Second Unrelated Donor Hematopoietic Cell Transplantation for Primary Graft Failure

Abstract

Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count of ≥ 500/ μL without recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and other diseases (n=3). The median age was 29 years. Twenty-four patients received second grafts from a different unrelated donor. Among 98 patients who received a second graft from the same donor, 28 received products that were previously collected and cryopreserved for the first transplantation. One-year overall survival after second transplant was 11% with 10 patients alive at last follow up. We observed no differences between patients who received grafts from the same or different donors, or in those who received fresh or cryopreserved product. The outcomes after a second allogeneic HCT for primary graft failure are dismal. Identifying risk factors for primary graft failure can decrease the incidence of this complication. Further studies are needed to test whether early recognition and hastened procurement of alternative grafts can improve transplant outcomes for primary graft failure.

Graft failure in the modern era of allogeneic hematopoietic SCT

“…1,2 The most obvious manifestation of graft failure is primary graft failure, where the patient never recovers from neutropenia (ANC o0.5 Â 10 9 /L), resulting in pancytopenia and an urgent need for re-transplantation. In contrast, secondary graft failure occurs because of loss of donor cells after initial engraftment.…”

Salvage allogeneic hematopoietic SCT for primary graft failure in children

“…The incidence of graft failure is assumed to range from 2 to 20%, and the frequency depends on various factors such as stem cell source 1,2 and preconditioning regimen, [3][4][5] underlying disease, 5 HLA disparity 2,6,7 and the presence of anti-HLA Abs. 8 Salvage HSCT can rescue pGF patients, [9][10][11][12][13][14] and recent studies on adult pGF patients have showed the feasibility of using reduced-intensity conditioning containing fludarabine (FLU) and low-dose irradiation, 13,[15][16][17] including short-term preconditioning regimen 10,18 and an advantage of PBSC as the stem cell source for salvage HSCT. 19,20 However, the management of pGF patients is usually difficult because of their poor clinical status.…”

Salvage haploidentical transplantation for graft failure using reduced-intensity conditioning

“…14 Salvage transplantation is generally attempted; however, the overall survival varies from 11 to 37%, with major obstacles being infections arising from prolonged neutropenia and damaged organ function as a result of previous transplantation. [14][15][16][17] Particularly, patients who undergo CBT or haplo-SCT almost always lack both matchedrelated and -unrelated donors during the clinically relevant period. Therefore, salvage transplantation is also limited to either CBT or haplo-SCT.…”