Coverage Policy Manual
Policy #: 2005005
Category: Surgery
Initiated: February 2005
Last Review: August 2018
  Cord Blood as a Source of Stem Cells for Potential Disease

Description:
Blood harvested from the umbilical cord and placenta shortly after delivery of neonates contains stem and progenitor cells capable of restoring hematopoietic function after myeloablation.  This “cord” blood has been used as an alternative source of allogeneic stem cells.  Cord blood is readily available and is thought to be antigenically “naïve”, thus hopefully minimizing the incidence of graft-versus-host disease and permitting the broader use of unrelated cord blood transplants.  Several cord blood banks have now been developed in Europe and the United States.
 
Some cord blood banks are offering the opportunity of collecting and storing a neonate’s cord blood for some unspecified future use in the unlikely event that the child develops a condition that would require allogeneic transplantation.  In addition, some cord blood is collected and stored from a neonate for use by a sibling in whom an allogeneic transplant is anticipated due to a history of leukemia or other condition requiring allogeneic transplant.
 
Regulatory Status
 
According to the U.S. Food and Drug Administration (FDA), cord blood stored for potential use by a patient unrelated to the donor meets the definitions of “drug” and “biological products.” As such, products must be licensed under a biologics license application or an investigational new drug application before use. Facilities that prepare cord blood units only for autologous and/or first- or second-degree relatives are required to register and list their products, adhere to Good Tissue Practices issued by the FDA, and use applicable processes for donor suitability determination (FDA, 2013).
 

Policy/
Coverage:
The collection and/or storage of cord or placental blood cells for an unspecified future use as an autologous stem-cell transplant in the original donor, or for some unspecified future use as an allogeneic stem-cell in a related or unrelated donor is not covered.  (Unspecified future use is defined as a use for a medical condition that does not now exist).

Rationale:
Member health plans and contracts issued by Arkansas BCBS condition coverage of services, among other factors, upon satisfaction of the Primary Coverage Criteria, as defined in the health plan or contract.  In order to be covered, medical services, drugs, treatments, procedures, tests, equipment or supplies (“interventions”) must be recommended by your treating physician and meet all terms of the health plan or contract, including all requirements of the Primary Coverage Criteria.  (There are 4 major Primary Coverage Criteria categories listed; category applies to cord blood storage for unspecified future use): The intervention must be a health intervention intended to treat a medical condition.  A “health intervention” is an item or service delivered or undertaken primarily to diagnose, detect, treat, palliate or alleviate a medical condition or to maintain or restore functional ability of the mind or body.  A “medical condition” means a disease, illness, injury, pregnancy or a biological or psychological condition.”
 
The storage of cord or placental stem cells from a neonate for an unspecified future use does not meet the Primary Coverage Criteria because there is no “medical condition” or “health intervention” involved, as defined in the ABCBS member health plan or contract.
 
Some Arkansas BCBS members have older contracts that do not include the Primary Coverage Criteria, but which provide that no coverage is available where treatment is not medically necessary for diagnosis or treatment of an illness or injury.  The storage of cord or placental stem cells from a neonate for an unspecified future use does not meet such older contracts’ criteria for coverage because there is no illness or injury requiring diagnosis or treatment.
 
2014 Update
A literature search conducted through September 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Unrelated Allogeneic Cord Blood Transplant
 
A 2014 study by Liu et al compared outcomes after unrelated donor cord blood transplantation versus matched-sibling donor peripheral blood transplantation (Liu, 2014). The study included patients age 16 years or older who had hematologic malignancies. A total of 70 patients received unrelated cord blood and 115 patients received HLA-identical peripheral blood stem cells, alone or in combination with bone marrow. Primary engraftment rates were similar in the 2 groups, 97% in the cord blood group and 100% in the peripheral blood stem-cell group. Rates of most outcomes, including grades III to IV acute GVHD and 3-year disease-free survival were also similar between groups. However, the rate of chronic GVHD was lower in the unrelated-donor cord blood group. Specifically, limited or extensive chronic GVHD occurred in 12 of 58 (21%) evaluable patients in the cord blood group and 46 of 109 (42%) evaluable patients in the peripheral blood stem cell group, p=0.005.
 
Studies have identified the importance of a minimum cell dose. For example, a 2013 analysis of data from the Korean Cord Blood Registry found that the presence of at least 3.91 X 105/kg of infused CD34+ cells was significantly associated with overall survival (p=0.03) in unrelated donor cord blood transplants in children and adolescents (Park, 2014).
 
A French study evaluating double unit transplants in adults with hematologic malignancies found an engraftment rate of 93% (127 of 136) and a median overall survival rate of 17.5 months (Wallet, 2013).
  
2015 Update
A literature search conducted through September 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Wagner and colleagues published a randomized controlled trial (RCT) comparing outcomes after double-unit (n=111) or single-unit (n=113) cord-blood transplants (Wagoner, 2014). The study included patients aged 1 to 21 years who had high-risk acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome for whom there were 2 cord-blood units available with adequate cell doses and HLA matches on at least 4 of 6 loci. The primary outcome, 1-year overall survival rate, was 65% (95% confidence interval [CI], 56% to 74%) after double-unit transplant and 73% (95% CI, 63 to 80) after single-unit transplant. The difference between groups was not statistically significant (p=0.17). Similarly, 1-year disease-free survival was 64% (95% CI, 54% to 72%) in the double-unit transplant group and 70% (95% CI, 60% to 77%) in the single-unit transplant group (p=0.11). However, rates of acute grade II and IV GHVD was significantly higher in the double-unit transplant group (23%; 95% CI, 15% to 31%) than the single-unit transplant group (13%; 95% CI, 7% to 20%; p=0.02). The incidence of chronic GVHD after 1 year was similar in the 2 groups (32%; 95% CI, 23% to 40%, after double-unit transplant; and 30%, 95% CI, 22% to 29% after single-unit transplant; p=0.51).
 
2016 Update
A literature search conducted through June 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below:
 
Ongoing
(NCT01728545) The Collection and Storage of Umbilical Cord Blood for Transplantation; planned enrollment 250000; completion date June 2099.
 
(NCT00012545) Collection and Storage of Umbilical Cord Stem Cells for Treatment of Sickle Cell Disease; planned enrollment 99999999; completion date none provided.
 
 
American College of Obstetricians and Gynecologists
In 2015, the American College of Obstetricians and Gynecologists published a committee opinion on umbilical cord blood banking (Committee Opinion No. 649). The statement discussed counseling patients about options for umbilical cord blood banking, as well as benefits and limitations of this practice. Relevant recommendations include the following:
  • “Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice for the timing of umbilical cord clamping.”
  •  “The current indications for cord blood transplant are limited to select genetic, hematologic, and malignant disorders.”
“The routine storage of umbilical cord blood as “biologic insurance” against future disease is not recommended.”
 
2017 Update
A literature search conducted through July 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Transplantation of 2 umbilical cord blood units (or double-unit transplants) has been evaluated as a strategy to overcome cell dose limitations with 1 cord blood unit in older and heavier patients. Initial experience at a university showed that using 2 units of cord blood for a single transplant in adults improved rates of engraftment and OS (Barker, 2005).
 
2018 Update
A literature search was conducted through July 2018.  There was no new information identified that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
PROPHYLACTIC COLLECTION AND STORAGE OF CORD BLOOD
No studies have compared outcomes after prophylactic collection and storage of cord blood from a neonate for individuals who have an unspecified future need for transplant to standard care without cord blood collection and storage.
 
Also, although blood banks are collecting and storing neonate cord blood for potential future use, data on the use of cord blood for autologous stem cell transplantation are limited. A position paper from the American Academy of Pediatrics noted that there is little evidence of the safety or effectiveness of autologous cord blood transplantation for treatment of malignant neoplasms (AAP, 2017).
 
Section Summary: Prophylactic Collection and Storage of Cord Blood
There is a lack of published evidence comparing outcomes after prophylactic collection and storage of cord blood from a neonate for individuals who have an unspecified future need for transplant with standard care without cord blood collection and storage.

CPT/HCPCS:
38205Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
38206Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38207Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage
88240Cryopreservation, freezing and storage of cells, each cell line
S2140Cord blood harvesting for transplantation, allogeneic
S2142Cord blood-derived stem-cell transplantation, allogeneic
S2150Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre and post transplant care in the global definition

References: Barker JN, Weisdorf DJ, DeFor TE, et al.(2005) Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. Feb 1 2005;105(3):1343-1347. PMID 15466923

Committee Opinion No. 648:(2015) Umbilical Cord Blood Banking Obstet Gynecol. Dec 2015;126(6):e127-129. PMID 26595583

Committee Opinion No. 648:(2015) Umbilical Cord Blood Banking. Obstet Gynecol. Dec 2015;126(6):e127-129. PMID 26595583

Food and Drug Administration (FDA).(2014) Cord Blood Banking: Information for Consumers (July 23, 2012). http://www.fda.gov/biologicsbloodvaccines/resourcesforyou/consumers/ucm236044.htm. Accessed August, 2014.

Liu HL, Sun ZM, Geng LQ, et al.(2014) Similar survival, but better quality of life after myeloablative transplantation using unrelated cord blood vs matched sibling donors in adults with hematologic malignancies. Bone Marrow Transplant. May 19 2014. PMID 24842525

Park M, Lee YH, Kang HR, et al.(2014) Unrelated donor cord blood transplantation for non-malignant disorders in children and adolescents. Pediatr Transplant. Mar 2014;18(2):221-229. PMID 24372660

Shearer WT, Lubin BH, Cairo MS, et al.(2017) Cord Blood Banking for Potential Future Transplantation Pediatrics. Nov 2017;140(5). PMID 29084832

Wagner JE, Jr., Eapen M, Carter S, et al.(2014) One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. Oct 30 2014;371(18):1685-1694. PMID 25354103

Wallet HL, Sobh M, Morisset S, et al.(2013) Double umbilical cord blood transplantation for hematological malignancies: a long- term analysis from the SFGM-TC registry. Exp Hematol. Jul2 2013. PMID 23831606


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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