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Haploidentical versus matched related donor in Hodgkin’s lymphoma

Jordan Gauthier of CHRU Lille in Lille, France, and colleagues published findings of a retrospective review of transplant outcomes in Hodgkin’s lymphoma patients from either a haploidentical or matched related donor. The findings were published in the online version of Biology of Blood and Marrow Transplantation in January 2018. 

This multicenter review had a primary objective to compare rates of graft-versus-host disease-free relapse-free survival (GRFS) in Hodgkin’s lymphoma patients with advanced disease.  Graft-versus-host disease-free was defined as the absence of grade 3 or 4 GvHD. 

Patient population
  • N = 151 patients
    • Haploidentical (Haplo) donor = 61 patients
    • Matched related donor (MRD) = 90 patients
  • Haplo donor relationships
    • Sibling = 49%
    • Parent = 34%
    • Offspring = 6%
    • Unknown = 10%
  • Conditioning regimen
    • Non-myeloablative (NMA): Haplo = 93%
    • Reduced intensity (RIC): MRD = 94%
    • Total body irradiation (TBI): Haplo = 92% vs MRD = 8%
  • Bone marrow stem cell source: Haplo = 51% vs MRD = 14%
Key Findings
  • Platelet recovery at 30 days: Haplo = 71% vs MRD = 61%, P = 0.001
  • No differences in neutrophils at 30 days, time to neutrophil recovery or chimerism at day +100
    • Neutrophil recovery day +30: Haplo = 98% vs MRD = 99%, P = 0.17
    • Time to neutrophil recovery: Haplo = 19 days vs MRD = 18 days
    • Full chimerism at day +100: Haplo = 64% vs MRD = 61%
  • Two-year GRFS univariate analysis
    • Haplo = 58% vs MRD = 42%, P = 0.03
    • NMA = 58% vs RIC = 41%, P = 0.03
    • No difference in GRFS based on disease status, PET scan positivity, stem cell source or age at transplant
  • Two-year cumulative incidence of relapse univariate analysis
    • Complete response (CR) = 10% vs non-CR = 28%, P = 0.004
    • PET positive at transplant = 24% vs PET negative at transplant = 11%, P = 0.03
    • Age ≤ 28 years = 24% vs age ≥ 28 years = 11%, P = 0.04
    • No difference in incidence of relapse based on donor type, stem cell source or conditioning regimen
    • Two-year overall survival was not influence by any of the observed variables
    • Two-year non-relapse mortality was not influence by any of the observed variables
  • Multivariate analysis for GRFS
    • MRD lower GFRS vs haplo (HR = 2.95, 95% CI 1.72-5.1)
    • Non-CR status lower GRFS vs CR (HR = 1.74, 95% CI 1.12-2.68) P = 0.01
    • Anti-thymocyte globulin (ATG) increased GRFS vs no ATG (HR = 0.52, 95% CI 0.32-0.85), P = 0.001

Data from this retrospective chart review suggests that haploidentical donors may lead to improved GRFS in Hodgkin’s lymphoma.  However, the donor selection did not influence overall survival or 2-year incidence of disease relapse. The haploidentical patients all received cyclophosphamide after transplant and ultimately had a lower incidence of chronic GvHD. This represents a promising treatment option for patients with advanced Hodgkin’s lymphoma.

References
  1. Gauthier, J, et al. Better outcome with haploidentical over HLA-matched related donors in patients with Hodgkin’s lymphoma undergoing allogeneic haematopoietic cell transplantation—a study by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy. Bone Marrow Transplantation 2018; 1-10. doi.org/10.1038/s41409-017-0018-z.
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