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After a donor transplant, everyone takes medicines to stop the donor's immune cells attacking their body (graft-versus-host disease). The combination depends on the donor, the pre-transplant treatment and whether the cells came from blood or marrow. Newer combinations reduce graft-versus-host disease; in the main trial they did not lengthen life, and each has its own side effects.
EBMT 2024 (GRADE, ten PICO questions, 22 experts and a methodologist; abstract read): rabbit anti-T-cell globulin (ATG) or post-transplantation cyclophosphamide (PTCy) is standard prophylaxis in peripheral blood stem cell transplants from unrelated donors; ruxolitinib is the new standard for steroid-refractory acute and chronic GVHD; belumosudil is added for steroid-refractory chronic GVHD. The panel states its recommendations favour European practice.
BMT CTN 1703 (phase III, 431 adults, reduced-intensity conditioning, matched related or matched or 7/8 unrelated donors): PTCy-tacrolimus-mycophenolate mofetil gave more GVHD-free, relapse-free survival at one year than tacrolimus-methotrexate (52.7% against 34.9%; HR 0.64), with no substantial difference in overall or disease-free survival, relapse, transplant-related death or engraftment.
ABHH/SBTMO 2026 (GRADE systematic review, 11 PICO questions, 54 studies): calcineurin inhibitor plus methotrexate reduces acute GVHD (very low quality); calcineurin inhibitor plus mycophenolate can be preferred after myeloablative conditioning for less mucositis and toxicity; adding rATG is recommended; calcineurin inhibitor plus mycophenolate after reduced-intensity conditioning; high-dose PTCy (50 mg/kg days +3 and +4) with a calcineurin inhibitor with or without mycophenolate for haploidentical donors, and with reduced chronic GVHD in matched donors (RCTs) at the cost of more haemorrhagic cystitis (cohorts); PTCy with ATG raises EBV reactivation; abatacept added to calcineurin inhibitor and methotrexate lowers grade III to IV acute GVHD (very low quality).
Why: The best-tested combination differs between a sibling, an unrelated or a half-matched donor, and between blood and marrow grafts.
“The choice of GvHD prophylaxis should therefore be guided by donor type (matched sibling, matched unrelated, or haploidentical), conditioning regimen (myeloablative versus non-myeloablative/reduced intensity), and graft source (peripheral blood or bone marrow).”
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
Why: Both reduce graft-versus-host disease in this setting and are the European standard.
“(2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors”
Why: In a randomised trial it gave more people a year free of severe GVHD and relapse, though survival was similar.
“Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate.”
Why: Compared with the sirolimus-based version, it caused less bladder bleeding and liver blockage, with the same GVHD control.
“In patients undergoing haploidentical allo-HCT for malignant diseases, using either myeloablative or non-myeloablative conditioning and bone marrow or peripheral blood grafts, a regimen with high-dose PTCy plus CNI with or without MMF, compared with high-dose PTCy plus sirolimus and MMF, reduces hemorrhagic cystitis and sinusoidal obstructive syndrome risks, despite showing no significant differences in the risk of Grade II–IV or III–IV aGvHD, cGvHD, NRM, OS, or EFS.”
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
Why: GVHD control is similar, with less mouth ulceration and less kidney and lung toxicity.
“However, the combination with MMF can be recommended due to lower toxicity (nephrotoxicity and respiratory failure), particularly with tacrolimus and the lower incidence of mucositis (regardless of cyclosporine and tacrolimus), when compared to the combination with methotrexate.”
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026 · Quality of evidence: very low to moderate
Why: It reduced acute GVHD in pooled studies without a clear survival change.
“In patients undergoing allo-HCT, the use of rATG in combination with standard GvHD prophylaxis is recommended over standard prophylaxis alone.”
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026 · Quality of evidence: very low to moderate
Why: The combination reduces GVHD but, in pooled studies, raised the risk of the Epstein-Barr virus reactivating.
“In patients undergoing allo-HCT with haploidentical, related or unrelated matched donors or unrelated mismatched donors, the regimen combining high-dose PTCy plus ATG is associated with reduced risks of Grade II-IV aGvHD, and cGvHD, as well an increased risk of EBV reactivation when compared with other regimens lacking this combination.”
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
EBMT 2024 is the current European standard (GRADE, ten PICO questions) and makes ATG or PTCy standard for unrelated-donor peripheral blood transplants; only its abstract could be read. BMT CTN 1703 is the one phase III trial read: PTCy-tacrolimus-mycophenolate improved GVHD-free, relapse-free survival over tacrolimus-methotrexate after reduced-intensity conditioning, without a survival difference. ABHH/SBTMO 2026 is the most recent full GRADE systematic review read; it reaches compatible conclusions but rates most evidence very low to moderate, mostly from observational studies, and is written with low- and middle-income settings in mind. None of the sources read names one regimen as best for every transplant: all tie the choice to donor, conditioning and graft source.
EBMT, The Lancet Haematology 2024 · New England Journal of Medicine 2023 · ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
Where it differs: Adds abatacept to calcineurin inhibitor and methotrexate for matched or mismatched unrelated donors.
Evidence: Randomised trials pooled by ABHH: 28% lower risk of grade III to IV acute GVHD at three months and 12% lower relapse at 24 months, no difference in chronic GVHD or survival. Quality of evidence: very low.
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
Where it differs: Ciclosporin, mycophenolate and sirolimus for related or unrelated matched or mismatched donors.
Evidence: Lower grade II to IV acute GVHD and better two-year survival; quality of evidence very low to low.
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
Where it differs: Replaces methotrexate with sirolimus alongside tacrolimus.
Evidence: Three pooled randomised trials showed no greater benefit than calcineurin inhibitor plus methotrexate for acute or chronic GVHD or mortality.
ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026
| Recommendation | Grade, as printed | Source |
|---|---|---|
| CNI plus mycophenolate after myeloablative matched-donor transplant “Quality of Evidence: varied between very low and moderate, depending on the analyzed outcome.” | Quality of evidence: varied between very low and moderate | ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026 |
| Adding rATG to standard prophylaxis “Quality of Evidence: ranged from very low to moderate, depending on the outcome assessed.” | Quality of evidence: ranged from very low to moderate | ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026 |
| Abatacept plus CNI and methotrexate | Quality of evidence: very low | ABHH and SBTMO, Hematology, Transfusion and Cell Therapy 2026 |
| ATG or PTCy standard for unrelated-donor PBSC transplants | GRADE (strength not stated in the abstract) | EBMT, The Lancet Haematology 2024 |
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