📌 The essentials On June 30, 2026, the FDA approved Tregzi (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq, Orca Bio) for use in matched-donor hematopoietic stem cell transplantation (HSCT) with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease (cGVHD)-free survival in adults with hematological malignancies such as leukemia. Tregzi is the first FDA-approved therapy that uses highly purified regulatory T cells (Tregs), and the first cell therapy specifically designed to reshape the donor graft before it ever reaches the patient. What Tregzi is not: it is not a post-transplant drug added to prevent GVHD after the fact. It replaces the standard unmanipulated graft entirely, substituting an engineered, precision-sorted cellular product for the conventional “bag of cells” approach that has defined allogeneic transplantation for decades. The clinical basis: Phase 3 PRECISION-T trial (NCT05316701), 187 patients with AML, ALL, MDS, or mixed-phenotype acute leukemia, randomized to Tregzi plus single-agent tacrolimus versus conventional allogeneic HSCT plus tacrolimus and methotrexate. Primary endpoint: cGVHD-free survival (cGFS). Results at 12 months: cGFS 78% (Tregzi) versus 38.4% (standard transplant); HR 0.26 (95% CI 0.14 to 0.47); p less than 0.00001. Cumulative incidence of moderate-to-severe cGVHD: 12.6% versus 44.0%; HR 0.19; p=0.00002. Overall survival: 93.9% versus 83.1% (HR 0.49; p=0.12, not statistically significant at this analysis). Non-relapse mortality: 3.4% versus 13.2% (p=0.03). GVHD-free and relapse-free survival (GRFS): 63.1% versus 30.9% (p less than 0.001). Grade 3 or 4 acute GVHD by day 180: 6.2% versus 16.5%. Grade 3 or higher infections at 1 year: 44% versus 51%. Rehospitalization after discharge: 27.3% versus 45.7%. Primary publication: Meyer EH et al. Blood. 2026;147(11):1168-1177. Regulatory designations: Orphan Drug Designation; Regenerative Medicine Advanced Therapy (RMAT) Designation; Priority Review. Eligible population: adults with hematological malignancies undergoing 8/8 HLA-matched allogeneic HSCT with myeloablative conditioning. The approval does not currently cover mismatched or haploidentical transplant settings.

Most people who know someone with leukemia know the basic arc of the story. The diagnosis. The decision to pursue a stem cell transplant because nothing else can cure it. The months of waiting for a matched donor. The grueling conditioning chemotherapy to destroy the diseased bone marrow. The transplant itself. And then, if everything goes well, the slow and fragile process of immune reconstitution, of watching for signs that the new immune system is attacking the body it was supposed to save.

That last chapter is the one that Tregzi was built to change.

Chronic graft-versus-host disease affects between 30% and 70% of allogeneic stem cell transplant recipients. It is the leading cause of non-relapse mortality and long-term disability in transplant survivors. Patients who develop it can spend years managing symptoms across multiple organ systems: skin rashes that progress to tightening and fibrosis, dry eyes that cause permanent damage, mouth sores that make eating painful, liver inflammation, and scarring in the joints and lungs. For a patient who survived a blood cancer, this is a profoundly cruel outcome. They beat the disease, but the cure has made them chronically ill in a different way.

Tregzi (Orca Bio), approved June 30, 2026, is the FDA’s first approval of a precision-engineered cell therapy designed to prevent this outcome at the source. Rather than adding another immunosuppressive drug after a standard transplant, Tregzi rebuilds the graft itself, sorting and purifying the donor cells into three precisely defined populations and delivering them in a controlled sequence designed to prevent GVHD while preserving the immune activity that keeps the cancer from coming back.

The Phase 3 PRECISION-T trial showed that 78% of patients who received Tregzi were alive without moderate-to-severe chronic GVHD at one year, compared to 38.4% of those who received a conventional transplant. Non-relapse mortality dropped from 13.2% to 3.4%. Rehospitalization after the initial transplant discharge fell from 45.7% to 27.3%. These are large improvements in outcomes that have not meaningfully changed in decades.

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What Hematological Malignancies and Allogeneic Transplantation Are

Hematological malignancies are cancers of the blood, bone marrow, and lymphatic system. The diseases covered in PRECISION-T include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), and mixed-phenotype acute leukemia (MPAL). These are among the most aggressive blood cancers, with high rates of relapse after standard chemotherapy, particularly in patients with high-risk disease features.

For many patients with these diagnoses, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative treatment. The procedure involves destroying the patient’s diseased bone marrow with high-dose chemotherapy and sometimes radiation (the myeloablative conditioning regimen), then infusing stem cells from a healthy matched donor. The donor stem cells engraft in the bone marrow, reconstitute the immune system, and ideally provide ongoing graft-versus-leukemia (GVL) activity, meaning the donor immune cells continue recognizing and eliminating any residual or relapsed leukemia cells.

The procedure works. But it carries risks that have limited its wider use and dramatically affected the quality of life of patients who survive it.

The fundamental tension at the heart of every transplant

The same donor T cells that provide graft-versus-leukemia activity are the cells that cause graft-versus-host disease. Tamp down the donor immune response too aggressively to prevent GVHD, and relapse risk increases. Allow the donor immune response to proceed without sufficient control, and GVHD occurs. Standard GVHD prophylaxis with tacrolimus plus methotrexate, or post-transplant cyclophosphamide, reduces but does not eliminate this risk. Chronic GVHD affecting 30% to 70% of recipients represents the field’s inability, over several decades, to cleanly resolve this tension.

Tregzi’s approach is not to add another immunosuppressive layer on top of the standard graft. It is to engineer the graft itself so that the cell populations responsible for GVHD are controlled from the start, while the populations responsible for immune reconstitution and anti-leukemia activity are preserved.

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What Chronic GVHD Is and Why It Matters Clinically

Chronic graft-versus-host disease develops when donor T cells recognize host tissues as foreign and mount a persistent immune attack against them. Unlike acute GVHD, which typically occurs within the first 100 days after transplant and primarily targets the skin, liver, and gastrointestinal tract, chronic GVHD can affect virtually any organ system and persists for months to years.

The clinical manifestations range from manageable to profoundly disabling. Skin involvement ranges from rash to progressive fibrosis that limits joint mobility. Ocular involvement causes dry eye syndrome that can lead to corneal damage. Oral involvement produces painful sores and restricted mouth opening. Pulmonary involvement causes bronchiolitis obliterans, an irreversible scarring of the small airways. Hepatic involvement produces abnormal liver function. Musculoskeletal involvement causes fasciitis and joint contractures.

Moderate-to-severe chronic GVHD, the degree targeted as the primary endpoint in PRECISION-T, is clinically defined by involvement that substantially impairs function or requires systemic immunosuppression. Patients with moderate-to-severe cGVHD are, by definition, spending significant portions of their post-transplant lives managing a chronic inflammatory illness while already being immunocompromised.

The treatment of established chronic GVHD is difficult. Corticosteroids are the first-line standard but produce substantial side effects with long-term use and do not reliably induce sustained remission. Ibrutinib and ruxolitinib are approved for steroid-refractory cGVHD, but the best outcome in steroid-refractory disease is still living with a controlled chronic illness. Prevention is always preferable to treatment.

Who gets allogeneic transplants and how common GVHD is Approximately 25,000 allogeneic stem cell transplants are performed annually in the United States. The majority involve 8/8 HLA-matched donors, which is the setting studied in PRECISION-T. Chronic GVHD occurs in an estimated 30% to 70% of matched-donor allo-HSCT recipients, with moderate-to-severe disease in roughly 30% to 40%. It is the single leading cause of non-relapse mortality and long-term morbidity in transplant survivors, accounting for more late deaths after transplantation than cancer relapse in some populations. Despite this burden, meaningful improvements in cGVHD prevention have been slow to materialize over the past two decades. Standard GVHD prophylaxis regimens have not substantially changed, and the rates of cGVHD have remained relatively stable even as transplant-related mortality from other causes has declined.

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How Tregzi Works: Precision Cell Engineering Rather Than Immune Suppression

Understanding Tregzi requires understanding what is wrong with the standard allogeneic graft, and why sorting matters.

In a conventional allogeneic transplant, the donor undergoes mobilization with growth factors to push hematopoietic stem cells into the peripheral blood, and those cells are collected by apheresis. The resulting graft is essentially unmanipulated: it contains stem cells, conventional T cells (Tcons), regulatory T cells (Tregs), and a range of other cell populations, all infused together in proportions that reflect whatever happened to be in the donor’s blood that day. The immune system is reconstituted, but the balance between the cells that cause GVHD and the cells that suppress it is left largely to chance.

Tregzi replaces this approach with three precisely sorted and separately delivered cell populations:

Hematopoietic stem and progenitor cells (HSPCs): These are the cells that engraft in the bone marrow and rebuild the entire blood and immune system from scratch. In Tregzi, HSPCs are highly purified, with the goal of maximizing engraftment efficiency while removing cells that could contribute to GVHD.

Highly purified regulatory T cells (Tregs): Tregs are a specialized subset of CD4-positive T cells whose primary function is immune regulation, specifically the suppression of excessive or misdirected immune responses. In healthy individuals, Tregs prevent autoimmunity by keeping other immune cells from attacking self-tissues. In the transplant setting, Tregs can suppress the alloreactive T cell response that drives GVHD. In a standard graft, Tregs are present but are vastly outnumbered by conventional T cells. In Tregzi, they are sorted, purified, and delivered at a substantially higher proportion than occurs in any natural graft.

Conventional T cells (Tcons): Tcons are infused 48 hours after the stem cells and Tregs, in a lower total dose than in a standard graft. This delayed, reduced-dose delivery is central to the approach: by the time the Tcons arrive, the Tregs are already present and active, able to suppress the GVHD-inducing activity of the incoming Tcons while allowing enough conventional T cell activity to support immune reconstitution and preserve graft-versus-leukemia effect.

The sorting and purification process is performed using Orca Bio’s high-precision cell manufacturing platform, which uses fluorescence-activated cell sorting (FACS) technology to separate cell populations with a level of purity not achievable through standard density gradient or selection methods. The manufacturing facility is in Sacramento, California.

Dr. Robert Negrin, professor of medicine and blood and marrow transplantation at Stanford Medicine and one of the foundational researchers behind the regulatory T cell transplant concept, described the approval as representing a defining moment for the transplant community, noting that the peer-reviewed findings demonstrated this precision-engineered cell therapy delivered improved GVHD-free survival alongside less toxicity, including fewer serious infections and lower non-relapse mortality.

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The PRECISION-T Trial: Complete Data

Design

PRECISION-T (NCT05316701) was a randomized, multicenter, open-label, controlled Phase 3 trial conducted across 19 transplant centers in the United States. The trial enrolled 187 adults with AML, ALL, high-risk MDS, or mixed-phenotype acute leukemia who were undergoing their first allogeneic HSCT from an 8/8 HLA-matched related or unrelated donor with a myeloablative conditioning regimen.

Patients were randomized 1:1 to:

• Tregzi (HSPCs plus purified Tregs on day 0, followed by Tcons on day 2) plus single-agent tacrolimus as GVHD prophylaxis
• Conventional peripheral blood stem cell (PBSC) allograft plus tacrolimus and methotrexate as standard GVHD prophylaxis

The primary endpoint was chronic GVHD-free survival (cGFS), defined as time from transplantation to death or the onset of moderate-to-severe chronic GVHD, whichever occurred first. Secondary endpoints included cumulative incidence of moderate-to-severe cGVHD, overall survival, GVHD-free and relapse-free survival (GRFS), and non-relapse mortality. Primary results were published in Blood in 2026 (Meyer EH et al. Blood. 2026;147(11):1168-1177).

Primary and key secondary results at 12 months

Endpoint	Tregzi	Standard transplant	Result
cGVHD-free survival (cGFS)	78.0%	38.4%	HR 0.26 (95% CI 0.14 to 0.47); p less than 0.00001
Moderate-to-severe cGVHD (cumulative incidence)	12.6%	44.0%	HR 0.19 (95% CI 0.08 to 0.43); p=0.00002
Overall survival	93.9%	83.1%	HR 0.49; p=0.12 (not statistically significant)
Non-relapse mortality	3.4%	13.2%	p=0.03
GVHD-free and relapse-free survival (GRFS)	63.1%	30.9%	p less than 0.001
Grade 3 or 4 acute GVHD by day 180	6.2%	16.5%	HR 0.37; p=0.044
Grade 3 or higher infections at 1 year	44%	51%	Reduced with Tregzi
Rehospitalization after discharge	27.3%	45.7%	Substantially lower
Hospitalization days per patient	30.6	40.8	Fewer with Tregzi

Source: Meyer EH et al. Blood. 2026;147(11):1168-1177. PRECISION-T NCT05316701.

Reading the numbers carefully

The primary endpoint result is large and highly statistically significant: a 74% reduction in the hazard of death or moderate-to-severe chronic GVHD (HR 0.26). At 12 months, 78% of Tregzi patients were alive without moderate-to-severe cGVHD, compared to 38.4% on the standard arm. This is not a marginal improvement. It is the difference between fewer than 4 in 10 standard transplant recipients avoiding this outcome versus nearly 8 in 10 Tregzi recipients.

The non-relapse mortality finding deserves particular emphasis. Non-relapse mortality is death from transplant complications rather than the underlying cancer, and it represents the preventable deaths that better transplant care should be able to eliminate. In PRECISION-T, the NRM rate fell from 13.2% to 3.4%, a statistically significant reduction. Nearly one in seven patients in the standard arm died from transplant complications rather than their leukemia or MDS. With Tregzi, that figure drops to approximately one in thirty.

The overall survival result (93.9% versus 83.1%) is clinically meaningful in its absolute terms but did not reach statistical significance at this analysis, with a p-value of 0.12. This is an important limitation to acknowledge. The trial was not powered for OS as a primary endpoint, the median follow-up was 8.5 to 9 months, and OS data continue to mature. Whether the large NRM reduction will translate into a statistically significant OS benefit with longer follow-up is the key unanswered question in this dataset.

The GRFS result (63.1% versus 30.9%) is also reported descriptively rather than as a formal efficacy claim, because the pre-specified interim OS analysis did not cross the statistical boundary required to advance to formal GRFS testing in the hierarchical analysis plan. The directional benefit is substantial and consistent, but its formal statistical status reflects the trial’s sequential testing structure rather than any ambiguity about the clinical observation.

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Safety: What the PRECISION-T Data and Prescribing Information Cover

The safety profile from PRECISION-T was generally more favorable for Tregzi than for the standard transplant arm across most clinically relevant metrics, which is unusual in a trial comparing an investigational therapy to a well-established comparator.

Adverse reactions expected in any allogeneic transplant:

The most common adverse reactions with Tregzi reflect the expected consequences of myeloablative conditioning and immune reconstitution rather than toxicity specific to the Tregzi product. These include mucositis, gastrointestinal toxicity (nausea, vomiting, diarrhea), rash, edema, hemorrhage, and infections. Grade 3 or 4 cytopenias were frequent, as expected in any patient who has undergone myeloablative chemotherapy and is in the process of bone marrow reconstitution.

Warnings and precautions from the Tregzi prescribing information:

Graft-versus-host disease (boxed warning): Acute and chronic GVHD, including life-threatening and fatal cases, can still occur following Tregzi. The Treg approach substantially reduces the incidence and severity but does not eliminate the risk. Patients must receive single-agent calcineurin inhibitor prophylaxis (tacrolimus) as specified in the prescribing information and must be monitored for GVHD signs and symptoms throughout the post-transplant period. Acute GVHD presents as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Chronic GVHD may include skin rash, mouth sores, dry eyes, liver inflammation, and development of scar tissue in the skin and joints, as well as lung damage.

Infusion reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur because of DMSO, human serum albumin (HSA), Dextran, or murine protein present in the Tregzi formulation. Appropriate resuscitation measures must be available during infusion.

Graft failure: Failure of the Tregzi graft to engraft can result in fatal aplasia. All 88 patients (100%) treated with Tregzi in the PRECISION-T trial achieved sustained engraftment, which is a notable finding, but graft failure remains a risk that must be monitored post-infusion.

Serious infections: Immunosuppression following myeloablative conditioning and during immune reconstitution creates vulnerability to bacterial, viral, and fungal infections. In PRECISION-T, grade 3 or higher infection incidence at 1 year was 44% with Tregzi versus 51% with standard transplant, a favorable difference, but the absolute rate of serious infections remains substantial in both arms. Antimicrobial prophylaxis and monitoring protocols consistent with institutional transplant standards apply.

Malignancy: As with all allogeneic transplant regimens, secondary malignancies including post-transplant lymphoproliferative disorder (PTLD) have been reported. Long-term surveillance is required.

Embryo-fetal toxicity: The myeloablative conditioning regimen used before Tregzi infusion can cause infertility and fetal harm. Patients of reproductive potential should discuss fertility preservation options before initiating conditioning.

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What This Means for Transplant Centers, Patients, and Families

For transplant centers

Tregzi introduces a new logistical framework for allogeneic transplantation. It is not a drop-in replacement for standard apheresis products. The manufacturing process requires:

• Coordination with Orca Bio’s manufacturing facility in Sacramento, California for cell processing, sorting, and product release
• A two-infusion sequence: Tregs and HSPCs on day 0, Tcons 48 hours later on day 2
• Modified GVHD prophylaxis with single-agent tacrolimus rather than the standard tacrolimus-plus-methotrexate combination

Transplant centers must be credentialed to administer Tregzi and will require integration of Orca Bio’s logistics and quality processes into their existing transplant programs. Orca Bio has announced the opening of a facility in Princeton, New Jersey, in addition to its Sacramento manufacturing base, to support east coast transplant center access.

Dr. Amandeep Salhotra of City of Hope noted that relapse-free survival was comparable between arms in the trial, suggesting that the precision cell-dosing approach preserves antileukemic activity while reducing GVHD. This is a critical finding for hematologists who have been cautious about aggressive Treg-based approaches on the grounds that reducing donor T cell activity might allow the cancer to come back.

For patients and families

The practical meaning of these data for a patient facing an allogeneic transplant for AML, ALL, or high-risk MDS is worth spelling out directly.

With a standard transplant plus tacrolimus/methotrexate, approximately 44% of patients will develop moderate-to-severe chronic GVHD within the first year. With Tregzi, that falls to approximately 12.6%. The chance of being alive without chronic GVHD at one year more than doubles. Non-relapse mortality, meaning the risk of dying from transplant complications rather than the cancer, drops by roughly four-fold, from 13.2% to 3.4%. Rehospitalization after the initial discharge drops from 45.7% to 27.3%, meaning substantially fewer patients are bouncing back to the hospital in the months after transplant.

Whether Tregzi is the right choice for a specific patient depends on eligibility (the 8/8 HLA-matched donor requirement currently applies), transplant center availability, individual disease and risk factors, and clinical discussion with a board-certified hematologist or transplant physician. The PRECISION-T data apply to patients with AML, ALL, high-risk MDS, and mixed-phenotype acute leukemia undergoing first allogeneic transplant with myeloablative conditioning.

Importantly, Tregzi has not yet been studied in mismatched, haploidentical, or reduced-intensity conditioning transplant settings. Those populations and approaches represent a large fraction of real-world transplant practice, and whether Tregzi’s benefits extend beyond the PRECISION-T-defined population is a question that ongoing and future studies will need to address.

Regulatory designations and what they signal

Tregzi received Orphan Drug Designation (reflecting the rare disease burden it addresses), Regenerative Medicine Advanced Therapy (RMAT) Designation (the cell and gene therapy equivalent of Breakthrough Therapy Designation, enabling intensive FDA engagement during development), and Priority Review. The RMAT designation in particular indicates that the FDA considered the preliminary evidence from early-phase Orca-T studies to represent substantial improvement over available therapies even before Phase 3 data were complete.

For related HED coverage on cell and gene therapy approvals in blood cancers and primary immunodeficiency, see our post on KRESLADI (marnetegragene autotemcel), the first gene therapy approved for severe Leukocyte Adhesion Deficiency Type I and our post on Hympavzi (marstacimab) expanding to include children aged 6 to 11 and patients with hemophilia inhibitors.

If you or someone you love is navigating a blood cancer diagnosis and considering transplant options, the National Bone Marrow Transplant Link (nbmtlink.org; 1-800-546-5268) and the Leukemia and Lymphoma Society (lls.org; 1-800-955-4572) both maintain current patient resources, transplant center referral support, and peer-to-peer patient connection programs.

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Sources

FDA approval announcement: FDA approves allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. FDA.gov. June 30, 2026.

Orca Bio FDA approval press release: Orca Bio’s TREGZI Receives U.S. FDA Approval as First and Only Precision-Engineered Cell Therapy for Allogeneic Transplant in Adults with Hematological Malignancies. BusinessWire. June 30, 2026.

Drugs.com approval news: FDA Approves Tregzi (Orca-T) as First and Only Precision-Engineered Cell Therapy for Allogeneic Transplant. drugs.com. June 30, 2026.

PRECISION-T primary publication in Blood: Meyer EH et al. Orca-T versus conventional graft in matched-donor hematopoietic stem cell transplantation. Blood. 2026;147(11):1168-1177.

PRECISION-T trial registration: NCT05316701. ClinicalTrials.gov.

BioPharm International (clinical summary with limitations): FDA Approves Tregzi, First Regulatory T-Cell Immunotherapy to Reduce Chronic GVHD. biopharminternational.com. July 2026.

Pharmacy Times (full endpoint data): FDA Approves Tregzi for Adults With Hematological Malignancies. pharmacytimes.com. July 2026.

Blood Cancers Today (primary publication analysis): Orca-T Reduces Chronic GVHD in Phase 3 Transplant Trial. bloodcancerstoday.com. May 2026.

AML Hub (complete endpoint table): FDA approves Orca-T for adults with hematological malignancies undergoing matched-donor allo-HSCT. aml-hub.com. July 2026.

Oncology Nursing News: FDA Approves Tregzi for Chronic GVHD-Free Survival in Blood Cancer. oncnursingnews.com. July 2026.

European Pharmaceutical Review (12-month data summary): US approval of Orca’s Tregzi landmark advance for stem cell transplants. europeanpharmaceuticalreview.com. July 2026.

Targeted Oncology (Dr. Salhotra mechanism interview): Dr Salhotra Details Orca-T’s Performance in Phase 3 Precision-T Trial. targetedonc.com. July 2026.

Targeted Oncology (ASH 2025 QOL and hospitalization data): Phase 3 Data Highlight Orca-T’s Clinical Benefits in Heme Malignancies. targetedonc.com. April 2026.

CancerNetwork (investigator quote): FDA OKs Regulatory T-Cell Immunotherapy in Hematologic Malignancies. cancernetwork.com. July 2026.

BioSpace coverage: Orca opens up Treg cell therapy with FDA nod for allogeneic blood cancer treatment. biospace.com. July 2026.

Chronic GVHD overview: Graft-Versus-Host Disease. StatPearls. NCBI.

Allogeneic HSCT overview: Hematopoietic Stem Cell Transplantation. StatPearls. NCBI.

Ibrutinib cGVHD approval: FDA approves ibrutinib for chronic graft-versus-host disease. FDA.gov.

Ruxolitinib cGVHD approval: FDA approves ruxolitinib for chronic graft-versus-host disease. FDA.gov.

ACS leukemia overview: Leukemia. American Cancer Society.

Tregzi prescribing information: TREGZI Prescribing Information. Orca Bio. 2026.

Tregzi approval history: Tregzi FDA Approval History. drugs.com.

Patient resources: National Bone Marrow Transplant Link: 1-800-546-5268 | Leukemia and Lymphoma Society: 1-800-955-4572 | Aplastic Anemia and MDS International Foundation | Orca Bio patient information | Be The Match (donor registry and transplant support)

Disclaimer: Health Evidence Digest provides general information about FDA approvals and health research for educational purposes. This content is not a substitute for professional medical advice. Treatment decisions for hematological malignancies, including the decision to pursue allogeneic stem cell transplantation and the choice of graft product, must be made in close collaboration with a board-certified hematologist or hematopoietic cell transplant specialist at an accredited transplant center. Tregzi is indicated for use in matched-donor HSCT with myeloablative conditioning in adult patients; eligibility criteria in the prescribing information should be reviewed carefully by treating physicians.