Cyclophosphamide May Enable More Patients With High-Risk Hematologic Malignancies to Receive Stem Cell Transplants

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A novel treatment strategy using cyclophosphamide-based graft-vs-host disease prophylaxis may enable more patients with high-risk hematologic malignancies to receive stem cell transplantation from mismatched unrelated donors. These findings were presented by Al Malki et al at the 2024 ASCO Annual Meeting (Abstract 6503) and will be presented by Jimenez et al the upcoming European Hematology Association 2024 Hybrid Congress (Abstract S260). The research may help expand the donor pool for stem cell transplantation and could particularly benefit underrepresented racial and ethnic groups.


Identifying a matched donor has historically been a major barrier among patients with hematologic malignancies requiring bone marrow or blood stem cell transplantation. Patients without eligible donors within their families often turn to the National Marrow Donor Program—a registry containing over 40 million potential donors. However, not all patients—especially those from racial and ethnic minorities—find a matched donor. For instance, only about 50% of Hispanic patients and 25% of Black patients can find a fully matched donor compared with more than 70% of White patients. Patients currently face barriers to finding a donor in the registry, including the high proportion of White donors and the genetic diversity of mixed-race patients, which can complicate matching.

Donor compatibility is determined by a set of protein markers on blood cells called human leukocyte antigens (HLA). The odds that a sibling has a fully or partially matched HLA are 25% and 50%, respectively. With the increasing use of cyclophosphamide over the past decade, partially matched relatives have increasingly been identified as viable donors.

Cyclophosphamide may be capable of mitigating the effect of the cells that mediate graft-vs-host disease, a condition in which the transplant mounts an immune attack on the patient.

Study Methods and Results

Researchers evaluated the efficacy of cyclophosphamide in 70 high-risk patients with a median age of 65 years and advanced hematologic malignancies receiving peripheral blood stem cell transplantation from mismatched unrelated donors. This stem cell source has largely supplanted bone marrow transplantation as a result of the ease of donation via a procedure that collects the cells from the blood. The patients received a reduced-intensity conditioning regimen to prepare them for transplantation followed by stem cells from the donors. The researchers noted that the new approach involved administering cyclophosphamide several days following stem cell transplantation.

The researchers revealed that the donors were matched at 4/8 to 7/8 on a 1 to 8 scale—in which a score of 8 corresponded with a perfect match across all key HLA markers. At match levels of 5/8 and above, more than 99% of the patients from a wide range of racial and ethnic groups were expected to find a donor.

After a follow-up of 1 year, the researchers found that the overall survival rate was 79%, comparable to survival rates seen in patients receiving transplantation from fully matched donors. Further, 51% of the patients were free of graft-vs-host disease and did not experience relapse.

In previous studies, the researchers demonstrated that cyclophosphamide yielded high survival rates in 80 patients receiving bone marrow transplantation from unrelated mismatched donors.


The researchers hope the novel strategy may allow a larger proportion of patients to find better donors, including younger individuals with healthier grafts, and receive more effective treatment. The findings may also be significant for medical centers with highly diverse patient populations.  

“The outcomes seem to be very comparable to those of a fully matched donor,” highlighted senior study author Antonio Jimenez Jimenez, MD, a clinician and researcher at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.

The researchers detailed that the new findings are part of an ongoing phase II study enrolling about 300 patients at more than 30 medical sites. Patients in a second arm of the study will receive a more intense regimen prior to transplantation designed to ablate the bone marrow. A third arm will investigate pediatric patients.

Additionally, the researchers plan to explore how to optimize cyclophosphamide delivery, combine it with other treatments, minimize toxicity, and address other related issues.

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