![Microscopic image of blood cancer cells.](https://emed.news/wp-content/uploads/2024/05/blood-cancer.png)
![Microscopic image of blood cancer cells.](https://emed.news/wp-content/uploads/2024/05/blood-cancer.png)
Researchers at the University of Miami Miller School of Medicine’s Sylvester Comprehensive Cancer Center and colleagues conducted a study that suggests more patients with high-risk blood cancers may be able to receive transplanted stem cells from unrelated, partially matched donors thanks to a novel treatment strategy utilizing Cyclophosphamide, an older medication.
Findings from the novel strategy may increase the pool of donors, with patients from underrepresented racial and ethnic groups potentially benefiting the most. These findings will be presented at the annual meetings of the European Hematology Association and the American Society of Clinical Oncology (ASCO).
A significant obstacle for patients with blood malignancies requiring bone marrow or blood stem cell transplants has always been finding a matching donor.
Patients frequently use the National Marrow Donor Program if they do not have a family member who qualifies. More than 40 million potential donors are listed on the registry, but not everyone is matched, especially those from racial and ethnic minorities who are underrepresented. More than 70% of White patients can identify a fully matched donor; only around half of Hispanic and a quarter of Black patients can do so.
However, because the earlier medication cyclophosphamide has been repurposed, finding a donor has become much simpler. Successful results are being achieved with the new strategy, which involves giving cyclophosphamide many days after transplantation. At the ASCO meeting on May 31, new data will be presented. The results indicate that patients who get blood stem cells from unrelated, partially matched donors have excellent success rates.
Antonio Jimenez Jimenez, M.D., a Sylvester clinician and researcher who has been a major primary investigator in the trials supporting the use of cyclophosphamide, stated, “The outcomes seem to be very comparable to those of a fully matched donor.” Along with researchers from other institutions, he led this study, including the National Marrow Donor Program, City of Hope Medical Center, and Memorial Sloan Kettering Cancer Center.
Monzr Al Malki, M.D., a researcher at City of Hope, will present the results at ASCO. On June 14, Jimenez Jimenez will present the results at the annual congress of the European Hematology Association (EHA) in Madrid.
At Sylvester and elsewhere, the strategy is already being widely adopted, which is helping more patients discover donors and access life-saving care. It’s been revolutionary, Jimenez Jimenez said.
A group of protein markers on blood cells known as HLAs (human leukocyte antigens) indicate donor compatibility. According to Jimenez Jimenez, HLAs represent the immune system’s “QR code”. A sibling’s likelihood of having a fully matched HLA is 25%, while their likelihood of a partial match is 50%. The past ten or so years have seen a rise in the successful use of partially matched relatives as donors because of the increased usage of cyclophosphamide.
Cyclophosphamide prevents graft vs host disease (GVHD), a fatal transplant adverse effect. Under this condition, the patient’s transplant mounts an immunological attack. It is believed that the medication lessens the impact of the cells that mediate GVHD.
More recently, scientists have begun speculating about whether cyclophosphamide is also effective in transplants from unrelated donors who are partially matched. In a seminal earlier study, Jimenez Jimenez and colleagues demonstrated that the medication produced good survival rates in eighty patients undergoing bone marrow transplants from unrelated, partially matched donors.
The cyclophosphamide treatment for patients undergoing peripheral blood stem cell (PBSC) transplantation is evaluated in this new study. The ease of donating through a process that separates the cells from the blood has contributed to the widespread replacement of bone marrow transplantation with this source of stem cells.
Researchers looked at information from 70 adult patients with advanced blood malignancies in this first round of the investigation. After receiving stem cells, patients underwent a “reduced-intensity” conditioning regimen to get them ready for transplantation.
The researchers will present at ASCO a 79% one-year overall survival rate that is online with survival rates observed in cases of fully matched donors. Other indicators showed promise as well, according to Jimenez Jimenez. 51% of patients had not relapsed and were clear of GVHD after a year.
“Impressive,” are the data, Jimenez said. Especially considering that the trial included high-risk patients and the participants’ average age was 65, Jimenez added. He added that the study was “very permissive” about the extent of donor mismatch that was permitted.
On a scale ranging from 1 to 8, where 8 represents a perfect match across all eight major HLA markers, the match levels of the donors ranged from 4 to 7/8. More than 99 percent of individuals from a variety of racial/ethnic backgrounds match levels of 5/8 and above.
More patients will be able to discover donors and undergo treatment thanks to the new strategy. According to Jimenez Jimenez, it also implies that they may frequently locate better donors, such as younger people with healthier grafts.
According to the researchers, medical facilities like Sylvester that serve a wide range of patient demographics should take particular note of these findings. Patients are overcoming the challenges associated with searching the registry for a donor, such as the large percentage of white donors and the genetic diversity of mixed-race people, which can make HLA matching more difficult. Patients are no longer in need of an ideal fit.
The results are part of a phase 2 trial that is currently being conducted at over 30 medical sites, including Sylvester, with over 300 patients enrolled. To ablate the bone marrow, patients in the second arm of the trial undergo a more rigorous regimen before receiving a transplant. A third branch looks into cases involving children.
Jimenez Jimenez and his associates are also looking for ways to reduce toxicity, maximize the distribution of cyclophosphamide, combine it with other treatments, and answer other relevant issues.
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