Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs.

[Familial hyperaldosteronism]. / Genetica dell'iperaldosteronismo primitivo.

Primary aldosteronism is a disorder characterized by hypertension and hypokalemia due to aldosterone secretion out of renin-angiotensin control. It is generally caused by aldosterone-producing adenoma or adrenocortical hyperplasia but, in some cases, it is due to genetic alterations. Familial type I hyperaldosteronism is the result of anomalous regulation of aldosterone secretion from ACTH (which normally regulates cortisol synthesis). Aldosterone hypersecretion can be suppressed by exogenous glucocortcoids such as dexamethasone. This autosomal dominant disorder is caused by unequal cross-over between two genes with wide sequence homology: CYP11B1 and CYP11B2. The hybrid gene is the product of fusion between the ACTH-responsive regulatory portion of the 11b-hydroxylase gene (CYP11B1) and the coding region of the aldosterone synthase gene (CYP11B2). Familial type I hyperaldosteronism is a disease with incomplete penetration and variable expressivity, especially in relation to hypertension. The marked variability in hypertension severity can mirror an interaction between the hybrid gene and other hereditary factors involved in the regulation of blood pressure. Familial type II hyperaldosteronism is another autosomal dominant form of hyperaldosteronism due to aldosterone hyper-secretion not suppressible by dexamethasone. This disorder is unrelated to mutation of the hybrid gene. The genetic cause of type II hyperaldosteronism is presently unknown, but a genome-wide search has revealed that the disorder is linked with a locus on chromosome 7 in a region that corresponds to cytogenetic band 7p22.

Mobilization and collection of PBSC in healthy donors: a retrospective analysis of the Italian Bone Marrow Transplantation Group (GITMO).

BACKGROUND AND OBJECTIVE: The number of allogeneic transplants of peripheral blood stem cells (PBSC) is rapidly increasing. Collection of PBSC in healthy subjects currently implies the administration of G-CSF or GM-CSF and, of course, the use of apheretic devices. These procedures involve potential risks, in particular the risk of leukemia secondary to growth-factor treatment. To evaluate the current practice of PBSC mobilization and collection, and initially assess the short-term side effects and efficiency of procedures, the GITMO (Gruppo Italiano Trapianti di Midollo Osseo) promoted a retrospective cooperative study among the Italian centers. METHODS: Seventy-six healthy individuals donating to their HLA-identical or partially matched sibling recipients in seven Italian centers form the basis of the present analysis. The data were retrospectively collected by proper forms, pooled and analyzed by means of a commercially available statistical soft package. RESULTS: All donors received G-CSF as mobilizing agent with different schedules according to each single center policy. A median of 2.5 (range 1-4) aphereses per donor were run. The most frequent side effect was bone pain. In no case did the medium term follow-up reveal subjective complaints or laboratory modifications. After G-CSF mobilization, WBC and lymphocytes counts increased to a maximum of (mean +/- SD) 48.1 +/- 15.6 x 10(9)/L and 4.2 +/- 1.5 x 10(9)/L, respectively. The peak was reached on day 5 in both cases. Platelets decreased after the apheretic procedures, reaching a minimum of (mean +/- SD) 77 +/- 26 x 10(9)/L on day 8 and returning to normal values on day 11. Overall, the apheretic collection yielded (mean +/- SD) 18.6 +/- 19.2 x 10(8)/kg donor body weight MNC; 10.4 +/- 5.7 x 10(6)/kg CD34+ cells; 90.6 +/- 75.9 x 10(4)/kg CFU-GM and 4.3 +/- 1.8 x 10(8)/kg CD3+ cells. The target dose of 4 x 10(6)/kg CD34+ cells was harvested in 51.3% donors after a single apheresis, in 85.5% after the second, and in nearly 100% after a maximum of 3 aphereses. INTERPRETATION AND CONCLUSIONS: These data demonstrate that collection of adequate numbers of circulating progenitors is feasible and well tolerated in healthy donors. However, only careful monitoring of donors and international cooperation will help to definitively assess the long-term safety of G-CSF for mobilization of PBSC.