MMUD Stem Cell Transplant: High 1-Year Survival Rate

Mismatched Donor Transplants Show Promise, Expanding Access for Diverse Patients

New research presented at the 2025 Transplantation & Cellular Therapy Meetings highlights the success of mismatched unrelated donor transplants using peripheral blood stem cells and post-transplant cyclophosphamide, especially for patients from diverse ethnic backgrounds who frequently enough face challenges finding suitable donors.

February 15, 2025

Overcoming HLA Barriers in Stem Cell Transplants

For years, patients with hematologic malignancies who lacked a fully matched donor faced daunting odds. Finding a perfectly matched unrelated donor, especially for individuals from racial and ethnic minorities, was a meaningful hurdle. But groundbreaking research is changing the landscape of stem cell transplantation, offering new hope and expanding access to life-saving treatments.

The ACCESS trial (NCT04904588), a phase 2 multicenter study, investigated the use of post-transplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in mismatched unrelated donor (MMUD) transplants. The study, which compared outcomes using peripheral blood stem cells to a previous trial (the 15 MMUD trial) that used bone marrow, showed encouraging results. The trial crucially included a diverse patient population, with 71% of participants identifying as non-white or Hispanic.

The findings, presented at the 2025 Transplantation & Cellular Therapy Meetings in Honolulu, Hawaii, revealed an notable 84% (95% CI, 73%-90%) one-year overall survival rate in adult patients receiving myeloablative conditioning (MAC). This survival rate is comparable to past data from HLA-matched donor peripheral blood stem cell transplants.

“The study results also emphasize that PTCy has enabled safe and effective myeloablative conditioning,reducing barriers for diverse patients.”
Jeff Auletta, MD, senior vice president of health equity at the National Marrow Donor Program and chief scientific officer of the Centre for International Blood and Marrow Transplant Research

The ACCESS trial: A Closer Look

The ACCESS trial was meticulously designed to evaluate the effectiveness of MMUD peripheral blood stem cell transplants. Dr.Auletta, a leading expert in the field, explained the trial’s structure:

“The ACCESS trial is a multicenter, phase 2 trial designed to compare overall survival in patients receiving mismatched unrelated donor peripheral blood stem cells as an allograft source for hematologic malignancies. We are comparing this overall survival data to our previous trial, the 15 MMUD trial, which used mismatched, unrelated donor bone marrow.”
Jeff Auletta, MD

The trial comprised three strata: two focused on adult patients receiving peripheral blood stem cells from a mismatched, unrelated donor under either myeloablative or reduced-intensity conditioning, and a third exclusively for pediatric patients receiving mismatched unrelated donor bone marrow allografts with myeloablative chemotherapy. The primary endpoint was overall survival at one year.Results from the reduced-intensity cohort were previously presented, with the myeloablative adult cohort findings unveiled at the Tandem Meetings.

Peripheral Blood Stem Cells vs. Bone Marrow: A Practical Advancement

Traditionally, bone marrow was a common source for stem cell transplants. Though, peripheral blood stem cells have become the preferred choice due to thier ease of collection and faster engraftment. The ACCESS trial builds upon the foundation laid by the 15 MMUD trial, which established the feasibility of mismatched unrelated donor transplants using bone marrow.

“The 15 MMUD trial was a feasibility study that established the potential for mismatched, unrelated donor transplants using bone marrow. The ACCESS trial builds on that work by focusing on practicality, as peripheral blood stem cells are more commonly used in clinical practice. Our goal was to confirm that using peripheral blood stem cells was at least as effective as using bone marrow in this context.”
Jeff Auletta, MD

By demonstrating comparable outcomes with peripheral blood stem cells, the ACCESS trial paves the way for wider adoption of this approach, simplifying the transplant process for both patients and clinicians. This is particularly relevant in the U.S., where access to specialized medical procedures can be geographically and socioeconomically challenging.

The Role of Post-Transplant Cyclophosphamide (PTCy)

The high survival rate observed in the ACCESS trial can be attributed to the use of post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis. GVHD occurs when the donor’s immune cells attack the recipient’s tissues, and it remains a major complication of allogeneic stem cell transplantation. PTCy selectively eliminates alloreactive T cells,preventing GVHD without compromising the graft-versus-tumor effect,which is crucial for eradicating the underlying malignancy.

“The key factor is the use of posttransplant cyclophosphamide as GVHD prophylaxis. This approach has allowed us to overcome the HLA barrier… The use of posttransplant cyclophosphamide has enabled the successful use of HLA-mismatched transplants, whether from haploidentical related donors or mismatched, unrelated donors.”
Jeff Auletta,MD

PTCy has revolutionized the field of hematopoietic stem cell transplantation and is now a standard component of GVHD prophylaxis in both matched and mismatched transplants. Its effectiveness has been demonstrated in numerous clinical trials, and its use has substantially improved outcomes for patients undergoing allogeneic stem cell transplantation.

Check out highlights from the plenary session here at #TCTM25! pic.twitter.com/85mUe5867t

— transplantation & Cellular Therapy Meetings (@TCT_Meetings) February 16, 2025

Addressing Ethnic Disparities in Transplant access

One of the most significant implications of this research is its potential to address long-standing ethnic disparities in access to stem cell transplantation. Historically, patients from racial and ethnic minorities have faced significant challenges in finding fully matched donors due to the underrepresentation of these groups in donor registries. This has led to poorer outcomes for these patients.

“First, this study shows that a graft source is available for all patients. Our modeling at the CIBMTR, based on the NMDP national registry, demonstrates that when confined to 8/8 HLA-matched unrelated donors, we can find a donor for 78% of White non-Hispanic patients but only 29% of Black/African American patients. However, by expanding to 7/8 mismatched unrelated donors, we increase the availability to 84% of African American patients. With 6/8 mismatched donors, we exceed 90% across all ancestry groups. This means we can now find a donor for nearly all patients.”
Jeff Auletta, MD

By expanding the donor pool to include mismatched unrelated donors, this research opens the door to life-saving grafts for all patients, regardless of ancestry. This is particularly important in the U.S., where the population is becoming increasingly diverse, and where disparities in healthcare access and outcomes continue to be a major concern.

Myeloablative Conditioning: Safe and Effective for More Patients

Myeloablative conditioning is a high-intensity chemotherapy regimen used to eradicate the patient’s existing bone marrow before transplant. While effective in preventing disease relapse,it is also associated with significant toxicity.The ACCESS trial provides evidence that myeloablative conditioning can be safely and effectively used in the context of mismatched unrelated donor transplantation, expanding treatment options for patients who require this approach.

“Second, this study confirms that myeloablative conditioning is both safe and effective for patients who meet the inclusion criteria.Myeloablative therapy can help prevent disease relapse, and being able to safely offer it in the context of mismatched unrelated donor transplantation is an important step forward.”
Jeff Auletta, MD

The OPTIMIZE Trial: Reducing Infections, Improving Outcomes

Building on the success of the ACCESS trial, researchers are now focusing on further improving outcomes by reducing the burden of infections seen in previous studies. The OPTIMIZE trial, currently enrolling patients, aims to lower the dose of post-transplant cyclophosphamide in an effort to minimize infections while maintaining GVHD protection. Infection-free survival is a key outcome of this trial.

“We are always looking to improve… Our next step is the OPTIMIZE trial, which is currently enrolling patients. This trial aims to reduce the burden of infections seen in previous studies, likely related to posttransplant cyclophosphamide exposure. By lowering the dose of posttransplant cyclophosphamide, we hope to reduce infections while maintaining GVHD protection. The trial focuses on infection-free survival as a key outcome.”
Jeff Auletta, MD

This reflects an ongoing commitment to refining transplant protocols and addressing the specific challenges faced by patients undergoing allogeneic stem cell transplantation. This is particularly relevant in the U.S., where hospital-acquired infections are a major concern, and where efforts to improve patient safety are constantly underway.

Addressing Social Vulnerability

Recognizing that social factors can significantly impact treatment outcomes, the ACCESS trial also examined social vulnerability among enrolled patients. Researchers analyzed patients’ social vulnerability based on their zip codes and patient-reported outcomes, including education level, income, insurance, and distance from the transplant center.

“This trial also examined social vulnerability among enrolled patients… Our findings highlighted that these patients are highly vulnerable, yet they were able to enroll in a clinical trial… This study provides valuable insight into these barriers and how we can address them through support services and systemic changes.”
Jeff Auletta, MD

These findings underscore the importance of addressing social determinants of health to improve transplant access and outcomes for underserved populations. This includes providing support services such as transportation assistance, financial aid, and culturally sensitive education and counseling.

Implications for Community Oncologists

The findings from the ACCESS trial and related research have significant implications for community oncologists, who are often the first point of contact for patients with hematologic malignancies. Community oncologists should be aware of the availability of mismatched unrelated donor transplantation and the potential benefits of this approach for patients who lack a fully matched donor. They should also be prepared to discuss the risks and benefits of myeloablative conditioning and post-transplant cyclophosphamide with their patients.

Moreover, community oncologists play a crucial role in identifying and addressing social barriers to transplant access. They should be familiar with resources available to support patients, such as financial assistance programs, transportation services, and language translation services. By working collaboratively with transplant centers and other healthcare providers, community oncologists can help ensure that all patients have access to the best possible care.

“This research represents a pivotal moment in the field. We can now provide a donor for nearly all patients, which is a significant milestone. Not long ago, physicians had to have arduous conversations with patients about the lack of a suitable donor. This work provides hope, and we are committed to translating that hope into successful transplant outcomes.”
Jeff Auletta, MD

Key Takeaways: Expanding Hope and Access

The ACCESS trial and related research represent a significant step forward in the field of stem cell transplantation. By demonstrating the safety and effectiveness of mismatched unrelated donor transplants using peripheral blood stem cells and post-transplant cyclophosphamide, this work has expanded access to life-saving treatments for patients from diverse ethnic backgrounds who often face challenges finding suitable donors.

This research also highlights the importance of addressing social determinants of health to improve transplant access and outcomes for underserved populations. By working collaboratively with transplant centers, community oncologists, and other healthcare providers, we can ensure that all patients have the chance to benefit from these advances.

Key Finding	implication for U.S. Patients
84% 1-year overall survival with MMUD peripheral blood stem cell transplants using PTCy.	Increased hope for patients lacking matched donors, regardless of ethnicity.
MMUDs expand donor pool for diverse ethnic backgrounds.	Improved access to transplants for African American, hispanic, and other minority patients who are underrepresented in donor registries.
Safe and effective myeloablative conditioning with MMUD.	Wider applicability of a more aggressive treatment approach when needed.
OPTIMIZE trial aims to reduce infections post-transplant.	potentially fewer complications and improved quality of life for transplant recipients.
Social vulnerability analysis informs support service advancement.	More complete care addressing financial, logistical, and social challenges faced by patients.

Reference: al Malki MM,Bo-Subait S,Logan BR,et al. Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis following mismatched unrelated donor peripheral blood stem cell transplantation using myeloablative conditioning – results from the access trial. Presented at: 2025 Transplant and Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI. Abstract 84.

Given the emphasis on access adn social vulnerability in the article, how can we ensure fair and equitable access to MMUD transplants for all patients, regardless of their socioeconomic status or geographic location?

Mismatched Donor Transplants: A Conversation with Dr. Evelyn Reed

Archyde news Editor Interviews Dr. Evelyn Reed, Leading Hematologist, on Breakthroughs in Stem Cell Transplantation

Introduction

Welcome to Archyde News. Today, we’re delving into a groundbreaking area of hematology: mismatched unrelated donor (MMUD) transplants and their profound impact on patient access and outcomes. To discuss these advancements, we are joined by Dr. Evelyn Reed, a leading hematologist and researcher specializing in stem cell transplantation. Dr. Reed, welcome.

Dr. Reed: Thank you for having me. It’s a pleasure to be here.

Understanding the ACCESS Trial and its Importance

Archyde News Editor: dr.Reed,recent research presented at the 2025 Transplantation & Cellular Therapy Meetings highlights the success of MMUD transplants. Could you provide a concise overview of what the ACCESS trial accomplished and why it’s so meaningful?

Dr. Reed: Certainly. the ACCESS trial (NCT04904588) investigated MMUD transplants—specifically, using peripheral blood stem cells and post-transplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis. Previous challenges existed in finding perfectly matched donors, especially for diverse patient populations. this trial’s results, with an 84% one-year overall survival rate in adult patients receiving myeloablative conditioning(MAC), demonstrate MMUDs are a viable and effective strategy, significantly expanding access to life-saving treatments.

Addressing Ethnic Disparities in Transplant Access

Archyde News Editor: One of the most promising aspects of this research is its potential to address ethnic disparities in transplant access. Could you elaborate on how MMUD transplants help bridge this gap?

Dr. Reed: Absolutely. Historically, patients from racial and ethnic minorities have faced lower donor availability as of underrepresentation in donor registries. By utilizing MMUDs, we expand the donor pool. Such as, using 7/8 matched donors increases donor availability for African American patients significantly. With 6/8 mismatched potential, it is possible to find a donor for the majority of patients across different ancestry groups. This means more patients, regardless of their background, can receive potentially life-saving transplants.

The Crucial role of Post-Transplant Cyclophosphamide (PTCy)

Archyde News Editor: The use of post-transplant cyclophosphamide (PTCy) appears crucial for the success of MMUD transplants. Can you explain its role in preventing GVHD and why it’s so effective?

Dr. Reed: PTCy is indeed a game-changer.GVHD is a serious complication where the donor’s immune cells attack the recipient’s tissues. PTCy selectively eliminates alloreactive T cells, effectively preventing GVHD but preserving the graft-versus-tumor effect, which is vital for eradicating the underlying malignancy. It has revolutionized GVHD prophylaxis, making MMUD transplants safer and more prosperous.

Peripheral Blood Stem Cells vs. Bone marrow

archyde news Editor: The ACCESS trial utilized peripheral blood stem cells,building upon earlier studies that used bone marrow. What are the practical advantages of using peripheral blood stem cells in this context?

Dr. Reed: Peripheral blood stem cells have emerged as a preferred choice due to their relative ease of collection and faster engraftment compared to bone marrow. The ACCESS trial confirmed that using peripheral blood stem cells is just as effective, streamlining the transplant process for both patients and clinicians. This is particularly valuable in settings with limited access to specialized medical resources.

Outlook and Next Steps: The OPTIMIZE Trial

Archyde News Editor: What is the OPTIMIZE trial and what are the ultimate goals?

Dr. Reed: Building on the success of the ACCESS study, the OPTIMIZE trial aims to further improve outcomes by reducing infections often associated with aggressive treatment. This trial is evaluating a reduced dose of PTCy to minimize infections while maintaining GVHD prophylaxis. The main goal is to improve infection-free survival, which directly enhances the quality of life for patients after stem cell transplants.

Impact on Community Oncologists and Patient Care

Archyde News Editor: how should community oncologists in the U.S. and internationally adapt to these advances in treatment and care? What are the implications for patients?

Dr.Reed: This research provides an opportunity to significantly enhance awareness and training of community oncologists on the benefits of MMUD transplants. Furthermore, it is key that community oncologists are prepared to discuss the potential risks and benefits of treatments like myeloablative conditioning and PTCy. Community oncologists must be prepared to support patients facing financial,logistical,or social barriers. Ultimately, the goal is to increase the ease of the process by coordinating with transplant centers to provide support programs. This will make these procedures and therapies accessible for all patients.

Addressing Social Vulnerability

Archyde News Editor: You also touched on the trial’s analysis of social vulnerability. Why is this critically important, and how can we improve access to transplants for patients who face social and economic challenges?

Dr. Reed: We found that many patients enrolled in clinical trials have many social challenges to overcome. We hope these findings inspire support services that can assist patients with a multitude of needs. Ultimately, we aim to streamline the process, and provide resources that make these procedures more accessible to this population.

A Final Thought

Archyde news Editor: Dr. Reed, this is truly groundbreaking work. What is your main message you would like readers to take away from this?

Dr. Reed: This research represents a major step forward. We’re able to offer a donor for nearly all patients, which wasn’t possible a few years ago. Not long ago, physician had to have very tough conversations about donors not being available. This provides hope, and we are committed to translating this into successful transplant outcomes. The study represents a pivotal moment in the field. We can now provide a donor for nearly all patients, which is a significant milestone.

Call to Action

Archyde News Editor: Thank you, Dr. Reed, for sharing your expertise. These advances are creating a more inclusive and effective approach to stem cell transplantation.The conversation around MMUDs is evolving constantly. What further developments are you anticipating, and what questions can we ask to ensure future advancements?

Dr. reed: I anticipate ongoing research and collaboration. My hope, however, is that people will comment on this article with their thoughts on what aspects of this treatment are important. We must encourage innovation and build complete support systems. We need to remember we are improving treatment for a diverse population. By addressing logistical,social,and financial issues we can improve care for all patients.