In utero stem cells transplantation after a mild immunosuppression: evidence of paternal ABO cDNA in β β β β β-thalassaemia affected fetus

Background. In utero haematopoietic stem cell transplantation (IUHSCT) could represent an alternative option to therapeutic abortion after prenatal diagnosis of thalassaemia. However, although in immunodeficiency syndromes chimerism has been described, in thalassaemia poor clinical success has been reported. One of the reasons is probably the graft failure due to an immune response of the fetuses. Materials and methods. Therefore, we set up a clinical protocol by which two female fetuses affected by ß-thalassaemia at 20 and 21 weeks of gestation were prenatally treated with low-dose dexamethasone and then transplanted with paternal circulating haematopoietic progenitor cells. Results. Chimerism analysis performed after birth showed the presence, in both newborns, of Y cells in peripheral blood. Moreover, in one case an erythroid microchimerism was shown by the presence of paternal ABO allele A cDNA obtained from mononuclear peripheral blood cells at 2 months of age and by an unusual HbA value of 14.4%, thus indicating a slight transitory engraftment of infused paternal stem cells. However, because of both babies required transfusions before 12 months, these data confirm the difficulty for long-term successful with IUHSCT. Conclusions. To obtain safe and successful results for fetuses with β β β β β-thalassaemia will remain a challenge of the next years. Introduzione I rapidi progressi conseguiti nelle indagini genetiche e molecolari hanno consentito di individuare numerose malattie genetiche ereditarie in periodi precoci di gestazione, mediante il campionamento dei villi coriali (CVC) e l'analisi del DNA. Il trapianto in utero di cellule staminali ematopoietiche (In utero Haematopoietic Stem Cell Transplantation, IUHSCT) potrebbe rappresentare una opzione alternativa all'aborto terapeutico in alcune emopatie genetiche ereditarie, quali le emoglobinopatie, in quanto, potenzialmente, potrebbe consentire la nascita di un neonato sano. Tuttavia, attualmente, l'attecchimento dopo IUHSCT si è ottenuto soltanto in caso di feti affetti da disordini immunologici, quali la sindrome di Bare (sindrome dei linfociti "nudi") o l'immunodeficienza combinata grave (Severe Combined ImmunoDeficiency, SCID