Search

Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as "natural gene therapy" in patients with FA, we sought to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30-year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB-chromosomal breakage test. Relative to non-mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub-cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non-mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long-term clinical outcomes.

Animal models have recently clarified the lung injury after allogeneic hematopoietic transplantation. These works have confirmed the role of donor T lymphocytes in immune-mediated inflammatory reactions in the lung. We report here a fatal case of a 3-year-old child who developed acute respiratory failure coinciding with the onset of hyper-acute graft versus host disease (aGVHD) after allogeneic peripheral stem cell transplantation. aGVHD was refractory to treatment and the patient died on day +28. Lung necropsy showed interstitial pneumonia and peribronchial and perivascular infiltration by mononuclear cells, with no viral inclusions. These findings are not specific but have been found by some authors in animal models with acute immune-mediated lung injury related with donor T lymphocytes. Immune-mediated lung injury, as defined by animal models, should be considered in patients with severe signs of systemic aGVHD while excluding other known etiologies of pulmonary disease.

Animal models have recently clarified the lung injury after allogeneic hematopoietic transplantation. These works have confirmed the role of donor T lymphocytes in immune-mediated inflammatory reactions in the lung. We report here a fatal case of a 3-year-old child who developed acute respiratory failure coinciding with the onset of hyper-acute graft versus host disease (aGVHD) after allogeneic peripheral stem cell transplantation. aGVHD was refractory to treatment and the patient died on day +28. Lung necropsy showed interstitial pneumonia and peribronchial and perivascular infiltration by mononuclear cells, with no viral inclusions. These findings are not specific but have been found by some authors in animal models with acute immune-mediated lung injury related with donor T lymphocytes. Immune-mediated lung injury, as defined by animal models, should be considered in patients with severe signs of systemic aGVHD while excluding other known etiologies of pulmonary disease.