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

Abstract

Summary:In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLAmatched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/ day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.

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

“…At our institution, we launched a protocol in 2000 using Cy at 60 mg/kg plus ATG (group B); early results on the first 22 of the 34 patients reported here have been published. 14 In this paper, we provide an update and a comparison between the two regimens; one salient conclusion is that the radiation therapy arm (group A) had a significantly inferior overall survival when compared to the nonradiation arm. Another important finding is that the use of higher doses of Cy in group B led to a significantly higher incidence of hemorrhagic cystitis.…”

“…[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.…”

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

“…[1][2][3][4][5] However, FA patients with myelodysplasia or clonal abnormality on presentation are a distinct group that requires more intensive conditioning prior to SCT as the presence of either may herald the development of AML and hence is a marker for an adverse outcome. 6,7 This has been recognized even in the earlier publications addressing transplant in FA patients; in a cohort of 17 patients reported by Flowers et al in 1992, 5 had evidence of leukemic transformation before SCT; 4 of them were conditioned with CY 120 mg/kg plus 12 GY fractionated TBI and 1 received busulfan 14 mg/kg and CY 100 mg/kg; 4 died of transplant-related mortality and 1 was reported alive with no evidence of disease, 8 years post-SCT.…”

“…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.…”

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“…2 Low-dose cyclophosphamide (20-80 mg/kg) has been used as a backbone for most FA-conditioning regimens. [10][11][12] In our cohort, we used different conditioning regimens, reflecting an evolution in the conditioning protocols over the years, as well as the practice of using TBI in patients with myelodysplasia based on local experience. At our center, the TBI-based conditioning regimen was used between 1988 and 2006, whereas fludarabine-based conditioning was used from 2007 to 2013.…”