Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older with Severe Aplastic Anemia

Abstract

We report on 499 patients with severe aplastic anemia aged ≥ 50years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n = 275, 55%) or HLA-matched (8/8) unrelated donors (n = 187, 37%) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.03 to 1.92; P = .03) and after unrelated donor transplantation (HR, 1.47; 95% CI, 1 to 2.16; P = .05). The 3-year probabilities of survival for patients with performance scores of 90 to 100 and less than 90 after HLA-matched sibling transplant were 66% (range, 57% to 75%) and 57% (range, 47% to 76%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57% (range, 48% to 67%) and 48% (range, 36% to 59%). Age at transplantation was not associated with survival, but grades II to IV acute graft-versus-host disease (GVHD) risks were higher for patients aged 65years or older (subdistribution HR [sHR], 1.7; 95% confidence interval, 1.07 to 2.72; P = .026). Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor (CNI) + methotrexate (sHR, .52; 95% CI, .33 to .81; P = .004) and CNI alone or with other agents (sHR, .27; 95% CI, .14 to .53; P < .001) compared with CNI + mycophenolate. Although donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes.

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study

“…Our study revealed ECOG score was an independent prognostic factor for survival after HSCT in 40 years old and older SAA patients. Physical status was confirmed by several other studies to be a factor associated with outcomes after HSCT . Besides, heavily pretreated sufferings and repeated transfusion might also lead to the impaired organ function and worsen the physical status.…”

“…Physical status was confirmed by several other studies to be a factor associated with outcomes after HSCT. 8,27,28 Besides, heavily pretreated sufferings and repeated transfusion might also lead to the impaired organ function and worsen the physical status. This suggested that patients should receive HSCT in good performance status and would probably benefit from an upfront HSCT.…”

Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years

“…27 As OS of patients with SAA transplanted using MSD and MUD now exceeds 80%, evaluation of outcomes that take into account not only failurefree survival but also GVHD becomes the optimal assessment tool. 26,27 Despite a higher risk for GVHD in older transplanted patients in the reported literature, 24 we show that FCC conditioning is as effective as in younger patients at reducing the risk for GVHD, and significantly lower than other groups using predominantly ATGbased settings. 18,24 The low sample size and retrospective nature of study remains a drawback to this study.…”

“…26,27 Despite a higher risk for GVHD in older transplanted patients in the reported literature, 24 we show that FCC conditioning is as effective as in younger patients at reducing the risk for GVHD, and significantly lower than other groups using predominantly ATGbased settings. 18,24 The low sample size and retrospective nature of study remains a drawback to this study. The study lacks the power to detect small differences in survival between the 2 groups.…”

“…However, among those patients receiving alemtuzumab as part of conditioning, rate of chronic GVHD was low, at 17%. 24 A retrospective comparison from the European Blood and Marrow Transplant Registry reported a significant reduction in acute and chronic GVHD with alemtuzumab compared with ATG-based conditioning regimens. 25 Alemtuzumab-based conditioning with fludarabine and low-dose CY (FCC) in SAA HSCT is an irradiation-free regimen for unrelated donor (UD) HSCT, and is associated with stable mixed T-cell chimerism and very low rates of acute and chronic GVHD and sustained myeloid engraftment persisting beyond withdrawal of immunosuppression as a result of a state of mutual donor and recipient T-cell tolerance.…”