Improvements in Stem Cell Transplants for AML With CRISPR


Guenther Koehne, MD, PhD, discusses findings from a phase 1/2 trial that are being presented at the American Society of Hematology 2023 Annual Meeting.

Guenther Koehne, MD, PhD, deputy director and chief of blood and marrow Transplant, hematologic oncology and benign hematology, Baptist Health Medical Group, discusses a phase 1/2 study (NCT04849910) where he served as the principal investigator. The abstract is being presented at this year's American Society of Hematology 2023 Annual Meeting.

The study is a first-in-human phase 1/2 open-label multicenter trial to establish the safety of trem-cel, a CRISPR/Cas9 gene-edited allograft lacking CD33, as a donor allograft for CD33-positive patients with acute myeloid leukemia at high risk of relapse.


Some patients with high-risk acute myeloid leukemia relapse earlier. And that is also, I think, a big step forward that we now don't consider a acute myeloid leukemia all the same. They are risk-stratified from the beginning : FLT3-positive AMLs, TD53-mutated AML, and some others we know are very high risk of relapse, so they will relapse despite of allogeneic transplants. So what's happening there is now we can certainly come in with post-transplantation maintenance treatments, as we do in multiple myeloma. But that's a little complicated, more complicated, because the markers that are expressed on the leukemia cell that can be targeted are also expressed on the normal healthy hematopoietic stem cell, and therefore, you would eliminate the healthy stem cells at the same time as you're trying to knock off the leukemia cell population. But now, I'm proud to say I'm a principal investigator of a clinical trial that uses CRISPR technology. That is gene editing of downregulating the expression of CD33 on the normal hematopoietic stem cells prior to the transplant. And with that, now we have a CD33 that is highly overexpressed on leukemia cell populations. So if we now have a CD33-negative stem cell product from the donor, and infuse this into the patient, then the patients have a normal reconstitution normal blood production, normal recovery of this white cells, platelets, but the cells are all CD33-negative. And now we can go in with treatments that target CD33.

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