Improving Survival, Quality of Life, and Cost-Effectiveness for Allo-HCT

With a variety of patient, disease, and systematic factors that can affect survival, strengthening the outcomes of allogeneic hematopoietic cell transplant (HCT) is an imposing challenge that requires deliberate improvements on multiple levels. At Roswell Park Comprehensive Cancer Center in Buffalo, New York, the Transplant and Cellular Therapy program demonstrated the importance of these processes, as their research found a marked improvement in 1-year overall survival and other benefits to patients after a system-level redesign took place, according to findings published in Transplantation and Cellular Therapy.¹

“We were able to do several programmatic changes in terms of graft-vs-host disease [GVHD] prophylaxis, donor selection, maintenance therapy, and even timing of discharge to improve clinical outcomes, quality of life for patients, and overall experience for both patients and their caregivers,” said Brian C. Betts, MD, in an interview with Targeted Oncology^TM.

The overall survival (OS) rate at 1 year in 2024 was 92.6% compared with 63.9% across 2021 to 2023 (P <.0001) with a nonrelapse mortality rate of 1% vs 28%, respectively. In addition to the OS benefit, the cumulative incidence of grade 2 to 4 acute GVHD was 32%, grade 3 to 4 in 5%, and chronic GVHD requiring systemic therapy in 18% at 1 year. Patients were also able to be discharged as early as day +5 after transplant and reduce the median length of hospitalization.

Betts, vice chair of strategic initiatives for the Transplant & Cellular Therapy Program at Roswell Park and senior author of the study, explained that the adaptations made at Roswell Park, coinciding with the adoption of posttransplant cyclophosphamide (PTCy) as GVHD prophylaxis, are achieving these unprecedented outcomes in patients while simultaneously improving the quality of care and expanding the availability of allogeneic HCT to patients in their region.

Targeted Oncology: What would you highlight as the most important results from your findings?

Brian C. Betts, MD: Two things: one being the OS, which was around 92% [at 1 year], which is phenomenal, and the reduction in the risk of death posttransplant from the procedure itself. A lot has happened over the past 3 to 4 years to help make this possible, one of them being use of PTCy. For an allogeneic [HCT], we usually think of the day of stem cell infusion as being day 0. For PTCy, cyclophosphamide is given on days +3 and +4, and that’s a way to prune out the T cells that would go on to cause [GVHD] but leave the immune effectors intact. It also includes the use of tacrolimus and mycophenolate mofetil on day +5.

One thing we did in addition to using cyclophosphamide is that we had a universal end point for the exposure to tacrolimus. [Johns Hopkins Medicine] does a similar approach, where we stop tacrolimus without a taper on day 60,² and we’ve seen that it helps with immune reconstitution posttransplant [and] probably assists with making vaccinations more impactful and [causes] less toxicities from tacrolimus in general, which can be a real concern posttransplant. Overall, we are able to effectively liberate patients from immune suppression early posttransplant.

The other thing we did was looking at age of donor in terms of donor selection. Typically, when you’re looking at donor options, if you have if you have a patient in their 40s to 60s, we’d ask if they had any siblings…if they’re full matches, we’d typically use them, but we found that using donors [younger] than the age of 40, ideally less than 30 [and] potentially in their 20s, added to the OS of the recipients.

That was even regardless of mismatch, and that was consistent with data from the [Center for International Blood and Marrow Transplant Research], which also showed that if you use a mismatched donor, you can achieve similar outcomes where you can essentially [reach] OS [rates above] 80%.³ This massive reduction in [GVHD], where we’re essentially seeing rates less than 5% for severe [GVHD],¹ that allows us to focus on the real problem posttransplant, which is relapse. When you don’t have other ongoing toxicities from transplantation, whether it’s GVHD or cytopenias, it opens the door for other modalities like maintenance therapy to help reduce that risk of relapse more comprehensively. We’ve brought that into the program here, too.

Safer transplants mean higher patient volumes, so the question becomes, how can you accommodate the rise in access to care? We have a system where we can use our outpatient transplant unit via [an] early discharge system, where patients leave the hospital on day +5, which is phenomenal. Typically, they’d leave 3 or 4 weeks out from cell infusion, but this allows them to leave at day +5.

We require a radius of about an hour or so from the center to facilitate the day +5 discharge. Otherwise, we have a local lodging system that that can accommodate patients [who] live further away, but it’s ideal if they can go home. Patients can leave on day +5. Regardless of the intensity of the conditioning regimen…we’re typically able to get patients out by day +5. That bundle of things has made the outcomes phenomenal, reduced medical costs, and improved quality of life for patients.

How did Roswell Park improve their workflow and procedures for HCT?

The big one was collaborating with our colleagues both in the leukemia service, regional referral partners, and the National Marrow Donor Program [NMDP]. We’re putting a lot of pressure on the unrelated donor pool, so it was helpful to have support from entities like the NMDP that has programs to accommodate the use of unrelated donors at scale.

The NMDP have a system where they can alert us to donors [who] are more ready than others. They have a readiness score,⁴ which is very helpful. Once we have HLA typing for donor selection, we can get results very quickly. So…if you’re using unrelated donors, is there a delay to transplant? We didn’t see that at all. They were able to move very quickly. The big thing is having strong collaborative ties with the leukemia service, so they can help us with maintenance therapy posttransplant and guide patients in need of transplantation to our experts.

How do you manage the transition of care and ensure these patients are safely getting back to referring physicians?

[We are] coordinating the receipt and handoff of patients in their journey through transplant. They have to be referred to us in the first place so we can work them up for [HCT], but it’s also nice to have a collaborative model where you work with the referring physician too. We empower the referring physicians to assist with posttransplant planning, such as early marrow assessments and consideration of maintenance therapy. The early discharge model helps support this collaborative model with the referring physician.

How do you monitor and care for these patients over a longer period of time?

We’re following the patients up to 2 years and sometimes even beyond. Alicia Lieberman, MD, MS, is our rheumatologist who helps with management of chronic GVHD. She also provides cell therapy expertise for noncancer indications [such as] autoimmunity. Thankfully, chronic GVHD has become more of a rare entity here, but when it does happen, we’re prepared to address it. We also have a robust survivorship clinic here at Roswell Park, which assists with managing things like bone density posttransplant, timely pulmonary function tests, and those types of things. Having that level of support both in survivorship and in longer-term follow-up…is important.

Are physicians and patients becoming aware of the improved safety and wider accessibility of HCT?

We’re trying to get that information out…. A lot of [physicians] may have somewhat dated impressions of how things are posttransplant, primarily from their experiences during training. Now in the current era with [PTCy], a lot of the toxicity we witnessed as trainees is pretty rare, and when we do see it, it’s a lot less severe, which is fantastic. But the only way for people to know that is to educate them and let them know. We’ve tried to be pretty systematic with getting all that information out.

When I first got here, we traveled throughout western New York to inform [physicians], and we’ve made a lot of friendships that way. A lot of our relationships with those close colleagues were formed by those initial educational tours. I think letting people know is important, and the only way to inform people is just to educate them.

How are the broader advances in HCT in the past 5 years affecting patients with more difficult-to-treat disease?

PTCy and this improvement in outcomes gives us a couple of options. When patients relapse, it gives us a platform for second transplants if they’re needed. That used to be challenging for adult patients, [though] a little more frequent on the pediatric side. For adult patients, second transplants were not common, but now with the outcomes we can achieve with PTCy and donor selection and careful conditioning regimens, second transplants are feasible, effective, and safe. When someone does unfortunately deal with relapsed disease, we have a lot more tools available to fix that, and a second transplant can be just as effective as a first.

That’s an alternative to our old standby, which was donor lymphocyte infusions, which can be helpful too. But there are a couple of caveats there. The donor has to be available and willing to do the apheresis for the leukocytes, and typically you have to pair it with some other modality like chemotherapy or targeted therapy. Having the ability to do a second transplant is a nice option to have, especially withsimilarly good outcomes.

The other thing is, as transplant becomes safer…[we may be] able to apply transplant in noncancer diseases, like autoimmunity, sickle cell disease, and other areas where we may not have thought of cell therapy. For sickle cell disease and thalassemia, we have the option of gene therapy, but it’s not widely available at all centers. Now that allogeneic [HCT] is as safe as it is, it’s a nice alternative if that’s needed, which helps provide access to care and can achieve similar excellent outcomes in sickle cell disease.

What do you see as the next major step in further improving the transplant program?

The big thing is…stopping tacrolimus early, [approximately] day 60. That’s important because it allows for early effective lymphopoiesis. If we had to do something like [chimeric antigen receptor [CAR] T-cell therapy] as a consolidative maneuver posttransplant, you’d have lymphocytes available to apherese and collect to produce CAR T cells. We’re moving towards that platform.

Roswell Park is New York State’s first and only gene and cell therapy hub, and our academic GMP [good manufacturing practice] facility is probably the biggest in the country, with about 20 clean rooms. We have an active trial studying CD83 CAR T for relapsed/refractory acute myeloid leukemia, and allows for patients who have relapsed posttransplant.⁵ Having an [HCT] platform where patients are off immune suppression and have robust lymphocyte counts gives them this option to be able to pursue CAR T if relapse were to occur, because if someone is on prolonged immune suppression, either because they’re still on prophylaxis or because they developed GVHD, trying to acquire enough T cells to make a CAR T in the first place could be pretty challenging. There are a lot of reasons to like this newer way of doing things.

How might the recent FDA approval of Orca-T (Tregzi) affect how patients are treated with stem cells?

It is interesting science. They’ve done a lot of work to develop this over the past couple of years. The thing that will be impactful for Orca-T is if they could develop in a way that wouldn’t require a calcineurin inhibitor. If they had an OrcaT–based platform that didn’t require a calcineurin inhibitor, that would be pretty exciting.

For us at Roswell Park, patients [who] we don’t think could tolerate a calcineurin inhibitor, we’ve moved to using the ABC regimen. It incorporates PTCy, but also includes abatacept [Orencia], bortezomib [Velcade], and [antithymocyte globulin (ATG)], but no tacrolimus, which is good. We think of that for patients [who] have renal challenges or a lower glomerular filtration rate.

These are early days for us with using ABC. We all like it because it still includes cyclophosphamide. It includes a lower dose of cyclophosphamide, so not only could you consider that for someone who’s got kidney issues, but for someone who you’re worried with potential cardiotoxicity from cyclophosphamide.

What advice do you have for hematologic oncologists who are observing these advances in allogeneic HCT?

[I advise] being open to allogeneic HCT and realizing that there have been a lot of advancements in terms of safety outcomes and improved quality of life with the procedure. If you have a patient [whom] you’re not sure [meets] transplant eligibility, it’s probably good to still send them for a consult to your local transplant center, just so that they can be evaluated, because even when you think there might be limitations in terms of their eligibility, nowadays those may not be as much of a concern, and it could still be done safely.

REFERENCES

1. Holtan SG, Herr MM, Mallhi K, et al. System-level redesign of an allogeneic hematopoietic cell transplantation program associated with high 1-year survival and reduced cost. Transplant Cell Ther. Published online July 5, 2026. doi:10.1016/j.jtct.2026.06.050

2. DeZern AE, Elmariah H, Zahurak M, et al. Shortened-duration immunosuppressive therapy after nonmyeloablative, related HLA-haploidentical or unrelated peripheral blood grafts and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2020;26(11):2075-2081. doi:10.1016/j.bbmt.2020.07.037

3. Spellman SR, Xu K, Oloyede T, et al. Current activity trends and outcomes in hematopoietic cell transplantation and cellular therapy - a report from the CIBMTR. Transplant Cell Ther. 2025;31(8):505-532. doi:10.1016/j.jtct.2025.05.014

4. What is the Donor Readiness Score? National Marrow Donor Program. Accessed July 21, 2026. https://tinyurl.com/2vwfysdp

5. Roswell Park Launches Exclusive CD83 CAR T-Cell Clinical Trial for Patients with Relapsed or Refractory AML. News release. Roswell Park Comprehensive Cancer Center. April 14, 2026. Accessed July 21, 2026. https://tinyurl.com/3avnpk8d