Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update.

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

[Temporary hearing threshold shift in policemen after firearm training]. / Spostamento temporaneo di soglia uditiva in agenti di polizia dopo esercitazioni in poligono di tiro.

BACKGROUND: The paper involves exposure to noise of the State Police officers connected with the use of firearms. The noise generated by these weapons is of short duration and high intensity. METHODS: The research was carried out during the sessions of firearm training of State Police officers to assess exposure to noise. RESULTS: The values of the various investigations, both audiometric and phonometric, carried out made it possible to demonstrate a significant exposure and a temporary increase in the threshold, above the frequency of 6000 Hz. CONCLUSION: Even taking account of the abatement from use of headphones, an exposure was demonstrated that was above the statutory limits, as was confirmed by the temporary hearing threshold shift.

[Exposure to air pollutants in the city of Bari]. / Esposizione ad inquinanti atmosferici nella città di Bari.

BACKGROUND: Air pollution leads to increased levels of morbidity and mortality for cardiovascular and respiratory diseases in populations living in urban environments. OBJECTIVES: Our study tested the possibility of using sampling techniques that are typical of industrial hygiene to measure exposure to atmospheric pollutants and using personal samplers for concentrations of certain pollutants to which an ordinary resident of Bari is exposed on a daily basis. METHODS: We monitored dusts (PM10, PM2.5), CO, CO2, humidity, ventilation and noise, by dynamical sampling along a route on foot, bicycle, motorbike and automobile and then compared the results with data provided by fixed stations distributed in the municipality of Bari. RESULTS: By comparing our data with those values provided for by the law, we found out that the concentrations of all pollutants resulted to be higher than 50 microg/m3, with the exception of the measurements carried out along the route by car. The measurements of PM2.5 were, on average, similar to the values of PM10 for the route on foot, but they were totally different for the measurements made along the route by car, bicycle and motorbike. Moreover, comparing our data with those obtained from the municipal network of fixed stations, we found that results provided by our measurements were higher for PM10. CONCLUSIONS: Considering that compliance with the limits set by law refers to average values over 24 hours, we can conclude that those hours in which pollutant concentration reaches a risk level shall be considered especially regarding groups of people with respiratory disorders.

[Music through earphones: an underestimated risk]. / Musica da auricolari: rischio sottostimato.

BACKGROUND: The authors studied exposure to the noise generated by digital music listening devices (MP3) as used by young people. OBJECTIVES: to study the level of sound emission of some of these devices at 100%, 75% and 50% volume. METHODS: Using a mannequin, the LeqA, LmaxA, LeqC and the peak in C of nine of the most commonly used devices was measured at levels of sound emission of 100%, 75% and 50%. RESULTS: It was found that all the devices exceeded 100 dBA of Leq at 100% of the listening volume. We therefore estimated the Lex8, as recommended in Italian Law 195/06, to which these young people are exposed using the devices for 15, 30, and 60 minutes/day. CONCLUSIONS: Young people undergoing daily exposures for only 15 minutes at maximal listening volume exceed the limit value of daily occupational exposure for workers, which Law 195/06 fixes at 87 dBA.

No-occupational exposure to noise.

The aim of the research was to evaluate the risk for the health of the disco-goers related to no-professional exposition to noise produced by speakers of discos. The noise has been measured in the middle of a disco using a class 1 phonometer. The exposition level was calculated using the formula quoted in the D.Lgs 277/91 (Italian legislative decree) and the possible damage was calculated using the Casini's formula. The calculated daily exposition level was 99,1 dBA and the weekly exposition was 92.1 dBA. The results indicate that the hypacusia damage due to these expositions can be considered almost sure.

[Occupational exposure to inhalation anesthetics: 10 years of measurements at hospitals in Puglia]. / Esposizione professionale ad anestetici inalatori: 10 anni di misure in ospedali pugliesi.

The Authors provide the data gathered from measurements of nitrous oxide in the operating room of Puglia during the period between 1993 and 2003. They prove significant reductions of pollution according with time and they verify lower pollution levels in the operating rooms of private hospitals with respect to public facilities. The importance of the maintenance of gas distribution and evacuation systems is shown and a method of environmental and biological monitoring is provided. Finally, the Authors prove the utility of the graphic representation of the measurements, conduced utilising dedicated instrumentation.

[Non-occupational exposure to noise]. / Esposizione extraprofessionale a rumore.

The authors report the data related to the measures effected in some environments where leisure time activities are developed. In the light of the elevated values, the authors have effected the calculation of the Lep,d as laid down by D.Lgs 277/91 to verify the existence of conditions of risk that result verified.

Increment of sister chromatid exchange frequencies (SCE) due to epichlorohydrin (ECH) in vitro treatment in human lymphocytes.

Although several studies have examined the effects on health of exposure to epichlorohydrin (ECH) through normal industrial operations and production, there is still considerable interest in its potential harmful effects on humans. The aim of the present study was to evaluate ECH effects in vitro through controlled investigations by using sister chromatid exchange (SCE), micronucleus (MN), and chromosome aberrations (CA) as the test battery. Cultures for cytogenetic tests were set up from blood samples of four healthy non-smoking and three smoking males. The experiments were performed using four different concentrations: 10(-10) M, 10(-8) M, 10(-6) M, and 10(-4) M, of ECH in DMSO. Analysis of variance showed that concentrations of ECH had significant effects on SCE/cell frequencies in the lymphocyte cultures of all donors (F=100.25, P<0.001). We were unable to find any evidence of significant increases in CA and MN frequencies in ECH-treated lymphocyte cultures with respect to the controls.

Malignancy: X-Linked Cytochrome B Positive Chronic Granulomatous Disease treated by Bone Marrow Transplantation.

Chronic granulomatous disease is caused by a genetic defect in the oxidase of phagocytic cells which results in increased susceptibility to recurrent infections. Conventional treatment includes the use of antimicrobials and interpheron-gamma. This study was performed to assess the clinical efficacy of allogeneic bone marrow transplantation in definitively correcting the functional underlying defect of chronic granulomatous disease. An 8-year-old boy with a rare type X-linked cytochrome b positive chronic granulomatous disease underwent allogeneic bone marrow transplantation after conditioning with busulfan and cyclophosphamide. The patient's HLA identical sister was marrow donor. The post-transplant outcome was uneventful. During the 9 year follow-up period the patient has been constantly free of infections, maintained an excellent clinical performance with full correction of the granulocyte functional defect. This case confirms that allogeneic bone marrow transplantation is the only treatment capable to cure chronic granulomatous disease to those patients who cannot be optimally treated with conventional therapy.

Sister chromatid exchange (SCE) and micronucleus (MN) frequencies in lymphocytes of gasoline station attendants.

Peripheral blood lymphocytes from 22 men with low average exposure (229 micrograms/m3 = 0.72 ppm) to benzene and 19 control men were investigated for Sister Chromatid Exchange (SCE) frequency. The majority of the men (21 exposed, 19 controls) were also investigated using the micronucleus assay (MN). The exposed subjects were employed at 10 different gas stations in or near the city (Bari/South Italy). SCE frequencies were significantly related with age and smoking habits, on the contrary no relation was observed between SCE and length of employment (SCE = 7.41 + 0.03.age (*) + 0.0001.length of employment (n.s.) + 0.03.cigarette consumption (*); F = 4.87; p < 0.01; (*) significant; (n.s.) non-significant). MN frequencies were significantly increased in relation with length of employment; but no relation was observed when age and smoking habits were taken into consideration (regression model: MN = 18.03 + 0.006.age (n.s.) + 0.32.length of employment (*) - 0.1.cigarette consumption (n.s.); F = 4.138; p < 0.05).

[Benzene pollution in the city of Bari]. / Inquinamento da benzene nella città di Bari.

The Authors reported data of benzene concentrations obtained in Bari during period of time between 1990 and 1995; the measured levels of benzene concentrations are not in accord with referent values prescribed by the law, mostly always they are exceeded. Present study also discuss problems related to gasoline consumption and the number of cars in circulation.

Growth after recombinant human growth hormone (rhGH) treatment in transplanted thalassemic patients.

The aim of this study was to evaluate the treatment effects with recombinant human growth hormone (rhGH) in a group of patients after bone marrow transplantation for thalassemia major. At the end of treatment we divided the subjects into two groups according to the outcome of the therapy: responder and nonresponder. Responder group: after 24 months of rhGH administration, growth rate was still significantly higher in respect to start of treatment (P < 0.0001). Plasma levels of IGF-I rose significantly (P < 0.003). The serum levels of serum asparate aminotransferase (SGOT) and alanine aminotransferase (SGPT) were higher compared to normal values but improved in non-responder patients. There was no difference in the mean concentration of these parameters before and after treatment (P = NS). Non-responder group: these patients had a worsening of the growth rate during rhGH administration. There was no increase of the IGF-I levels. Single values of transaminase and ferritin levels were higher than in responder patients before and after treatment. There was a significant correlation between IGF-I, SGOT, SGPT and ferritin in all patients before and after therapy. It appears from these data that rhGH administration is worth serious consideration in patients after BMT for thalassemia major presenting impaired growth hormone secretion. This treatment can offer good results only in cases where the normal hepatic synthesis of IGF-I is conserved and where liver damage has not reached irreversible conditions, as we have seen in the responder group.

[Efficacy of estrogen-progestin replacement therapy after bone marrow transplantation]. / Efficacia del trattamento sostitutivo con estro-progestinici in pazienti sottoposte a trapianto di midollo osseo.

Ovarian failure is a common consequence of chemotherapy and radiotherapy in women undergoing bone marrow transplantation. The longer survival in these women has raised, during the past years, the need for a better quality of life. The objective of the present study has been to evaluate perspectively the potential benefit of hormonal replacement therapy in 24 women who underwent bone marrow transplantation. The data obtained indicated that hormonal replacement therapy results effective in preventing and/or relieving the multiple manifestations of gonadal failure, including amenorrhea, hot flashes, atrophy of genital apparatus, osteoporosis and cardiovascular disease.

Growth and endocrine function following bone marrow transplantation for thalassemia.

Twenty two patients with thalassemia major who received successful bone marrow transplantation (BMT) were followed to verify the impact of the transplant procedure on subsequent growth and development. The transplant preparative regimen consisted of busulphan and cyclophosphamide. Growth and endocrinological function were assessed during the first 4 years following BMT. At the time of transplant most patients showed growth retardation. The median difference between chronological age and bone age was -9.5 months for the boys and -8.5 months for the girls. Patients > 7 years old at the time of BMT showed a significant worsening of their growth delay at 48 months following BMT compared with 12 months before transplantation. Patients < 7 years at the time of BMT had their growth retardation constant over time span after transplantation. Moreover six of 11 younger patients showed an improvement of their growth delay compared with one of 11 older patients. The outcome of height standard deviation score at 24 and 48 months following BMT was strictly correlated with the level of serum transaminases and ferritin. Sixteen patients had impaired growth hormone secretion after a provocative test evaluated at 24 months after transplant. At 48 months there was no significant increase in the mean peak GH levels. This study confirms that the growth retardation of patients with thalassemia major is multifactorial.

CD8 serum levels in acute graft-versus-host disease diagnosis.

Attempts to identify an early and discriminating marker of acute graft-versus-host disease (aGvHD) have been unsuccessful. The levels of soluble CD4 and soluble CD8 in serum correlate with T cell subset activation and may be important in monitoring and characterizing immunological processes. We determined serum soluble CD4 (sCD4) and sCD8 levels with a two-site sandwich enzyme immunoassay on patients' serum samples collected prior to bone marrow transplantation and weekly after transplantation until day +28. No significant increment of sCD4 was documented in each determination. sCD8 rose significantly before diagnosis or development of maximal clinical symptoms in patients with grade II-III aGvHD than grade 0-I aGvHD [at day +21--median value 447 IU/ml; range 94-713; versus 1136 IU/ml, range 790-1416 (P = 0.002); at day +28--median value 443 IU/ml, range 73-992, versus 1164 IU/ml, range 625-1960 (P = 0.005)]. On the day of marrow infusion the sCD8 levels were significantly higher in patients who subsequently developed grade II-III than in patients with grade 0-I aGvHD (median value 155 IU/ml, range 10-332, versus 350 IU/ml, range 283-830; P = 0.003). Careful monitoring of sCD8 is a useful tool for a prompt aGvHD diagnosis and may be used in a clinical bone marrow transplantation setting.

Amebiasis after bone marrow transplantation.

A patient undergoing BMT for acute non-lymphocytic leukemia (ANLL) developed bloody diarrhea due to amebiasis. The infection was successfully treated with intensive and prolonged antiparasitic therapy.

The role of hemapheresis technology in allogeneic bone marrow transplantation.

In this paper the impact of hemapheresis technology on 238 allogeneic bone marrow transplants performed in Pescara from 1982 through 1993 is described. Granulocyte transfusions were limited to patients with neutrophil level < 0.2 x 10(9)/L. An average of 4 units of packed red blood cells were required to maintain adequate hemoglobin levels. Patients with major ABO incompatibility showed an increased requirement of red blood cell support as compared to patients ABO-matched and ABO minor mismatched. For platelet support single-donor platelets collected on a blood-cell separator were given. A total of 1548 platelet transfusions were examined. The median number of platelet transfusions for each patient was 5. Platelet refractoriness occurred in 44% of patients. The hemorrhage related mortality was 0.9%. The advancement made in the field of hemapheresis technology, as well as the improved transplant technique, have contributed to increase the post-transplant survival from 17% in the early experience (1976-1982) to 88% in the recent years (1992-1993).