panel on Bone Marrow and Stem

Cell Transplantation, and the Hematology Disease Site Group. Cancer Care

Ontario Program in Evidence-based Care. Stem cell transplantation in

adults. Recommendations Report. Toronto, ON: Cancer Care Ontario;

2009.

38. Bay JO, Cabrespine-Faugeras A, Tabrizi R, et al. Allogeneic hematopoietic

stem cell transplantation in ovarian cancer-the EBMT experience. Int J

Cancer. 2010;127(6):1446-1452.

39. Geller MA, Cooley S, Judson PL, et al. A phase II study of allogeneic natural

killer cell therapy to treat patients with recurrent ovarian and breast

cancer. Cytotherapy. 2011;13(1):98-107.

40. De Giorgi U, Nicolas-Virelizier E, Badoglio M, et al. High-dose

chemotherapy for adult-type ovarian granulosa cell tumors: A

retrospective study of the european society for blood and marrow

transplantation. Int J Gynecol Cancer. 2017;27(2):248-251.

41. Birrer MJ, Fujiwara K. Medical treatment for relapsed epithelial ovarian,

fallopian tubal, or peritoneal cancer: Platinum-resistant disease. UpToDate

[online serial]. Waltham, MA: UpToDate; reviewed April 2017.

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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.

Copyright © 2001-2019 Aetna Inc.

http://www.aetna.com/cpb/medical/data/600_699/0635.html 09/25/2019 Proprietary


AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number: 0635 Hematopoietic

Cell Transplantation for Ovarian Cancer

There are no amendments for Medicaid.

www.aetnabetterhealth.com/pennsylvania annual 10/01/2019

http://www.aetnabetterhealth.com/pennsylvania

Documents

0635 Hematopoietic Cell Transplantation for Ovarian Cancer - Aetna€¦ · 01/03/2019 · and the 4th leading cause of cancer death in American women. Each year about 25,400 new