Corrected hematopoietic stem cells (HSCs) have engraftment and proliferation advantages in patients who have Fanconi anemia (FA) subtype A without cytotoxic conditioning, according to research published in Nature Medicine.

Mutations in FANCA account for the majority of cases of FA, although 22 genes related to FA have been discovered so far. Patients with FA are at higher risk for congenital abnormalities or cancer, and 70% to 80% of patients have bone marrow failure within the first decade of life.

In this study ( Identifier: NCT03157804), the authors collected CD34+ cells from 4 pediatric patients (aged 3-6 years) before any developed severe bone marrow failure. Preclinical research suggested that FA patients may benefit from a transplantation with low numbers of gene-corrected HSCs using lentiviral-vector-mediated gene therapy. The researchers reinfused the 4 patients with gene-corrected HSCs when the patients developed evidence of bone marrow failure.

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During the follow-up period of 18 to 30 months, none of the 4 initial patients had serious adverse events from the lentiviral-vector-mediated gene therapy. Using peripheral blood counts, the therapy showed a halt in bone marrow failure progression. Results also showed sustained corrected leukocytes and corrected CD34+ cells, suggesting progressive engraftment and long-term hematological recovery. The 2 patients with the highest levels of gene marking had ongoing expansion of corrected repopulating clones. These patients also received the highest number of infused cells.

The autologous gene therapy used in the study may not increase later incidence of solid tumors as opposed to allogeneic transplantation. The authors also speculated that an improved hematological response from this treatment could produce better responses to chemotherapy if solid tumors develop in the future.

At 30 months of follow up, no genetic or cytogenetic abnormalities were observed in any of the patients. Because of the safety and feasibility of this gene therapy, the authors suggest this treatment could be implemented earlier in the disease course to avoid bone marrow failure or other hematological complications.

“The progressive engraftment of corrected HSCs in [nonconditioned] patients with FA supports that gene therapy should constitute an innovative low-toxicity therapeutic option for this life-threatening disorder,” the authors conclude.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Río P, Navarro S, Wang W, et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat Med. 2019;25(9):1396-1401. doi:10.1038/s41591-019-0550-z