MDS, and the transplant itself
Allogeneic hematopoietic cell transplant JCO, epub 9 June 2021
BMT CTN 1102: a matched donor, and reduced-intensity transplant, improved survival in older higher-risk MDS
This multicenter biologic-assignment trial compared reduced-intensity allogeneic hematopoietic cell transplantation with hypomethylating therapy or best supportive care. People aged 50 to 75 with intermediate-2 or high-risk de novo MDS were assigned by whether a matched donor was identified within 90 days. Between January 2014 and November 2018, 384 people enrolled at 34 centers. The primary outcome was overall survival at 3 years.
In the intention-to-treat analysis, adjusted 3-year overall survival was 47.9% (95% CI 41.3 to 54.1) in the donor arm and 26.6% (95% CI 18.4 to 35.6) in the no-donor arm (P = .0001), an absolute difference of 21.3% (95% CI 10.2 to 31.8). Three-year leukemia-free survival was 35.8% (95% CI 29.8 to 41.8) versus 20.6% (95% CI 13.3 to 29.1; P = .003). The abstract says the survival benefit was seen across subgroups examined, and that transplant should be part of the plan for fit older adults with higher-risk MDS. Median follow-up for survivors was 34.2 months in the donor arm and 26.9 months in the no-donor arm.
This is older than October 2024. It is included because no later randomised comparison of transplant versus no transplant in MDS was opened for this review. The journal HTML did not load. The figures are from the NCBI PubMed record for PMID 34106753.
Source: PubMed 34106753, Nakamura and colleagues, Journal of Clinical Oncology
Conditioning before allogeneic transplant Published 25 April 2024
RICMAC long-term follow-up: reduced-intensity and myeloablative conditioning looked similar at 10 years in MDS
The EBMT phase 3 RICMAC trial randomised adults with MDS, aged 18 to 65, to myeloablative busulfan/cyclophosphamide (n = 64) or reduced-intensity busulfan/fludarabine (n = 65), then allogeneic transplant from a matched or one-antigen-mismatched donor. This 2024 paper is a non-preplanned long-term analysis. Median follow-up was 6.2 years (range 0.4 to 12.5).
Ten-year overall survival was 54.0% after reduced-intensity conditioning and 44.4% after myeloablative conditioning (p = 0.15). Ten-year relapse-free survival was 43.9% and 44.2% (p = 0.78). The discussion states a 10-year overall survival of 49% (95% CI 38.3 to 60.1) irrespective of regimen, relapse incidence about 25% in each arm, and non-relapse mortality about 30% in each arm. In a subgroup with low-risk cytogenetics, reduced-intensity conditioning had better overall survival (p = 0.002), relapse-free survival (p = 0.02), and lower non-relapse mortality (p = 0.015). The authors limit the comparison to these two regimens. Recruitment was 2004 to 2012, so the result is about durability, not a new graft product.
Source: Niederwieser and colleagues, Bone Marrow Transplantation, 2024
Preparative regimen for allogeneic transplant FDA, 21 January 2025
FDA approves treosulfan with fludarabine before allogeneic transplant in AML or MDS
On 21 January 2025 the FDA approved treosulfan (Grafapex) with fludarabine as a preparative regimen for allogeneic hematopoietic stem-cell transplantation in adults and children 1 year and older with AML or MDS. Efficacy is from MC-FludT.14/L Trial II (NCT00822393), which compared treosulfan with busulfan, both with fludarabine. Eligible adults were 18 to 70 years old, with Karnofsky status at least 60%, and either age at least 50 or an HCT comorbidity index above 2. Randomisation was 280 treosulfan and 290 busulfan.
Overall survival, stratified by donor type and risk group, had a hazard ratio of 0.67 (95% CI 0.51 to 0.90) for treosulfan versus busulfan. In AML the hazard ratio was 0.73 (95% CI 0.51 to 1.06). In MDS it was 0.64 (95% CI 0.40 to 1.02). Those two disease-specific intervals include 1, so this page does not treat the MDS slice as a separately significant survival result. The labelled treosulfan dose is 10 g/m2 daily on days −4, −3, and −2, with fludarabine 30 mg/m2 daily on days −6 through −2, and stem-cell infusion on day 0.
Source: FDA approval announcement, treosulfan
The graft, and graft-versus-host disease
Donor graft: stem and progenitor cells plus T cells FDA, 30 June 2026
FDA approves Tregzi, a manipulated donor graft, for adults with hematologic malignancies
On 30 June 2026 the FDA approved allogeneic regulatory T-cell immunotherapy with hematopoietic stem and progenitor cells and T cells-vldq (Tregzi, Orca Bio). The indication on the FDA page is use in matched-donor hematopoietic stem-cell transplantation with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in adults with hematologic malignancies. The product is given as three parts: stem and progenitor cells and regulatory T cells on day 0, then conventional T cells on day +2 to +3. This is not described as a CAR-T product.
Precision-T (NCT05316701) randomised 187 adults with acute leukemias or MDS: 93 to Tregzi plus tacrolimus, and 94 to an unmanipulated allograft plus tacrolimus and methotrexate. Chronic GVHD-free survival had a hazard ratio of 0.26 (95% CI 0.14 to 0.47; P < .00001). Median follow-up was 8.48 months (range 0 to 22) and 9.03 months (range 0 to 20). The cumulative incidence of moderate-to-severe chronic GVHD at 12 months was 12.6% (95% CI 5.3 to 23.1) versus 44.0% (95% CI 31.3 to 56.1). All 88 patients treated with Tregzi reached a neutrophil count of 500/mm3 within 28 days; 53 of 88 (60.2%) met the page’s stricter definition of recovery on three consecutive days. Follow-up on this announcement is short. Full prescribing information was not yet posted on the page that was opened.
Source: FDA approval announcement, Tregzi
Allogeneic mesenchymal stromal cells FDA, 18 December 2024
FDA approves Ryoncil for steroid-refractory acute GVHD in children
On 18 December 2024 the FDA approved remestemcel-L-rknd (Ryoncil), allogeneic bone-marrow mesenchymal stromal cells from a healthy donor, for steroid-refractory acute graft-versus-host disease in children 2 months and older. The FDA page calls it the first FDA-approved mesenchymal stromal cell therapy. It is an infusion for a complication of allogeneic transplant, not a replacement for the hematopoietic graft.
MSB-GVHD001 (NCT02336230) was a single-arm study in 54 children with grade B to D steroid-refractory acute GVHD after allogeneic transplant, excluding grade B skin alone, and excluding children already given a second-line therapy. Day-28 overall response was 70% (95% CI 56.4 to 82.0): complete response 30% (95% CI 18.0 to 43.6) and partial response 41% (95% CI 27.6 to 55.0). Median duration of that response, until progression, new systemic therapy, or death, was 54 days (range 7 to 159+). The labelled dose is 2 × 106 cells/kg intravenously twice a week for 4 weeks, eight infusions, at least 3 days apart. There was no randomised control on the page that was opened.
Source: FDA approval announcement, remestemcel-L-rknd
Severe aplastic anemia
Nicotinamide-enhanced cord-blood stem cells FDA announcement, 8 December 2025
FDA approves Omisirge for severe aplastic anemia when no compatible donor is available
On 8 December 2025 the FDA announced approval of Omisirge (omidubicel-onlv) for severe aplastic anemia. The page calls it the first hematopoietic stem-cell transplant therapy approved for that disease. The new use is adults and children 6 years and older, after reduced-intensity conditioning, when a compatible donor is not available. The same page says Omisirge is also indicated for adults and children 12 years and older with hematologic malignancies. That older indication was not re-opened as a separate approval letter.
The product is donated cord-blood stem cells cultured with nicotinamide. The severe aplastic anemia evidence on this page is an ongoing open-label single-arm study. In the efficacy population, 12 of 14 patients had early and sustained neutrophil engraftment. Median time to neutrophil recovery was 11 days (range 7 to 20). Autoimmune cytopenias occurred in 25%. Common side effects listed include febrile neutropenia, viral and bacterial infection, hyperglycemia, immune thrombocytopenia, and pneumonia. This is not evidence about matched-sibling transplant, which the same page describes as a usual option when a donor exists.
Source: FDA press announcement, Omisirge for severe aplastic anemia
Sickle cell disease and transfusion-dependent beta-thalassemia
Autologous genome-edited hematopoietic stem cells US label revised July 2026
Casgevy: edited autologous blood stem cells, US label now from age 2
The DailyMed label for Casgevy (exagamglogene autotemcel), updated July 2026 and marked revised 7/2026, describes an autologous genome-edited hematopoietic stem-cell therapy. The indication is patients aged 2 years and older with sickle cell disease and recurrent vaso-occlusive crises, or with transfusion-dependent beta-thalassemia. Initial US approval is listed as 2023. A major change to indications is dated 07/2026. The minimum dose is 3 × 106 CD34+ cells/kg, given once after myeloablative conditioning. It is the patient’s own cells, edited at the BCL11A erythroid enhancer so that fetal hemoglobin rises. Ages 2 to under 5 are an extrapolation: the label says clinical trials did not study children under 5.
In sickle cell disease, Trial 1 (NCT03745287, age 12 and older) reported a VF12 response, no protocol-defined severe crisis for at least 12 consecutive months, in 29 of 31 efficacy-evaluable patients (93.5%). Trial 4 (NCT05329649, age 5 to under 12) reported VF12 in all 8 efficacy-evaluable patients. A separate pediatric-use section gives VF12 as 86% at ages 12 to under 18 (12 patients in that band in Trial 1) and 100% at ages 5 to under 12. Those are not the same denominator as 29 of 31. For thalassemia, Trial 2 (NCT03655678, age 12 and older) reported transfusion independence for 12 months (TI12) in 32 of 35 (91.4%). Trial 5 (NCT05356195, age 5 to under 12) reported TI12 in 8 of 9 efficacy-evaluable patients (89%), a set that included one child who died of veno-occlusive disease, hemophagocytic lymphohistiocytosis, pneumonia, and multi-organ failure before month 16. Studies were single-arm. Patients with an available 10/10 matched related donor were excluded.
Source: DailyMed, Casgevy label, revised July 2026
Autologous genome-edited hematopoietic stem cells EU authorisation 9 February 2024 · product information updated 3 September 2025
EMA: Casgevy remains described, on the page opened, for age 12 and older
The EMA medicine page states a conditional marketing authorisation on 9 February 2024. Casgevy is described as genetically modified stem cells taken from the patient’s own blood, used when stem-cell treatment is appropriate and no suitable donor is available. The indication printed there is transfusion-dependent beta-thalassemia, and severe sickle cell disease with recurrent vaso-occlusive crises, both in patients 12 years and older for whom transplant is appropriate and an HLA-matched related donor is not available. Product information was last updated 3 September 2025, and a later procedure is dated 10 February 2026. The age wording on the overview that was opened was still 12 years, not the US age of 2. This review did not open the September 2025 or February 2026 variation documents, so it does not claim what those updates changed.
The benefit figures on that overview, from interim results of two ongoing single-arm studies, are 39 of 42 people with thalassemia aged 12 to 35 who kept hemoglobin above 9 g/dL without transfusion for at least 12 consecutive months, and 28 of 29 people with severe sickle cell disease aged 12 to 35 who had no painful crisis for at least 12 consecutive months. None of those 29 needed hospitalisation for a painful crisis over that period. These are not the same counts as the later US label above.
Source: EMA EPAR, Casgevy
Outside blood disease: one approved product that failed
Allogeneic adipose mesenchymal stem cells EMA, 13 December 2024
Alofisel withdrawn in the EU after ADMIRE-CD II did not beat placebo
Alofisel (darvadstrocel) was an approved stem-cell product: mesenchymal stem cells from adult donor fat, for complex perianal fistulas in adults with Crohn’s disease when a conventional or biologic medicine had not worked well enough. It was authorised in 2018. On 13 December 2024 the EMA reported that the marketing company was withdrawing it because benefit was no longer demonstrated.
ADMIRE-CD II was a randomised placebo-controlled study of a single administration in 568 adults with Crohn’s disease and complex perianal fistulas. Combined remission at 24 weeks was 48.76% with Alofisel and 46.32% with placebo, difference 2.37%, p = 0.571. Secondary endpoints were also not met. The EMA said the safety profile was consistent with earlier studies and that no new safety signal was identified. No new patients were to be treated after 13 December 2024. This is the non-hematology result opened for this window. It is a negative result, not a reason to use mesenchymal cells for fistulas.
Source: EMA, Alofisel withdrawn from the EU market, 13 December 2024