UH Seidman Expert Argues for More Focus on Combination Haplo-Cord Transplant

Innovations in Cancer | January 2025

As a treatment for leukemia, haplo-cord transplant is not new. The combination of umbilical cord blood transplant with progenitor cells from partially HLA-matched adult donors has been used for more than two decades, beginning in Spain with the first reports dating back to 1999.

Koen van Besien, MD, PhD

However, daunting technical challenges have kept it from wide adoption, says Koen van Besien, MD, PhD, Director of the Wesley Center for Immunotherapy at UH Seidman Cancer Center and Division Chief of Hematology and Cellular Therapy at UH Cleveland Medical Center. The holder of the Don C. Dangler Chair in Stem Cell Research, Dr. van Besien is one of the world’s leading authorities on haplo-cord transplant.

He explains how cord blood transplant was pioneered in the late ‘80s when Broxmeyer and Gluckman reported how blood from the umbilical cord of newborns could be used for stem cell transplantation. Within a couple of years, cord blood transplantation was widely used. It had many advantages, including low rates of chronic graft vs. host disease and low rates of relapse.

“But the cord blood grafts are very slow to engraft,” Dr. van Besien says, leading to prolonged hospitalization and risk for infections. “The procedure that we have used is technically complicated. We need a sophisticated stem cell lab and to do some purification of the haplo graft. Not all centers have access to this. As a result, it's something that has not reached the mainstream of allogeneic transplantation.”

But by combining cord blood grafts with donor grafts from relatives – so called haplo-identical donors, one can hasten the recovery of the patient, while maintaining the advantages of cord blood grafts. 

Dr. van Besien says new research suggests the time is right to more fully realize the potential of haplo-cord transplant. To that end, he and colleagues from around the world recently authored an important review article on the procedure, published in the journal Leukemia and Lymphoma.

The need for more and better treatment options demands that physicians who treat these cancers take another look, he says.

“Allotransplant is a curative procedure for leukemia. But it's not good enough, and it's never been good enough,” he says. “There's still too many patients relapsing, and too many patients having complications. We need to continue to look for better options. And this is one way in which we may be able to improve cure rates.”

In their review of the existing literature on haplo-cord transplant, Dr. van Besien and his colleagues cite data showing improved outcomes for patients.

“Comparison studies suggest considerably decreased rates of relapse and improved outcomes, compared with either haplo-identical transplant or CBU transplant, particularly in patients with advanced leukemia,” they write. Dr. van Besien has also seen this in his own practice.

“What we find in our own data is that when we give a haplotransplant and a cord blood graft, we get fast recovery because you give a lot of haplo cells,” he says. “But then, in the end, the cord blood graft takes over and seems to have more anti-leukemic efficacy. We've never done a randomized study, but we've compared our outcomes carefully with other centers, including MD Anderson, and we found that our outcomes are at better than the haplotransplants -- less graft versus host disease, faster engraftment and at superior survival without graft vs host disease.

Dr. van Besien says he’s especially interested in research out of China showing an effective, yet simplified process for haplo-cord transplant. In the Chinese studies, the haplo-identical graft is infused without special processing – as opposed to the European and American studies, in which the haplo-identical cells were purified in the lab. This simplification obviates the need for a complex lab procedure and should render haplo-cord transplant more readily available.

A prospective, randomized study conducted at five centers in China compared haplo-cord transplant with haplo-identical transplant for 268 patients with acute myeloid leukemia.

Results are promising. “They show that particularly in patients with very difficult to treat leukemia, patients’ relapse rates are much decreased, and the outcomes are superior,” Dr. van Besien says.

It’s all part, he says, of boosting public awareness of haplo-cord transplant as a viable treatment strategy.

“Through this review, we want to draw attention to all these data and inform the public of them,” he says. “It’s important to put the literature together to create awareness of what was done worldwide, and of the continued promise of haplo-cord transplantation.”

Contributing Expert:
Koen van Besien, MD, PhD
Don C. Dangler Chair in Stem Cell Research
UH Seidman Cancer Center
Chief, Hematology and Cellular Therapy
UH Cleveland Medical Center
Director, Wesley Center for Immunotherapy
UH Seidman Cancer Center
Clinical Professor
Case Western Reserve University School of Medicine