EBMT 2026 | Total marrow and lymphoid irradiation with PTCy-based GvHD prophylaxis in patients with AML

I mean, so at City of Hope, we’ve adopted an approach using total marrow and lymphoid radiation in combination with post-transplant Cy for patients with AML in first and second remission. So currently the two major causes of patients failing transplant are basically one, relapse, and two, chronic graft-versus-host disease and its associated infectious and organ failure consequences of being maintained on chronic immunosuppression. So at City of Hope, we basically created a regimen and this actually goes back to a study done by the investigators in Seattle and published in 1998, where they compared 15 gray to 15.75 gray to 12 gray of whole body radiation. And they showed that this resulted in a much lower relapse rate. However, the overall survival did not change because there was an increased non-relapse mortality rate, mostly related to infectious GVHD and mucositis problems. 

So based on that study, using TMLI, we are able to deliver augmented doses of radiation to the marrow, lymph node, spleen, basically where we think the disease resides. We’re also able to limit the radiation that the liver and the brain gets so that we can reduce the incidence of sinusoidal obstructive syndrome. And then the remaining normal organs are non-targeted and receive much lower doses of radiation, and that basically will reduce the toxicity of the regimen. Instead of giving the cytoxan pre-stem cell infusion, we’ve moved it to be given on day three and four, and its main role in the regimen is essentially to prevent patients from developing chronic graft versus host disease after day 100. 

So using this conditioning regimen and post-transplant cytoxan, we have shown that at one year, our non-relapse mortality rate is 0%. Our progression-free survival at one year is 88%. Our overall survival at one year is 100%. The risk of acute graft-versus-host disease of grade 2 to 4 was approximately 9%. And grade 3 to 4 was only around 2-3%. Our risk of chronic GVHD of moderate to severe was around about 7%, and that’s led to a graft-versus-host disease relapse-free survival, or GRFS, of 67% at one year. We also did a quality of life survey on these patients, pre-transplant at six months and around one year, using the FACT questionnaire, And this showed improvement in social and family well-being and also functional well-being. 

So basically, in summary, we think this is a safe, effective regimen with essentially no non-relapse mortality, at least at one year, and very good relapse-free survival and overall survival. In the future, we have expanded the study now to 55 patients. The last patient was just recently treated in January. So hopefully in about a year’s time, we’ll be able to report the follow-up of all 55 patients and also follow up of quality of life surveys of how patients are doing at two years.

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