Fludarabine based reduced intensity conditioning regimens in children undergoing allogeneic stem cell transplantation for severe aplastic anemia

Abstract

Fourteen children with a median age of 9.8 yr with SAA (10 males, four females) underwent related HLA identical allogeneic stem cell transplantation using Flu, Cy +/- ATG between 2004 and 2006. GVHD prophylaxis consisted of cyclosporine +/- mini methotrexate. Graft source included PBSCs (seven) or BM (seven). One patient expired <7 days post-transplant, while 12 (85.7%) patients engrafted with median neutrophil and platelet engraftment times of 13.8 and 14.5 days each. One patient had primary graft failure and expired on Day +27. Acute GVHD was seen in 25% of evaluable patients while limited chronic GVHD was seen in 33%. At a mean follow-up of 18 months, 12 patients (85.7%) are alive and well. Compared with a historical cohort of 12 children transplanted using Cy/ATG, there was faster engraftment (13.8 vs. 16.4 days; p = 0.002) with lower rejection rates (7.1 vs. 36.3%; p = 0.133) and improved event free (85.7 vs. 54.5%; p = 0.177) and overall survival (85.7 vs. 63.6%; p = 0.350). Flu with Cy +/- ATG reduces rejection and improves overall and event free survival in children with aplastic anemia.

Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

“…The same authors indicated that fludarabine increased engraftment rates, and showed minimal morbidity 23–26. George et al27 observed that fludarabine improved OS in children with AA.…”

Acquired Aplastic Anemia in Children

“…35 Small pediatric case series have shown excellent survival and engraftment with regimens containing fludarabine (180 mg/m 2 ) and dose-reduced CY (120 mg/kg). 36,37 While such a regimen may decrease rates of alkylating agent-induced gonadal dysfunction 38–40 , prospective randomized trials are needed to compare efficacy versus standard Cy-ATG regimens.…”

Reduced dose cyclophosphamide, fludarabine and antithymocyte globulin for sibling and unrelated transplant of children with severe and very severe aplastic anemia

“…The median cell infusion counts were as follows: total nucleated cells 18.2 9 10 8 /kg (range, 1.4-73.3), mononuclear cells 11.9 9 10 8 /kg (range, 0.8-40.8), CD34 6.5 9 10 6 /kg (range, 3.4-53.4), and CD3 62.7 9 10 7 /kg (1.6-182.2). Primary graft failure was not observed, and all patients showed neutrophil and platelet engraftment at a median of 11 days (range, [10][11][12][13][14][15][16][17][18][19][20][21][22], and 20 days (range, 14-35), respectively.…”

“…A key component of UD transplant is the conditioning regimen utilized, with some researchers advocating the inclusion of TBI into the regimen . In contrast, a non‐TBI, fludarabine (Flu)‐based conditioning method has been reported , and since then several studies have concluded that Flu, cyclophosphamide (Cy), and an antibody‐based immunosuppressant such as ATG or Campath (alemtuzumab) are effective in the UD transplant setting . At our institution, we have also implemented Flu–Cy–ATG for allogeneic HCT, the initial results of which have been published as part of a Korean multileft trial .…”