Pulmonary infections often complicate hematopoietic stem cell transplantation (HSCT) outcome. Unc... more Pulmonary infections often complicate hematopoietic stem cell transplantation (HSCT) outcome. Uncommon aetiologies, like Mycobacterium tuberculosis, should be considered when the clinical conditions do not fully improve with standard antimicrobial therapy and microbiological evaluations are repeatedly negative for bacteria and fungi. We describe an interesting pediatric case of miliary lung tuberculosis after HSCT, which was successfully treated after administering the appropriate therapy.
We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic ... more We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II-IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%).
Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication afte... more Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past. Patients and Methods The current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher’s exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome. Results Sixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD &amp;amp;amp;amp;amp;gt;II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts. Conclusions The study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.
The Role of Pharmacology in Pediatric Oncology, 1987
Cis-diamino-dichloroplatinum (CDDP) has been shown to be an effective agent in the treatment of p... more Cis-diamino-dichloroplatinum (CDDP) has been shown to be an effective agent in the treatment of pediatric solid tumors. The drug has usually been administered at a maximum dose of 100 mg/sq m either as a single dose or fractionated over 5 days [1–3]. In these schedules the toxicity of CDDP consists of nausea and vomiting, moderate myelosuppression, and cumulative nephrotoxicity and ototoxicity [4, 5]. These toxicities have usually been considered to be dose-limiting. However in a recent report Ozols et al [6] described good tumor responses to a combination of drugs which included ‘high dose CDDP’, administered in hypertonic saline to reduce nephrotoxicity [7], in adults with poor prognosis non-seminomatous testicular tumours who had failed to respond to CDDP in conventional doses.
Background &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Background &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Aims: The mechanical origins of the obstruction in sinusoidal obstruction syndrome are initiated by dehiscence of sinusoidal endothelial cells from the space of Disse. The biochemical changes that permit the dehiscence of the sinusoidal endothelial cells were investigated. Methods: In vitro and in vivo studies examined changes induced by monocrotaline, a pyrrolizidine alkaloid that induces sinusoidal obstruction syndrome
Introduction. Severe acute graft-versus-host disease (GVHD) remains the most relevant complicatio... more Introduction. Severe acute graft-versus-host disease (GVHD) remains the most relevant complication after allogeneic HSCT. Although its incidence in the pediatric population is lower than in adults, children with severe acute GVHD and who do not respond to first-line treatment with systemic steroids still have a poor prognosis. The exact incidence of steroid-refractory acute GVHD in children is still not precisely defined, as well as the risk of non-relapse mortality (NRM) due to steroid-refractory acute GVHD. Aim of our study was to analyze the frequency of acute GVHD unresponsive to first-line steroid treatment in children and adolescents given allogenic HSCT, to describe the second line treatment employed, and the outcome of patient with this complication. Patients and methods. This retrospective study included patients younger than 18 years at the time of transplantation and given a first allogeneic HSCT between 2010 and 2015 in one of the HSCT Centers of the Italian Association ...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, Jan 30, 2017
Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dys... more Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dystrophy, oral leukoplakia, and bone marrow failure. Pulmonary fibrosis and cancers are late manifestations. Allogeneic hematopoietic stem cell transplant represents the only cure for those with bone marrow failure with this disease, but outcomes reported are overall poor, with organ toxicities, graft failure, and graft-versus-host disease as main issues. Although reduced intensity conditioning regimens seem to be related to better outcomes, a standard regimen for dyskeratosis congenita has never been defined. Here, we report a successful long-term outcome of an 8-year-old girl with dyskeratosis congenita who received 2 consecutive allogeneic hematopoietic stem cell transplants from different unrelated donors, because of rejection after the first one, both conditioned with fludarabine-based reduced intensity conditioning regimen. The second transplant was complicated by severe hemorrhagic ...
La Pediatria medica e chirurgica : Medical and surgical pediatrics
Indwelling central venous catheter-related bacteremias are an important complication in patients ... more Indwelling central venous catheter-related bacteremias are an important complication in patients with cancer. In general they are due to Staphylococcus aureus and Candida, while bacteremias caused by Gram-negatives are less common and often related to infusate contaminans. We describe a survey of etiological surveillance of Broviac catheter-related infections at G. Gaslini Children's Hospital of Genoa, Italy. In the period 1989-1992 an increase of Broviac catheter-related bacteremias due to Gram-negatives was demonstrated as compared with previous years (1985-1988). At home parental management was suspected as an important risk factor, since this complication was frequently due to infusate contaminants and no epidemic cluster or positive surveillance culture was observed in the Hospital. Therefore at home management was changed, especially regarding heparin storage. The subsequent, prospective follow-up from July 1993 to December 1995 showed a significant decrease in catheter-re...
Pulmonary infections often complicate hematopoietic stem cell transplantation (HSCT) outcome. Unc... more Pulmonary infections often complicate hematopoietic stem cell transplantation (HSCT) outcome. Uncommon aetiologies, like Mycobacterium tuberculosis, should be considered when the clinical conditions do not fully improve with standard antimicrobial therapy and microbiological evaluations are repeatedly negative for bacteria and fungi. We describe an interesting pediatric case of miliary lung tuberculosis after HSCT, which was successfully treated after administering the appropriate therapy.
We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic ... more We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II-IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%).
Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication afte... more Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past. Patients and Methods The current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher’s exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome. Results Sixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD &amp;amp;amp;amp;amp;gt;II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts. Conclusions The study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.
The Role of Pharmacology in Pediatric Oncology, 1987
Cis-diamino-dichloroplatinum (CDDP) has been shown to be an effective agent in the treatment of p... more Cis-diamino-dichloroplatinum (CDDP) has been shown to be an effective agent in the treatment of pediatric solid tumors. The drug has usually been administered at a maximum dose of 100 mg/sq m either as a single dose or fractionated over 5 days [1–3]. In these schedules the toxicity of CDDP consists of nausea and vomiting, moderate myelosuppression, and cumulative nephrotoxicity and ototoxicity [4, 5]. These toxicities have usually been considered to be dose-limiting. However in a recent report Ozols et al [6] described good tumor responses to a combination of drugs which included ‘high dose CDDP’, administered in hypertonic saline to reduce nephrotoxicity [7], in adults with poor prognosis non-seminomatous testicular tumours who had failed to respond to CDDP in conventional doses.
Background &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Background &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Aims: The mechanical origins of the obstruction in sinusoidal obstruction syndrome are initiated by dehiscence of sinusoidal endothelial cells from the space of Disse. The biochemical changes that permit the dehiscence of the sinusoidal endothelial cells were investigated. Methods: In vitro and in vivo studies examined changes induced by monocrotaline, a pyrrolizidine alkaloid that induces sinusoidal obstruction syndrome
Introduction. Severe acute graft-versus-host disease (GVHD) remains the most relevant complicatio... more Introduction. Severe acute graft-versus-host disease (GVHD) remains the most relevant complication after allogeneic HSCT. Although its incidence in the pediatric population is lower than in adults, children with severe acute GVHD and who do not respond to first-line treatment with systemic steroids still have a poor prognosis. The exact incidence of steroid-refractory acute GVHD in children is still not precisely defined, as well as the risk of non-relapse mortality (NRM) due to steroid-refractory acute GVHD. Aim of our study was to analyze the frequency of acute GVHD unresponsive to first-line steroid treatment in children and adolescents given allogenic HSCT, to describe the second line treatment employed, and the outcome of patient with this complication. Patients and methods. This retrospective study included patients younger than 18 years at the time of transplantation and given a first allogeneic HSCT between 2010 and 2015 in one of the HSCT Centers of the Italian Association ...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, Jan 30, 2017
Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dys... more Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dystrophy, oral leukoplakia, and bone marrow failure. Pulmonary fibrosis and cancers are late manifestations. Allogeneic hematopoietic stem cell transplant represents the only cure for those with bone marrow failure with this disease, but outcomes reported are overall poor, with organ toxicities, graft failure, and graft-versus-host disease as main issues. Although reduced intensity conditioning regimens seem to be related to better outcomes, a standard regimen for dyskeratosis congenita has never been defined. Here, we report a successful long-term outcome of an 8-year-old girl with dyskeratosis congenita who received 2 consecutive allogeneic hematopoietic stem cell transplants from different unrelated donors, because of rejection after the first one, both conditioned with fludarabine-based reduced intensity conditioning regimen. The second transplant was complicated by severe hemorrhagic ...
La Pediatria medica e chirurgica : Medical and surgical pediatrics
Indwelling central venous catheter-related bacteremias are an important complication in patients ... more Indwelling central venous catheter-related bacteremias are an important complication in patients with cancer. In general they are due to Staphylococcus aureus and Candida, while bacteremias caused by Gram-negatives are less common and often related to infusate contaminans. We describe a survey of etiological surveillance of Broviac catheter-related infections at G. Gaslini Children's Hospital of Genoa, Italy. In the period 1989-1992 an increase of Broviac catheter-related bacteremias due to Gram-negatives was demonstrated as compared with previous years (1985-1988). At home parental management was suspected as an important risk factor, since this complication was frequently due to infusate contaminants and no epidemic cluster or positive surveillance culture was observed in the Hospital. Therefore at home management was changed, especially regarding heparin storage. The subsequent, prospective follow-up from July 1993 to December 1995 showed a significant decrease in catheter-re...
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