P. Fabritiis - Academia.edu (original) (raw)

Papers by P. Fabritiis

Bone Marrow Transplantation, 2016

Haematologica, 2000

To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients wit... more To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients with high-risk chronic lymphocytic leukemia (CLL) in remission after fludarabine therapy, the clinical impact of minimal residual disease (MRD) monitoring and the immunologic reconstitution after transplantation. Twenty CLL patients, in clinical complete remission (CR) after fludarabine, were offered an unmanipulated PBSC transplant and were longitudinally monitored for MRD and immunologic reconstitution. Due to unsatisfactory PBSC collection, 4 patients received bone marrow cells. All patients engrafted. Two patients died, one due to infection and one because of another neoplasia. Thirteen patients are at present in clinical CR after a median follow-up of 17 months and 18 patients are alive with a survival probability of 0.87 (+/-0.04) at 52 months after transplant. Fifteen patients had a molecular remission. Three of them showed a molecular relapse 16-28 months after autograft, followed b...

Haematologica, 1999

The prognosis of severe fungal infections, such as fusarium infections, in patients with aplastic... more The prognosis of severe fungal infections, such as fusarium infections, in patients with aplastic anemia is directly related to the recovery of bone marrow functions. In this study, in vitro anti-Fusarium activity of granulocytes was investigated, the case of disseminated infection in a child with very severe aplastic anemia is reported, and implications for management of such infective complications are discussed. The in vitro efficiency of PMNL from three untreated, normal blood donors and from two G-CSF-treated WBC donors in contrasting the growth of the Fusarium sp strain isolated from the patient we present was measured by a 3H-glucose uptake inhibition assay and confirmed by microscopic examination. Basic growth inhibitory activity of unstimulated PMNL on Fusarium cells was significantly enhanced in the presence of GM-CSF in all three blood donors tested. In one of the two G-CSF-treated donors, in vitro efficiency of PMNL in contrasting the growth of the fungus increased notab...

Haematologica, 2006

Home care (HC) has an increasingly expanding role in the global management of patients affected b... more Home care (HC) has an increasingly expanding role in the global management of patients affected by hematologic malignancies. Integrated strategies, including causal-targeted and supportive treatments according to hematologic expertise and a holistic approach inspired by the philosophy and practice of palliative medicine, may allow suitable management and the possibility for most patients to stay at home. Physical, social and psychological needs of patients are likely to vary according to the course of their disease and the treatments they are receiving. Therefore, consideration should be given to different models of care and how to tackle patients' diverse needs, as outlined by reported experiences which claimed that HC can provide appropriate solutions not only for terminally and chronically ill patients but also for those in other phases of disease. According to these studies and to our own experience, when appropriate measures and structured operating models are adopted, HC r...

Bone marrow transplantation, 1987

The efficacy of autologous bone marrow transplantation in leukemia and lymphoma may depend upon t... more The efficacy of autologous bone marrow transplantation in leukemia and lymphoma may depend upon the selective elimination of malignant cells from human bone marrow in vivo and in vitro. A cyclophosphamide derivative (ASTA-Z 7654) and etoposide (VP16-213) have been tested on lymphoma and leukemia cell lines in a model that may represent a bone marrow situation in complete remission. The influence of different concentrations of normal mononuclear cells and tumor cells in this model and the activity of the two chemotherapeutic agents in the presence of bone marrow cells or peripheral blood cells were evaluated. A major inhibitory effect was observed using the two agents in combination; low doses of ASTA-Z and VP16 consecutively added to the mixture of malignant cells and normal mononuclear cells resulted in a greater elimination of tumor line cells than with ASTA-Z alone at the current 100 micrograms/ml dose. In contrast, no major toxicity on normal human bone marrow precursors was obs...

Transplant Infectious Disease, 2013

The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) recei... more The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.

Cytokines in Hemopoiesis, Oncology, and AIDS, 1990

Transplantation proceedings, 2006

Cord blood banks are established worldwide as a result of the increased use of umbilical cord blo... more Cord blood banks are established worldwide as a result of the increased use of umbilical cord blood (UCB) transplantation. The outcomes of this procedure relate to the cell dose of the UCB unit and the UCB collection. The aim of this study was to evaluate whether the mode of collection influenced the biological features of the UCB units. We studied 151 UCB units consecutively collected in the cesarean setting with two different methods: in utero after infant delivery and before delivery of the placenta, and ex utero after delivery of placenta. Sixty-nine UCB units were collected in utero and 82 ex utero. The two groups were comparable for maternal and obstetric factors. The proportion of banked UCB units was similar in the two groups (38% vs 40%, respectively). No statistically significant differences were observed between the methods of collection in term of volume, white blood cell count, total nucleated cell content, CD34(+) cells, and CFU-GM. This preliminary study showed that t...

Background. Chronic graft-versus-host disease (cGVHD) is an important determinant of long term mo... more Background. Chronic graft-versus-host disease (cGVHD) is an important determinant of long term morbidity and mortality in allogeneic stem cell transplant patients. Standard primary treatment of cGVHD remains a combination of corticosteroids (CS) and calcineurin inhibitors. There is no standard therapy for those who fail to respond to CS, and CS-resistant GVHD is associated with high morbidity. Thus, therapeutic options are usually limited for those patients. Rituximab (RTX) has been recently reported to be effective in cGVHD. Aim. Aim of this study was to analyze the outcome of 8 patients treated with RTX as salvage therapy for refractory cGVHD in a single center. Patients and methods. This retrospective study describes 8 consecutive patients experiencing refractory cGVHD and who received intravenous infusions of RTX (375 mg/m2per infusion) at weekly intervals for 4 weeks. In case of incomplete clinical response, additional course of 4 weeks were given. Response to RTX was assessed 3 months after first infusion. Complete Remission (CR) was defined as resolution of all manifestations in involved organs, while partial remission (PR) was defined as an improvement in each involved organ; resistance wad defined as lack of a CR/PR. The benefit in cGVHD was also evaluated in term of CS taper. Results. Median age was 45 years (range 40-67). All patients ha received and failed at least one line of immunosuppressive therapy. Median duration of cGVHD before RTX was 21 months (range 2-50) and the median follow-up after RTX was 40 months (range 6-99). Overall, 4 patients responded to RTX administration. In addition RTX allowed a significant reduction (>50% starting dose) of CS dosage in 7 patients three months after first infusion. No major toxicities directly related to RTX were observed. During the study period one patient died: main cause was cGVHD progression. Conclusions. Despite its limited size, our study confirm that RTX is effective in 50% of patients with refractory cGVHD, in according with findings from other studies. Controlled prospective studies are mandatory to confirm these results.

Introduction. Cord blood banks are established worldwide as a result of the increased use of umbi... more Introduction. Cord blood banks are established worldwide as a result of the increased use of umbilical cord blood (UCB) transplantation. The outcomes of this procedure relate to the cell dose of the UCB unit and the UCB collection. The aim of this study was to evaluate whether the mode of collection influenced the biological features of the UCB units. Materials and methods. We studied 151 UCB units consecutively collected in the cesarean setting with two different methods: in utero after infant delivery and before delivery of the placenta, and ex utero after delivery of placenta. Results. Sixty-nine UCB units were collected in utero and 82 ex utero. The two groups were comparable for maternal and obstetric factors. The proportion of banked UCB units was similar in the two groups (38% vs 40%, respectively). No statistically significant differences were observed between the methods of collection in term of volume, white blood cell count, total nucleated cell content, CD34 ϩ cells, and CFU-GM. Conclusion. This preliminary study showed that the two methods of collection in the cesarean setting were overlapping and valid if performed according to standard operating procedures.

Case Reports, 2009

Immune thrombocytopoenia (ITP) is one of the most common autoimmune manifestations of B cell lymp... more Immune thrombocytopoenia (ITP) is one of the most common autoimmune manifestations of B cell lymphoproliferative diseases. The association with multiple myeloma (MM) and solid tumours is rare. Here, a case of ITP associated with asymptomatic multiple myeloma and colon carcinoma, refractory to standard therapy and responsive to rituximab, is described. ITP should be considered in the differential diagnosis of thrombocytopoenia in MM and colon cancer. Understanding of the potential risk and reversibility of ITP should aid in the management of these patients.

Leukemia, 1997

We studied the effect of phosphorothioate oligodeoxynucleothe evidence that mice carrying constru... more We studied the effect of phosphorothioate oligodeoxynucleothe evidence that mice carrying constructs encoding bcr-abl tides ([S]ODNs) complementary to the bcr-abl junction on cells fusion products develop CML-like syndrome. 6,7 These obsertaken at diagnosis from 41 patients with Philadelphia-positive vations have provided the rationale for assessing the ability of chronic myelogenous leukaemia (CML). Experiments included antisense (AS) ODNs specifically targeting the bcr-abl junction the evaluation of the anti-leukaemic effect of 16-and 26-mer to suppress CML cell growth. antisense [S]ODNs on both mononuclear and CD34 ؉ cells, evaluation of incubation time and correlation of colony growth We have previously demonstrated that exposure of leuinhibition with the down-regulation of p210 bcr-abl. At the same kaemic blasts from patients with CML in blast crisis to syntime, the uptake of [S]ODNs by mononuclear and purified thetic 18-mer ODNs complementary to the bcr-abl junction CD34 ؉ cell populations and the cross-hybridization of 26-and suppresses leukaemic colony formation while sparing normal 16-mer [S]ODNs with the complementary sequences were granulocyte-macrophage colony formation. 8 Similarly, SCID evaluated. After incubation for 120 h with 26-mer antisense [S]ODNs on mononuclear cells, overall mean colony recovery mice carrying Philadelphia-positive cells systemically treated was 41.9% of the untreated control samples; in particular, a with [S]ODNs complementary to the bcr-abl breakpoint juncsignificant reduction in colony formation was observed in 22 tion survived significantly longer than control mice. 9 The issue of the 35 cases tested. The effect of 26-mer ODNs on CD34 ؉ of whether Philadelphia-positive cells from patients in chronic cells was comparable to that observed on mononuclear cells phase show similar sensitivity to AS ODN treatment as do in terms of colony inhibition; however, a higher proportion of cases showed a significant inhibition of colony formation. In blast cells, has been subsequently explored, although contracomparison with the 26-mer antisense [S]ODNs, the anti-leudictory results have been reported. We have found a modest kaemic effect of the 16-mer antisense [S]ODNs was less evident specific inhibition (20-30%) of CML colony formation after on mononuclear cells and comparable on CD34 ؉ cells; howshort-term incubation with junction-specific bcr-abl antisense ever, a more specific effect was evident on both target cells. ODNs; 10 however, junction-nonspecific ODNs were not Hybridization experiments confirmed a partial cross-reactivity evaluated. Recently, Mahon et al 11 reported preliminary data when the 26-mer ODNs were hybridized with their complementary sequence; this did not occur when 16-mer ODNs were simisuggesting that in vitro treatment of cells from six CML larly tested. Experiments aimed at evaluating the effect of the patients in chronic phase resulted in a reduced colony formaincubation time showed a significant increase in anti-leukaemic tion (66% inhibition) in five of the six patients, together with effect after a 120 h incubation period compared to that measa 50% inhibition of S-phase index as compared to cultures ured after a 24 h incubation period; this was parallelled by a incubated with sense ODNs. More recently, however, Kirkprogressive increase in the intracellular concentrations of [S]ODNs from day 1 to day 5. The accumulation of [S]ODNs land et al 12 treated, in vitro, cells from 15 patients with CML in correlated with a marked down-regulation of p210 bcr-abl levels chronic phase with bcr-abl [S]ODNs; no difference in colony which was first detectable after 72 h of treatment. The downnumbers was observed between sense-and antisense-treated regulation of p210 bcr-abl levels following treatment with [S]ODNs cultures in the majority of cases and the inhibition was nonshowed a correlation between the effect of antisense [S]ODNs sequence-specific in the responding patients. These studies on leukaemic colony formation and protein expression. These studies confirm that, under optimal conditions of target cell cul-suggest that CML chronic phase cells are heterogeneous in ture and ODN size, antisense [S]ODNs complementary to the their sensitivity to ODN treatment and raise the possibility that bcr-abl junction have specific anti-leukaemic effects. a variety of factors related both to CML cells (eg number of Keywords: bcr-abl oligonucleotides; p210 bcr-abl ; chronic myelomature myeloid cells and proportion of cells in the monocytegenous leukaemia; CD34 + cells

11th Annual meeting of the EBMT, 1985

Autologous hemopoietic stem cell infusion after high dose chemo/radiotherapy performed in BP of C... more Autologous hemopoietic stem cell infusion after high dose chemo/radiotherapy performed in BP of CGL is able to reinduce II CP in 90% of patients; however the median survival does not last more than 6 months. This report concerns 5 patients with Phl positive CGL in BP treated with BAVC regimen followed by hemopoietic stem cells reinfusion. An intensification program of cyclic chemotherapy has been applied after ABMT with the aim to prolong the survival of these patients. Since 1980 the majority of CGL patients seen at the Institute of Hematology of Rome were subjected to collection and cryopreservation of hemopoietic stem cells from bone marrow (BM) or peripheral blood (PB). Details of the methods have been described elsewhere (1,2). Of the 5 patients presented in this report 4 received stem cells collected from PB and 1 from BM. Four patients were males, median age was 39 years (range 29–41). Therapy during CP consisted of hydroxyurea; no splenectomy had been performed in any patient. Type of transformation was myeloid in 4 cases and mixed in one. BAVC conditioning regimen consisted of BCNU 800 mg/mq day 1; AMSA 150 mg/mq/day on days2–4; VP-16 150 mg/mq/day days 2–4; CA 300 mg/mq/day c.i. days 2–4. Stem cells were reinfused 24 hours after last dose chemotherapy with a median of 11×108(range 3–21) nucleated cells/kg body weight. After complete hematological reconstitution (25–30 days) from autologous infusion an intensification program of cyclic chemotherapy was begun consisting of 3 courses of L-VAMP (VCR 1.5 mg/mq i.v. hour 0,MTX 200mg/mq c.i. hours 1–3,CA 500 mg/mq c.i. hours 3–7, ASNASI 5000 U/mq i.m. hour 24,PDN 40 mg/mq/day days 1–5);3 courses of DAT (DNR 60 mg/mq i.v. day l,CA 60 to 150 mg/mq/8 hours s.c. days 1–5,6-TG 70 mg/mq/8 hours p.o. days 1–5) and 3 courses of HiDAC (CA 1 g/mq/12 hours c.i. in 3 hours on hour 0,12; ASNASI 6000 U/mq i.v. on hour 18).

Biology of Brain Tumour, 1986

$Research paper thumbnail of P-045 Chronic myelomonocytic leukemia evolved from refractory anemia: The unusual course of a myelodysplastic syndrome$

Transfusion Medicine, 2006

Clinical diagnosis of acute foetal distress (AFD) is based on several parameters such as abnormal... more Clinical diagnosis of acute foetal distress (AFD) is based on several parameters such as abnormal foetal heart rate (FHR) pattern and/or meconium liquid staining (MLS). Standards for cord blood (CB) banking indicate that AFD should be considered as exclusion criteria for CB collection, but precise guidelines on how to proceed with CB collection in the presence of AFD signs during labour are not available. We evaluated whether the presence of FHR abnormality and/or MLS during labour 1) reduced the CB collection activity; 2) were associated with the infant's acidaemia or asphyxia and 3) deteriorated the biological characteristics of CB units. Thirty-three units of CB were evaluated for biological parameters, gas values and newborn's Apgar score. The results were compared with a control group of 33 consecutive units previously banked. No differences were observed between the two groups and all but one newborn showed normal Apgar score and absence of metabolic acidaemia. The results showed that 1) AFD reduced the CB collection activity by 10% each year; 2) the majority of CB units collected in the presence of abnormal FHR and/or meconium have biological characteristics eligible for banking; 3) FHR alterations or meconium in the presence of normal gas analysis do not represent certain diagnosis of AFD.

Supportive Care in Cancer, 2012

ABSTRACT

Nature Clinical Practice Oncology, 2006

Proteasome inhibition represents a new anticancer approach, with the potential effect of arrestin... more Proteasome inhibition represents a new anticancer approach, with the potential effect of arresting tumor growth, metastasis and angiogenesis through the activation of multiple mechanisms. Bortezomib is a biologically active agent, producing predictable, dose-related and reversible proteasome inhibition; it has shown antitumor activity in various malignancies and is the first proteasome inhibitor to be used in clinical practice. Several trials demonstrated that bortezomib is relatively well tolerated, causing manageable nonhematologic and hematologic toxicity. The drug was approved in 2003 by the FDA for the treatment of patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on the last therapy; its application was expanded recently for second-line treatment. This article summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors.