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2151 Outcomes of Patients Undergoing Fludarabine and Melphalan-Based Conditioning with Post-Transplant Cyclophosphamide for Peripheral Blood Stem Cell Allogeneic Hematopoietic Cell Transplant: Donor Type Effect

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Biological therapies, Clinical Research, real-world evidence, Therapies, Transplantation
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Tamer Othman, MD1, Paul B. Koller, MD2, Dongyun Yang, PhD3*, Sally Mokhtari, PhD4, Amanda Blackmon, DO, MS2*, Vaibhav Agrawal, M.D.5, Hoda Pourhassan, MD6, Brian J. Ball, MD2, Idoroenyi Amanam, MD7, Shukaib Arslan, MD2*, Salman Otoukesh, MD2, Karamjeet S. Sandhu, MD8, Ibrahim Aldoss, MD2, Haris Ali, MD2, Amandeep Salhotra, MD5, Ahmed Aribi, MD2*, Andrew Artz, MD, MS9, Yazeed Samara, MD2*, Pamela S. Becker, MD, PhD2, Vinod Pullarkat, MD2, Forest Marc Stewart, MD2, Eileen Patricia Smith, MD2, Anthony Stein, MD2, Guido Marcucci, MD2, Stephen J. Forman, MD, FACP10, Ryotaro Nakamura, MD11 and Monzr M. Al Malki, MD5

1City of Hope, San Lorenzo, CA
2Hematology/HCT, City of Hope National Medical Center, Duarte, CA
3Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA
4Clinical and Translational Project Development, City of Hope National Medical Center, Duarte
5Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
6Hematology/HCT, City of Hope, Duarte, CA
7City of Hope National Medical Center, Duarte, CA
8City of Hope National Medical Center, La Crescenta, CA
9City of Hope, Duarte, CA
10Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA
11Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Comprehensive Cancer Center, Duarte, CA


Reduced intensity conditioning (RIC) has expanded eligibility of older patients (pts) with hematological disorders for allogeneic hematopoietic cell transplant (HCT). Fludarabine and melphalan (FM) has been shown to improve disease control with an acceptable toxicity profile when combined with CNI-based GVHD prophylaxis regimens. The emergence of post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis has improved outcomes of HCT across different HLA disparities and improved accessibility of HCT, especially in patient with no available matched donor. With recent data showing improved outcomes with RIC (Bolaños-Meade et al. NEJM 2023 and Shaw et al, JCO 2021), PTCy has been proposed as the standard of care for GVHD prophylaxis regardless of donor type. Herein, we report the largest experience with FM and PTCy as GVHD prophylaxis.


We retrospectively reviewed pts who underwent FM-based PBSC HCT with PTCy as GVHD prophylaxis at City of Hope from January 2015 to December 2021. Descriptive statistics were used to describe baseline characteristics. Kaplan-Meier Curves and log-rank tests were used to calculate and compare overall survival (OS) and disease-free survival (DFS), respectively. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and GVHD were calculated and compared via a competing-risk analysis and Gray’s test, respectively. Multivariate analyses (MVA) were performed using the multivariable Cox regression model for OS and DFS, and multivariable Fine and Gray regression model for the other variables. The primary aim was to evaluate the effect of donor types on HCT outcomes.


Baseline characteristics of 248 pts are summarized in Table 1. The median age was 63 (range, 20-82). 63.9% were male. The most common diagnoses were AML (n=90), MDS/MPN (n=58), lymphoma (n=40), and ALL (n=39). Of 248 pts, 89 (35.9%) received HCT from a matched related/unrelated donor (MRD/MUD), 118 (47.6%) from a haplo-identical (haplo) donor and 49 (19.8%) from a mismatched unrelated donor (MMUD).

The median times to neutrophil and platelet engraftment were 18 days (range, 18-19) and 32 days (range, 30-34), respectively. On MVA, MRD/MUD was associated with faster engraftment over haplo donors for neutrophils (hazard ratio [HR] 0.64, 95% CI, 0.47,0.87, P=0.015) and for platelets (0.49, 95% CI, 0.34-0.70, p<0.001), compared to MRD/MUD but there was no difference in engraftment between haplo and MMUD.

With a median follow-up for surviving pts of 24.4 months (range, 3.3-81.2), the 2-year OS and DFS for the all pts were 60.4% (95% CI, 53.7-66.5) and 55.5% (95% CI, 48.9-61.6), respectively. The 2-year OS and DFS for pts receiving haplo donors, MMUD, and MRD/MUD were 56.1%, 52.6%, and 72.5%, and 50.7%, 46.7%, and 68.4%, respectively (Figure 1). On MVA, compared with MRD/MUD, the 2-year OS was lower with haplo (HR 2.02, 95% CI, 1.19-3.42) and with MMUD (HR 2.03, 95% CI, 1.11-3.72 (p=0.023), while there was no difference between haplo and MMUD. Additionally, donor age >=35 years was associated with lower OS (HR 1.57, 95% CI, 1.04-2.35, p=0.031). There was a trend toward lower DFS with haplo (HR 1.61 (95% CI, 1.00-2.60)) and with MMUD, HR 1.73 (95% CI, 0.99-3.02, (p=0.093) when compared with MRD/MUD.

2-year NRM and CIR for all pts were 27.7% (95% CI, 22.1-33.5) and 16.8% (95% CI, 12.3-21.9), respectively. There were no differences in CIR based on donor type on MVA (p=0.87). NRM was higher in haplo and MMUD compared to MRD/MUD but this lost significance (p=0.13) in MVA after adjusting for KPS (HR 1.79, 95% CI, 0.98-3.26, p=0.019) and donor age >=35 years (HR: 1.87, 95% CI, 0.93-3.74, p=0.049). Day 100 CI of grade 2-4 and grade 3-4 acute GVHD for all pts were 39.5% (95% CI, 33.4-45.6) and 14.5% (95% CI, 10.5-19.2) and the 1-year CI of extensive chronic GVHD was 31.0% (95% CI, 25.2-37.0) There were no differences in grade 3-4 acute GVHD at day 100 or 1-year CI of extensive chronic GVHD based on donor type (p=0.46 and 0.13, respectively), although MVA revealed a strong trend towards a higher CI of grade 2-4 aGVHD at day 100 with MMUD group, HR 1.73 (95% CI, 1.02,2.95), p=0.079)


FM with PTCy was associated with promising disease control and acceptable NRM. Outcomes of pts undergoing MRD/MUD appears to be superior in this setting due to decreased NRM, while outcomes of pts undergoing HCT with haplo or MMUD are comparable. Donors <35 years was the strongest predictor of improved outcomes.

Disclosures: Koller: takeda: Consultancy, Speakers Bureau; treadwell therapuetics: Consultancy, Other: safety review committee; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sandhu: Autolus Therapeutics: Consultancy; City of Hope Medical Center: Current Employment. Aldoss: Pfizer: Consultancy; Amgen: Consultancy, Honoraria; Jazz: Consultancy; Sobi: Consultancy; KiTE: Consultancy; Takeda: Consultancy. Ali: BMS: Speakers Bureau; Blueprints: Speakers Bureau; Pharmaessentia: Consultancy; GSK: Consultancy; Karyopharm: Consultancy; Incyte: Research Funding. Salhotra: Rigel Pharma: Research Funding; Sanofi: Speakers Bureau; OrcaBio: Research Funding; Jazz Pharma: Research Funding; Kura Oncology: Research Funding; Gilead: Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Aribi: Kite, a Gilead Company: Consultancy; Seagen: Consultancy. Artz: Abbvie: Consultancy; Astra Zeneca: Other: Advisory Board; Radiology Partner: Current equity holder in private company, Other: Spouse equity interest; Magenta Therapeutics: Other: Advisory Board. Becker: Glycomimetics: Research Funding; Pfizer: Research Funding; GPCR Therapeutics: Research Funding; Notable Labs: Research Funding; Accordant Health Services: Membership on an entity's Board of Directors or advisory committees. Pullarkat: Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Stein: Sanofi: Current Employment, Current holder of stock options in a privately-held company. Marcucci: Ostentus Therapeutics: Current equity holder in private company, Research Funding. Nakamura: BMT CTN Steering Committee: Membership on an entity's Board of Directors or advisory committees; NCTN Lymphoma Steering Committee: Membership on an entity's Board of Directors or advisory committees; Leukemia & Lymphoma Society: Other: grant reviewer; Miyarisan: Research Funding; Sanofi: Consultancy; Napajen: Consultancy; Blue Bird: Consultancy; NCCN: Other: guideline panel for HCT; Jazz Pharmaceuticals: Consultancy, Other: research collaboration; International Consortium: Other: consortium chair; Mt. Sinai: Other: Acute GVHD; Omeros: Consultancy. Al Malki: Tscan: Consultancy.

OffLabel Disclosure: Cyclophosphamide is not approved for GVHD prevention

*signifies non-member of ASH