Sequential conditioning in hematopoietic stem cell transplantation in elderly high-risk myeloid blood cancer patients: long-term survival, disease control, and immune recovery across donor types in a matched-pair analysis.
Sequential conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimens might offer improved disease control in high-risk myeloid patients. But concerns remain regarding toxicity, infection risk and delayed immune reconstitution (IR), particularly in older and HLA-haploidentical transplant recipients. To address these concerns, we comprehensively compared safety, feasibility and clinical outcome across HLA-matched related (MRD), matched unrelated (MUD) and haploidentical donor (Haplo) HSCT and longitudinally characterize IR patterns and their associations with post-transplant outcomes.
We conducted a retrospective matched-pair analysis comparing MRD-, matched MUD- and Haplo-HSCT in elderly patients matched for (1) disease activity: p = 1.0; (2) disease status: p = 1.0; (3) modified disease risk index (DRI): p = 0.9; (4) hematopoietic cell transplantation comorbidity index (HCT-CI): p = 0.92; and (5) age: p = 0.95. Outcomes included disease-free (DFS) and overall survival (OS), relapse, non-relapse mortality (NRM), graft-versus-host disease (GvHD), toxicity, infections, and donor-specific IR dynamics and their impact on clinical outcomes.
With a median follow-up of more than 9 years, no significant differences were observed in long-term disease control and survival among the three groups (5-y DFS/OS: MRD = 41%/41%, MUD = 56%/63%, Haplo = 58%/58%; p = 0.52/0.55). Cumulative incidences (CI) of 5-y-NRM and 1-y moderate and severe chronic GvHD (cGvHD) rates were comparable among the three groups (NRM/cGvHD: MRD = 19%/13%, MUD = 29%/6%, Haplo = 18%/19%; p = 0.3/0.57). Overall immune cell recovery after one year was comparable among groups, though early recovery of CD3+ T and NK cells was delayed after Haplo-HSCT. Subgroup analysis revealed that higher early CD4+ T and lower B cell counts were associated with increased CI of acute GvHD III-IV° (p = 0.04/0.03). Additionally, NK recovery at one year was associated with improved DFS and OS as well as lower relapse incidence.
Sequential therapy is safe and feasible in elderly patients with high-risk or active disease across all three transplant platforms. The observed associations between IR and clinical outcomes highlight the relevance of immune monitoring for anticipating post-transplant complications and guiding individualized prophylactic and therapeutic strategies. Prospective studies are needed to further investigate these findings and define the underlying mechanisms.
We conducted a retrospective matched-pair analysis comparing MRD-, matched MUD- and Haplo-HSCT in elderly patients matched for (1) disease activity: p = 1.0; (2) disease status: p = 1.0; (3) modified disease risk index (DRI): p = 0.9; (4) hematopoietic cell transplantation comorbidity index (HCT-CI): p = 0.92; and (5) age: p = 0.95. Outcomes included disease-free (DFS) and overall survival (OS), relapse, non-relapse mortality (NRM), graft-versus-host disease (GvHD), toxicity, infections, and donor-specific IR dynamics and their impact on clinical outcomes.
With a median follow-up of more than 9 years, no significant differences were observed in long-term disease control and survival among the three groups (5-y DFS/OS: MRD = 41%/41%, MUD = 56%/63%, Haplo = 58%/58%; p = 0.52/0.55). Cumulative incidences (CI) of 5-y-NRM and 1-y moderate and severe chronic GvHD (cGvHD) rates were comparable among the three groups (NRM/cGvHD: MRD = 19%/13%, MUD = 29%/6%, Haplo = 18%/19%; p = 0.3/0.57). Overall immune cell recovery after one year was comparable among groups, though early recovery of CD3+ T and NK cells was delayed after Haplo-HSCT. Subgroup analysis revealed that higher early CD4+ T and lower B cell counts were associated with increased CI of acute GvHD III-IV° (p = 0.04/0.03). Additionally, NK recovery at one year was associated with improved DFS and OS as well as lower relapse incidence.
Sequential therapy is safe and feasible in elderly patients with high-risk or active disease across all three transplant platforms. The observed associations between IR and clinical outcomes highlight the relevance of immune monitoring for anticipating post-transplant complications and guiding individualized prophylactic and therapeutic strategies. Prospective studies are needed to further investigate these findings and define the underlying mechanisms.
Authors
Haebe Haebe, Stauffer Stauffer, Drolle Drolle, Prevalsek Prevalsek, Schmidt Schmidt, Fichaux Fichaux, Weigand Weigand, Fraccaroli Fraccaroli, Tischer Tischer
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