7 results on '"di Grazia, C."'
Search Results
2. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation.
- Author
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Larocca A, Piaggio G, Podestà M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, and Bacigalupo A
- Subjects
- Adolescent, Adult, Female, Graft vs Host Disease mortality, Humans, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation mortality, Transplantation, Homologous, Treatment Failure, Antigens, CD34, Graft Survival, Peripheral Blood Stem Cell Transplantation methods
- Abstract
Background and Objectives: A proportion of patients develop poor graft function (PGF) following an allogeneic hemopoietic stem cell transplant (HSCT). It is uncertain whether a boost of donor marrow or blood cells is beneficial in terms of trilineage recovery and non-relapse-related mortality (NRM)., Design and Methods: The aim of this study was to compare outcomes in patients with PGF and full donor chimerism following an allogeneic HSCT who did or did not receive a boost of donor stem cells. The study included patients with primary PGF--i.e. those failing to achieve sustained graft function- and secondary PGF--i.e. those developing PGF after complete hematologic recovery. We studied 54 patients with PGF: 20 patients received no further donor cell infusion (group A), 14 received a boost of unmanipulated marrow or blood cells from the original donor, without further conditioning (group B), and 20 received donor cells after CD34 selection without conditioning (group C). The three groups were comparable for disease phase, patients' age, donor type, primary or secondary PGF, full donor chimerism and duration of PGF., Results: Trilineage recovery was seen in 40%, 36% and 75% of the patients in, respectively, groups A, B and C (p=0.02). In multivariate Cox analysis trilineage recovery was more frequent in patients with secondary PGF (RR of complete recovery 2.82, p=0.01) and in patients receiving CD34+-selected cells (RR of complete recovery 3.0; p=0.007). There was no effect of donor type on hematologic recovery. The rate of NRM was 55%, 64%, 20% in groups A, B and C, respectively (p=0.06) and was highly correlated with trilineage recovery (RR 0.36, p<0.0001). PGF was the primary cause of death in 30%, 21% and 10% of the patients in the three groups, graft-versus-host disease (GVHD) in 5%, 36%, and 10%., Interpretations and Conclusions: In patients with poor graft function (a) a boost of CD34+-selected peripheral blood donor cells is associated with a high chance of trilineage recovery and a low risk of acute GVHD; (b) a boost of unmanipulated donor cells does not seem to offer a survival advantage over no infusion of cells; and (c) NRM is lower when using peripheral blood cells for the boost. These data may be useful when discussing second stem cell donations for patients with poor graft function.
- Published
- 2006
3. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation.
- Author
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Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S, Raiola AM, di Grazia C, Dominietto A, Tedone E, Piaggio G, Podesta M, Bruno B, Oneto R, Lombardi A, Frassoni F, Rolla D, Rollandi G, Viscoli C, Ferro C, Garbarino L, and Van Lint MT
- Subjects
- Actuarial Analysis, Adult, Anti-Infective Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation statistics & numerical data, Cause of Death, Combined Modality Therapy, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematologic Neoplasms drug therapy, Hematologic Neoplasms mortality, Hematopoietic Stem Cell Transplantation mortality, Hematopoietic Stem Cell Transplantation statistics & numerical data, Humans, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Infection Control, Infections etiology, Infections mortality, Leukemia drug therapy, Leukemia mortality, Leukemia surgery, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial mortality, Male, Middle Aged, Multiple Organ Failure, Neutropenia chemically induced, Neutropenia complications, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation methods, Peripheral Blood Stem Cell Transplantation mortality, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Premedication, Remission Induction, Retrospective Studies, Salvage Therapy, Survival Analysis, Transplantation Conditioning methods, Transplantation Conditioning mortality, Transplantation, Homologous methods, Transplantation, Homologous statistics & numerical data, Treatment Outcome, Bone Marrow Transplantation mortality, Hematologic Neoplasms surgery, Transplantation, Homologous mortality
- Abstract
Background and Objectives: Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of transplants done in the previous decade. The aims of this study were to determine whether these relationships still hold and whether the outcome of transplants is continuing to improve., Design and Methods: We analyzed 1180 consecutive patients with leukemia (n=979) or other hematologic malignancies (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and 2001-2002. Changes during these eras include increasing patient age, more unrelated transplants, more patients with advanced disease, different graft-versus-host disease (GvHD) prophylaxis, and different management of infections., Results: The actuarial 2-year transplant-related mortality (TRM) differed significantly between the transplant eras (p<0.001) with a significant interaction with disease phase (p=0.018). In patients in first remission (n=585) TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a consequence of reductions in GvHD, infections and multiorgan failure among patients in remission but not among those who relapse. The actuarial 2-year survival has improved significantly in patients in first remission (54%, 66%, 72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed patients (31%, 25%, 36%, 21%)., Interpretation and Conclusions: In conclusion, TRM has been significantly reduced in first remission patients, suggesting an allograft should be considered in this phase, when appropriate, without delay. There has been no improvement in survival for patients beyond first remission, due to persisting high risk of infections and organ toxicity, a possible consequence of prolonged pre-transplant chemotherapy and neutropenia.
- Published
- 2004
4. Treatment of acute graft versus host disease with low dose-alternate day anti-thymocyte globulin.
- Author
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Graziani F, Van Lint MT, Dominietto A, Raiola AM, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Fiorone M, Bruno B, and Bacigalupo A
- Subjects
- Adult, Bone Marrow Transplantation immunology, Bone Marrow Transplantation mortality, Graft vs Host Disease mortality, Humans, Infections, Middle Aged, Survival Rate, Time Factors, Antilymphocyte Serum administration & dosage, Antilymphocyte Serum therapeutic use, Graft vs Host Disease drug therapy
- Abstract
Background and Objectives: The efficacy of antithymocyte globulin (ATG) in the treatment of graft-versus-host disease (GvHD) is controversial. In the present study we report on the use of low dose ATG (thymoglobuline, Sangstat) and steroids in 28 patients with moderate to severe acute GvHD., Design and Methods: Fifteen patients received ATG as first-line treatment within 14 days of the diagnosis of GvHD (median 8 days, range 4-13). Twelve patients received ATG as second-line therapy, more than 14 days after diagnosis (median 32 days, range 14 to 98). The proportion of patients with severe (grade III-IV) GvHD at the time of ATG therapy was 4/15 in the former group and 7/13 in the latter (p=0.1)., Results: On day 30 after ATG the overall proportion of responders was 80% in the group administered ATG early and 38% in those given it later (p=0.03). The overall actuarial 3-year transplant-related mortality was 40% vs 74% for the early vs late ATG groups (p=0.03); the actuarial 3-year survival was, respectively, 49% vs 23% (p=0.04). For patients with GvHD grade III-IV the actuarial 1-year TRM was 47% for those given ATG early, 87% for the late ATG group and 82% for a concurrent control group of 26 patients not treated with ATG., Interpretation and Conclusions: In conclusion, ATG may be considered for early treatment of acute GvHD, within a few days from the onset of the disease. A prospective trial has been started to test whether, in this setting, low dose ATG with steroids is superior to steroids alone.
- Published
- 2002
5. High prevalence of hepatitis G virus infection in Hodgkin's disease and B-cell lymphoproliferative disorders: absence of correlation with hepatitis C virus infection.
- Author
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De Renzo A, Persico E, de Marino F, di Giacomo Russo G, Notaro R, di Grazia C, Picardi M, Santoro L, Torella R, Rotoli B, and Persico M
- Subjects
- Adolescent, Adult, Aged, B-Lymphocytes pathology, Comorbidity, Female, Flaviviridae Infections complications, Flaviviridae Infections epidemiology, Hepacivirus, Hepatitis C complications, Hepatitis C diagnosis, Hepatitis C epidemiology, Hepatitis, Viral, Human diagnosis, Hepatitis, Viral, Human epidemiology, Hodgkin Disease epidemiology, Hodgkin Disease etiology, Humans, Italy epidemiology, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders etiology, Male, Middle Aged, Prevalence, GB virus C, Hepatitis, Viral, Human complications, Hodgkin Disease virology, Lymphoproliferative Disorders virology
- Abstract
Background and Objectives: During the last decade an epidemiological association between hepatitis C virus (HCV) and B-cell lymphoproliferative disorders (B-LPD) has been reported; the same association has not been observed for Hodgkin's disease (HD). Hepatitis G virus (HGV) shares genetic and biological features with HCV, thus it might also be involved in lymphomagenesis., Design and Methods: The aim of this study was to compare the prevalence of HCV and HGV infection in patients at diagnosis of B-LPD or HD., Results: We tested 227 consecutive untransfused patients (127 with B-LPD and 100 with HD) and 110 healthy controls. The prevalence of HCV infection was significantly higher in B-LPD patients than in controls (17.3% vs. 1.8%, p<0.002 ), whereas it was the same in HD patients as in controls. In contrast, the prevalence of HGV was significantly higher in patients, both those with B-LPD (7.8% vs. 0.9%, p<0.03) and those with HD (13% vs. 0.9%, p<0.002), than in controls. Among the various B-LPD tested, HGV infection was more frequent in B-NHL (11.5%)., Interpretation and Conclusions: Our data support the hypothesis that HGV infection may play a role in lymphomagenesis and that this role is different and separate from that of HCV.
- Published
- 2002
6. Conventional hematopoietic stem cell transplants from identical or alternative donors are feasible in recipients relapsing after an autograft.
- Author
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di Grazia C, Raiola AM, Van Lint MT, Lamparelli T, Gualandi F, Berisso G, Bregante S, Dominietto A, Mordini N, Bruno B, Frassoni F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Blood Donors, Female, Hematologic Neoplasms therapy, Humans, Karnofsky Performance Status, Male, Middle Aged, Recurrence, Transplantation, Autologous, Transplantation, Homologous methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Transplantation, Homologous standards
- Abstract
Background and Objectives: The risk of relapse after autologous bone marrow transplantation (ASCT) is high and is related to the type of malignancy and phase of the disease. The outcome for the patient who relapses after an autologous transplant is poor. Some of these patients achieve a remission with conventional chemotherapy, but it is usually short-lasting. Most of them succumb to the original disease. One further therapeutic possibility is an allogeneic transplant which would confer the potential advantage of a graft-versus-leukemia effect in addition to the lack of tumor contamination of the graft and to a high-dose intensity conditioning regimen., Design and Methods: We have studied the outcome of 31 patients with hematologic malignancies who underwent an allogeneic hematopoietic stem cell transplant (HSCT) after failing an autologous transplant because of relapse (n=29) or persistent aplasia (n=2). The median age at allograft was 36 years (18-55) and the interval from autograft to allograft was 21 months (3-141). The source of stem-cells was unmanipulated bone marrow (n=26) or growth-factor-mobilized peripheral blood (n=5). The donor was an HLA-identical sibling (n=7), or an alternative donor (n=24) (family mismatched n=11, or matched unrelated n=13). The conditioning regimen was cyclophosphamide and thiotepa (n=22), or cyclophosphamide and total body irradiation (n=9) Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine (CyA) + methotrexate (MTX)., Results: Acute GvHD was scored as 0-I, II, or III-IV in 39%, 48%, and 13% of the patients, respectively. Sixteen patients died of transplant-related complications and one of progressive disease. With a median follow-up of 220 days (9-2104) the actuarial 2-year transplant-related mortality (TRM) was 51%, the actuarial relapse risk 37%, the actuarial survival 46%. Fifteen patients (48%) are alive in complete remission, with a median follow-up of 32 months (range 2-71)., Interpretation and Conclusions: These data suggest that patients relapsing after an autotransplant should be screened for potential related or unrelated donors: although TRM remains high there is a definite chance of long-term disease-free survival if these patients are allografted.
- Published
- 2001
7. Fanconi's anemia cells are relatively resistant to H2O2-induced damage.
- Author
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Notaro R, Montuori N, di Grazia C, Formisano S, Rotoli B, and Selleri C
- Subjects
- Adolescent, Adult, Cells, Cultured, Child, Child, Preschool, Erythrocytes metabolism, Female, Hematopoietic Stem Cells metabolism, Humans, Male, Erythrocytes pathology, Fanconi Anemia blood, Fanconi Anemia pathology, Hematopoietic Stem Cells pathology, Hydrogen Peroxide toxicity, Oxidants toxicity, Oxidative Stress
- Abstract
Background and Objective: Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by skeletal abnormalities, late onset bone marrow failure and susceptibility to neoplasias. Reduced defense against oxidative stress is thought to be one of the cell damaging mechanisms. We investigated in vitro the effects of oxidative stress on red blood cells (RBC) and on hematopoietic progenitor growth of normal donors and of FA patients., Design and Methods: The effects of hydrogen peroxide (H2O2) on RBC and hematopoietic progenitors were studied in vitro by erythrophagocytosis assay and by hematopoietic progenitor colony assay, respectively., Results: In an erythrophagocytosis assay using normal monocytes, RBC from nine FA patients showed increased binding index (defined as the percentage of monocytes with adherent or phagocytosed RBC) compared to that obtained with RBC from nine normal controls. Upon exposure to H2O2, the binding index of normal RBC increased, while that of FA RBC remained unchanged. In a set of different experiments, H2O2 treatment of peripheral blood mononuclear cells (PBMNC) caused a significant decrease of the number of colonies from circulating progenitor cells in all normal subjects; the inhibition was dose-dependent and direct as proven by using normal purified CD34+ cells. In nine FA patients colony assays from intact cells showed a decreased number of circulating progenitors as compared to normal subjects; however, H2O2 treatment of FA PBMNC did not cause any further decrease of the plating efficiency., Interpretation and Conclusions: Untreated FA cells behave as normal cells after exposure to the toxic effects of H2O2. However, since H2O2 exposure is inoffensive to circulating FA RBC and hematopoietic progenitors, it seems that a selection for cells resistant to further oxidative stress has taken place in the residual hematopoiesis of FA patients. We may surmise that the survival of cells that have suffered from oxidative damage may have increased the risk of their leukemic transformation.
- Published
- 1998
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