Caring for patients after MMUD HCT is more familiar than you think

Heather Stefanski, MD, PhD | 6 min read • Oct. 26, 2026

Quick takeaways

PTCy didn’t just open the door to transplant for more patients—it changed what happens after

As I think back over the past decade, few scientific advances have changed hematopoietic cell transplantation (HCT) like the use of post-transplant cyclophosphamide (PTCy) in the haploidentical (haplo) related donor and mismatched unrelated donor (MMUD) settings.

Just glancing at the CIBMTR® (Center for International Blood and Marrow Transplant Research®) allogeneic transplant data, you can see the growth in haplo and MMUD transplant.1

That growth also represents a meaningful shift in access for patients who have a low likelihood of finding a fully matched unrelated donor. 

Growth in haplo and MMUD transplant

Line graph showing the rise of haplo and MMUD transplants in the U.S. from 2014–2024, with key clinical trial milestones marked.
Adapted from Current Uses and Outcomes of Cellular Therapy in the US, Summary Slides 2025.

 

The increase in haplo and MMUD transplant is striking. But it’s only part of the story.

Because the story isn’t just about getting more patients to transplant.

It’s about helping them thrive in the months and years after transplant—whether their cells come from a fully matched related or unrelated donor (MRD or MUD), MMUD or haplo donor.

While some of the main characters of the post-transplant story have changed, the care story itself likely sounds reassuringly familiar.

What PTCy changes after transplant—and what it doesn’t

I've had some clinicians ask me, "Is caring for a patient after an MMUD transplant using PTCy fundamentally different from caring for a patient after MRD, MUD or haplo transplant?"

It's a legitimate question.

If you're a transplant physician like me who's been in the field for more than two decades, you'll remember the paper by Stephanie Lee, MD, published in Blood in 2007.

It showed that in the context of calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis, there was a decrease in overall survival for every HLA mismatch.2

Historical overall survival by HLA match level with CNI-based GVHD prophylaxis

Bar chart comparing 1-year and 5-year overall survival rates across 8/8, 7/8, and 6/8 HLA match levels.
Adapted from Lee SJ, et al. Blood. 2007;110(13):4576-4583.

We didn’t use an MMUD unless there was absolutely no other option.

The risk of mortality with CNI-based prophylaxis was simply too high to justify a mismatched donor otherwise.

But times have changed.

We have data from the 15-MMUD and ACCESS clinical trials that show MMUD transplant using bone marrow or peripheral blood stem cells (PBSCs) is feasible, has a reassuring safety profile and has overall survival similar to other donor types.3–5

Here’s what I tell clinicians today who ask about caring for patients after MMUD HCT.

The care framework for a patient after an MMUD transplant and a patient who had a matched donor transplant is not uniquely different with PTCy.

What changes the care equation isn’t the donor type—it’s the GVHD prophylaxis.

When we use a standard PTCy dose, we’re giving a chemotherapy agent at a significant dose of 50 mg/kg.

Any patient who receives PTCy can potentially experience acute side effects, such as:

  • Infection6
  • Cytopenia
  • Organ toxicity, particularly renal function
  • Hemorrhagic cystitis

However, we're beginning to see encouraging observations that we may be able to preserve the benefits we see with standard doses of PTCy while reducing the negative side effects.

what we're learning

OPTIMIZE clinical trial early observations

At the March 2026 EBMT meetings, CIBMTR presented early observations from the OPTIMIZE clinical trial—a study sponsored by NMDP℠ and led by CIBMTR, which completed enrollment in 2025. While not yet confirmed by final clinical data, the early observations are reassuring—both for infection burden and immune recovery.

Before I get to the observations, a little background on OPTIMIZE.

CIBMTR and NMDP opened the clinical trial in late 2023 to study the impact of a reduced dose of PTCy for adults (25 mg/kg). Our goal was to understand if we could decrease infection risk but keep effective GVHD prevention in MMUD transplant.7

The early observations from OPTIMIZE are notable in three ways.

White icon of a shield on a dark blue background.

Safety

We had safety triggers that would lead us to stop the trial if they were activated.

For example, primary graft failure, severe acute GVHD or death by 100 days after transplant.

Those safety triggers were not activated.8,9

White icon of two buildings on a dark blue background.

Immune recovery

In a sample cohort, we saw differences in immune recovery based on conditioning intensity.

Patients who received reduced intensity conditioning (RIC) had faster immune recovery than those who received myeloablative conditioning (MAC).8

This isn't surprising. RIC patients have less bone marrow suppression to recover from—but it does suggest that conditioning intensity may be a meaningful variable in managing infection risk in the post-transplant period.

White icon of two buildings on a dark blue background.

Acute infection burden

Looking at the first 100 days after transplant, we compared patients on the ACCESS clinical trial who received a standard dose of PTCy to those on OPTIMIZE who received a reduced dose. We saw a decrease in the amount of infection burden in OPTIMIZE patients relative to ACCESS patients.

There's an important caveat. The two studies used different infection classifications. ACCESS used CTCAE grading while OPTIMIZE used Blood and Marrow Transplant Clinical Trials Network (BMT CTN) grading.6,9

Even accounting for those differences, the absolute number of infections and severity both appear lower in OPTIMIZE patients. That's a clinically reassuring signal, even if it's not a definitive head-to-head comparison.

The differences in immune recovery also correlate with infection burden. The RIC patients who had faster immune recovery had less infection burden than MAC patients.9

There are questions still to be answered

While the early observations are reassuring from a safety standpoint and interesting from a scientific perspective, we need to wait for the mature data to answer two important questions.

  1. Will these early observations be the same when the full data are analyzed?
  2. What will acute and chronic GVHD look like in patients who received reduced-dose versus standard-dose PTCy?

While we wait for those answers, there’s one thing we already know well: PTCy’s effect on GVHD is what makes MMUD and haplo transplant viable—and it’s changing how we think about long-term care.

What PTCy has truly changed: the incidence, severity and timing of GVHD

We know that severe acute and chronic GVHD was a major factor in the poor outcomes we used to see in MMUD transplant with CNI-based prophylaxis.10

With PTCy, those negative effects have been lessened—especially in the mismatched setting. That’s not to say patients will never develop severe life-threatening acute or chronic GVHD with PTCy.

But this is what we are seeing.4

Down arrow icon.

Less acute and chronic GVHD

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Less severe cases of GVHD

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Later GVHD manifestation

 

That shift in GVHD timing and severity has meaningful implications for how transplant centers and local hematology/oncology practices divide the work of long-term follow-up care.

The care team conversation that should never stop

The best post-transplant care I’ve seen starts with conversations that happen before the patient ever arrives at the transplant center. And it depends on the relationship the transplant team builds with the local hematology/oncology team that will carry the patient’s long-term care.

I always want the hematologist/oncologist to reach out early for transplant consultation, and it goes beyond starting an early donor search.

We know that the earlier a patient is referred to transplant, the better the outcomes.11 And that takes coordinated care.

Early co-consulting allows the transplant physician to understand what the hematologist/oncologist has planned for treatment timing. And it allows the hematologist/oncologist to understand what the transplant physician needs to know in order to get the patient to transplant.

After transplant, that communication is just as important. Transplant centers want hematologists/oncologists to contact them when they have a question.

Hematologists/oncologists carry a broad practice load—a post-transplant patient may be one of a handful they’re following in any given month. That’s not a limitation; it’s an opportunity for the transplant team to be a consistent resource.

However, the transplant team isn’t the only resource available to hematology/oncology practices.

NMDP developed post-transplant care guidelines for hematology/oncology practices in partnership with leading transplant organizations.

The guidelines include:

  • Long-term screening and preventive care
  • Vaccination timing
  • Chronic GVHD screening—including a body-area photo atlas that’s particularly useful for clinicians who don’t see GVHD frequently

They’re designed to be accessible at the point of care online, through the NMDP transplant guidelines app for either iOS or Android, or as a downloadable PDF.

The conversations between the transplant center and hematology/oncology practice should never stop.

It's always in the best interest of the patient for their care team to have open, free conversation.

The progress is real—and so is the work still ahead

In the last 10 to 15 years, we've come so far in our ability to help patients get to transplant and experience good long-term outcomes.

There are more options for patients who couldn't have reached transplant not long ago. Better supportive care for infection. Better GVHD prevention. More treatments beyond steroids to help patients who have acute and chronic GVHD.

But we also know there's still work to be done.

GVHD has not gone away. Relapsed disease continues to be a factor. Overall survival is better than 20 years ago—but there's room for improvement.

That's what makes ongoing clinical trials like the ACCELERATE trial—an adaptive platform trial that continually evaluates new innovations against a shared control group12—so important.

Scientific discovery will move our field forward. Our shared responsibility is to ensure every patient realizes the full promise of those discoveries.

The obligation now is to make sure that progress reaches every patient, at every center, in every community. That's the work we’re all in together.

About the author

Dr. Heather Stefanski smiling at the camera. She has shoulder-length dark hair. She's wearing a pink blazer over a black shirt.

Heather Stefanski, MD, PhD, is senior vice president of Clinical Innovation and Partnerships at NMDP. She’s board certified in Pediatrics and Pediatric Hematology/Oncology.

Before joining NMDP, she was an associate professor of Pediatrics at the University of Minnesota, providing clinical care and conducting research involving children with life-threatening blood and immune system disorders. One of her focus areas was using cord blood units in hematopoietic cell transplants and CAR-T cell therapy.

Currently she’s focused on overcoming HLA barriers in hematopoietic cell transplant using alternative donors to ensure all patients can receive their life-saving cell therapy.

Related The Cell Therapy Lens article

What the data now show about mismatched unrelated donor HCT
By Steven Devine, MD | 10 min read  • April 24, 2026

Explore the new evidence that’s changing how we think about mismatched unrelated donor transplantation—and what it means for expanding access to allogeneic transplant for all patients.

Read the deep-dive article

References

  1. Broglie L, Xu K, Oloyede T, Chen M, Allbee-Johnson M. Current Uses and Outcomes of Cellular Therapy in the US, Summary Slides 2025. 
  2. Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576–4583. doi: 10.1182/blood-2007-06-097386
  3. Shaw BE, Jimenez-Jimenez AM, Burns LJ, et al. National Marrow Donor Program–sponsored multicenter, Phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2021;39(18):1971–1982. doi: 10.1200/JCO.20.03502
  4. Al Malki MM, Bo-Subait S, Logan B, et al. Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis after mismatched unrelated donor peripheral blood stem cell transplantation. J Clin Oncol. 2025;43(25):2772–2781. doi: 10.1200/JCO-25-00856
  5. Al Malki MM, Bo-Subait S, Logan B, et al. Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study. Blood. 2025;146(Supplement 1):936. doi: 10.1182/blood-2025-936
  6. Auletta JJ, Stanek J, Bo-Subait S, et al. Infection burden in mismatched unrelated donor hematopoietic cell transplantation: results from the ACCESS trial. Blood Adv. Published online July 14, 2026. doi:10.1182/bloodadvances.2026020882
  7. ClinicalTrials.gov. HLA-mismatched unrelated donor peripheral blood stem cell transplantation with reduced dose post transplantation cyclophosphamide GVHD prophylaxis (OPTIMIZE). Updated May 29, 2025. Accessed July 2, 2026. https://clinicaltrials.gov/study/NCT06001385
  8. Auletta JJ, Corrigan D, Bupp C, et al. Early immune recovery in mismatched unrelated donor peripheral blood stem cell transplantation using reduced-dose post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis: Results from the OPTIMIZE trial. Presented at: EBMT 52nd Annual Meeting; March 23, 2026; Madrid, Spain. Abstract O205-02. https://www.ebmt.org/sites/default/files/2026-03/AM26_Abstracts Book_final_v.pdf
  9. Auletta JJ, Corrigan D, Bupp C, et al. Infection burden in mismatched unrelated donor hematopoietic cell transplantation using reduced-dose post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis: results from the OPTIMIZE trial. Presented at: EBMT 53rd Annual Meeting; March 24, 2026; Madrid, Spain. Abstract B074. https://www.ebmt.org/sites/default/files/2026-03/AM26_Abstracts Book_final_v.pdf
  10. Shaffer BC, Gooptu M, DeFor TE, et al. Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis attenuates disparity in outcomes between use of matched or mismatched unrelated donors. J Clin Oncol. 2024;42(28):3277–3286. doi:10.1200/JCO.24.00184
  11. Pagel JM, Othus M, Garcia-Manero G, et al. Rapid donor identification improves survival in high-risk first-remission patients with acute myeloid leukemia. JCO Oncol Pract. 2020;16(6):e464–e475. doi:10.1200/JOP.19.00133
  12. ClinicalTrials.gov. A platform protocol to investigate post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis in patients with hematologic malignancies undergoing mismatched unrelated donor peripheral blood stem cell transplantation (ACCELERATE). Updated March 17, 2026. Accessed July 2, 2026. https://clinicaltrials.gov/study/NCT06859424