Publications by authors named "Salvatore Leotta"

28 Publications

  • Page 1 of 1

Low content of clonogenic progenitors on day+18 is associated with acute graft-versus-host disease and predicts transplant-related mortality.

Exp Hematol 2021 Jan 11. Epub 2021 Jan 11.

Department of Hematology and Bone Marrow Transplantation Unit, Azienda Universitaria Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy.

A marrow reaction associated with acute-graft-versus-host disease (a-GVHD) has been demonstrated in experimental models; its existence in human transplantation is controversial. The aim of the present study was to investigate whether clonogenic marrow precursors are an early marker for a-GVHD and transplant-related mortality (TRM). We prospectively studied 133 patients for colony-forming units-granulocyte-monocyte (CFU-GM) at day +18/+19 posttransplantation. CFU-GM frequency below the 25th percentile was predictive of an acute GVHD score I°-IV° when evaluated in multivariate logistic regression analysis (odds ratio = 13.551, 95% confidence interval [CI]: 1.583-116.031, p = 0.01). In the group with a clonogenic frequency below the 25th percentile, the cumulative incidence of GVHD grades II-IV was significantly more frequent with respect to the group with a frequency greater than the 25th percentile, 86% versus 54% (Gray test: p = 0.02). In multivariate Cox proportional analysis, a CFU-GM frequency below the 25th percentile at day +18 was associated with reduced overall survival (OS) (hazard ratio = 1.778, 95% CI: 1.022-3.093, p = 0.04). Patients with a frequency of CFU-GM greater than the 25th percentile had increased TRM with respect to patients with a clonogenic cell frequency greater than the 25th percentile (33.5% vs. 13.0%, p = 0.01). Patients were divided based on median content of viable CD34+ cells, and measurement of viable CD34+ cells was predictive for OS (p = 0.005) and TRM (p = 0.003). A weak correlation was observed between CFU-GM frequency in marrow at day +18 and levels of IL-2 receptor (IL-2R) in plasma (r = -0.226, p = 0.03). We conclude that marrow progenitor cell counts, on day +18 may be a useful marker for identifying patients at risk for severe a-GVHD, TRM, and inferior survival.
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http://dx.doi.org/10.1016/j.exphem.2021.01.002DOI Listing
January 2021

Plerixafor on-demand in association with low-dose cyclophosphamide and G-CSF in the mobilization of patients with multiple myeloma: High effectiveness, low toxicity, and affordable cost.

Leuk Res Rep 2020 30;14:100227. Epub 2020 Oct 30.

SODc Terapie Cellulari e Medicina Trasfusionale, Azienda Ospedaliera Careggi, Firenze, Italy.

In CD34+ cells mobilization of patients with multiple myeloma (MM), the use of Cyclophosphamide (CTX) at a dose of 2 g/m has low efficacy although also lower toxicity. The suboptimal mobilizing effect of low-dose CTX, however, may be overcome by plerixafor (PLX) on demand. We conducted a prospective multicenter study in 138 patients with MM to evaluate CTX 2 g/m in association with granulocyte-colony stimulating factor (G-CSF) and on-demand PLX. We compared results with a historical group of MM patients (n = 138) mobilized using CTX at a dose of 4 g/m. CD34+ cells greater than 2 × 10/kg in max three aphereses were harvested in 98.6% of patients in the on-demand PLX study group while in 84.0% in the historical group, (p = 0.0001). In the on-demand-PLX study group, a successful harvest greater than 5 × 10/kg in max three aphereses was observed in 85.5% of patients versus 62.3% of patients in the historical control group, (p=0.0001). In the on-demand-PLX study group, 4.3% (6/138) of patients had febrile complications. Salvage mobilization in the on-demand PLX study group was 1.4%. In conclusions, on-demand PLX + CTX 2 g/m2 + G-CSF 10 μg/kg has higher efficacy and lower toxicity compared with CTX 4 g/m2 + G-CSF. An analysis of costs is presented.
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http://dx.doi.org/10.1016/j.lrr.2020.100227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649636PMC
October 2020

Second-line Dasatinib Therapy Improved Compliance and Deep Molecular Responses in Imatinib-intolerant Chronic Myeloid Leukemia Patients.

Anticancer Res 2020 Sep;40(9):5313-5317

Hematology Section and BMT Unit, Rodolico Hospital, AOU Policlinico - V. Emanuele, Catania, Italy

Background/aim: Imatinib (IM) is the standard-of-care treatment for most chronic myeloid leukemia (CML) patients in chronic phase (CP). However, some patients suffer from low-grade side-effects that, in the long run, severely affect the quality of life and require treatment discontinuation due to toxicities. Fortunately, there are several therapeutic alternatives for these patients. Among them, the second-generation tyrosine kinase inhibitor dasatinib (DAS), used as second-line treatment, has shown to be a valid option in patients with CP-CML after intolerance to prior IM.

Patients And Methods: Herein, we report on seven CP-CML patients who achieved a stable major molecular response (MMR) with IM-therapy, but were shifted to DAS treatment due to recurrent low-grade IM-intolerances (grades 1-2).

Results And Conclusion: All patients received conventional DAS treatment with a median daily dose of 83.3 mg. Treatment was well tolerated and side-effects were mild. In addition, after a median follow-up of 25 months (range=24-43 months) a deep molecular response (DMR) (either MR or MR) was achieved in all patients after 24 months of treatment. This finding, although limited to a small cohort of CP-CML patients, supports the view that a therapy switch from IM to DAS induces a reduction of symptom burden, improves patient compliance and shows clinical efficacy in achieving and sustaining deep molecular responses.
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http://dx.doi.org/10.21873/anticanres.14538DOI Listing
September 2020

Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation.

Front Immunol 2019 7;10:3158. Epub 2020 Feb 7.

Unità di Trapianto di Midollo, Divisione di Ematologia, Azienda Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy.

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, = 0.002; TIM-3, = 0.0007), while TRM could be predicted by sIL2-Rα ( = 0.0005), IFN-gamma ( = 0.01), and IL-6 ( = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939-19.910), = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308-5.347), = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy.
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http://dx.doi.org/10.3389/fimmu.2019.03158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020780PMC
November 2020

Clinical Benefit of Long-Term Disease Control with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

J Clin Med 2019 Oct 16;8(10). Epub 2019 Oct 16.

Division of Hematology, AOU "Policlinico - Vittorio Emanuele", Via Santa Sofia 78, 95124 Catania, Italy.

Background: We retrospectively analysed relapsed/refractory MM (RRMM) patients treated with pomalidomide and dexamethasone (PomaD) either in real life, or previously enrolled in an interventional (STRATUS, MM-010) or currently enrolled in an observational study (MM-015) to provide further insights on safety and tolerability and clinical efficacy.

Methods: Between July 2013 and July 2018, 76 RRMM patients (including 33 double refractory MM) received pomalidomide 4 mg daily given orally on days 1-21 of each 28-day cycle, and dexamethasone 40 mg weekly (≤75 years) or 20 mg weekly for patients aged > 75 years. In nine patients a third agent was added to increase the response: Cyclophosphamide (in two fit patients) or clarithromycin (in seven frail patients). Patients received subcutaneous filgrastim as part of the prophylaxis regimen for neutropenia.

Results: A median number of six (range 2-21) PomaD cycles were given. The regimen was well tolerated with grade 3-4 haematological and non-haematological adverse events in 39 (51%) and 25 (33%) patients, respectively. In patients who developed serious AE, pomalidomide dose reduction (11%, 14%) or definitive discontinuation (18%, 23%) were applied. All patients have been evaluated for response within the first two cycles. The disease control rate (DCR), i.e., those patients that had a response equal or better than stable disease (≥ SD), was high (89%), with 44% overall response rate (ORR) after six cycles. The achieved best responses were complete remission (CR, 5%), very good partial remission (VGPR, 4%), partial remission (PR, 35%), minimal response (MR, 7%), and stable disease (SD, 38%). After a median follow up of 19.6 months, median progression free survival was 9.4 months, and overall survival (OS) was 19.02 months. Univariate analysis showed that double refractory patients, or who received more than three previous lines had shorter PFS. At 18 months, regardless of the depth of response, patients with a disease control of at least six months, defined as maintenance of a best clinical and/or biochemical response to treatment for almost six months, had prolonged PFS (35.3% versus 20.6%, = 0.0003) and OS (81.2% versus 15.9%, < 0.0001) Conclusions: Our findings indicate that PomaD is a safe and well-tolerated regimen in real-life, associated with prolonged PFS and OS with acceptable toxicity. Moreover, Pd induced disease control in most intensively pre-treated patients and some of them achieved longer PFS than that obtained with the previous treatment.
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http://dx.doi.org/10.3390/jcm8101695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832641PMC
October 2019

Pomalidomide-Responsive Extramedullary Myeloma Relapsed after Allogeneic Hematopoietic Transplant and Refractory to Multiple Lines of Chemotherapy.

Chemotherapy 2019 18;64(2):110-114. Epub 2019 Sep 18.

Divisione di Ematologia - Ospedale Policlinico, Catania, Italy.

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.
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http://dx.doi.org/10.1159/000502473DOI Listing
November 2019

CMV Management with Specific Immunoglobulins: A Multicentric Retrospective Analysis on 92 Allotransplanted Patients.

Mediterr J Hematol Infect Dis 2019 1;11(1):e2019048. Epub 2019 Sep 1.

IRCCS San Raffaele Scientific Institute, Milano, Italy, Hematology and Bone Marrow Transplantation Unit.

CMV represents one of the most severe life-threatening complications of allogeneic stem cell transplantation (allo-SCT). Pre-emptive treatment is highly effective, but toxicity and repetitive reactivation of CMV represent a significant challenge in the clinical practice. The use of anti-CMV specific immunoglobulins (Megalotect) is controversial. We retrospectively collected data on 92 patients submitted to allo-SCT for hematological malignancies, in whom Megalotect was used either for prophylaxis (n=14) or with pre-emptive therapy, together with an anti-CMV specific drug (n=78). All the patients were considered at high-risk, due to the presence of at least one risk factor for CMV reactivation. The treatment was well tolerated, with no reported infusion reactions, nor other adverse events, none of the 14 cases treated with Megalotect as prophylaxis developed CMV reactivation. 51/78 (65%) patients who received Megalotect during pre-emptive treatment achieved complete clearance of CMV viremia, and 14/51 patients (29%) developed a breakthrough CMV infection. 7/78 patients (9%) developed CMV disease. The projected 1-year OS, 1-year TRM, and 1-year RR is 74%, 15%, and 19%, respectively. No differences were observed in terms of OS, TRM, and RR by comparing patients who achieved a complete response after treatment versus those who did not. These retrospective data suggest that Megalotect is safe and well-tolerated. When used as prophylaxis, no CMV reactivation was recorded. Further prospective trials are warranted to identify the best set of patients who can benefit from Megalotect alone or in addition to anti-CMV specific drugs.
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http://dx.doi.org/10.4084/MJHID.2019.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736170PMC
September 2019

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO).

Biol Blood Marrow Transplant 2019 12 7;25(12):2388-2397. Epub 2019 Aug 7.

Institute of Hematology L. and A. Seragnoli, University Hospital S. Orsola-Malpighi, Bologna, Italy.

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%).
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http://dx.doi.org/10.1016/j.bbmt.2019.07.037DOI Listing
December 2019

Feasibility, Tolerability and Efficacy of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real-Life Survey of the Sicilian Myeloma Network.

J Clin Med 2019 Jun 19;8(6). Epub 2019 Jun 19.

Division of Hematology, Azienda Policlinico-OVE, University of Catania, 95125 Catania, Italy.

The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known about safety and efficacy of KRd outside a clinical trial context. Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers. Median age was 62 years; patients had received a median of two previous lines of treatment (range 1-10) and 52% were refractory to previous treatment. Median number of KRd cycles was 12 (2-29), with a mean duration of treatment of 12 months; 21 patients had received at least 18 cycles. Overall response rate was 61%, including 18% complete response. Median PFS was 22.9 months, median OS was not reached. Creatinine clearance >30 mL/min, quality of the best achieved response and standard Fluorescence In Situ Hybridization (FISH) risk were independent predictors of favorable outcome. Patients who received the full-dosage of carfilzomib in the first two cycles had a better outcome. KRd was effective and well tolerated and in a considerable proportion of patients, therapy continued beyond the 18th cycle. The finding of a better outcome in patients with the higher cumulative dose of carfilzomib in the first two cycle encourages to maintain the maximum tolerated dose.
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http://dx.doi.org/10.3390/jcm8060877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617295PMC
June 2019

Remission of Bile Acid Malabsorption Symptoms Following Treatment With the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide.

Gastroenterology 2019 08 6;157(2):569-571. Epub 2019 Apr 6.

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2019.04.002DOI Listing
August 2019

B-ALL Relapses After Autologous Stem Cell Transplantation Associated With a Shift from e1a2 to e14a2 Transcripts: A Case Report.

Anticancer Res 2019 Jan;39(1):431-435

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Background/aim: The Philadelphia chromosome is found in 30% of acute lymphoblastic leukemia (ALL) patients, a distinct ALL subgroup where the BCR-ABL fusion gene is associated with poor prognosis. Treatment with tyrosine kinase inhibitors (TKIs) often induces complete remission and these patients subsequently undergo an autologous stem cell transplantation (ASCT). However, 20% of subjects experience a relapse associated with the selection of point-mutations in the BCR-ABL kinase domain. We report the clinical evolution of a Philadelphia-positive ALL patient co-expressing the e1a2 and e14a2 BCR-ABL transcript at diagnosis.

Materials And Methods: Multiplex reverse transcriptase (RT)-PCR was used to detect BCR-ABL transcripts and their levels were measured by quantitative Real Time PCR. Clonal sequencing and next-generation sequencing (NGS) were used to identify mutations.

Results: Although the patient underwent ASCT following treatment with multiple TKIs, he relapsed twice. The first time he exhibited the e1a2 transcript and the second time he presented only the e14a2 variant. Mutation analysis, performed by clonal sequencing and NGS, detected two alterations after the first relapse and a single mutation at the time of the second relapse.

Conclusion: The observed shift from the e1a2 to the e14a2 variant and the selection of TKI-resistant clones heavily contributed to the fatal evolution of the disease.
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http://dx.doi.org/10.21873/anticanres.13130DOI Listing
January 2019

Long-Term Molecular Remission Achieved by Antibody Anti-CD22 and Ponatinib in a Patient Affected by Ph'+ Acute Lymphoblastic Leukemia Relapsed after Second Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Chemotherapy 2018 29;63(4):220-224. Epub 2018 Oct 29.

Division of Hematology and BMT - Ospedale Policlinico, Catania, Italy.

Ph'+ acute lymphoblastic leukemia (Ph'+-ALL) is an oncohematologic disorder for which allogeneic bone marrow transplantation still offers the only chance of cure. However, relapse is the main reason for treatment failure, also after hematopoietic stem cell transplantation (HSCT). New drugs, such as third generation tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have expanded the therapeutic landscape, especially in patients who relapsed before HSCT. Very few reports, up to now, have described the use of both classes of these new agents in combination with donor lymphocyte infusions (DLI) in the setting of patients who relapsed after HSCT. We report on a young patient affected by Ph'+-ALL, who relapsed after the second HSCT and who reached molecular remission and long-term disease control by treatment with the anti-CD22 monoclonal antibody inotuzumab ozogamicin, DLI, and the 3rd generation TKI ponatinib.
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http://dx.doi.org/10.1159/000492941DOI Listing
December 2018

Access to alternative donor hematopoietic search and transplantation for acute leukemia in different macro-regions of Italy. A GITMO/IBMDR study.

Bone Marrow Transplant 2018 03 21;53(3):291-299. Epub 2017 Dec 21.

Hematology, University Hospital Sant'Orsola-, Malpighi, Bologna, Italy.

Hematopoietic Stem Cell Transplantation activity levels vary across European countries. No data are available on the homogeneity of access to the transplant procedure for patient with leukaemia, within any European country. We measured homogeneity of the rate of alternative donor search in patients affected by acute leukaemia resident in each Italian region and macro-region during years 2010-2013. A total of 2747 alternative donor searches were studied. Twenty-one percent of all donor searches were made through extra-regional migration. Rate of alternative donor searches varied among the country's regions and macro-regions. The rate of donor searches was 38% lower in South Italy than in North Italy, and the rate of alternative donor transplantations performed was 45% lower. A reduced rate of alternative donor search in South macro-region was observed in all age cohorts. Despite the overall allogeneic transplant rate in Italy is relatively high, there are wide regional differences in access to transplant from alternative donor. Extra-regional migration cannot completely compensate for the lower access to transplant of acute leukaemia patients living in those regions where transplant activity is low.
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http://dx.doi.org/10.1038/s41409-017-0026-zDOI Listing
March 2018

Cost-effectiveness of on-demand plerixafor added to chemotherapy and granulocyte-colony stimulating factor for peripheral blood stem cell mobilization in multiple myeloma.

Leuk Lymphoma 2018 01 2;59(1):42-48. Epub 2017 Jun 2.

f Istituto di Fisiologia Clinica, CNR , Reggio Calabria , Italy.

We here report final results of a phase II/III prospective study that evaluated in Multiple Myeloma the use of on-demand plerixafor (PLX) added to mobilizing chemotherapy for patients showing predictive signs of mobilization failure. A total of 111 patients with MM were registered, all received cyclophosphamide 4 g/m and granulocyte colony-stimulating factor (G-CSF). Overall, a successful CD34+ cell mobilization was achieved in 97.2% (108/111) of patients. Minimum harvest (≥2.0 × 10 CD34+ cells/kg) was achieved in 97.2% (108/111) and optimal harvest success (≥4.0 × 10 CD34+ cells/kg) was achieved in 84.6% (94/111). Multivariate analysis showed that patients who received on-demand PLX treatment had significantly higher likelihoods of successfully achieving both the minimal (p = .006) and optimal harvest (p = .05) in respect to a historical control group mobilized without any PLX. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful minimal harvest, was €40.6 per patient.
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http://dx.doi.org/10.1080/10428194.2017.1324161DOI Listing
January 2018

Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision: A Systematic Review.

Dis Colon Rectum 2016 Dec;59(12):1209-1221

1 Department of Surgery, Hillerød University Hospital, University of Copenhagen, Hillerød, Denmark 2 Department of Surgery, Zealand University Hospital, University of Copenhagen, Køge, Denmark 3 Department of Radiology, Hillerød University Hospital, University of Copenhagen, Hillerød, Denmark 4 Department of Internal Medicine, Gentofte University Hospital, University of Copenhagen, Hellerup, Denmark 5 Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, København Ø, Denmark.

Background: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes.

Objective: The purpose of this study was to describe the pattern of mesocolic lymph node metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection.

Data Sources: EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip node; lymph node resection colon; and complete or total and mesocolic excision.

Study Selection: Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were excluded.

Main Outcome Measures: The risk of metastases in the central mesocolic lymph nodes was measured.

Results: A total of 2052 articles were screened, of which 277 underwent full-text review. The 47 studies fulfilling the inclusion criteria were very heterogeneous, and meta-analyses were not considered appropriate. The risk of central mesocolic lymph node metastases for right-sided cancers varies between 1% and 22%. In sigmoid cancer, the risk is reported in ≤12% of the patients and is associated with advanced T stage.

Limitations: The retrospective design and heterogeneity, in terms of definitions of lymph node location, tumor sites, stage, morphology, pathology assessment, and inclusion criteria (selection bias), of the included studies were limitations. Also, anatomic definitions were not uniform.

Conclusions: The present literature cannot give a theoretical explanation of a better oncological outcome after extended lymph node dissection. Consensus for a standardization of anatomical definitions and surgical and pathological assessments is warranted for future mapping studies.
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http://dx.doi.org/10.1097/DCR.0000000000000658DOI Listing
December 2016

Treatment of hyperthyroidism with radioiodine targeted activity: A comparison between two dosimetric methods.

Phys Med 2016 Jun 27;32(6):847-53. Epub 2016 May 27.

Section of Radiological Sciences, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

Radioiodine therapy is an effective and safe treatment of hyperthyroidism due to Graves' disease, toxic adenoma, toxic multinodular goiter. We compared the outcomes of a traditional calculation method based on an analytical fit of the uptake curve and subsequent dose calculation with the MIRD approach, and an alternative computation approach based on a formulation implemented in a public-access website, searching for the best timing of radioiodine uptake measurements in pre-therapeutic dosimetry. We report about sixty-nine hyperthyroid patients that were treated after performing a pre-therapeutic dosimetry calculated by fitting a six-point uptake curve (3-168h). In order to evaluate the results of the radioiodine treatment, patients were followed up to sixty-four months after treatment (mean 47.4±16.9). Patient dosimetry was then retrospectively recalculated with the two above-mentioned methods. Several time schedules for uptake measurements were considered, with different timings and total number of points. Early time schedules, sampling uptake up to 48h, do not allow to set-up an accurate treatment plan, while schedules including the measurement at one week give significantly better results. The analytical fit procedure applied to the three-point time schedule 3(6)-24-168h gave results significantly more accurate than the website approach exploiting either the same schedule, or the single measurement at 168h. Consequently, the best strategy among the ones considered is to sample the uptake at 3(6)-24-168h, and carry out an analytical fit of the curve, while extra measurements at 48 and 72h lead only marginal improvements in the accuracy of therapeutic activity determination.
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http://dx.doi.org/10.1016/j.ejmp.2016.05.059DOI Listing
June 2016

Influence of the X-ray beam quality on the dose increment in CT with iodinated contrast medium.

J Xray Sci Technol 2016 ;24(2):267-78

PH3DRA (Physics for Dating Diagnostic Dosimetry Research and Applications) Laboratories, Department of Physics and Astronomy, University of Catania, Catania, Italy.

Background: In computed tomography (CT), the image contrast is given by the difference in X-ray attenuation in the various tissues of the patient and contrast media are used to enhance image contrast in anatomic regions characterized by similar attenuation coefficients.

Objective: Aim of the present work is to enlarge the range of applicability of the method previously introduced for organ dosimetry in contrast-enhanced CT, by studying the effects of X-ray beam quality on the parameters of the model. Furthermore, an experimental method for the evaluation of the attenuation properties of iodinated solutions is proposed.

Methods: Monte Carlo simulations of anthropomorphic phantoms were carried out to determine a bi-parametrical (a and b) analytical relationship between iodine concentration and dose increase in organs of interest as a function of the tube kilo-voltage peak potential (kVp) and filtration. Experimental measurements of increments in Hounsfield Units (HU) were conducted in several CT scanners, at all the kVp available, in order to determine the parameter γ which relates the HU increment with the iodine mass fraction. A cylindrical phantom that can be filled with iodine solutions provided with an axial housing for a pencil ionization chamber was designed and assembled in order to measure the attenuation properties of iodine solutions under irradiation of a CT scanner and to obtain a further validation of Monte Carlo simulations.

Results: The simulation-derived parameters of the model, a and b, are only slightly dependent upon the tube kilo-voltage peak potential and filtration, while such scanner-dependent features influence mainly the experimentally-derived γ parameter. Relative dose variations registered by the ionization chamber inside the iodine-filled cylindrical phantom decrease when the X-ray mean energy increases, and reaches about 50% for 10 mg/ml of iodine.

Conclusions: The dosimetric method for contrast-enhanced CT can be applied to all CT scanners by adopting average simulative parameters and by carrying out a simple measurement with a series of iodine contrast solutions. The novel experimental methodology introduced can provide a direct measurement of iodine attenuation properties.
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http://dx.doi.org/10.3233/XST-160551DOI Listing
December 2016

A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In-labelled radiopharmaceuticals.

Phys Med 2015 Jul 13;31(5):536-41. Epub 2015 May 13.

Department of Biomedical Sciences and of Morphologic and Functional Imaging, University of Messina, Messina, Italy.

The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations.
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http://dx.doi.org/10.1016/j.ejmp.2015.04.015DOI Listing
July 2015

Acute GVHD after allogeneic hematopoietic transplantation affects early marrow reconstitution and speed of engraftment.

Exp Hematol 2015 Jun 20;43(6):430-8.e1. Epub 2015 Feb 20.

Section of Epidemiology, Clinical Physiology Institute Centro Nazionale Delle Ricerche, Reggio Calabria, Italy.

Our aim was to study the influence of acute graft-versus-host disease (a-GVHD) on primary engraftment times after allogeneic transplantation. Primary engraftment and frequency of marrow granulocyte-macrophage colony-forming units and erythroid burst-forming units, at day +18, were studied in 126 allogeneic transplants. Patients were grouped according to the time when a-GVHD treatment with corticosteroids was started. The no-a-GVHD group are those who, during the first 3 months, had no need for a-GVHD treatment; the early-a-GVHD group are those who needed a-GVHD treatment within 19 days; and the postengraftment-a-GVHD group are those who were not on corticosteroid treatment at the time of engraftment but needed it after day +19. The no-a-GVHD group reached a neutrophil count (N) > 0.5 × 10(9)/L in a median of 17.8 days. The postengraftment-a-GVHD group reached N > 0.5 × 10(9)/L in a median of 21.4 days (p = 0.0003). The early-a-GVHD group had N > 0.5 × 10(9)/L in a median of +17.0 days (p = 0.23). When factors important for engraftment were studied in a multivariate analysis, postengraftment a-GVHD was a significant factor in delayed neutrophil and platelet engraftment. Both the early-a-GVHD and postengraftment-a-GVHD groups showed a significant reduction in frequency of granulocyte-macrophage colony-forming units and erythroid burst-forming units found in marrow at day +18. In conclusion, a-GVHD may influence early marrow reconstitution and is a relevant factor for primary myeloid and platelet engraftment.
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http://dx.doi.org/10.1016/j.exphem.2015.02.002DOI Listing
June 2015

Plerixafor on-demand combined with chemotherapy and granulocyte colony-stimulating factor: significant improvement in peripheral blood stem cells mobilization and harvest with no increase in costs.

Br J Haematol 2014 Jan 21;164(1):113-23. Epub 2013 Oct 21.

Programma di Trapianto Emopoietico, Azienda Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy; Istituto Oncologico del Mediterraneo, Viagrande, Italy.

To date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34(+) cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34(+) cells 2 × 10(6) /kg decreased from 20·9 to 4·0% (P = 0·0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.
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http://dx.doi.org/10.1111/bjh.12606DOI Listing
January 2014

Monte Carlo study of the dose enhancement effect of gold nanoparticles during X-ray therapies and evaluation of the anti-angiogenic effect on tumour capillary vessels.

J Xray Sci Technol 2013 ;21(2):237-47

Section of Radiological Sciences, Department of Biomedical Sciences and of Morphologic and Functional Imaging, University of Messina, Messina, Italy.

Gold nanoparticles (GNPs) are a promising radiosensitizer agent in radiotherapy. Through a simulation performed with the Geant4 Monte Carlo code, we evaluated the dose enhancement effect of GNPs during therapies with an x-ray tube operating at 150 kV (E = 55 keV and E(max) = 150 keV) and we studied the impact of GNP diffusion out of the tumour vessels, in terms of antiangiogenic and cytotoxic effects. Firstly, a single x-ray beam was assumed to irradiate a parallelepiped volume of soft tissue, in which a GNP-doped "target" volume was placed at different depths. Average dose enhancement factors (DEF) in presence of GNPs were obtained as a function of the target depth and GNP concentration, uniformly distributed; values ranging between 1.6 for 10 mg Au/g at 0 cm and 7.2 for 200 mg Au/g at 5 cm were determined. Furtherly, a second geometry was adopted, in which a blood capillary vessel (10 μm thick and 10 μm of inner radius) was placed at the centre of a cubic volume of soft tissue; doses and DEFs to the capillary endothelium as well as to the surrounding viable tumour were evaluated, for different models of GNP diffusion. Our results indicate that the radial DEF profiles around the vessel are in close relationship with the radial profiles of GNP concentration assumed, except for at sharp gradients of concentration. DEFs at the endothelium ranged from 1.6 to 6.5, for GNP concentrations in the blood of 10 and 200 mg/ml, respectively. These data can be helpful for the development of new and more specific GNP-based radiosensitizers of potential interest in radiotherapy, exploiting the combined benefit of anti-angiogenic and cytotoxic dose enhancement effects.
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http://dx.doi.org/10.3233/XST-130374DOI Listing
January 2014

Early measurement of CD34+ cells in peripheral blood after cyclophosphamide and granulocyte colony-stimulating factor treatment predicts later CD34+ mobilisation failure and is a possible criterion for guiding "on demand" use of plerixafor.

Blood Transfus 2013 Jan 10;11(1):94-101. Epub 2012 Oct 10.

Bone Marrow Transplant Unit, Vittorio Emanuele Hospital, Catania, Italy.

Background: Early identification of predictive factors of failure to mobilise CD34+ cells could enable rational use of plerixafor during first mobilisation, avoiding the need for a second mobilisation course. However, "on demand" administration of plerixafor needs to be driven by established parameters to avoid inappropriate use.

Materials And Methods: To address this issue, we studied the value of the peripheral blood CD34+ count, measured early (on days +10, +11, +12 and +13), in predicting the mobilisation outcome in the ensuing days. We retrospectively collected data from three Italian centres on 233 patients affected by multiple myeloma or lymphoma who underwent a first or second attempt at mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor. To assess the diagnostic value of peripheral blood white blood cell and CD34+ cell counts with respect to "mobilisation failure", we considered failed mobilisation as "disease" and the CD34+ cell count in peripheral blood, on a specific day, as a "diagnostic test". For various thresholds, we measured sensitivity, false positive rate, specificity and positive predictive value (PPV) as well as the area under the receiver-operating characteristic curves (AUC).

Results: A CD34+ cell count <10 × 10(6)/L on day 13 had high sensitivity (1.00) and high specificity (1.00) for predicting subsequent mobilisation failure, with an AUC of 1.0. However, good prediction was also obtained using a lower threshold (CD34+ cell count: <6 × 10(6)/L) at an earlier time (day 12). The PPV of the day 13 threshold was 1.00 while that of the day 12 one was 0.87.

Discussion: We propose that patients with <6 × 10(6)/L CD34+ cells in peripheral blood on day 12 and <10 × 10(6)/L on day 13 following mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor are candidates for "on demand" use of plerixafor, making the administration of this expensive agent more efficient and avoiding its inappropriate use.
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http://dx.doi.org/10.2450/2012.0004-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557479PMC
January 2013

Chemosensitivity of nonleukemic clonogenic precursors in AML patients in complete remission: association with CD34(+) mobilization and with disease-free survival.

Exp Hematol 2012 Jan 20;40(1):35-47.e2. Epub 2011 Oct 20.

Bone Marrow Transplantation Unit, Department of Hematology, Azienda Ospedaliera Policlinico-Vittorio Emanuele, Catania, Italy.

A high number of CD34(+) cells in the peripheral blood during mobilization in patients with acute myeloid leukemia (AML) in complete remission (CR) is associated with a high relapse rate. The variability in chemoresistance of normal bone marrow precursors has been hypothesized as explanation for the variable CD34 mobilization in AML. In 37 patients with AML in CR, we determined the chemosensitivity of bone marrow clonogenic precursors to maphosphamide and etoposide, which was then correlated with the degree of CD34(+) mobilization. In an enlarged set of 49 patients, we also studied the importance of chemosensitivity of marrow precursors for disease-free survival and relapse incidence. Significant correlations were demonstrated between the peak number of CD34(+) cells and residual growth of colony-forming unit granulocyte-macrophage (CFU-GM) after maphosphamide (R = 0.550; p = 0.0003) and after etoposide (R = 0.793; p = 0.0003). It was possible to identify three groups of AML patients based on chemosensitivity. The mean CD34(+) peak was 33 × 10(6)/L in the hyperchemosensitive group, 141 × 10(6)/L in the normochemosensitive (p = 0.03), and 379 × 10(6)/L in the chemoresistant group (p = 0.002). Failed CD34(+) mobilization was observed in 72% of the hyperchemosensitive group, 23% of the normochemosensitive group, and 0% of the chemoresistant group (p = 0.001). Hyperchemosensitivity of CFU-GM, together with a low platelet count, were independent factors important in the failure of CD34(+) cell mobilization. A disease-free survival significantly inferior to that of all other patients was associated with chemoresistance of CFU-GM (log rank, p = 0.030) and with chemoresistance of burst-forming unit erythroid (BFU-E) (log rank, p = 0.033). Chemoresistance of CFU-GM (p = 0.048) and BFU-E (p = 0.017) was also associated with increase relapse incidence. Nonleukemic nature of these precursors was demonstrated studying minimal residual disease from single colony cells. In conclusion, we found that hyperchemosensitivity of normal nonleukemic CFU-GM is associated with a high risk of CD34(+) cell mobilization failure, while a chemoresistant pattern in CFU-GM and BFU-E is associated with poor disease-free survival and increased cumulative incidence of relapse.
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http://dx.doi.org/10.1016/j.exphem.2011.10.002DOI Listing
January 2012

Usability and trust in e-banking.

Psychol Rep 2007 Dec;101(3 Pt 2):1118-24

Department of Social and Political Studies, University of Milano, Italy.

This study assessed the role of usability in trust of e-banking services. A questionnaire was administered to 185 Italian undergraduate working students who volunteered for the experiment (M age = 30.5 yr., SD = 3.1). Participants were differentiated on computer ability (Expert, n = 104; Nonexpert, n = 81) and e-banking use (User, n = 93; Nonusers, n = 92). Analysis showed that the website usability of e-banking services did not play a very important role for the User group. Instead, institution-based trust, e.g., the trust in the security policy of the Web merchant, customers, and the overall trust of the bank were the crucial factors in the adoption of e-banking.
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http://dx.doi.org/10.2466/pr0.101.4.1118-1124DOI Listing
December 2007

Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients.

Leuk Lymphoma 2007 Oct;48(10):1950-60

Divisione Clinicizzata di Ematologia e Unità di Trapianto di Midollo Osseo, Catania, Italy.

We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m(2) + G-CSF 10 microg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN) > 0.5 x 10(9)/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 microg/kg resulted in a maximum length of neutropenia (PMN < 0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.
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http://dx.doi.org/10.1080/10428190701573240DOI Listing
October 2007

Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin.

Blood 2006 May 31;107(10):4177-81. Epub 2006 Jan 31.

Divisione Ematologia 2, Ospedale San Martino, 16132 Genoa, Italy.

Newly diagnosed patients with acute graft-versus-host disease (GvHD, grades I-IV; n = 211) were given 6-methylprednisolone (6MPred) 2 mg/kg per day for 5 consecutive days; 150 patients (71%) tapered 6MPred on day +5 and were considered responders; 61 patients (29%) could not taper their steroid dose and were considered nonresponders. The cumulative incidence of transplant-related mortality (TRM) for responders and nonresponders is, respectively, 27% and 49% (P = .009), and the 5-year survival is 53% and 35% (P = .007). Nonresponders on day +5 (n = 61) were randomized to receive 6MPred 5 mg/kg per day for 10 days alone (n = 34) or in combination with rabbit anti-thymocyte globulin (ATG, 6.25 mg/kg in 10 days; n = 27). The 2 groups were balanced for clinical and GvHD characteristics. One month after randomization, 26% had a complete response; 23%, a partial response; 33%, stable GvHD; 10%, worsened; and 8%, died. There was no significant difference in response, TRM, and survival between the non-ATG and ATG group. In conclusion, 5 days of prednisolone as first-line therapy of acute GvHD identifies patients with different risk of TRM, and second-line therapy with a combination of 6MPred + ATG does not improve patient outcome, compared with 6MPred alone.
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http://dx.doi.org/10.1182/blood-2005-12-4851DOI Listing
May 2006

Acute promyelocytic leukemia during pregnancy: report of 3 cases.

Int J Hematol 2004 Jan;79(1):31-6

Chair and Division of Haematology with Bone Marrow Transplantation Unit, University of Catania, Catania, Italy.

Acute promyelocytic leukemia (APL) is characterized by onset at a young age and a life-threatening hemorrhagic diathesis, which is attributed to a disseminated intravascular coagulation (DIC)-like coagulopathy. The discovery of all-trans-retinoic acid has changed the course of APL treatment by reducing the onset of DIC and inducing a complete and durable remission in more than 90% of patients. The occurrence of APL during pregnancy is not a frequent event, but the management of these patients raises many therapeutic and ethical dilemmas and requires a careful clinical case evaluation of fetal and maternal risk, coagulation status, the parents' wishes, and therapeutic options. Here we describe 3 patients with APL diagnosed during pregnancy. Clinical data and the therapeutic approaches are presented. In the discussion, we analyze clinical decisions and therapeutic options and compare our cases with those found in the literature.
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http://dx.doi.org/10.1007/BF02983530DOI Listing
January 2004

[Prevalence and significance of type-2 diabetes mellitus in chronic liver disease, correlated with hepatitis C virus].

Ann Ital Med Int 2003 Jan-Mar;18(1):31-6

Unità Operativa Complessa di Medicina, Presidio Ospedaliero di Acireale CT.

A high prevalence of type 2 diabetes mellitus in patients with hepatitis C virus (HCV)-related chronic liver diseases has been reported in numerous studies. Other studies failed to confirm this observation. We have studied the relative prevalence of type 2 diabetes mellitus in two groups of patients respectively presenting with HCV-related chronic liver disease (224 patients) and chronic liver diseases of other etiologies (30 hepatitis B virus-HBV-related chronic liver disease, 22 alcoholic liver cirrhosis), in order to confront them. Our study revealed a higher prevalence of diabetes mellitus in the group of patients with HCV-related chronic liver disease in comparison with the group of patients with chronic liver disease of other etiologies (32.5 vs 15.3%; p = 0.03). Patients with HBV-related liver disease had diabetes in 6.6% of cases, and the difference with patients with HCV-related disease was significant (p = 0.007). Our study confirms a higher prevalence of type 2 diabetes mellitus in patients with HCV-related chronic liver disease. It could be suggested that type 2 diabetes mellitus in patients with HCV-related chronic liver disease could be facilitated by hepatic iron overload and mitochondrial damage.
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July 2003