Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation

Abstract

Summary:Five patients with confirmed Fanconi's anemia (FA) and myelodysplasia and/or leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC. The median age at SCT was 12.6 year (range, 6.2-15 years). Conditioning regimen consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median time to engraftment (defined as ANCX0.5 Â 10 9 /l) was 16 days (range, 12-26 days). The median time to a self-sustaining platelet count of X20 Â 10 9 /l was 27 days (range, 12-40 days). All patients engrafted. Two patients developed acute GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one patient developed chronic GVHD of the liver. Four are alive and well with no evidence of the disease; one patient died of bacterial sepsis after controlling her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing SCT is adequate; the regimen is well tolerated and may be curative for such patients.

Allogeneic stem cell transplantation in Fanconi anemia patients presenting with myelodysplasia and/or clonal abnormality: update on the Saudi experience

“…In our experience, the CY/TBI regimen has been associated with tolerable toxicity. Our long-term followup confirms the 4 patients previously reported with successful outcome 8 to remain alive and well. By using the same regimen, 6 additional patients have been successfully transplanted since; 1 of them from a partially matched unrelated cord blood unit.…”

“…The addition of ATG to the GVHD prophylaxis regimen has been practiced previously in FA patients by us and by others because FA patients are considered at a higher risk for GVHD development. 1,3,4,8,11 Supportive care All the patients were treated in HEPA-filtered rooms and were isolated until engraftment; the engraftment was defined as an absolute neutrophil count of 500 Â 10 6 /l for 3 consecutive days. All the patients received intravenous immunoglobulins every 2 weeks at a dose of 500 mg/kg from day À4 until day þ 90, as well as, acyclovir 45 mg/kg/ day from day À3 to day þ 28.…”

“…[8][9][10] Here we offer an update of our experience at King Faisal Specialist Hospital and Research Center (KFSHRC) in 11 patients with FA who presented with myelodysplasia and/ or clonal abnormalities including one who presented with frank acute myeloid leukemia (AML); five of these patients have been reported earlier. All the patients underwent allogeneic SCT using a uniform radiation-containing conditioning regimen.…”

Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy

“…[22][23][24] In conclusion, this study provides evidence that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT; however, the use of more aggressive therapy including total body irradiation maybe warranted in patients who present with myelodysplasia and/or clonal abnormality in order to eradicate the abnormal clone. 25,26 …”

Matched-related allogeneic stem cell transplantation in Saudi patients with Fanconi anemia: 10 year's experience

“…[1][2][3][4][5] For bone marrow failure, it has been universally accepted and proven that allogeneic SCT is the therapy of choice, [6][7][8][9][10][11][12][13][14][15] but the optimal conditioning regimen remains undetermined.…”