Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning

Abstract

Summary:We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n ¼ 40) or busulphan (n ¼ 28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (Po0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression posttransplant was the development of chronic extensive GVHD (Po0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.

Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism

“…4 Not surprisingly, we experienced more patients with MC after conditioning with RIC than with myeloablative conditioning, which has been described by others. [21][22][23] More importantly, however, high MC was no different using RIC than with myeloablative conditioning. High MC was correlated with graft failure and it is therefore undesirable.…”

400 cGy TBI with fludarabine for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation

“…Factors such as the type of hematologic malignancy, amount of pretransplant therapy, source of hematopoietic stem cells, composition of the hematopoietic graft and whether patients received a related vs unrelated donor have been correlated with the development of CDC after RIC allogeneic HSCT. [27][28][29] We have also previously reported that killer immunoglobulin-like receptor/ligand matching may influence the achievement of T-cell CDC and the development of graft rejection after RIC allogeneic HSCT. 8 Strategies to enhance achievement of T-cell CDC may include increasing pretransplant conditioning intensity further and the use of prophylactic donor lymphocyte infusions.…”

Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning

“…Valcarcel et al 40 studied 68 patients transplanted after conditioning with fludarabine (30 mg/m 2 on days À8 to À4) and melphalan (70 mg/ m 2 on days À3 and À2) in patients with lymphoid malignancies or fludarabine (30 mg/m 2 on days À9 to À5) and busulfan (total 10 mg/kg) in patients with myeloid malignancies. GVHD prophylaxis consisted of CSP and a short course of methotrexate (MTX).…”