The Imperfect Match: Offering Transplants to More Blood Cancer Patients

Article Summary
  • A new study shows treatment success in patients with high-risk blood cancers transplanted with stem cells from unrelated, partially matched donors.
  • The approach expands the donor pool, enabling more patients to receive transplants. Patients from under-represented racial and ethnic groups stand to benefit the most.
  • The findings were presented at the 2024 annual meeting of the American Society of Clinical Oncology and will also be presented at the 2024 annual meeting of the European Hematology Association.

Finding a matched donor has long been a major hurdle for patients with blood cancers who need bone marrow or blood stem cell transplants.

Patients without an eligible family member often turn to the National Marrow Donor Program. The registry contains more than 40 million potential donors, but not everyone finds a match, particularly people from under-represented racial and ethnic groups. Only about half of Hispanic and a quarter of Black patients can find a fully matched donor, compared to more than 70% of white patients.

The search for a donor has recently become a lot easier with a new treatment approach. A repurposed older drug, cyclophosphamide, is leading to successful outcomes from partially matched donors when administered several days after transplantation.

Antonio Jimenez Jimenez, M.D., a physician-scientist at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, has been a key primary investigator in the studies supporting the use of cyclophosphamide.

New data on the approach will be presented May 31 at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO). The findings show high rates of success in patients receiving blood stem cells from unrelated, partially matched donors.

Sylvester Comprehensive Cancer Center's Dr. Jimenez Jimenez
Dr. Antonio Jimenez Jimenez

“The outcomes seem to be very comparable to those of a fully matched donor,” said Dr. Jimenez Jimenez, who led the study alongside researchers from the National Marrow Donor Program, City of Hope Medical Center and Memorial Sloan Kettering Cancer Center, among other institutions.

The approach is already being taken up widely at Sylvester and elsewhere, leading to more patients finding a donor and receiving life-saving treatment.

“It’s been transformational,” said Dr. Jimenez Jimenez.

The “QR Code” of the Immune System

Donor compatibility is determined by a set of protein markers on blood cells called HLAs (human leukocyte antigens). HLAs are the “QR code” of the immune system, said Dr. Jimenez Jimenez.

The chance that a sibling has a fully matched HLA is 25%, and the chance of a partial sibling match is 50%. With the increasing use of cyclophosphamide over the last decade or so, partially matched relatives have increasingly been successfully tapped as donors.

Cyclophosphamide counteracts a deadly side effect of transplantation called graft versus host disease (GVHD). In this condition, the transplant mounts an immune attack on the patient. The drug is thought to mitigate the effect of the cells that mediate GVHD.

More recently, researchers have been asking if cyclophosphamide also works for transplants from partially matched donors who are unrelated.

In one key previous study, Dr. Jimenez Jimenez and his colleagues showed that the drug yielded high survival rates in 80 patients receiving bone marrow transplants from partially matched, unrelated donors.

Expanding the Donor Pool

The new study assesses cyclophosphamide treatment in patients receiving peripheral blood stem cell (PBSC) transplantation. This stem cell source has largely supplanted bone marrow transplantation, partly because of the ease of donation via a procedure that collects the cells from the blood.

In this initial phase of the study, the researchers examined data from 70 adult patients with advanced blood cancers. Patients received a “reduced-intensity” conditioning regimen to prepare them for transplantation, followed by stem cells from unrelated, partially matched donors.

The researchers reported an overall high survival rate of 79% at one year, comparable to survival rates seen with fully matched donors. Other metrics were also promising, said Dr. Jimenez Jimenez. After one year, 51% of patients were free of GVHD and had not relapsed.

The data are “impressive,” said Dr. Jimenez Jimenez, particularly since the study enrolled high-risk patients and the average age was 65. The study was also “very permissive” with the degree of donor mismatch allowed, he said.

Donors had match levels from 4/8 to 7/8 on a one-to-eight scale, in which eight corresponds to a perfect match across eight key HLA markers. At match levels of 5/8 and above, more than 99% of people from a wide range of racial and ethnic groups are expected to find a donor.

The new approach means that more patients can find a donor and receive treatment. It also means that they can often find better donors, such as younger individuals with healthier grafts, said Dr. Jimenez Jimenez.

The findings are particularly relevant for medical centers with highly diverse patient populations, like Sylvester. Patients are overcoming the barriers to finding a donor in the registry, including the high proportion of white donors and the genetic diversity of mixed-race individuals, which can complicate HLA matching. Patients no longer need a perfect match.

Future Questions

The new findings are part of an ongoing, phase 2 study enrolling about 300 patients at more than 30 medical sites, including Sylvester. Patients in a second arm of the study are receiving a more intense regimen prior to transplant, designed to ablate the bone marrow. A third arm investigates pediatric patients.

Dr. Jimenez Jimenez and his colleagues are also investigating how to optimize cyclophosphamide delivery, combine it with other treatments, minimize toxicity and address other related questions.

City of Hope researcher Monzr Al Malki, M.D., will present the findings at ASCO. Dr. Jimenez Jimenez will present the data at the European Hematology Association (EHA) annual congress in Madrid, June 14.

Tags: ASCO, ASCO 2024, blood cancers, Dr. Antonio Jimenez Jimenez, Health Equity, stem cell therapies, Sylvester Comprehensive Cancer Center, transplant