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Every donor transplant includes drugs to stop the new immune system attacking the body. A randomised trial in 2023 changed the usual choice: cyclophosphamide after the transplant, with tacrolimus and mycophenolate, worked better than the older combination. Prevention is not free, because the same drugs hold back the response to infection.
The standard for decades was a calcineurin inhibitor, ciclosporin or tacrolimus, with methotrexate. BMT CTN 1703 tested that against post-transplantation cyclophosphamide with tacrolimus and mycophenolate mofetil in adults with haematological cancers receiving a reduced-intensity conditioned transplant from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor. The primary endpoint was GvHD-free, relapse-free survival at one year, counting grade III or IV acute GvHD, chronic GvHD needing systemic immunosuppression, relapse or progression, and death from any cause as events. Among 214 patients on the experimental regimen and 217 on the standard, the hazard ratio was 0.64 (95 per cent CI 0.49 to 0.83, P = 0.001), and adjusted GvHD-free, relapse-free survival at one year was 52.7 per cent against 34.9 per cent. The trial reported that patients on the experimental regimen appeared to have less severe acute or chronic GvHD and a higher incidence of immunosuppression-free survival at one year, and that overall and disease-free survival, relapse, transplantation-related death and engraftment did not differ substantially between the groups.
That last clause is the honest part. The regimen that halved the composite did not, in this trial, lengthen life; what it changed was how much GvHD and how much immunosuppression a person lived with. For a reader deciding what to ask about, that is still a real difference, and it is the difference the trial was designed to measure.
The European cohort of 2017 transplants gives a observational cross-check from before the trial: prophylaxis with antithymocyte globulin or post-transplant cyclophosphamide was associated with a chronic GvHD incidence of 28.7 per cent, against 30.6 per cent with calcineurin inhibitors and 58.4 per cent with methotrexate or mycophenolate regimens, all comparisons P less than 0.01. Observational comparisons of prophylaxis regimens are confounded by donor type and conditioning intensity, which is why the randomised result carries the weight.
What prevention costs. Post-transplant cyclophosphamide is given after the graft, at a point when it kills proliferating alloreactive T cells of both directions while sparing regulatory T cells and the graft itself; it also delays immune reconstitution and is associated with more early infection and with cytomegalovirus reactivation in some series. Antithymocyte globulin depletes T cells more broadly and more durably, with the same trade. Every prophylaxis decision is a position on one axis: less graft-versus-host disease at one end, more infection and potentially more relapse at the other. The European cohort's finding that patients who developed chronic GvHD relapsed less often, 14.5 per cent against 27.2 per cent, is the other half of that axis made visible.
In practice prophylaxis is chosen by donor type, graft source, conditioning intensity and the disease being treated, and post-transplant cyclophosphamide has moved from a haploidentical-donor technique to a standard option in matched and mismatched unrelated donor transplants on the strength of BMT CTN 1703.
Alloreactive donor T cells proliferate in the first days after the graft meets host antigen. Cyclophosphamide given on days 3 and 4 is selectively toxic to those dividing cells while regulatory T cells, which express high levels of aldehyde dehydrogenase, survive it; the graft's haematopoietic stem cells survive for the same reason. Calcineurin inhibitors instead suppress T cell receptor signalling continuously, and methotrexate blocks proliferation non-selectively, which is why the three have different infection and reconstitution profiles.
Query for this technology: (TITLE:"Preventing graft-versus-host disease, and what prevention costs" OR ABSTRACT:"Preventing graft-versus-host disease, and what prevention costs" OR TITLE:"GvHD prophylaxis" OR ABSTRACT:"GvHD prophylaxis" OR TITLE:"post-transplant cyclophosphamide" OR ABSTRACT:"post-transplant cyclophosphamide" OR TITLE:"PTCy" OR ABSTRACT:"PTCy") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Preventing graft-versus-host disease, and what prevention costs, not a curated reading list.
Shares When steroids fail: ruxolitinib for steroid-refractory GvHD, Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, gvhd.
Shares When steroids fail: ruxolitinib for steroid-refractory GvHD, Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, gvhd.
Shares When steroids fail: ruxolitinib for steroid-refractory GvHD, Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, gvhd.
Shares When steroids fail: ruxolitinib for steroid-refractory GvHD, Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, gvhd.
Shares Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation and the tags rejuvenation, survivorship, transplant, gvhd.
Shares Chronic graft-versus-host disease, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation and the tags rejuvenation, survivorship, transplant.
Shares Rebuilding an immune system: the timeline, lineage by lineage, Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it, After a transplant or cell therapy: what to ask for, Survivorship and late effects are neglected and the tags rejuvenation, survivorship, transplant.
Shares Rebuilding an immune system: the timeline, lineage by lineage, Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it, Graft-versus-host disease (GVHD) and graft-versus-leukaemia, After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant.