Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation

Abstract

Summary:Failure to engraft after hematopoietic stem cell transplantation (graft dysfunction) or to sustain engraftment (graft rejection) is a formidable complication due to many possible factors. These include inadequate stem cell numbers, infections, graft-versus-host disease and immunological mediated processes. Fortunately, this complication is uncommon and can be overcome by additional hematopoietic stem cell infusions. Multiple treatment alternatives have been explored including hematopoietic growth factors, additional infusions of stem cells alone, with augmented immunosuppression or with additional cytotoxic therapy. Various sources of the additional stem cells are feasible including the original donor, using another donor, using stem cells collected from the marrow or after cytokine mobilization from the peripheral blood. This report will overview this complication and review the various studies that have attempted to define both cause and therapy. However, a lack of well-designed prospective studies has made definitive recommendations difficult although basic principles have been established.

Salvage allogeneic hematopoietic SCT for primary graft failure in children

“…There are reports showing that some cases can achieve engraftment without any preconditioning regimen; 26,27 however, it is generally accepted that most pGF cases require some preconditioning treatment. 14 We consider that myeloablative conditioning is not required for the salvage HSCT in pGF patients because their marrow is already hypocellular; however, reduced-intensity conditioning may help engraftment. Our study showed that FLU and alkylating agents provide better engraftment probability without increasing NRM.…”

“…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.…”

Haploidentical SCT in children: an update and future perspectives

“…24 Several factors may be involved in this severe complication, such as compromised host marrow microenvironment, 25 infections with herpes viruses, 26 inadequate stem cell numbers 27 or, on the other hand, persistent host immunity, mediated by residual T and NK cells and HLA disparity. 28 It has been shown that CD3 þ /CD8 þ T cells of recipient origin frequently emerge in graft rejection.…”

Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ+ cells by add-back after a reduced intensity preparative regimen containing low-dose TBI

“…7 GF can be affected by many factors such as disease, prior therapy, conditioning regimen, T-cell dose, CD34 cell dose and T-cell depletion technique. 3,[19][20][21][22][23] A matched comparison between the present study and our prior study using CD3-depleted grafts is difficult because stem cell dose, proportion of patients with NM and proportion receiving low-dose TBI are somewhat different between the two studies. Recent studies reported that a GF rate after αβ-depleted HHCT for pediatric patients ranged from 12 to 16.2%.…”