PubMed Health⌕ Search

Biomedical subjects

F Aversa

Publications and source records attributed to F Aversa.

At least 55 records · Page 3Linked to original sources
PubMed1993

Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs.

Rejection of T-depleted BMTs is predominantly mediated by alloreactive host T cells. A low but significant number of radiochemoresistant clonable T cells can be detected following a conventional cytoreductive protocol given prior to T-depleted BMT. Elimination of these cells increases the engraftment rate. We found no clonable T cells at the end of the conditioning regimen in 100 ml of peripheral blood from 47 patients who received an HLA-identical T-depleted BMT. None rejected the graft and none displayed mixed chimerism. In addition, although no clonable T cells were detected in nine patients who received a mismatched BMT, two rejected their graft. However, in three mismatched patients, who for clinical reasons received a modified pre-BMT schedule, the presence of host clonable T cells was associated with immunological rejection. These findings suggest that the detection of clonable T cells should prove a valuable indicator for optimising immunosuppression prior to T-depleted BMT.

Adolescent↗
PubMed1992

Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin.

In Hodgkin's disease, Hodgkin and Reed-Sternberg cells consistently express the antigen CD30. We investigated the possible therapeutic role of an immunotoxin prepared by covalent linking of an anti-CD30 monoclonal antibody (Ber-H2) to saporin (SO6), a type-1 ribosome-inactivating protein. The immunotoxin (0.8 mg/kg in one or two doses) was given to four patients with advanced refractory Hodgkin's disease. In three, there was rapid and substantial reduction in tumour mass (50% to greater than 75%). Clinical responses were transient (6-10 weeks). In-vivo binding of the immunotoxin to tumour cells was shown by immunohistology in two patients. Antibodies to both parts of the immunotoxin developed in all patients.

Antibodies, Monoclonal↗
PubMed1992

Interstitial pneumonitis after hyperfractionated total body irradiation in HLA-matched T-depleted bone marrow transplantation.

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

Adolescent↗
PubMed1991

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation.

From July 1985 to December 1989, 72 evaluable patients aged between 6 and 51 (median age 27 years) suffering from haematological malignancies received an allogeneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce the risk of graft-versus-host-disease (GvHD); 57 were matched and 15 mismatched. Three different conditioning regimens were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mismatched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in three doses per day, 5 h apart, over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of interstitial pneumonia (IP) was 12.3% in matched and 46.7% in mismatched patients. Our results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in our matched patients.

Adolescent↗
PubMed1990

Using teicoplanin for empiric therapy of febrile neutropenic patients with haematological malignancies.

The cumulative experience with teicoplanin in treating febrile neutropenic patients included in three different comparative clinical trials conducted at a single institution during a 3-year period, is presented. 152 febrile episodes in 129 neutropenic patients were treated with i.v. teicoplanin (6 mg/kg/d) combined with amikacin (15 mg/kg/d) plus ceftazidime (90 mg/kg/d). The study population comprised 75 patients with acute leukaemia and 77 marrow recipients: 53% (81/152) had a central venous catheter in place and 68% (103/152) had severe neutropenia (less than 100/mm3) at the beginning of the febrile episode. The overall response rate of the evaluable febrile episodes was excellent: 88% (107/122) improved. Bacteraemias due to Gram-positive cocci accounted for 75% of the total (42/56) and pathogens in the blood isolates were mostly staphylococci (coagulase-negative 14, coagulase-positive 13) and streptococci (13). The response rate of Gram-positive bacteraemias was good: 88% (37/42) improved and 75% (9/12) of Gram-positive bacteraemias having teicoplanin as the only antibiotic with in vitro activity against the infective strains were cured. Death due to infection accounted for 7% of total febrile episodes (11/152). Side effects were documented in 14% of the episodes. In a setting of high prevalence of Gram-positive infections caused by strains with a high rate of resistance to aminoglycoside and beta-lactam antibiotics, there may be an advantage in including teicoplanin in the initial empiric antibiotic regimen for febrile neutropenic cancer patients.

Acute Disease↗
PubMed1989

Norfloxacin prophylaxis for neutropenic patients undergoing bone marrow transplantation.

To prevent bacterial infections in the neutropenic post-transplant period, norfloxacin 400mg twice daily was administered as oral prophylaxis to 44 marrow recipients isolated in laminar airflow rooms (LAFRs). Patients had a mean age of 30 years (8-50) and a male/female ratio of 29/15. The mean duration of prophylaxis was of 41 days (20-80), that of neutropenia (PMN less than 1000 x 10(6)/l) of 31 days (6-76) and that of severe neutropenia (PMN less than 100 x 10(6)/l) of 19 days (10-55). All but two patients developed one or more febrile episodes (total episodes: 71), 33 of which were documented infections. Eighteen bacteraemias occurred and all were caused by Gram-positive cocci: five by coagulase-negative staphylococci (three methicillin resistant), four by coagulase-positive (one methicillin resistant), seven by streptococci (four S. sanguis, one S. milleri, one group B, one group C), and two by enterococci. All streptococcal and enterococcal strains, but only one MR coagulase-positive staphylococcus, proved to be resistant to norfloxacin. Norfloxacin was well tolerated and no prophylactic course had to be interrupted because of side effects. In conclusion, norfloxacin adequately prevents infections caused by Gram-negative bacilli in bone marrow recipients isolated in LAFRs, but Gram-positive infections still remain a problem in these patients indicating the need for improving this prophylactic regimen.

Adolescent↗
PubMed1988

Acquisition of Ig isotype diversity after bone marrow transplantation in adults. A recapitulation of normal B cell ontogeny.

To gain insight into the prolonged susceptibility to infections noted after allogeneic bone marrow transplantation (BMT), multiple parameters of the humoral immune system were serially monitored in ten bone marrow recipients. IgM B cells appeared in the circulation 2 to 4 mo after engraftment. During the first 6 mo, the IgM B cells expressed low levels of CD21 (C3d/EBV receptors) and were largely CD38+. IgG and IgA B cells were also found to coexpress surface IgM and IgD, indicating that they may be involved in a process of isotype switch. These features are characteristic of neonatal B cells. To explore the pattern of Ig isotype switch, the emergence of plasma cell precursors for each of the four IgG subclasses was examined by culturing blood lymphocytes with PWM or LPS and enumerating bone marrow plasma cells. A marked IgG2 and IgG4 plasma cell deficiency and a relative increase in IgG1 and IgG3 plasma cells were detected both in vitro and in vivo. Serum IgG2 and IgG4 levels were deficient for more than 18 mo after BMT, elevated IgG1 levels accounting for the normal or increased levels of total IgG. The data suggest that a selective unresponsiveness to polysaccharide Ag and IgG2 subclass deficiency may contribute to the late bacterial infections in BMT recipients. These features of gradual development of the humoral immune system in adults undergoing successful marrow engraftment reproduce some of the maturational steps that occur during normal B cell ontogeny over the first 1 to 2 yr of life.

Adolescent↗
PubMed1988

Hyperfractionated total body irradiation for T-depleted HLA identical bone marrow transplants.

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) (120 cGy/3 fractions per day: total dose = 1440 cGy/4 days) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease (GVHD) nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached.

Adult↗
PubMed1988

Teicoplanin in empirical combined antibiotic therapy of bacteraemias in bone marrow transplant patients.

Teicoplanin in combination with amikacin and ceftazidime was used as empirical therapy in treating 46 febrile episodes in 34 consecutive patients undergoing allogenic bone marrow transplantation. All but four of these febrile episodes occurred in neutropenic patients and 50% of them proved to be bacteraemias (23/46). Cure was achieved in 90% of Gram-positive bacteraemias (18/20) and in six of them teicoplanin was the only antibiotic with activity in vitro against the infecting strain. All (3/3) Gram-negative bacteraemias were cured. Central venous catheter removal was required in five patients (three tunnel infections, one exit-site infection and one thrombophlebitis). Two failures occurred among Gram-positive bacteraemias and in one case the patient died of infection. Four instances of side effects were documented but only one was severe (hearing loss).

Adolescent↗
PubMed1987

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients.

The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate, in a prospective randomized trial, the role of teicoplanin, a new glycopeptide antibiotic, when it was added to amikacin plus ceftazidime, as an empiric therapy of fever in these patients. Of 47 evaluable episodes, 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime. The overall response to therapy of patients treated with teicoplanin was slightly better (82% improvement) than that obtained with amikacin plus ceftazidime (52%). The response rate of patients with gram-positive bacteremias was 80% (4 of 5) to the regimen that included teicoplanin; 25% (1 of 4) of the patients treated with amikacin plus ceftazidime responded to treatment; and for patients with gram-negative bacteremias, the response rates were, respectively, 100% (4 of 4) and 70% (7 of 10). The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound (less than 100/mm3) and persistent neutropenia (83 versus 30% improvement). Furthermore, a good response rate of patients with gram-positive bacteremias (seven of eight; 87% improvement) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin. No severe side effects were documented in any patient. Teicoplanin, as a drug administered as a single daily dose, seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients.

Acute Disease↗
PubMed1985

Anaemia and agranulocytosis associated with ticlopidine therapy.

Although ticlopidine has proven anti-aggregant properties, complications due to side-effects, particularly to the haemopoietic system, have been noted since it was recently launched on the market. We here report a case of bicytopenia (anaemia and granulocytopenia) associated with ticlopidine treatment.

Agranulocytosis↗