Heather Knox

Urban Health Today

<p>Immune-suppressing drug cyclophosphamide could reduce the risk for graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) using cells from partial donors, according to a non-randomized, multicenter trial in the <em>Journal of Clinical Oncology</em>.</p>
<h2><strong>ACCESS Trial: Addressing Barriers to Transplantation</strong></h2>
<p>For patients from underrepresented groups who are less likely than non-Hispanic White patients to find matched donors, the possibility of transplanting using a partial match addresses disparities in access by increasing the donor pool.</p>
<p>“We called the study ACCESS because it was about breaking down barriers to transplantation caused by historical inequities in being able to identify suitable donors for racially and ethnically diverse patients in need of HCT,” explained study coauthor Steven Devine, MD, of <a href="https://www.nmdp.org" target="_blank" rel="noopener">NMDP</a>, to <em>Urban Health Today</em>. “Using a method called post-transplant cyclophosphamide, we are able to effectively prevent GVHD, the major complication of transplantation. This now allows us to find suitable donors for virtually all patients regardless of their ancestry. Many racially diverse patients were unable to identify suitable donors in the past due to requirements for more stringent HLA [human leukocyte antigen] matching,”</p>
<p>The ability to broaden donor search criteria also improves outcomes in other ways. “This would permit prioritization of other donor characteristics associated with better survival, such as younger donor age,” the study authors wrote.</p>
<h2><strong>Post-Transplant Cyclophosphamide for GVHD</strong></h2>
<p>The prospective, phase II, non-randomized ACCESS trial included 145 adult patients from 21 centers undergoing their first allogeneic HSCT from mismatched unrelated donors (MMUDs). Researchers divided patients into two groups: those receiving myeloablative conditioning (MAC) HSCT and those receiving reduced-intensity or non-myeloablative (RIC/NMA) conditioning HSCT. All patients received peripheral blood stem cell grafts and a regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.</p>
<p>Patients were diagnosed with acute or chronic leukemia without circulating blasts and under 5% bone marrow blasts, myelodysplastic syndrome, or lymphoma in remission. Fifty-nine percent self-identified as being part of an underrepresented group (71% of the MAC group and 46% of the RIC/NMA group), which Devine remarked is “unprecedented for an HCT trial.” Researchers screened patients for social determinants of health using the Centers for Disease Control and Prevention’s social vulnerability index, with 73% of the MAC group and 52% of RIC/NMA patients having scores indicating medium to high vulnerability.</p>
<p>Donors were from 18 to 35 years old and were required to have high-resolution HLA matching at 4/8, 5/8, 6/8, or 7/8 alleles (types <em>HLA-A</em>, <em>HLA-B</em>, <em>HLA-C</em>, and <em>HLA-DRB1</em>). The majority were 7/8 HLA-allele matched, followed by 6/8, 5/8, and 4/8, respectively.</p>
<h2><strong>Key Findings and Future Research</strong></h2>
<p>The 1-year overall survival (OS) rate was 83.8% in MAC patients and 78.6% in RIC/NMA patients. Eight percent of MAC patients and 10% of RIC/NMA patients experienced grades III to IV acute GVHD at 6 months. Moderate/severe chronic GVHD was experienced by 10.3% of MAC patients and 8.6% of RIC/NMA patients at 1 year. Overall, 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS as those whose donors matched at seven of eight alleles.</p>
<p>Researchers acknowledged the limitations of this study: “This exploratory analysis was underpowered and therefore not definitive. Nevertheless, the results observed in the 46 recipients within the &lt;7/8 donor group are encouraging and support searching for &lt;7/8 MMUDs in recipients who could benefit from HSCT but otherwise lack a suitable 7/8, haploidentical related, or cord blood donor.”</p>
<p>They also noted that many participants involved in the trial reported social and financial vulnerabilities that might have otherwise excluded them from transplant access. “Now that HLA barriers have been overcome, we need to focus on all the other non-HLA barriers to transplantation like social determinants of health, including financial hardship and issues with having caregivers,” Devine explained. “However, the results of the ACCESS study provide hope for all patients that we can now find a good donor for virtually all patients in need of a lifesaving transplant.”</p>
<div class="post-references"><h3>References</h3><p>Malki M., et al. <em>J Clin Oncol</em>. Published online June 16, 2025. doi:<a href="https://ascopubs.org/doi/10.1200/JCO-25-00856" target="_blank" rel="noopener">10.1200/JCO-25-00856</a></p>
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<p>Immune-suppressing drug cyclophosphamide could reduce the risk for graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) using cells from partial donors, according to a non-randomized, multicenter trial in the <em>Journal of Clinical Oncology</em>.</p><h2><strong>ACCESS Trial: Addressing Barriers to Transplantation</strong></h2><p>For patients from underrepresented groups who are less likely than non-Hispanic White patients to find matched donors, the possibility of transplanting using a partial match addresses disparities in access by increasing the donor pool.</p><p>“We called the study ACCESS because it was about breaking down barriers to transplantation caused by historical inequities in being able to identify suitable donors for racially and ethnically diverse patients in need of HCT,” explained study coauthor Steven Devine, MD, of <a href="https://www.nmdp.org" target="_blank" rel="noopener">NMDP</a>, to <em>Urban Health Today</em>. “Using a method called post-transplant cyclophosphamide, we are able to effectively prevent GVHD, the major complication of transplantation. This now allows us to find suitable donors for virtually all patients regardless of their ancestry. Many racially diverse patients were unable to identify suitable donors in the past due to requirements for more stringent HLA [human leukocyte antigen] matching,”</p><p>The ability to broaden donor search criteria also improves outcomes in other ways. “This would permit prioritization of other donor characteristics associated with better survival, such as younger donor age,” the study authors wrote.</p><h2><strong>Post-Transplant Cyclophosphamide for GVHD</strong></h2><p>The prospective, phase II, non-randomized ACCESS trial included 145 adult patients from 21 centers undergoing their first allogeneic HSCT from mismatched unrelated donors (MMUDs). Researchers divided patients into two groups: those receiving myeloablative conditioning (MAC) HSCT and those receiving reduced-intensity or non-myeloablative (RIC/NMA) conditioning HSCT. All patients received peripheral blood stem cell grafts and a regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.</p><p>Patients were diagnosed with acute or chronic leukemia without circulating blasts and under 5% bone marrow blasts, myelodysplastic syndrome, or lymphoma in remission. Fifty-nine percent self-identified as being part of an underrepresented group (71% of the MAC group and 46% of the RIC/NMA group), which Devine remarked is “unprecedented for an HCT trial.” Researchers screened patients for social determinants of health using the Centers for Disease Control and Prevention’s social vulnerability index, with 73% of the MAC group and 52% of RIC/NMA patients having scores indicating medium to high vulnerability.</p><p>Donors were from 18 to 35 years old and were required to have high-resolution HLA matching at 4/8, 5/8, 6/8, or 7/8 alleles (types <em>HLA-A</em>, <em>HLA-B</em>, <em>HLA-C</em>, and <em>HLA-DRB1</em>). The majority were 7/8 HLA-allele matched, followed by 6/8, 5/8, and 4/8, respectively.</p><h2><strong>Key Findings and Future Research</strong></h2><p>The 1-year overall survival (OS) rate was 83.8% in MAC patients and 78.6% in RIC/NMA patients. Eight percent of MAC patients and 10% of RIC/NMA patients experienced grades III to IV acute GVHD at 6 months. Moderate/severe chronic GVHD was experienced by 10.3% of MAC patients and 8.6% of RIC/NMA patients at 1 year. Overall, 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS as those whose donors matched at seven of eight alleles.</p><p>Researchers acknowledged the limitations of this study: “This exploratory analysis was underpowered and therefore not definitive. Nevertheless, the results observed in the 46 recipients within the &lt;7/8 donor group are encouraging and support searching for &lt;7/8 MMUDs in recipients who could benefit from HSCT but otherwise lack a suitable 7/8, haploidentical related, or cord blood donor.”</p><p>They also noted that many participants involved in the trial reported social and financial vulnerabilities that might have otherwise excluded them from transplant access. “Now that HLA barriers have been overcome, we need to focus on all the other non-HLA barriers to transplantation like social determinants of health, including financial hardship and issues with having caregivers,” Devine explained. “However, the results of the ACCESS study provide hope for all patients that we can now find a good donor for virtually all patients in need of a lifesaving transplant.”</p><div class="post-references"><h3>References</h3><p>Malki M., et al. <em>J Clin Oncol</em>. Published online June 16, 2025. doi:<a href="https://ascopubs.org/doi/10.1200/JCO-25-00856" target="_blank" rel="noopener">10.1200/JCO-25-00856</a></p>
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Immune-suppressing drug cyclophosphamide could reduce the risk for graft-versus-host disease in hematopoietic stem cell transplantation using cells from partial donors.