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Hematopoietic stem cell transplantation in FANCJ/BRIP1 fanconi anemia

Bone Marrow Transplantation volume 52, pages 463–465 (2017)Cite this article

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A defect in the FANCJ/BRIP1 gene was described in 2005 to be associated with fanconi anemia (FA).1 BRIP1, also termed BACH1, is a DNA helicase that interacts with the tumor suppressor protein BRCA1. FANCJ/BRIP1 mutation induces disruption of the FA pathway downstream of FANCD2/FANCI monoubiquitination.2 We previously showed that the truncating mutation in FANCJ/BRIP1 c.2392C>T (p.Arg798*) is common in Saudi FA patients presenting with severe aplastic anemia, compared to only about 2% in Europeans.3 Hematopoietic stem cell transplant (HSCT) is the only effective therapy of severe aplastic anemia associated with FA. Early reports showed that reduction in the intensity of the conditioning regimen could safely correct the bone marrow failure in FA.4 The outcome of transplant in FANCJ/BRIP1 FA has not been previously reported given the rarity of this type in other populations. Here we present the outcome of four Saudi patients with FANCJ/BRIP1 subtype who underwent HSCT. All four patients presented with severe aplastic anemia with no evidence of cytogenetic abnormality, myelodysplastic syndrome or leukemia and were transfusion dependent for variable lengths of time.

Patient and transplant characteristics of the four patients are summarized in Table 1. Supportive care was consistent for all patients. All rooms were HEPA-filtered. All blood products were leukocyte-reduced and irradiated. All patients received Pneumocystis carinii pneumonia prophylaxis. IV Ig support was provided in the first 100 days post transplant. Acyclovir prophylaxis was given to all patients starting with conditioning and continued for one year. Patients were started on broad-spectrum antibiotic when their ANC dropped to <1 × 109/L. Prophylactic antifungal treatment was provided with voriconazole or caspofungin. Patients who developed positive CMV PCR received preemptive antiviral therapy with foscarnet or ganciclovir and CMV immune globulins.

Table 1 Patient and transplant characteristics of FANCJ/BRIP1 Fanconi patients
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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, King Abdullah Specialist Children’s Hospital, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia

    A Alsultan, M Essa & R Alsudairy

  2. Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    A Alsultan

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  1. A Alsultan
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  2. M Essa
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  3. R Alsudairy
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Correspondence to R Alsudairy.

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Alsultan, A., Essa, M. & Alsudairy, R. Hematopoietic stem cell transplantation in FANCJ/BRIP1 fanconi anemia. Bone Marrow Transplant 52, 463–465 (2017). https://doi.org/10.1038/bmt.2016.296

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