Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients Aged over 70 Years with Myelofibrosis

Background: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically presents in the elderly population. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative option for MF. However, allo-HCT carries significant morbidity in older patients. Our study aims to determine the clinical factors that can help predict allo-HCT outcomes in patients over 70 years.

Methods: We analyzed the publicly available Center for International Blood and Marrow Transplant Research (CIBMTR) P-5646 dataset (Murthy et al.) containing 872 patients with chronic-phase MF who received allo-HCT from 2008 to 2019. Outcomes of interest included overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), relapse rate, and non-relapse mortality (NRM) in the subgroup with age 70 years or above. OS, DFS, and GRFS were censored at 24 months per the dataset. Hazard ratios (HR) with 95% confidence intervals (CI) were determined using univariate and multivariate Cox regression analyses were performed. Statistical analysis was conducted using R version 4.3.2, with statistical significance defined as p <0.05.

Results: We identified 51 patients from the dataset and included them in our analysis. The median age at HCT was 71.8 (range 70.1-77.9) years, of which 32 (62.7%) were male and 47 (92.2%) were non-Hispanic Caucasian. The median time from diagnosis to transplant was 27.3 months. Splenomegaly before HCT was present in 54% of patients. Ruxolitinib was used before HCT in 69% of patients. MF Dynamic International Prognostic Scoring System (DIPSS)-Plus risk categories were intermediate-1 (4%), intermediate-2 (63%), and high-risk (33%). The type of donor used was matched unrelated donors (MUD, 82%), matched related donors (MRD, 12%), and mismatched unrelated donors (MMUD, 6%) patients, respectively. Most (94.1%) of grafts were from peripheral blood stem cells. The 24-month OS, DFS, and GRFS rates were 58.8%, 30.6%, and 12.2%, respectively. A trend for inferior OS (HR 4.46, 95% CI 1.00- 19.97, p=0.05) and inferior DFS (HR 3.89, 95% CI 0.88-17.27, p=0.07) was found in Hispanic patients, which was a significant predictor after multivariate adjustments (HR for OS 13.67, 95% CI 1.71-108.50, p=0.01 and HR for DFS 14.38, 95% CI 2.17-95.40, p=0.006, respectively). The use of MMUD was associated with significantly inferior OS (HR 7.14, 95% CI 1.31-38.98, p=0.02), DFS (HR 6.26, 95% CI 1.33-29.54, p=0.02) and GRFS (HR 4.70, 95% CI 1.06-20.83, p=0.04) compared to HLA-identical sibling donors, and only impact on OS remained significant after multivariate adjustments (HR 10.29, 95% CI 1.25-84.99, p=0.03). No association between clinical factors and other outcomes was found.

Conclusion: Outcomes after allogeneic HCT are acceptable in elderly patients with MF, with a 2-year survival rate of 59%. Patients of Hispanic ethnicity and the use of MMUD were associated with inferior outcomes. Careful patient selection and use of matched donors are suggested.

Keywords: Hematopoietic cell transplantation, Allogeneic transplantation, Donor type, Myelofibrosis, Elderly, Survival outcome, Clinical outcome

Yacoub:Acceleron: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; PharmaEssentia: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Apellis: Consultancy; Notable Labs: Consultancy; BMS: Consultancy; Incyte: Consultancy; CTI Pharma: Consultancy; Servier: Consultancy; Celgene: Consultancy. Hamadani:Myeloid Therapeutics: Speakers Bureau; Takeda: Research Funding; AbbVie: Consultancy; Sanofi Genzyme: Speakers Bureau; Genentech: Speakers Bureau; Autolus: Consultancy; Caribou: Consultancy; DMC, Inc: Speakers Bureau; Allovir: Consultancy; Genmab: Consultancy; Forte Biosciences: Consultancy; BMS: Consultancy; CRISPR: Speakers Bureau; CRISPR: Consultancy; Spectrum Pharmaceuticals: Research Funding; Kite Pharma: Consultancy, Speakers Bureau; Astellas Pharma: Research Funding; Omeros: Consultancy; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy. McGuirk:CRISPR therapeutics: Consultancy; Legend biotech: Consultancy; Sana technologies: Consultancy; Autolus: Consultancy; Novartis: Consultancy; BMS: Consultancy; Caribou bio: Consultancy; Kite: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; NEKTAR therapeutics: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.