Bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing 3 Gy of total body irradiation, cyclophosphamide with or without antithymocyte globulin

Abstract

We have employed the 3 Gy total body irradiation (TBI) containing conditioning regimen to bone marrow transplantation (BMT) for severe aplastic anemia (SAA) in pediatric patients irrespective of donor type since March 1986. The outcome of BMT for 17 SAA patients is favorable. Eight patients received BMT from human leukocyte antigen matched-related donors (MRD) and nine received BMT from alternative donors. The conditioning regimen consisted of 3-Gy TBI and cyclophosphamide of 200 mg/kg in the BMT from MRD. In the case of BMT from alternative donor, antithymocyte globulin 10 mg/kg was added to the regimen. Fifteen of 17 patients (88%) engrafted on median of day 18 (range, 11-26) and all 13 evaluable patients showed complete donor chimerism by median 30 (range, 13-47) days after BMT. Fourteen patients have survived with a median follow-up of 67 (range, 2-228) months and the probability of survival was 81.9% (95% CI, 63.3-100%). No late complications including second malignancies caused by TBI have been observed and all three female patients have regular menstruation. In conclusion, TBI of 3 Gy appears to be an appropriate dose regarding to ensure engraftment and avoid the risk of late adverse event for SAA patients.

Outcomes of matched sibling and alternative donor stem cell transplantation for 26 children with severe aplastic anemia

“…Inagaki et al [23] conducted a regimen on 18 SAA children with 3 Gy TBI and cyclophosphamide for MSD transplantation and additional ATG for AD transplantation, which resulted in 81.9% survival rate, 12% graft rejection, 59% acute GVHD, and 35% chronic GVHD. Grade II-IV acute GVHD in 63% MSD transplantations explained the overall high rate of acute GVHD.…”

Unrelated cord blood transplantation in children with idiopathic severe aplastic anemia

“…Historically, preparative regimens of unrelated adult donor HSCT for aplastic anemia have utilized CY (200 mg/ kg), ATG and TBI at various dosages. 28,29 A 90% engraftment rate was reported in most series using a TBI dose of 3-5 Gy but the success in HLA-mismatched cases was less consistent. 29 In a dose de-escalation study Deeg et al 8 showed that when combined with CY and equine ATG, a single fraction of 2 Gy TBI was equally efficacious and less toxic than when 4 or 6 Gy was used.…”

Gonadal function in patients with severe aplastic anaemia and refractory cytopenia of childhood who undergo bone marrow transplantation after receiving 3‐Gy total body irradiation and high‐dose cyclophosphamide

“…For patients with an HLA‐mismatched related donor (MMRD) or MUD, ATG (Zetbulin; Fresenius Biotech GmbH, Munich, Germany) was added to the regimen at 2·5 mg/kg/d on days −5 to −2. Donor selection, graft‐ versus ‐host disease prophylaxis, and other procedures for BMT were previously described (Inagaki et al , ).…”