Publications (48)178.66 Total impact
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Article: Molecular and functional characterization of human bone marrow adipocytes.
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ABSTRACT: Adipocytes are a cell population largely located in the human bone marrow cavity. In this specific microenvironment where adipocytes can interact with a variety of different cells, the role of fat is mainly unknown. This is the first study that characterized mature adipocytes isolated from human bone marrow (BM-A) molecularly and functionally to better understand their roles into the hematopoietic microenvironment. Healthy BM-A were isolated after collagenase digestion and filtration. We studied the morphology of BM-A, their gene expression and immunophenotypic profile and their functional ability in the hematopoietic microenvironment, comparing them with adipocytes derived from adipose tissue (AT-A). BM-A showed an unilocular lipid morphology similar to AT-A and they didn't lose their morphology in culture. They showed a comparable pattern of stem cell-surface antigens to AT-A. In line with these observations, molecular data showed that BM-A expressed some embryonic stem cells genes, such as Oct4, KLf4, c-myc, Gata4, Tbx1 and Sox17, while they didn't express the stem cell markers Sox2 and Nanog. Moreover, BM-A had long telomeres that were similar to bone marrow mesenchymal stem cells (MSCs). Notably, BM-A supported the survival and differentiation of hematopoietic stem cells in long-term cultures. Altogether, these results showed that BM-A are stromal cells with a gene expression pattern that distinguished them from AT-A. BM-A showed stem cell properties through their hematopoietic supporting function, which was certainly linked to their role in the maintenance of the bone marrow microenvironment. Depending on specific demands, BM-A may acquire different functions based on their local environment.Experimental hematology 02/2013; · 3.11 Impact Factor -
Article: Proposed definition of 'poor mobilizer' in lymphoma and multiple myeloma: an analytic hierarchy process by ad hoc working group Gruppo ItalianoTrapianto di Midollo Osseo.
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ABSTRACT: Many lymphoma and myeloma patients fail to undergo ASCT owing to poor mobilization. Identification of poor mobilizers (PMs) would provide a tool for early intervention with new mobilization agents. The Gruppo italianoTrapianto di Midollo Osseo working group proposed a definition of PMs applicable to clinical trials and clinical practice. The analytic hierarchy process, a method for group decision making, was used in setting prioritized criteria. Lymphoma or myeloma patients were defined as 'proven PM' when: (1) after adequate mobilization (G-CSF 10 μg/kg if used alone or ≥5 μg/kg after chemotherapy) circulating CD34(+) cell peak is <20/μL up to 6 days after mobilization with G-CSF or up to 20 days after chemotherapy and G-CSF or (2) they yielded <2.0 × 10(6) CD34(+) cells per kg in ≤3 apheresis. Patients were defined as predicted PMs if: (1) they failed a previous collection attempt (not otherwise specified); (2) they previously received extensive radiotherapy or full courses of therapy affecting SC mobilization; and (3) they met two of the following criteria: advanced disease (≥2 lines of chemotherapy), refractory disease, extensive BM involvement or cellularity <30% at the time of mobilization; age ≥65 years. This definition of proven and predicted PMs should be validated in clinical trials and common clinical practice.Bone marrow transplantation 05/2011; 47(3):342-51. · 3.00 Impact Factor -
Article: BU/melphalan and auto-SCT in AML patients in first CR: a 'Gruppo Italiano Trapianto di Midollo Osseo (GITMO)' retrospective study.
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ABSTRACT: AML patients (total 129; median age =50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median follow-up of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of post-remission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age <55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.Bone marrow transplantation 10/2009; 45(4):640-6. · 3.00 Impact Factor -
Article: Allogeneic stem cell transplantation following reduced-intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome.
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ABSTRACT: The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12-82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL.Leukemia 12/2007; 21(11):2316-23. · 9.56 Impact Factor -
Article: Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection.
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ABSTRACT: Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.Bone Marrow Transplantation 09/2007; 40(3):245-9. · 3.75 Impact Factor -
Article: Treatment of refractory chronic GVHD with rituximab: a GITMO study.
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ABSTRACT: The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or =6) and the median follow-up after Rituximab was 11 months (1-88). Overall response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%), liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3, vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the study period 8/38 died: causes of death were cGVHD progression (n=3), disease relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival is currently 76%. We confirm that Rituximab is effective in over 50% of patients with refractory cGVHD and may have a beneficial impact on survival.Bone Marrow Transplantation 09/2007; 40(3):273-7. · 3.75 Impact Factor -
Article: Consolidation therapy for adult acute myeloid leukemia: a systematic analysis according to evidence based medicine.
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ABSTRACT: Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.Leukemia and Lymphoma 07/2006; 47(6):1091-102. · 2.58 Impact Factor -
Article: Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen.
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ABSTRACT: The engraftment ability of mesenchymal cells was investigated in 26 patients receiving allogeneic transplantation from HLA-identical siblings with reduced-intensity conditioning (RIC). The stem cell source was bone marrow (BM) in eight patients and G-CSF-mobilized peripheral blood hematopoietic cells in 18 cases. A total of 32 patients engrafted very quickly and the chimerism evaluation (both on myeloid and on lymphoid subsets) showed that they were full donor by day 60. At the time of the study they were in complete hematological remission and displayed a full donor hematopoiesis. Two patients showed early disease progression while one did not engraft. Forty-eight out-marrow samples harvested from the 26 patients generated a marrow stromal layer adequate for the chimerism evaluation. Monocyte-macrophage contamination of marrow stromal layers was always reduced below 2% by repeated trypsinizations and treatment with the leucyl-leucine (leu-leu) methyl ester. The chimerism evaluation was performed by PCR analysis of STRs microsatellites and the amelogenin locus, by using capillary electrophoresis (CE) and by FISH analysis in case of the sex mismatch. In eight patients, a partial donor origin of stromal cells was shown (7-86% cells of donor). The source of hematopoietic cells was BM in three patients and mobilized peripheral blood in the other five.Leukemia 03/2006; 20(2):329-35. · 9.56 Impact Factor -
Article: Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.
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ABSTRACT: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. Aggressive NHL patients do not benefit from upfront HDS/HDT.Annals of Oncology 01/2006; 16(12):1941-8. · 6.43 Impact Factor -
Article: Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies.
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ABSTRACT: Older age and a previously failed autologous stem-cell transplantation (SCT) are poor prognostic factors for patients receiving myeloablative conditioning and allogeneic SCT. Reduced-intensity conditioning (RIC) regimens achieved a significant reduction of treatment-related mortality, but the influence of previously described risk factors on the outcome of this novel transplantation strategy have not been fully analyzed yet. One hundred fifty patients with advanced hematologic malignancies received a RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/m2), and cyclophosphamide (60 mg/kg), followed by an allogeneic transplantation from an HLA-identical sibling donor. Patients were divided into two cohorts according to age; 90 patients were younger than 55 years, and 60 patients were 55 years old or older. The other pretransplantation characteristics were fairly balanced. Actuarial 5-year nonrelapse mortality (NRM) rate was not statistically different between the groups (13% in the younger group and 19% in the older group). By univariate and multivariate analysis, NRM was significantly higher in older patients who previously experienced failure with an autograft. The occurrence of grade 3 to 4 acute graft-versus-host disease (GVHD) or extensive chronic GVHD was associated with a higher NRM in both age cohorts. Overall survival (OS) was not statistically different between the younger (66%) and older groups (61%). By multivariate analysis, refractory disease was associated with a worse OS irrespective of age group. RIC transplantations show a rather low NRM, and age > or = 55 years per se cannot be considered a risk factor anymore. The timing of transplantation and novel strategies for the prevention of severe GVHD could further improve patient outcome.Journal of Clinical Oncology 09/2005; 23(27):6690-8. · 18.37 Impact Factor -
Article: Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders.
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ABSTRACT: We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone. Haemopoietic reconstitution was significantly faster in patients receiving G-CSF+EPO (group B), with a median time of 10 days to achieve an ANC count >0.5 x 10(9)/l, compared to 11 days in the historical group (A). The median duration of severe neutropenia (ANC count <100/ml) was significantly shorter in group B compared to group A; platelet counts >20 x 10(9) and >50 x 10(9)/l were achieved at days + 13 and + 17, respectively in group B, compared to days + 14 and + 24, respectively, in group A (P = 0.015, 0.002) patients. The transfusion requirement was reduced in group B, with 0 (0-6) RBC units and 1 (0-5) platelet unit transfused in group B vs 2 RBC (0-9) and 2 platelet units (0-8) in group A. Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22). The mean cost of autotransplantation per group A patient was 23,988 Euro, compared with 18,394 Euro for a group B patient. Our study suggests that the EPO + G-CSF combination not only accelerates engraftment kinetics, but can also improve the clinical course of ASCT.Bone Marrow Transplantation 10/2004; 34(8):693-702. · 3.75 Impact Factor -
Article: A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group.
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ABSTRACT: The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5%) achieved complete remission and 4 (4.3%) partial remission. Three patients (3.2%) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9%, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.Brazilian Journal of Medical and Biological Research 06/2004; 37(5):719-28. · 1.13 Impact Factor -
Article: High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors.
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ABSTRACT: A total of 30 multiple myeloma patients (M=23, F=7; age 31-55 years, median 48) were allografted with peripheral blood stem cells (PBSC) from HLA-identical siblings. Time to transplantation was 3-107 months (median 8). Prior chemotherapy lines varied from 1 to 6 (median 1). Four patients were in complete remission (CR), 11 in partial remission (PR), 13 were considered to be nonresponders, and two had progressive disease. Most were conditioned with busulfan-melphalan. PBSC were collected by apheresis after G-CSF or sequential GM-CSF and G-CSF. The patients were grafted with 4.4-24.1 x 10(6)/kg CD34+ (median 7.9) and 0.9-7.9 x 10(8)/kg CD3+ cells (median 2.3). GVHD prophylaxis was methotrexate-cyclosporine. Engraftment was complete and rapid. Grades II-IV acute GVHD (aGVHD) developed in 16 (53%), but was grade III-IV only in five (17%); chronic GVHD (cGVHD) developed in 17 out of the 24 evaluable patients (71%). A total of 18 patients (71%) attained CR after transplantation. TRM was 30% overall, 16% at 100 days. There was only one relapse. Overall survival and event-free survival at 73 months were 60% and 67%, respectively. PCR negativity for IgH-gene rearrangement occurred in all persistently CR patients studied. PBSC allograft can induce long remissions, because of profound suppression of the neoplastic clone that is probably linked to the antitumor effect of cGVHD.Bone Marrow Transplantation 06/2003; 31(9):767-73. · 3.75 Impact Factor -
Article: Gemcitabine alone or combined with cisplatin in relapsed or refractory multiple myeloma.
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ABSTRACT: Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas > or = 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, th e response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.Leukemia and Lymphoma 06/2002; 43(6):1273-9. · 2.58 Impact Factor -
Article: Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience.
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ABSTRACT: Between May 1994 and May 2000, we autotransplanted 48 consecutive patients, 21 females and 27 males aged over 60 years (range: 60-78, median: 63). Sixteen patients had multiple myeloma (MM), 14 high-grade non-Hodgkin's lymphoma (HGNHL), six low-grade non-Hodgkin's lymphoma (LGNHL), nine acute myeloid leukemia (AML), one chronic lymphocytic leukemia (CLL), one Hodgkin's disease (HD) and one breast cancer; the performance status (WHO) was 0-1. Seventeen patients were in 1st CR (35.4%) and one in 2nd CR (2.1%), 25 in PR (52.1%), while five patients had been transplanted with progressive disease (10.4%); seven patients with MM received a double transplant. Patients received high-dose therapy including melphalan alone (13) or associated with other drugs (26), busulfan-cyclophosphamide (three), BEAM (11) and TBI (two). All patients took a median of 11 (range: 8-25) days to reach neutrophils >500/microl, 13 (range: 9-83) days to reach platelets > 20,000/microl and 17 (range: 11-83) days to reach platelets > 50,000/microl. Hematological toxicity, hospital stay and supportive care did not differ from those of a cohort of younger patients. At present, 31 patients are alive (14 in CR, five in PR, five in PD and seven in relapse) and 16 died from PD at a median follow-up of 37 months (1-67). Only one patient died from transplant-related toxicity. Quality of life, evaluated using a QLQ-C30 questionnaire in 25 patients at day +90, was good. In our experience PBPC mobilization and transplantation is feasible in patients aged > or = 60 years and the toxicity of this procedure is acceptable, with an early transplant-related mortality of 1.8%; therefore patients with hematological malignancies potentially curable with high-dose therapy (HDT) should also be candidates for HDT.Bone Marrow Transplantation 07/2001; 27(11):1189-95. · 3.75 Impact Factor -
Article: A predictive model of varicella-zoster virus infection after autologous peripheral blood progenitor cell transplantation.
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ABSTRACT: Varicella-zoster virus (VZV) frequently causes severe infections in patients who have undergone bone marrow transplantation. The frequency of, characteristics of, and risk factors for this infection were studied in 164 patients undergoing autologous peripheral blood progenitor cell transplantation (PBPCT). Twenty-six patients (15.8%) developed VZV infection, and the actuarial risk was 10% at 1 year. No patient had visceral dissemination or died because of VZV, although one-third of the patients developed postherpetic neuralgia. By multivariate analysis, a CD4(+) lymphocyte count of <200 cells/microL (P<.0001; odds ratio [OR], 2.0) and a CD8(+) lymphocyte count of <800 cells/microL (P=.0073; OR, 2.0) at day 30 after transplantation were factors associated with VZV infection. Patients with both these adverse factors had an actuarial risk of VZV of 48% at 1 year. Patients with deficiency in both CD4(+) and CD8(+) lymphocytes are at high risk of VZV infection. These patients should be considered as candidates for preventive therapy, but whether for antiviral therapy or vaccination remains to be investigated.Clinical Infectious Diseases 05/2001; 32(10):1414-22. · 9.15 Impact Factor -
Article: Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study.
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ABSTRACT: Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extrahaematological toxicity after high-dose therapy (HDT) has never been investigated. We compared two historical groups of patients who either received (group A, n = 35) or did not receive (group B, n = 33) amifostine (740 mg/m2) before high-dose (HD) melphalan, followed by autologous infusion of peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this dose level. Emesis grade 1-2 was the most important side-effect, but the interruption of infusion was never required. The incidence and median duration of severe mucositis (grade 3-4) was 21% and 0 d (range 0-11 d) in group A and 53% and 7 d (range 0-11 d) in group B. The duration of analgesic therapy was also significantly lower in group A (0 d; range 0-12) than in group B (6 d, range 0-20) (P = 0.0001). Severe diarrhoea (3% vs. 25%; P = 0.01) and emesis (9% vs. 34%; P = 0.01) were also reduced in group A in comparison with group B. No differences were observed between the two groups for haematological recovery. This retrospective study strongly suggests that amifostine can reduce severe mucositis and the use of analgesic drugs in this setting. A randomized study is warranted to confirm these preliminary results.British Journal of Haematology 09/2000; 110(2):300-7. · 4.94 Impact Factor -
Article: VACOP-B, high-dose cyclophosphamide and high-dose therapy with peripheral blood progenitor cell rescue for aggressive non-Hodgkin's lymphoma with bone marrow involvement: a study by the non-Hodgkin's Lymphoma Co-operative Study Group.
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ABSTRACT: Sequential treatment with the addition of high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) rescue has been reported to be active as front-line therapy in aggressive non-Hodgkin's lymphoma (NHL) with bone marrow (BM) involvement. We designed an intensive sequential therapy as front-line therapy in this subset of patients and conducted a phase II study. Patients with aggressive non-Hodgkin's lymphoma and BM involvement at diagnosis received 8 weeks of VACOP-B chemotherapy as induction therapy. The second phase included high-dose cyclophosphamide (HDCY) (7 g/m(2)) with granulocyte colony-stimulating factor (G-CSF) followed by leukaphereses. The third phase included HDT according to the BEAM protocol or melphalan (140 mg/m(2)) plus total body irradiation (8 Gy in a single dose). Forty patients were included in the study. According to the intention-to-treat, after VACOP-B, 11 (27.5%) and 22 (55%) patients achieved complete remission (CR) and partial remission (PR), respectively. Thirty-four received HDCY. After HDCY, 18 patients (45%) were in CR and 13 (32.5%) in PR. Twenty-nine underwent HDT plus peripheral blood cell rescue (PBPC) rescue. At the completion of treatment 29 patients (72.5%) were in CR, and 3 patients (7.5%) in PR. The actuarial 3-year overall survival, disease free survival and failure free survival are 48%, 55% and 40%, respectively. Overall severe toxicity was 7.5%. This phase II study suggests that the intensified treatment described is feasible and active in aggressive NHL with BM involvement. A randomized trial is now underway to test this approach.Haematologica 03/2000; 85(2):160-6. · 6.42 Impact Factor -
Article: Cell therapy: achievements and perspectives.
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ABSTRACT: Cell therapy can be considered as a strategy aimed at replacing, repairing, or enhancing the biological function of a damaged tissue or system by means of autologous or allogeneic cells. There have been major advances in this field in the last few years. This has prompted the Working Group on Hematopoietic Cells to examine the current utilization of this therapy in clinical hematology. The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of cell therapy and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. Lymphokine-activated killer (LAK) and tumor-infiltrating lymphocytes (TIL) have been used since the '70s mainly in end-stage patients with solid tumors, but the clinical benefits of these treatments has not been clearly documented. TIL are more specific and potent cytotoxic effectors than LAK, but only in few patients (mainly in those with solid tumors such as melanoma and glioblastoma) can their clinical use be considered potentially useful. Adoptive immunotherapy with donor lymphocyte infusions has proved to be effective, particularly in patients with chronic myeloid leukemia, in restoring a state of hematologic remission after leukemia relapse occurring following an allograft. The infusion of donor T-cells can also have a role in the treatment of patients with Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorders. However, in this regard, generation and infusion of donor-derived, virus specific T-cell lines or clones represents a more sophisticated and safer approach for treatment of viral complications occurring in immunocompromised patients. Whereas too few clinical trials have been performed so far to draw any firm conclusion, based on animal studies dendritic cell-based immunotherapy holds promises of exerting an effective anti-tumor activity. Despite leukemic cells not being immunogenic, induction on their surface of co-stimulatory molecules or generation of leukemic dendritic cells may induce antileukemic cytotoxic T-cell responses. Tumor cells express a variety of antigens and can be genetically manipulated to become immunogenic. The main in vitro and in vivo functional characteristics of marrow mesenchymal stem cells (MSCs) with particular emphasis on their hematopoietic regulatory role are reviewed. In addition, prerequisites for clinical applications using culture-expanded mesenchymal cells are discussed The opportuneness of using LAK cells or activated natural killer (NK) cells in hematologic patients with low tumor burden (e.g. after stem cell transplantation) should be further explored. Moreover the role of new cytokines in enhancing the antineoplastic activity of NK cells and the infusion of selected NK in alternative to CTL for graft versus leukemia (GVL) disease (avoiding graft versus host disease (GvHD) seems very promising. Separation of GVL from GvHD through generation and infusion of leukemia-specific T-cell clones or lines is one of the most intriguing and promising fields of investigations for the future. Likewise, strategies devised to improve immune-reconstitution and restore specific anti-infectious functions through either induction of unresponsiveness to recipient alloantigens or removal of alloreactive donor T-cells might increase the applicability and success of hematopoietic stem cell transplantation. (ABSTRACT TRUNCATED)Haematologica 01/2000; 84(12):1110-49. · 6.42 Impact Factor -
Article: Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF.
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ABSTRACT: Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36. 2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P = 0. 0001; odds ratio 3.4) and >5 days on ANC <100/microl (P = 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC <100/microl affected infection outcome (P = 0.0024) whereas the antibiotic regimen did not. After day +30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0. 8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Gram-positive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.Bone Marrow Transplantation 11/1999; 24(10):1079-87. · 3.75 Impact Factor
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Institutions
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2004–2013
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Università Politecnica delle Marche
- • Department of Clinical and Molecular Sciences - DISCLIMO
- • Clinic of Cardiology
Ancona, The Marches, Italy
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2011
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Ospedale San Carlo di Potenza
Potenza, Basilicate, Italy
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2005
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University of Milan
Milano, Lombardy, Italy
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1999
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University of Bologna
- Institute of Haematology
Bologna, Emilia-Romagna, Italy
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1998
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Università degli Studi di Torino
Torino, Piedmont, Italy
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