# Optimizing Allogeneic Hematopoietic Cell Transplantation for Older Patients with Hematologic Malignancies

> **NIH NIH R03** · UNIVERSITY OF PENNSYLVANIA · 2022 · $162,500

## Abstract

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are cancers of the blood and bone marrow that
primarily occur in older adults (those 60 years and older).1 The incidence of these myeloid neoplasms increases with age,
peaking beyond 75 years old.2 The overall incidence in the U.S. has been rising about 1.5% each year, reflective of an
aging population. The only potentially curative treatment is allogeneic hematopoietic cell transplantation (HCT). HCT is
physiologically stressful and associated with treatment-related mortality (TRM), which occurs in 10-20% of young and
healthy patients and in up to 40-50% of older patients with comorbidities. 3•4 We have seen a remarkable expansion in
the number of older patients receiving HCT due to the development of reduced intensity conditioning (RIC) approaches.
In 2000, patients over 60 represented <5% of transplant recipients, whereas in 2018 they represented 39% of HCT
recipients.5 Patients over 70 were almost never transplanted before 2007; in 2018 they made up 9% of HCT recipients. 5
Despite these trends, older patients, particularly those over 70, are often not offered HCT. 6 This creates a weighty
disparity: those most affected by these devastating disease are least likely to be offered the cure.
The recently FDA approved combination of azacitidine and venetoclax results in a 68% complete remission (CR) rate for
patients over the age of 70 with newly diagnosed AML, 7 whereas the prior standard-of-care (SOC) therapy in this age
group seldom did. The availability of a highly effective induction for this age group necessitates innovation in HCT since
(1) induction is not curative, with relapse occurring at a median of 12 months, (2) SOC HCT has a 5-year overall survival
(OS) of only 29% in older patients,8 and (3) patients over 75 years old are excluded from SOC HCT. To understand the
impact of SOC HCT recipients~ 60 years old, we measured geriatric parameters as part of the Frailty Study, which forms
the preliminary data for this grant. Patients who were deemed fit according to Fried's frailty phenotype (FP) enjoyed a 2-
year TRM of 12%, compared with 30% and 47% in pre-frail and frail recipients, respectively. 24 In addition, 66% of
patients had a decline in their frailty phenotype at Day 30 post-HCT and 90% of patients were pre-frail or frail at this
time point. This highlights that there is an unmet need for less toxic HCT strategies for older recipients.
Graft-vs-host disease (GVHD) is one of the most significant complications after HCT and a leading cause of morbidity and
mortality. Post-transplantation cyclophosphamide (PTCy) is a revolutionary GVHD prevention strategy that was
pioneered by one of my mentors, Dr. Luznik, and has replaced SOC GVHD prophylaxis strategies for HLA-mismatched
transplantation, in part due to my work9-17 and that of my collaborator on this project (Dr. Kanakry). 18-23 This project aims
to expand the use of PTCy beyond HLA-mismatched transplantation, reducing...

## Key facts

- **NIH application ID:** 10518677
- **Project number:** 1R03AG074068-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Shannon Rose McCurdy
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $162,500
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518677

## Citation

> US National Institutes of Health, RePORTER application 10518677, Optimizing Allogeneic Hematopoietic Cell Transplantation for Older Patients with Hematologic Malignancies (1R03AG074068-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10518677. Licensed CC0.

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