Medical Policy

This document addresses stem cell therapy products such as omidubicel, (Omisirge ^®, Gamida Cell, Ltd. Boston, MA) for hematologic malignancies (blood cancers) and non-malignant hematologic disorders such as severe aplastic anemia (SAA), which are amenable to stem cell transplantation. Omidubicel is the first U. S. Food and Drug Administration (FDA) approved stem cell therapy product for allogeneic stem cell transplantation.

Note: Please see the following related documents for additional information:

• TRANS.00016 Umbilical Cord Blood Progenitor Cell Collection, Storage and Transplantation
• CG-TRANS-03 Donor Lymphocyte Infusion for Hematologic Malignancies after Allogeneic Hematopoietic Progenitor Cell transplantation

Note: For additional stem cell transplant information and criteria, see the applicable transplant document:

• TRANS.00023 Hematopoietic Stem Cell Transplantation for Multiple Myeloma and Other Plasma Cell Dyscrasias
• TRANS.00024 Hematopoietic Stem Cell Transplantation for Select Leukemias and Myelodysplastic Syndrome
• TRANS.00027 Hematopoietic Stem Cell Transplantation for Pediatric Solid Tumors
• TRANS.00028 Hematopoietic Stem Cell Transplantation for Hodgkin Disease and non-Hodgkin Lymphoma
• TRANS.00029 Hematopoietic Stem Cell Transplantation for Genetic Diseases and Aplastic Anemias
• TRANS.00030 Hematopoietic Stem Cell Transplantation for Germ Cell Tumors
• TRANS.00031 Hematopoietic Stem Cell Transplantation for Autoimmune Disease and Miscellaneous Solid Tumors
• TRANS.00034 Hematopoietic Stem Cell Transplantation for Diabetes Mellitus

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

Use of ex-vivo expansion of cord blood stem cell products (for example, omidubicel) is considered medically necessary for individuals when the following criteria are met:

1. 12 years of age or older; and
2. Is a candidate for myeloablative allogeneic hematopoietic stem cell transplantation to treat a hematologic malignancy; and
3. The appropriate stem cell transplant criteria are met (see related policies above); and
4. Is eligible and planned for umbilical cord blood transplantation following myeloablative conditioning; and
5. Use is intended to reduce the time to neutrophil recovery and the incidence of infection.

Investigational and Not Medically Necessary:

Use of ex-vivo expansion of cord blood stem cell products (for example, omidubicel) is considered investigational and not medically necessary when the criteria above are not met including for treatment of severe aplastic anemia, and for all other indications.

This document describes clinical studies and expert recommendations, and explains whether omidubicel, (Omisirge) one-time infusion is appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Omidubicel (brand name Omisirge) is a stem cell therapy made from umbilical cord blood collected from donors at the time of birth. It is has been proposed as a way to help people with blood cancers or severe aplastic anemia, a disease resulting in low numbers of blood cells, who need a stem cell transplant but do not have a fully matched donor. Omidubicel is specially prepared in a lab to increase the number of helpful cells and is given as a one-time dose after chemotherapy. It was approved by the U.S. Food and Drug Administration (FDA) for people age 12 and older with some types of blood cancers in 2023, and for people age 6 and older with severe aplastic anemia in 2025. The reason for use of Omidubicel is to help the body recover faster after a transplant by speeding up the return of white blood cells and lowering the risk of infections.

What the Studies Show

Omidubicel has been tested in studies for people with blood cancers such as leukemia and lymphoma. A large international study showed that people who received omidubicel had faster recovery of white blood cells (12 days compared to 22 days with standard cord blood), fewer serious infections, and more days out of the hospital in the first 100 days. Platelet recovery, an important part of blood clotting, and quality of life were also better. After one-year following treatment with Omidubicel the results showed better physical and functional well-being in the omidubicel group. A long-term study found that people had a strong immune system for many years after the transplant, with low rates of the cancer returning. Another small study in people with sickle cell disease showed that most had full donor cell recovery and no signs of disease, but better studies are needed to know if this improves health. Another study also found fast and safe recovery, especially in racially diverse groups. For severe aplastic anemia, research is ongoing, and early results have not yet been published. The FDA approval was based on early findings from a study with a low number of participants. That study is still in progress and only includes a few people; better studies are needed to know if omidubicel improves health in people with severe aplastic anemia.

When is Omidubicel Clinically Appropriate?

Omidubicel (a lab-expanded cord blood stem cell product) may be appropriate in these situations:

• The person is 12 years or older; and
• Has a blood cancer and is planned for a myeloablative allogeneic stem cell transplant (a strong chemotherapy regimen followed by a transplant from a donor); and
• Meets transplant criteria described in other related documents; and
• Is eligible and planned for an umbilical cord blood transplant; and
• The treatment is intended to speed up white blood cell recovery and lower the chance of infection.

When is this not Clinically Appropriate?

Omidubicel is not considered appropriate if the criteria listed above are not met or for any other reason not listed. This includes use for severe aplastic anemia outside of current research settings. Although the FDA recently approved it for this use, there is not enough high-quality published research to show that it improves health. Omidubicel is not clinically appropriate in scenarios other than those listed above.

(Return to Description/Scope)

Summary:

Omidubicel (brand name Omisirge) is an ex-vivo expanded stem cell therapy derived from umbilical cord blood, designed to support recovery after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. It is FDA-approved for individuals aged 12 and older with blood cancers undergoing cord blood transplant and has shown significant clinical benefits, including faster neutrophil and platelet recovery, fewer serious infections, improved quality of life, and increased time spent outside the hospital compared to standard cord blood transplants. The therapy is particularly valuable for patients without a fully matched donor, offering a viable and effective alternative graft source. The current guidelines from the National Comprehensive Cander Network (NCCN) provides a Category 2A recommendation supporting the use of omidubicel for individuals undergoing UCB transplantation with a planned myeloablative conditioning regimen.

While omidubicel was recently approved for treating severe aplastic anemia (SAA) in individuals aged 6 and older, evidence for its effectiveness in this condition remains limited. The FDA’s decision was based on early findings from a small ongoing study without published outcome data. Due to the lack of robust, long-term clinical evidence and absence of endorsements from major transplant societies for use in SAA, omidubicel is considered investigational and not medically necessary for this indication outside of research settings. Its approved use remains confined to hematologic malignancies under specific clinical criteria.

Discussion:

Omidubicel for hematologic malignancies (blood cancers)

Omidubicel is a laboratory-expanded stem cell product used in bone marrow transplants. It is made from umbilical cord blood and is designed to help people with blood cancers who need a stem cell transplant but do not have a fully matched donor. In 2023, the Food and Drug Administration approved omidubicel for people aged 12 and older with certain blood cancers who are undergoing myeloablative conditioning before transplant. The goal is to speed up recovery of white blood cells and reduce infection risk. Omidubicel has shown faster recovery of white blood cells and platelets, fewer infections, and more time outside the hospital after transplant compared to standard cord blood transplants. It may also improve quality of life and long-term health outcomes.

A major international study found that people who received omidubicel had faster recovery of white blood cells (12 days compared to 22 days for standard cord blood) and fewer serious infections. They also spent more days out of the hospital within the first 100 days after transplant. Platelet recovery and quality of life were also better in the omidubicel group. These results suggest that omidubicel may be a better option than standard cord blood transplant for some people. Another analysis looked at quality of life after transplant and found that people receiving omidubicel reported better physical and functional well-being throughout the first year. A separate long-term study showed durable immune system recovery and a low relapse rate up to 10 years after transplant, supporting omidubicel’s safety and effectiveness over time. Additional research in people with sickle cell disease showed promising results, including full donor cell recovery and no sign of disease in most participants, although the small size of the study means more research is needed. A real-world study in diverse transplant centers also found that omidubicel helped patients recover quickly and safely, although it did not include a comparison group. Overall, studies show omidubicel may be a safe and effective transplant option for people without matched donors, especially in racially diverse populations.

Umbilical cord blood (UCB) is one option for sourcing cells for hematopoietic transplantation, a potentially curative treatment option for a number of hematologic malignancies and oncologic disorders. Peripheral blood and bone marrow are also options for sourcing hematopoietic cells. UCB transplantations are typically reserved for individuals who do not have an HLA-identical matched donor due to the increased risk of early treatment-related morbidity (delayed engraftment, graft failure and infections) and mortality (National Comprehensive Cancer Network [NCCN], 2024).

Omidubicel is a first-in-class, bone marrow transplant product that received Breakthrough Therapy Designation from the FDA and Orphan Drug Designation. On April 17, 2023, the FDA approved omidubicel for use in individuals (12 years and older) with hematologic malignancies who are planned for UCB transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. FDA approval of omidubicel was primarily based on the pivotal phase 3 international, multi-center, randomized clinical trial (RCT; [NCT02730299]) that assessed safety and efficacy compared to standard UCB transplantation in participants with hematologic malignancies such as lymphoma, leukemia and myelodysplastic syndrome (Horwitz, 2021). The study’s primary end point was time to neutrophil engraftment. Over the course of 3 years, (January 2017 to January 2020) 125 individuals ages 13 to 65 years (median age, 41 years) with hematologic malignancies were randomly assigned to omidubicel (n=62) versus standard UCB transplant (n=63; 33% single UCB grafts and 67% double UCB grafts). The majority of the 125 study participants were diagnosed with acute myeloid leukemia (AML; n=60) or acute lymphoblastic leukemia (ALL; n=41). Participants received myeloablative conditioning and prophylaxis for GvHD prior to transplant. The treatment arms were well balanced with respect to diagnosis, disease severity, age, gender, and racial diversity; 44% of the study population were non-white participants. Per protocol, 10 participants in the omidubicel arm and 8 in the UCB transplant arm did not proceed to transplant; the final ‘analyzed as treated’ sample included 108 participants (omidubicel, n=52; UCB, n=56). The median follow-up was 10 months post-transplant. The study’s primary outcome was met, with a significantly shorter time to neutrophil engraftment of 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm compared to 22 days (95% CI, 19-25 days) for the control arm (p<0.001). The cumulative incidence of neutrophil engraftment was 96% in the omidubicel arm and 89% for UCB graft transplants (p<0.001). The omidubicel arm had marginally significant faster platelet recovery (55% vs. 35% recovery by 42 days; p=0.03) and lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs. 57%; p=0.03). The cumulative incidence of first grade 3 viral infection during the first year after transplantation was also lower for those in the omidubicel arm (10% vs. 26%; p=0.02). The omidubicel arm participants spent more time out of hospital during the first 100 days post-transplant (median, 61 vs. 48 days; p=0.005) compared to the control transplant arm participants. The study was not powered to detect differences in mortality and did not demonstrate differences in GvHD nor survival between the study arms. At 210 days post-transplant, the non-relapse mortality rate was 11% in the omidubicel arm and 24% in the control arm (p=0.09). This phase 3 study demonstrated the feasibility and clinical benefit omidubicel may provide as an alternative to standard UCB transplant for individuals in need of an HSCT who lack an HLA-identical matched donor.

In 2023, Lin analyzed and published health-related quality of life (HRQL) measures from a post-hoc analysis of omidubicel’s pivotal RCT (Lin, 2023a). The 108 participants who received a transplant completed HRQL questionnaires at screening and on days 42, 100, 180, and 365 post-transplantation. In the current study, 75 participants who completed key questionnaires at baseline and at least 1 follow-up visit were included in the analysis; the baseline characteristics of completing participants were well balanced between the study arms. Throughout the first year post-transplant, the omidubicel arm demonstrated significantly more improvement in physical, functional, and total Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACTBM) scores (p<0.05). The HRQL improvements with omidubicel were observed as early as 42 days post-transplantation and were sustained through 1 year of follow-up. Across both study arms, adverse clinical outcomes, such as grade 3 viral infections and lower rates of engraftment, were associated with lower HRQL scores. This study demonstrates UBC transplant using omidubicel versus standard transplant methods, confers significant, clinically meaningful improvements in self-reported HRQL measures.

In 2023, Lin published results from a planned, pooled analysis comprised of 105 study participants diagnosed with hematologic malignancies or sickle cell hemoglobinopathy from 5 multicenter (26 academic centers worldwide) clinical trials who underwent omidubicel transplantation. The median age was 42 years (2-62, range) and 39% (n=41) participants were non-white. The most common diagnosis-types were AML (41%), ALL (27%), MDS (12%) and sickle cell disease (8%). The 3-year estimated overall survival and disease-free survival were 62.7% (95% CI, 52.1 to 71.6%) and 56.4% (95% CI, 45.9 to 65.6%), respectively (median follow-up of 22 months). With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3+, CD4+, CD8+, CD19+, CD116+CD56+, and CD123+ immune subsets revealed median counts remaining within normal ranges through 8 years of follow-up. Within the first year, secondary graft failure occurred in 5 participants (5%; 2 of which had sickle cell disease); no late cases were reported. The 3-year cumulative incidence of disease relapse was 22% and 2 participants were diagnosed with secondary hematologic malignancies (lymphoproliferative disorder at 17 and 20 months post-transplant). A single case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation which also occurred in a control arm participant who received a standard UCB transplant. This study provides the first evidence of omidubicel’s graft durability and safety over an extended period of follow-up.

In 2021, Parikh published the results of a phase 1/2 study in 13 individuals with severe sickle cell disease who received omidubicel in combination with an unmanipulated UCB graft and 3 who received a single omidubicel graft (n=16; median age of 13 years). Grafts were minimally matched (4 of 6 HLA alleles). A median CD341 expansion of approximately 80-fold was observed and led to rapid neutrophil engraftment at a median of 7 days. The incidence of acute GvHD was high (69% grade 2 to 4 at 100 days post-transplant) but resolved in all 11 surviving study participants in the double-cord group. Event-free survival in the double-cord group was 85% (median follow-up 4 years). All 3 study participants in the single cord group were alive 1 year post transplantation. Overall, 13 of the 16 study participants were alive at study analysis with full donor engraftment and no evidence of sickle cell disease after transplant. Further study of omidubicel in the setting of severe sickle cell disease is warranted in the setting of a randomized controlled trial.

First-in-class omidubicel has demonstrated clinically meaningful benefit, sustained durability and reasonable safety as an alternative to a standard UCB transplant in individuals with hematologic malignancies amendable to HSCT whom lack an HLA-identical matched UCB donor. The NCCN Guidelines for Hematopoietic Cell Transplantation (2025) have given a 2A recommendation for use of omidubicel for individuals planning an UCB transplantation. The NCCN guidelines state:

if an myeloablative conditioning regimen is planned for a recipient of UCB, omidubicel-onlv has been shown to shorten the time to engraftment and reduce the risk of some infections. If UCB transplant is being used, referral to a center with experience in UCB transplants is strongly recommended. If a myeloablative conditioning regimen is planned for a recipient of UCB, omidubicel-onlv, an ex vivo nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from a single cord blood unit, has been shown to shorten the time to engraftment and reduce the risk of some infections. In a phase III trial, median time to neutrophil engraftment for UCB transplantation with omidubicel-onlv was 12 days compared to 22 days for standard UCB transplantation (p<0.001).141 Similarly, platelet recovery was shorter in the omidubicel-onlv arm (55% vs. 35% recovery at 42 days; p=0.028). Grade 2-3 bacterial or invasive fungal infections were also less common in the omidubicel-onlv arm (37% vs. 57%; p=0.027)

The recommendation was based on the previously described pivotal trial (Horwitz, 2021). Expanded access and long-term follow-up studies of the pivotal trial cohort are ongoing. In 2025, Horwitz published findings from an Expanded Access Program (EAP) evaluating the clinical use of omidubicel in individuals with hematologic malignancies undergoing myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT). This multicenter, open-label, single-arm study was conducted at five U.S. transplant centers between August 2020 and May 2023 and included 29 participants who lacked matched sibling or unrelated adult donors. Eligible participants were 12 years or older and received a partially HLA-matched UCB unit that met specific minimum CD34+ and total nucleated cell dose criteria. All participants underwent myeloablative conditioning and received standard prophylaxis and supportive care. The primary endpoint was time to neutrophil engraftment, secondary outcomes including platelet engraftment, non-relapse mortality (NRM), disease-free survival (DFS), overall survival (OS), GvHD, infection rates, and overall safety. The cohort had a median age of 39 years (range 20-73), with 62% male and 45% identifying as non-white; acute leukemia was the most common diagnosis (65.5%). The median follow-up of 11.8 months. The results showed a median neutrophil engraftment of 12 days and platelet engraftment of 33.5 days. Rates of grade 3-4 acute GvHD by day 100 were 19%, and chronic GVvD at one year occurred in 9% of participants. Grade 2-3 bacterial infections occurred in 18% and grade 3 viral infections in 12% of participants. One-year DFS and OS were 76% and 87%, respectively. The authors concluded that omidubicel is a viable stem cell source for allo-HSCT in individuals without matched donors, particularly in racially diverse populations. Its use was associated with rapid engraftment and a favorable early safety profile. Limitations of the study include its open-label, single-arm design and lack of a control group, which may introduce selection bias and limit generalizability when compared to prior phase 3 data. The findings support continued clinical investigation of nicotinamide-based cell expansion strategies in transplantation hematology.

Additionally, a clinical trial of omidubicel for individuals diagnosed with non-Hodgkin lymphoma was terminated early with just 13 enrolled participants (target enrollment; n=99 [NCT05296525]).

Omidubicel for severe aplastic anemia (SAA)

Severe aplastic anemia (SAA) is a life-threatening bone marrow disorder in which the bone marrow cannot make enough blood cells. It is defined by markedly hypocellular marrow (less than 25 % of normal cellularity in bone marrow biopsy), and at least two of the following peripheral blood cytopenias: absolute neutrophil count less than 500/µL, platelet count less than 20,000/µL, or reticulocyte count less than 60,000/µL (or corrected reticulocyte index less than 1%) (European Working Group-Severe Aplastic Anemia in Childhood [EWOG-SAA], 2024). Additionally, in adults, diagnosis requires the exclusion of other causes such as hypoplastic myelodysplastic syndrome and inherited marrow failure.

Treatment for SAA depends on age and usually consists of either immunosuppressive therapy and/or HSCT preferably from a matched sibling or matched related donor. If a donor is not available, the use of umbilical cord transplant may be considered to treat SAA. Umbilical cord transplant typically has limitations of use including delayed hematopoietic recovery and increased risks of infections. Immunosuppressive therapy may be used when a transplant is not an option or while awaiting a donor. Both aim to restore blood cell production and reduce life-threatening complications. Recently, omidubicel has been studied as a treatment for SAA.

On December 5, 2025, the FDA approved omidubicel for adults and children 6 years and older with SAA following reduced intensity conditioning under the Orphan Drug and Priority Review designations. The FDA’s approval makes omidubicel the first cellular therapy for SAA; it was previously approved for treating hematologic malignancies. (FDA, 2025.)

The FDA approval was based on an ongoing, open-label, prospective, single arm, Phase II study (n=14), (NCT03173937) evaluating the ability of omidubicel to achieve sustained early engraftment. Inclusion criteria are; participants 4-75 years of age with severe aplastic anemia defined as bone marrow cellularity less than 30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count less than or equal to 1000 cells/ uL) or for participants receiving granulocyte transfusions, and absolute neutrophil count less than or equal to 1000 cells/ uL before beginning granulocyte transfusions, or a history of severe aplastic anemia transformed to MDS that meet the International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, less than 5% myeloblasts and less than 30% of cellularity in the bone marrow on screening morphologic analysis, or intolerance of or failure to respond to standard immunosuppressive therapy and identification of either at least one alternative donor (for example, HLA- haploidentical related donor) who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the omidubicel is rejected, umbilical cord blood unit/s are available for a salvage cord blood transplant in the event that the omidubicel is rejected, or availability of at least one greater than or equal to 4/8 HLA matched cord blood unit from the National Marrow Donor Program (NMDP). Exclusion criteria include candidates that have the following; an available and suitable HLA-identical matched related or unrelated donor, ECOG performance status greater than or equal to 2, a major comorbid illness or organ dysfunction precluding transplant survival, are pregnant or, if of childbearing potential, unwilling to use effective contraception/abstinence for 1 year, are HIV-positive, have Fanconi anemia confirmed by chromosome-breakage testing, have impaired cardiopulmonary function (DLCO less  than or equal to 40% adjusted for hemoglobin or lung volumes, LVEF less than or equal to 40%, significant hepatic or renal dysfunction (transaminases greater than 5× ULN, bilirubin greater than 4 mg/dL, creatinine clearance less than 50 mL/min/1.73 m² by 24-hr urine; serum creatinine greater than 2.5 mg/dL), an active infection not  adequately responding to therapy, a malignancy with risk of relapse or progression within 5 years, a known hypersensitivity to bovine products, gentamicin, or other components interfering with treatment, or donor-specific antibodies to the cord blood unit and, for Cohort 1, to the haploidentical donor. The study is still in progress and is limited by the small number of participants. Additionally, there are currently no published results available. Larger studies with long-term outcomes are needed to determine if omidubicel improves net health outcomes in people with severe aplastic anemia.

Current evidence for omidubicel in SAA is insufficient. No published clinical outcome data are available, and larger, rigorously designed studies with long-term follow-up are required to determine whether omidubicel confers a net health benefit. At present, the peer-reviewed literature lacks credible scientific evidence recognized by the relevant medical community to conclude that a one-time omidubicel infusion improves net health outcomes, is comparable to established therapeutic alternatives, or provides benefit outside of investigational settings.

Omidubicel for hematologic malignancies

In 2019, there were an estimated 550,000 individuals living with a malignant hematologic (blood) cancer in the U.S. (Centers for Disease Control and Prevention [CDC], 2022). Most hematologic cancers originate in the bone marrow where blood is produced. The three most common types of blood cancers are leukemia, lymphoma and myeloma (American Society of Hematology, 2023).

HSCT is an important treatment for hematologic diseases. While the number of individuals who could benefit from HSCT has increased due to advancements such as reduced intensity conditioning regimens that have made HSCT safer, the potential for transplant-associated morbidity and mortality remains significant. Most transplant centers use forums, boards or conferences where the treatment options of individual HSCT candidates are discussed (Majhail, 2015). The decision to transplant is unique to each individual and needs to include a specific risk-benefit analysis in partnership with the individual’s physicians and other caregivers. Okamoto (2017) notes:

The medical decision-making process for a transplant procedure is complex which requires assessing several factors besides the underlying indication for transplantation. Those include patient/disease factors, and transplant factors such as planed conditioning/graft vs host disease (GVHD) prophylaxis and stem cell source. Patient factors include their overall health and comorbidities, prior therapies, and how patients responded to those therapies, age, and disease/disease risk.

HSCT is a process which includes mobilization, harvesting, and transplant of stem cells after the administration of high dose chemotherapy (HDC) and/or radiotherapy. High-dose chemotherapy involves the administration of cytotoxic agents using doses several times greater than the standard therapeutic dose. In some cases, whole body or localized radiotherapy is also given and is included in the term HDC when applicable. The rationale for HDC is that many cytotoxic agents act according to a steep dose-response curve. Thus, small increments in dosage will result in relatively large increases in tumor cell kill. Increasing the dosage also increases the incidence and severity of adverse effects related primarily to bone marrow ablation (for example, opportunistic infections, hemorrhage, or organ failure). Bone marrow ablation is the most significant side effect of HDC. As a result, HDC is accompanied by a re-infusion of hematopoietic stem cells, which are primitive cells capable of replication and formation into mature blood cells, in order to repopulate the marrow. The potential donors of stem cells include:

Autologous - Stem cells can be harvested from the individual’s own bone marrow prior to the cytotoxic therapy.

Allogeneic - Stem cells harvested from a healthy, histocompatible donor.

Donor stem cells, either autologous or allogeneic, are most often collected from either the bone marrow or the peripheral blood. In addition, blood harvested from the umbilical cord and placenta shortly after delivery of neonates contains stem and progenitor cells. Although cord blood is an allogeneic source, these stem cells are antigenically “naïve” and thus, are associated with a lower incidence of rejection or graft versus host disease. The most appropriate stem cell source for a particular individual depends upon his or her disease, treatment history, and the availability of a compatible donor. The most appropriate source of stem cells for each individual must balance the risks of graft failure and re-infusion of malignant cells in autologous procedures, the risks of graft rejection, and graft versus host disease in allogeneic procedures.

UCB transplantations are typically reserved for individuals who do not have a HLA-identical matched donor due to the increased risk of early treatment-related morbidity (delayed engraftment, graft failure and infections) and mortality (National Comprehensive Cancer Network [NCCN], 2024). Ex vivo expansion of UCB stem cells prior to transplantation may help address this critical limitation. Omidubicel is an individualized cell product derived from a single banked UCB unit and consists of an ex vivo expanded CD133⁺ fraction and a nonexpanded CD133^- fraction. The active agent in the culture system, nicotinamide, is intended to inhibit cell differentiation and enhance the functionality of the cultured hematopoietic stem and progenitor cells.

The National Cancer Institute (NCI) notes that one randomized trial comparing omidubicel to standard cord blood transplant showed that omidubicel led to faster neutrophil and platelet engraftment, fewer bacterial and fungal infections, and reduced hospitalization within the first 3 months post-transplant. However, survival and GvHD outcomes were similar between groups (NCI, 2024).

Severe Aplastic Anemia

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder in which the bone marrow cannot make enough blood cells. It is defined by both markedly hypocellular marrow (less than 25% of normal cellularity in bone marrow biopsy), and at least two of the following peripheral blood cytopenias: absolute neutrophil count (ANC) less than 500/µL, platelet count less than 20,000/µL, or reticulocyte count less than 60,000/µL (or corrected reticulocyte index less than 1%) (European Working Group-Severe Aplastic Anemia in Childhood [EWOG-SAA], 2024). Additionally, in adults, diagnosis requires the exclusion of other causes such as hypoplastic myelodysplastic syndrome and inherited marrow failure.

SAA may lead to severe infections (from neutropenia), bleeding (from thrombocytopenia), and fatigue and anemia-related symptoms (from low red cells). Most SAA is acquired and immune-mediated, where the individual’s own T-cells destroy hematopoietic stem cells. Other causes may include certain medications or toxins, viral infections, radiation, and rarely, inherited bone marrow failure syndromes (National Heart, Blood, and Lung Institute [NHBLI], 2022). Treatment for SAA depends on age and usually consists of either immunosuppressive therapy and/or HSCT preferably from a matched sibling or matched related donor. If a donor is not available, the use of umbilical cord transplant may be considered to treat SAA. Umbilical cord transplant typically has limitations of use including delayed hematopoietic recovery and increased risks of infections. Immunosuppressive therapy may be used when a transplant is not an option or while awaiting a donor. Both aim to restore blood cell production and reduce life-threatening complications.

The 2024 American Society for Transplantation and Cellular Therapy (ASTCT) Evidence-Based Guidelines for Allogeneic Hematopoietic Cell Transplantation in Severe Aplastic Anemia do not address or recommend the use of omidubicel for SAA, as the guidance discusses omidubicel only in the context of hematologic malignancies. No other professional medical societies currently endorse or provide recommendations supporting omidubicel for the treatment of SAA.

Contraindications and Warnings

The current prescribing information for omidubicel (Omisirge, 2024) includes the following contraindications and black box warnings:

Contraindications:

Omidubicel is contraindicated in individuals with:

• Known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin or bovine material.

Black Box Warnings:

• Infusion reactions: Infusion reactions may be fatal. Monitor individuals during infusion and discontinue for severe reactions. Use is contraindicated in individuals with known allergy to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin, or bovine material.
• Graft versus Host Disease (GVHD): GVHD may be fatal. Administration of immunosuppressive therapy may decrease the risk of GVHD.
• Engraftment syndrome: Engraftment syndrome may be fatal. Treat engraftment syndrome promptly with corticosteroids.
• Graft failure: Graft failure may be fatal. Monitor individuals for laboratory evidence of hematopoietic recovery.

Ablative: A very high dose of a treatment, calculated to kill a tumor or malignant cells.

Allogeneic: Tissue or cells taken from different individuals from the same species.

Aplastic anemia: Bone marrow is unable to make blood cells.

Ex vivo: Occurring outside of the living body. Refers to a medical procedure in which an organ, cells, or tissue are taken from a living body for a treatment or procedure, and then returned to the living body.

Graft-versus-host disease (GVHD): The condition that results when the immune cells of a transplant (usually of bone marrow) react against the tissues of the person receiving the transplant.

Hematologic malignancy: A cancer of the blood or bone marrow, such as leukemia or lymphoma.

Hematopoietic progenitor cells: Primitive cells capable of replication and formation into mature blood cells in order to repopulate the bone marrow. Cells may be obtained from bone marrow, peripheral blood or umbilical cord blood.

Hematopoietic stem cells: Cells that give rise to distinct daughter cells, one cell that replicates the stem cell and one cell that will further proliferate and differentiate into a mature blood cell; also called progenitor cells.

HLA (human leukocyte antigen): A group of protein molecules located on bone marrow cells that can provoke an immune response.

Leukemia: A type of cancer found in the blood and bone marrow caused by the rapid production of abnormal white blood cells.

Lymphoma: A type of blood cancer that affects the lymphatic system (removes excess fluids from the body and produces immune cells).

Myeloma: A cancer of the plasma cells (white blood cells that produce disease- and infection-fighting antibodies in your body).

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for the following diagnoses and all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Horwitz ME, Stiff PJ, Cutler C, et al. Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. Blood. 2021; 138(16):1429-1440.
2. Horwitz ME, Schiller GJ, Tsai SB, et al. Omidubicel-onlv transplantation for hematologic malignancies: results of a multicenter expanded access program. Transplant Cell Ther. 2025: S2666-6367(25)01138-8.
3. Lin C, Sajeev G, Stiff PJ, et al. Health-related quality of life following allogeneic hematopoietic cell transplantation with omidubicel versus umbilical cord blood. Transplant Cell Ther. 2023a; 29(1):52.e1-52.e9.
4. Lin C, Schwarzbach A, Sanz J, Montesinos P, et al. Multicenter long-term follow-up of allogeneic hematopoietic cell transplantation with omidubicel: a pooled analysis of five prospective clinical trials. Transplant Cell Ther. 2023b; 29(5):338.e1-338.e6.
5. Okamoto S. Current indication for hematopoietic cell transplantation in adults. Hematol Oncol Stem Cell Ther. 2017; 10(4):178-183.
6. Parikh S, Brochstein JA, Galamidi E, et al. Allogeneic stem cell transplantation with omidubicel in sickle cell disease. Blood Advances. 2021; 5(3):843-852.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Society of Hematology (ASH). Blood Cancers. 2023. Available at: https://www.hematology.org/education/patients/blood-cancers. Accessed on December 14, 2025.
2. Centers for Disease Control and Prevention. USCS: hematologic cancer incidence, survival and prevalence. 2022. Available at: https://www.cdc.gov/united-states-cancer-statistics/?CDC_AAref_Val=https://www.cdc.gov/cancer/uscs/pdf/USCS-DataBrief-No30-September2022-h.pdf. Accessed on December 14, 2025.
3. European Working Group-Severe Aplastic Anemia. Current standard diagnostics for severe aplastic anemia in children and adolescents. V1.0 March 24, 2024. Available at: https://ewog-mds-saa.org/fileadmin/mediapool/10_andere/ewog-mds/pdf/SAA/Recommendations_for_Diagnostic_Work_Up_for_SAA_v1.0.pdf. Accessed on December 14, 2025.
4. Gamida Cell ltd. Evaluation of safety and efficacy of Allo GDA-201 NK Cells in patients with relapsed/refractory B Cell NHL. NLM Identifier: NCT05296525. Last updated on March 25, 2025. Available at: https://clinicaltrials.gov/ct2/show/NCT05296525. Accessed December 14, 2025.
5. Gamida Cell ltd. Stem cell transplantation with NiCord^® (Omidubicel) vs standard UCB in patients with leukemia, lymphoma, and MDS. NLM Identifier: NCT02730299. Last updated on April 6, 2025. Available at: https://clinicaltrials.gov/ct2/show/NCT02730299. Accessed December 14, 2025.
6. 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. 2015; 21(11):1863-1869.
7. National Cancer Institute. Blood-forming stem cell transplantation. Updated October 5, 2023. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant. Accessed on December 14, 2025.
8. National Cancer Institute. Pediatric hematopoietic stem cell transplant and cellular therapy for cancer (PDQ^®)-health professional version. Last updated June 13, 2024. Available at: https://www.cancer.gov/types/childhood-cancers/hp-stem-cell-transplant. Accessed on December 14, 2025.
9. NCCN Clinical Practice Guidelines in Oncology^®. © 2025 National Comprehensive Cancer Network, Inc. Hematopoietic cell transplantation (HCT). V3.2025. September 24, 2025. For additional information: http://www.nccn.org/index.asp. Accessed on December 18, 2025.
10. National Heart, Lung and Blood Institute (NHBLI). Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome. NLM Identifier. NCT03173937. Last updated November 24, 2025. Available at: https://clinicaltrials.gov/study/NCT03173937. Accessed on November 15, 2025.
11. Omisirge (Omidubidel-onlv). [FDA Product Information]. Gamida Cell Ltd., Boston, MA. Revised December 8, 2025. Available at: https://www.fda.gov/vaccines-blood-biologics/omisirge. Accessed on December 14, 2025.
12. United States Food & Drug Administration (FDA). December 8, 2025. FDA Approves First Cellular Therapy to Treat Patients with Severe Aplastic Anemia. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-severe-aplastic-anemia. Accessed on December 14, 2025.

1. American Cancer Society. Available at: http://www.acs.org. Accessed on December 14, 2025.
2. American Society for Transplantation and Cellular Therapy. Patient Education. Available at: https://www.astct.org/Education/Patient-Education. Accessed on December 14, 2025.
3. National Institutes of Health (NIH). National Heart, Lung, and Blood Institute (NHBLI). Aplastic Anemia. March 24, 2022. Available at: https://www.nhlbi.nih.gov/health/anemia/aplastic-anemia. Accessed on December 14, 2025.

Cellular Therapy
Cord Blood Stem Cell Therapy ProductOmidubicel (Omisirge)

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