Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

509 records · Page 29Linked to original sources

PubMedDate not supplied

Late effects in children after bone marrow transplantation: a review.

Since the number of children receiving a bone marrow transplantation (BMT) and becoming long-term survivors continues to increase, more attention has to be paid to detect long-term side effects in these unique patients. Follow-up studies to timely identify these untoward sequelae are a matter of particular concern for pediatricians due to the longer life expectancy of children cured by BMT. The more frequently recognized sequelae affecting lung, eyes, brain and the endocrine system have been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare children before marrow transplantation and radiotherapy has been indicated as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this growth impairment is especially observed in patients receiving total body irradiation (TBI) and prophylactic cranial irradiation prior to marrow transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impairment of liver somatomedin production or a direct radiation-induced skeletal dysplasia could not be excluded. Overt and compensated hypothyroidism have been reported after TBI and patients given single dose radiotherapy are at greater risk with an overall incidence of thyroid function abnormalities approaching 30-40%. Delayed puberty development was reported in boys and girls after a TBI-containing conditioning regimen, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to the growth impairment of prepubertal children. In post-pubertal patients amenorrhea, azoospermia and gonadal failure can be observed after radiotherapy and several patients can require hormonal substitutive therapy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abnormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recognized complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more frequently in patients given TB1 as single exposure. Decreased lacrimal gland function, with impairment of tear production is another late effect of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow Transplantation↗

PubMedDate not supplied

Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo).

Busulfan (BU) is an alkylating drug frequently used to prepare patients for bone marrow transplantation (BMT). Several studies have documented that there is important interpatient variability in BU disposition and systemic exposure, and that other drugs with a common metabolic pathway are capable of influencing BU clearance. We compared the BU pharmacokinetics and pharmacodynamics of 13 patients given BMT and receiving BU and itraconazole, with those of 26 matched controls who did not receive any anti-fungal agent, and with those of 13 matched patients treated with fluconazole as prophylaxis against fungal infections. The effect of itraconazole was best reflected in BU clearance since the BU dose was modified in some patients. BU clearance was decreased by an average of 20% in patients receiving itraconazole as compared to control patients and patients receiving fluconazole (p < 0.01). Mean BU clearance was 7.653 +/- 1.871 l/hr.m2 in the itraconazole patients, 10.103 +/- 2.007 l/hr.m2 in the fluconazole group and 9.373 +/- 1.702 l/hr.m2 in the control group. In this study itraconazole, but not fluconazole, markedly affected the pharmacokinetics of BU as an increase of BU plasma concentrations was observed. The nature of this interaction has not yet been fully characterized. Itraconazole and its analogues are inhibitors of both cytochrome P450 and lipoxygenase and since itraconazole can modulate BU pharmacokinetics, oxidative catabolism is probably a determinant of BU metabolism. This hypothesis should be tested in human metabolic studies.

Adolescent↗

PubMedDate not supplied

Circulating progenitor cell collection: experience from 275 leukaphereses in various malignancies and in healthy donors.

BACKGROUND: Blood cell transplantation has become a new type of support in high-dose chemotherapy (HDC) for several oncologic and hematologic diseases. Over the last few years the demand for circulating progenitor cell (CPC) collection by blood cell separators has grown dramatically, and transfusion services must manage new CPC programs. MATERIALS AND METHODS: A protocol for optimizing the collection and clinical use of CPC is described. The results of 275 harvestings were studied: 128 patients were divided into 5 groups according to tumor type (A: breast cancer; B: Hodgkin's disease; C: non-Hodgkin lymphoma; D: multiple myeloma; E: various solid tumors). An additional group (F) consisted of 11 healthy donors. Factors affecting collection (mobilizing regimen or previous radiation therapy) and side effects were investigated. RESULTS: The mean values of mononuclear cells (MNC x 10(7)/kg) and CD34+ cells (x 10(6)/kg) collected per leukapheresis in the 6 respective groups were: 31.4 and 4.6 in group A; 26.4 and 3.4 in group B; 21.8 and 5.8 in group C; 24.6 and 2.4 in group D; 26.8 and 2.9 in group E; 60 and 6 in group F. Previous chemotherapy and/or radiation therapy were the main factors influencing CPC harvesting. The different chemotherapy regimens employed demonstrated no significant differences in their mobilizing efficacy. Side effects related to leukapheresis were few (2.3% of the procedures) and manageable. CONCLUSIONS: CPC collection is feasible in a wide range of clinical situations. Careful clinical evaluation of patients, accurate monitoring of progenitor cell release and collection timing are important for obtaining a sufficient number of CPC for hemopoietic recovery. Previous chemotherapy and radiotherapy are the main factors influencing CPC harvests. The mobilizing regimens employed showed no substantial differences in their efficacy.

Adult↗

PubMedDate not supplied

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.

Adolescent↗

PubMedDate not supplied

Treatment of hypertension in chronic renal insufficiency.

Several trials clearly demonstrate the importance of correcting hypertension and proteinuria in slowing chronic renal insufficiency (CRI) progression. The relationship between hypertension and CRI is at least partly the consequence of impaired renal hemodynamics, mainly mediated by the renin-angiotensin system. Two classes of drugs have so far been shown to have an antiproteinuric and renoprotective effect, in addition to their antihypertensive action: ACE inhibitors and calcium-channel blockers (at least the non-dihydropyridines) which also interfere with the actions of angiotensin II. The same should be true for the newest angiotensin II receptor antagonists. To find conclusive evidence about the superior renoprotective effect of ACE inhibitors (or angiotensin II receptor antagonists) or calcium-channel blockers, we need well-designed, prospective, controlled and randomized long-term trials; the pharmacological rationale for combining the two classes of antihypertensive drugs is supported by the clinical need to reach a target blood pressure (120/80 mmHg) in CRI patients with proteinuria.

Age Factors↗