Here’s how readers responded to a You Make the Call question about allogeneic hematopoietic cell transplantation in a patient with Fanconi anemia.
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I would perform alloHCT as soon as possible with matched related donors using a bone marrow stem cell source (as graft-versus-host disease [GVHD] and malignancies are less likely in follow up based on a European Society for Blood and Marrow Transplantation [EBMT] study of Flu/Cy low dose/ATG and TBI 2 Gy). Conditioning for FA was based on the backbone of aplastic anemia: an association of cyclophosphamide (200 mg/kg) and ATG. Due to the chemosensitivity of FA cells and observation of serious adverse events with a high dose, the cyclophosphamide dose was reduced to 40 mg/kg and overall survival (OS) improved. Chronic GVHD was associated with worse OS (hazard ratio 3.1) in FA, linked to secondary malignancies, explaining the importance of ATG to limited GVHD. Graft failure was the primary factor limiting HSCT with unrelated donors in FA, as there was 24% primary graft failure and 16% OS. Utilization of fludarabine could limit engraftment failure and was included in many conditionings of FA. In an EBMT retrospective study of 795 HSCT in FA, fludarabine was associated with higher engraftment and less GVHD, which led to better OS. Despite radio-sensitivity of FA cells, low dose total body irradiation (2 Gy) is part of the conditioning to decrease tumor burden and avoid graft failure, especially in the unrelated donor setting.
For the triple X syndrome, I am unaware of data on management linked to association of two rare conditions. Diminution of alkylants and total body irradiation dose will reduce toxicity.
Please see an article by Parinda Mehta, MD, and colleagues published in Blood in 2017 for guidance on stem cell source and preparatory regimen for FA patients (Mehta PA, Davies SM, Leemhuis T, et al. Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multiinstitutional study. Blood. 2017;129:2308-15.).
Michael Grimley, MD
Cincinnati Children’s Hopsital