Work

Non-myeloablative allogeneic hematopoietic stem cell transplantation with pre-transplant immune depletion results in rapid full donor engraftment in pediatric patients with malignancy

Year: 2004

Type: article

Abstract: Background: There is limited experience with non-myeloablative (NM) allogeneic hematopoietic stem cell transplantation (alloSCT) in pediatric pts with cancer. In comparison to adults, children and adolescents have less immune depletion and improved reconstitution after chemotherapy, which might increase the risk of mixed donor hematopoietic chimerism after NM alloSCT. Prolonged periods of mixed chimerism may increase the risk of relapse in highly proliferative pediatric cancers. Methods: Twelve pediatric pts (age 7–20, median 14.5 years) with high-risk malignancies (Hodgkin’s disease, ALL, AML, CML, rhabdomyosarcoma, Ewing’s sarcoma) were treated with a novel immunoablative regimen. Fludarabine-based induction chemotherapy was administered for disease control and host immune depletion (1 to 3 cycles). This was followed by pre-transplant conditioning with cyclophosphamide (1,200 mg/m2/day) and fludarabine (30 mg/m2/day) × 4 days with or without melphalan (100 mg/m2 × 1 dose). Unmodified, G-CSF mobilized peripheral blood stem cells collected from HLA-matched siblings were employed (CD34 doses of 6.9–19 × 106/kg). Results: The regimen was associated with sequential lymphocyte depletion, although to a lesser degree than in 18 adult pts (age 33–67, median 50 years) treated on a parallel trial (Table 1). IL7 levels were inversely correlated with CD4 counts (r2 = 0.20, p = 0.0006). Hematopoietic recovery was rapid in all pts. Complete donor lymphoid chimerism (>97% by VNTR-PCR on CD3 sorted peripheral blood) was achieved in 9 of 11 pts by post-transplant day (D+) 14, while 2 had mixed chimerism that improved between D + 14 to D + 28 (70% → 85%, 85% → 95% donor). Complete donor whole blood (WB) chimerism (unsorted peripheral blood) was achieved in 7 of 11 pts by D + 14, while 4 pts had mixed chimerism (30%, 69%, 88%, 95% donor). D + 14 WB chimerism results were comparable to adult pts (13/18 complete, 5 mixed-65%, 95%, 95%, 95%, 95% donor). There was a trend towards a greater degree of mixed chimerism in younger pts and those with less pre-transplant immune depletion. Conclusions: Rapid, complete donor engraftment and chimerism can be achieved in pediatric pts with cancer using a NM alloSCT regimen. Pre-transplant immune depletion appears to be somewhat more difficult to achieve compared to adult pts, particularly in regard to CD8+ T cells. Intensive immune depletion might be required to consistently achieve rapid complete donor chimerism in pediatric pts undergoing NM alloSCT. TablePrePostDay 0PediatricsCD4206108 (54%)5.5 (99.0%)CD8361193∗ (69%)0.5 (100%)AdultsCD425370 (71%)2.3 (99.7%)CD821747∗ (81%)0.3 (99.9%)Data represent median cell counts/mm3 (% depletion); ∗p = 0.001; Pre: entry; Post: after induction; Day 0: after conditioning. Open table in a new tab Data represent median cell counts/mm3 (% depletion); ∗p = 0.001; Pre: entry; Post: after induction; Day 0: after conditioning.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2003.12.167