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Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34 + cells/mL required to initiate apheresis. A median of 21.8 CD34 + cells/mL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34 + cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34 + cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34 + cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34 + cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.

Aim: To determine the expression of two isoforms of the growth hormone (GH) receptor (GHR), which differ by the presence (GHR3+) or absence (GHR3–) of exon 3, and their correlation with circulating GH and insulin-like growth factor I (IGF-I) in normal subjects and in acromegalic patients. Methods: The expression of GHR isoforms was determined by reverse-transcriptase polymerase chain reaction in lymphocytes from 12 normal subjects and from 11 patients with acromegaly. The levels of GHR mRNA were normalized to those of β-actin, and ratios were calculated to assess the relative levels of expression. Results: All samples showed expression of both GHR isoforms, but the expression of GHR3+ and GHR3– was similar in acromegalic patients (6.0 ± 1.7 vs. 8.3 ± 2.0%, mean ± SE). In contrast, in healthy subjects, GHR3– was the predominant isoform (11.8 ± 3.0 vs. 5.1 ± 0.68%; p < 0.05), and the levels of expression of GHR3– correlated significantly with IGF-I. Conclusions: These data demonstrate coexpression of both GHR isoforms under normal and pathological conditions; however, GHR3– is the predominant form in normal subjects and shows a negative correlation with IGF-I levels.