Publications by authors named "Cristina Skert"

30 Publications

  • Page 1 of 1

GITMO REGISTRY STUDY ON ALLOGENEIC TRANSPLANTATION IN PATIENTS AGED OVER 60 FROM 2000 TO 2017. IMPROVEMENTS AND CRITICISMS.

Transplant Cell Ther 2021 Nov 21. Epub 2021 Nov 21.

Unit of Haematology and Stem Cell Transplant Centre, "San Camillo" Hospital, Rome, Italy.

Background: Nowadays, allogeneic stem cell transplantation (Allo-SCT) can be offered to patients up to the age of 70-72 years and represents one of the most effective curative treatments for many hematological malignancies.

Objectives: The primary objective of the study is to collect data from the allo-SCTs performed in Italy from 2000 to 2017 in patients over 60 years of age to evaluate the changes in safety and efficacy outcomes as well as their distribution and characteristics over time.

Study Design: The GITMO AlloEld study (ClinicalTrials.gov: NCT04469985) is a retrospective, analysis of the allo-SCTs performed 30 Italian transplant Centers on older patients (≥ 60 years) from 2000 to 2017 (n=1,996).

Results: For the purpose of analysis, patients were grouped into three time periods: time A: 2000-2005, n=256 (12%); time B: 2006-2011, n=584 (29%); and time C: 2012-2017, n=1156 (59%). After a median follow-up of 5.6 years, the 5-year Non Relapse Mortality (NRM) remained stable (time A: 32.8%; time B: 36.2%; and time C: 35.0%, p = 0.5); the Overall Survival (OS) improved (time A: 28.4%; time B: 31.8%; and time C: 37.3%, p = 0.012); and the Cumulative Incidence of Relapse (CIR) reduced (time A: 45.3%; time B: 38.2%; time C: 30.0%, p < 0.0001). The 2-year incidence of extensive cGVHD reduced significantly (time A: 17.2%; time B: 15.8%; and time C: 12.2%, p = 0.004). Considering times A and B together (2000-2011), the 2-year NRM was positively correlated to the HCT-CI score; patients with HCT-CI of 0, 1 or 2, or ≥3 had rates of NRM of 25.2%, 33.9%, and 36.1%, respectively, (p < 0.001). Meanwhile, after 2012, the HCT-CI score was not significantlly predictive of NRM.

Conclusions: The study shows that the transplant procedure in elderly patients became more effective over time. Relapse incidence remains the major problem and strategies to prevent it are under investigation (e.g. post-transplant maintenance). Today, the selection of patients aged over 60 could be improved by combining HCT-CI and frailty assessments to better predict NRM.
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http://dx.doi.org/10.1016/j.jtct.2021.11.006DOI Listing
November 2021

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL.

Cancers (Basel) 2021 Apr 27;13(9). Epub 2021 Apr 27.

Hematology Unit, Azienda Ulss3 Serenissima, Ospedale dell'Angelo, 30174 Venezia-Mestre, Italy.

In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph- ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18-40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60-80%. The present review examines the evidence for MRD-guided therapies in AYA's Ph- ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy.
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http://dx.doi.org/10.3390/cancers13092108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123823PMC
April 2021

Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population.

Ther Adv Hematol 2020 3;11:2040620720903531. Epub 2020 Feb 3.

UOC Ematologia, Ospedale dell'Angelo, Via Paccagnella 11, Venezia, Mestre, 30174, Italy.

The outstanding therapeutic progress achieved with modern pediatric regimens in childhood acute lymphoblastic leukemia (ALL) led efforts to explore whether a similar treatment approach could be equally effective and safe in older patients, starting initially with older adolescents and young adults (AYA), variably defined in different studies by an age between 15-18 and 25-39 years. Several comparative and noncomparative trials of this type have been carried out during the last two decades, enrolling thousands of patients. Almost without exception, the new strategy improved patients' outcomes compared with traditional adult treatments in B-lineage and T-lineage Philadelphia (Ph) chromosome-negative B-ALL, while the use of tyrosine kinase inhibitors (TKI) led to comparative progress in Ph+ ALL, a former high-risk subset more typically observed in older age groups. At present, highly effective pediatric-based regimens warrant 5-year survival rates of 60-70% in AYA patients. In view of these data, the same approach was progressively extended to older patients, improving the results up to 55 years of age. Issues of treatment compliance and drug-related toxicity have thus far prevented a comparable therapeutic advancement in patients aged >55 years. This critical review updates and summarizes with pertinent examples this global, positive therapeutic change, and examines how to promote further progress with new targeted therapies that include novel immuno-therapeutics and other agents developed against the many molecular dysfunctions detectable in various ALL subsets. Substantial progress is expected to occur soon, bringing AYA survival figures very close to that of children, and also to improve the outcome of ALL at all ages.
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http://dx.doi.org/10.1177/2040620720903531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997963PMC
February 2020

Counting circulating endothelial cells in allo-HSCT: an ad hoc designed polychromatic flowcytometry-based panel versus the CellSearch System.

Sci Rep 2019 01 14;9(1):87. Epub 2019 Jan 14.

Laboratory for Stem Cells Manipulation and Cryopreservation, Dpt of Transfusion Medicine, ASST Spedali Civili, Brescia, Italy.

Physio-pathologic interrelationships between endothelial layer and graft-versus-host disease (GVHD) have been described leading to assess the entity "endothelial GVHD" as the early step for clinical manifestations of acute GVHD. The availability of the CellSearch system has allowed us to monitor Circulating Endothelial Cells (CEC) changes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) as useful tool to help clinicians in GVHD diagnostic definition. We have compared CEC counts generated by an ad hoc designed polychromatic-flowcytometry (PFC) Lyotube with those of the CellSearch system. CEC were counted in parallel at 5 timepoints in 50 patients with malignant hematologic disorders undergoing allo-HSCT (ClinicalTrials.gov, NCT02064972). Spearman rank correlation showed significant association between CEC values at all time points (p = 0.0001). The limits of agreement was demonstrated by Bland Altman plot analysis, showing bias not significant at T1, T3, T4, while at T2 and T5 resulted not estimable. Moreover, Passing Bablok regression analysis showed not significant differences between BD Lyotube and CellSearch system. We show that CEC counts, generated with either the CellSearch system or the PFC-based panel, have a superimposable kinetic in allo-HSCT patients and that both counting procedures hold the potential to enter clinical routine as a suitable tool to assist clinicians in GVHD diagnosis.
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http://dx.doi.org/10.1038/s41598-018-36442-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331628PMC
January 2019

Bacterial Blood Stream Infections Negatively Impact on Outcome of Patients Treated with Allogeneic Stem Cell Transplantation: 6 Years Single-Centre Experience.

Mediterr J Hematol Infect Dis 2017 20;9(1):e2017036. Epub 2017 Jun 20.

Chair of Hematology, Clinical and Experimental Sciences Department, University of Brescia, Bone Marrow Transplant Unit, ASST-Spedali Civili, Brescia, Italy, Italy.

Background: Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia.

Objectives: The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance.

Methods: We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years.

Results: Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (. 57% and P. 24%). Fluoroquinolones resistance was frequent (90% for , 92% for E. , 90% for ). Methycillin resistance of was 100%, 76% of were ESBL positive and among resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). and were the species with the highest mortality (50% and 33%, respectively).

Conclusions: These data confirm that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.
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http://dx.doi.org/10.4084/MJHID.2017.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499498PMC
June 2017

Sequential monitoring of lymphocyte subsets and of T-and-B cell neogenesis indexes to identify time-varying immunologic profiles in relation to graft-versus-host disease and relapse after allogeneic stem cell transplantation.

PLoS One 2017 11;12(4):e0175337. Epub 2017 Apr 11.

Chair of Haematology, Stem Cell Transplantation Unit, University of Brescia, Brescia, Italy.

T and B lymphocyte subsets have been not univocally associated to Graft-versus-host disease (GVHD) and relapse of hematological malignancies after stem cell transplantation (SCT). Their sequential assessment together with B and T cell neogenesis indexes has been not thoroughly analysed in relation to these changing and interrelated immunologic/clinic events yet. Lymphocyte subsets in peripheral blood (PB) and B and T cell neogenesis indexes were analysed together at different time points in a prospective study of 50 patients. Principal component analysis (PCA) was used as first step of multivariate analysis to address issues related to a high number of variables versus a relatively low number of patients. Multivariate analysis was completed by Fine-Gray proportional hazard regression model. PCA identified 3 clusters of variables (PC1-3), which correlated with acute GVHD: PC1 (pre-SCT: KRECs≥6608/ml, unswitched memory B <2.4%, CD4+TCM cells <45%; HR 0.5, p = 0.001); PC2 (at aGVHD onset: CD4+>44%, CD8+TCM cells>4%; HR 1.9, p = 0.01), and PC3 (at aGVHD onset: CD4+TEMRA<1, total Treg<4, TregEM <2 cells/μl; HR 0.5, p = 0.002). Chronic GVHD was associated with one PC (TregEM <2 cells/μl at day+28, CD8+TEMRA<43% at day+90, immature B cells<6 cells/μl and KRECs<11710/ml at day+180; HR 0.4, P = 0.001). Two PC correlated with relapse: PC1 (pre-SCT: CD4+ <269, CD4+TCM <120, total Treg <18, TregCM <8 cells/μl; HR 4.0, p = 0.02); PC2 (pre-SCT mature CD19+ >69%, switched memory CD19+ = 0 cells and KRECs<6614/ml at +90; HR 0.1, p = 0.008). All these immunologic parameters were independent indicators of chronic GVHD and relapse, also considering the possible effect of previous steroid-therapy for acute GVHD. Specific time-varying immunologic profiles were associated to GVHD and relapse. Pre-SCT host immune-microenvironment and changes of B cell homeostasis could influence GVH- and Graft-versus-Tumor reactions. The paradoxical increase of EM Treg in PB of patients with GVHD could be explained by their compartmentalization outside lymphoid tissues, which are of critical relevance for regulation of GVH reactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175337PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388479PMC
September 2017

Extracorporeal Photopheresis for Treatment of Acute and Chronic Graft Versus Host Disease: An Italian Multicentric Retrospective Analysis on 94 Patients on Behalf of the Gruppo Italiano Trapianto di Midollo Osseo.

Transplantation 2016 Dec;100(12):e147-e155

1 Hematology, Bone Marrow Transplantation Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy. 2 Immunohematology and Transfusion Medicine Unit, AO Spedali Cvili, Brescia, Italy. 3 SODc Terapia Cellulare e Medicina Trasfusionale, AOU Careggi, Firenze, Italy. 4 Divisione di Ematologia, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy. 5 SC Ematologia, Istituto Nazionale Tumori, Milano, Italy. 6 Clinica Ematologica e Unità di terapie Cellulari, DISM, Università di Udine, Italy. 7 Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Italy. 8 Unità di Cellule Staminali, Istituto Europeo di Oncologia, Milano, Italy. 9 Medicina Trasfusionale, Azienda Ospedaliero-Universitaria di Udine, Italy. 10 UO di Emotrasfusione, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy. 11 Bone Marrow Transplant Unit SODc Ematologia, AOU Careggi, Firenze, Italy.

Background: Extracorporeal photopheresis (ECP) is considered a valid second-line treatment for acute and chronic graft versus host disease (GVHD).

Methods: Ninety-four patients with acute GVHD (aGVHD) (n = 45) and chronic GVHD (cGVHD) (n = 49), retrospectively recruited in 6 Italian centers, were submitted to ECP for second-line treatment. At the time of ECP, 22 (49%) and 23 (51%) of 45 patients with aGHVD were nonresponsive and in partial remission (PR) after steroids, respectively, and all the 49 patients with cGVHD were steroid refractory.

Results: Forty-one (91%) of 45 patients with aGVHD achieved complete remission (CR) after ECP. Fifteen (33%) of 45 patients developed cGVHD. The CR rate in patients who started ECP being nonresponsive and in PR after steroid was 86% and 96%, respectively. After a median follow-up of 20 months (range, 2-72), 15 (33%) of 45 patients developed cGHVD and 16 (35%) of 45 patients died, in 3 cases for aGVHD. A trend for a better survival was seen among patients who started ECP in PR after steroid (80% vs 50% at 2 years; P = 0.07). Overall, 22 (45%) of 49 patients and 17 (35%) of 49 patients with steroid refractory cGHVD achieved CR and PR after ECP, respectively. After a median follow-up of 27 months, 44 (90%) of 49 patients are alive, 21 of whom (48%) are on steroid.

Conclusions: Extracorporeal photopheresis is confirmed as an effective second-line treatment in both aGVHD and cGVHD, because it can induce a response in more than 80% of the patients and a long-term survival in at least 50% of the cases.
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http://dx.doi.org/10.1097/TP.0000000000001466DOI Listing
December 2016

Adult onset hemophagocytic lymphohistiocytosis prognosis is affected by underlying disease and coexisting viral infection: analysis of a single institution series of 35 patients.

Hematol Oncol 2017 Dec 3;35(4):828-834. Epub 2016 Jun 3.

Hematology, Spedali Civili, Brescia, Italy.

Adult onset hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which can develop as a complication of many disorders. Early diagnosis is essential in order to avoid a fatal outcome. To confirm the diagnosis of acquired HLH made in a single institution series of adult patients with HLH-04 criteria, we applied the HScore and evaluated prognostic factors associated with clinical outcome. The median age of 35 patients was 54 (range 17-81), M/F ratio was 20/15. In 26/35 (74.3%) patients, an underlying haematological disease was present (2 Multicentric Castleman Disease, 10 B-cell Non-Hodgkin Lymphoma [NHL] and 14 T/NK-cell NHL); an autoimmune disorder was observed in four (11.4%) patients (one Still Disease, one undifferentiated connective tissue disease and two haemolytic anaemia); in five (14.3%), no underlying disease was identified. A concomitant infection by EBV was observed in 10 patients (28.6%), CMV in 8 (22.9%), HHV8 in 6 (17.1%) and HIV in 1 (2.9%). Hyperferritinemia, fever and splenomegaly were present in more than 90% of patients, whereas bone marrow hemophagocytosis in 51% of cases only. According to HScore, 34/35 patients had a >75% and 32/35 >93% probability of HLH. Four-year overall survival and HLH-free survival were 17.8% (CI 1.9-33.8) and 23.8% (CI 7.3-40.3), respectively. By multivariate analysis, presence of oedema and hyperbilirubinemia were predictors of death, whereas there was a statistically significant trend for viral infection as predictor of poor prognosis. B-NHL diagnosis was confirmed as associated to a better prognosis in comparison with T/NK lymphoma (4-year HFS 53.3% vs. 0%, p = 0.09) and similar to other aetiologies. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/hon.2314DOI Listing
December 2017

Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.

Cancer Med 2016 Feb 29;5(2):265-74. Epub 2015 Dec 29.

Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.

Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML.
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http://dx.doi.org/10.1002/cam4.593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735778PMC
February 2016

Peripheral blood WT1 expression predicts relapse in AML patients undergoing allogeneic stem cell transplantation.

Biomed Res Int 2014 17;2014:123079. Epub 2014 Aug 17.

Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, P.le Ospedali Civili 1, 25123 Brescia, Italy.

To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 10(4) from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.
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http://dx.doi.org/10.1155/2014/123079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150519PMC
June 2015

Changes in circulating endothelial cells count could become a valuable tool in the diagnostic definition of acute graft-versus-host disease.

Transplantation 2014 Oct;98(7):706-12

1 Laboratory for Stem Cells Manipulation and Cryopreservation, A.O. Spedali Civili, Brescia, Italy. 2 Department of Transfusion Medicine, A.O. Spedali Civili, Brescia, Italy. 3 Chair of Hematology, Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, A.O. Spedali Civili, Brescia, Italy. 4 Address correspondence to: Camillo Almici, M.D., Laboratory for Stem Cells Manipulation and Cryopreservation, Department of Transfusion Medicine, A.O. Spedali Civili di Brescia, Pz.le Spedali Civili, 1-25123 Brescia, Italy.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is burdened by life-threatening complications, with graft-versus-host disease (GvHD) being the major cause of morbility and mortality. Recently, clinical and physiopathologic evidences showed that vascular endothelium can be a target of GvHD in the early phase and circulating endothelial cells (CECs) represent surrogate markers of endothelial damage.

Methods: Using the CellSearch System (Veridex LLC, Raritan, NJ), CECs were counted before (T1), after conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4), and after steroid treatment (T5) in 40 patients (7 Hodgkin's Disease, 13 Acute Myeloblastic Leukemia, 5 Acute Lymphoblastic Leukemia, 8 Multiple Myeloma, 3 Chronic Lymphocytic Leukemia, 1 Non-Hodgkin Lymphoma, 1 Chronic Myeloid Leukemia, 2 Severe Aplastic Anemia) undergoing allo-HSCT.

Results: The median CEC per milliliter at T1 was 20 (n=33, range 4-718), in comparison to a value of 2 (range, 1-14) in controls (P<0.001). At T3, CEC per milliliter were 47 (range, 16-148) in GvHD patients and 92 (range, 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts from time of engraftment (T4 vs. T3) was 44% (range, -43% to 569%) in GvHD patients versus 0% (range, -49% to 2%) in patients without GvHD (P=0.003), being confirmed as significant in multivariate analysis (odds ratio, 1.04; 95% confidence interval, 1.0-1.08; P=0.04).

Conclusion: Changes in CEC count can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT and could become a valuable tool in the diagnostic definition of GvHD.
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http://dx.doi.org/10.1097/TP.0000000000000385DOI Listing
October 2014

PBSC mobilization in lymphoma patients: analysis of risk factors for collection failure and development of a predictive score based on the kinetics of circulating CD34+ cells and WBC after chemotherapy and G-CSF mobilization.

Hematol Oncol 2015 Sep 29;33(3):125-32. Epub 2014 May 29.

Division of Hematology, AOU San Giovanni Battista, Turin, Italy.

Autologous stem cell transplantation (ASCT) is a potentially curative treatment of lymphoma, but peripheral blood stem cell (PBSC) mobilization fails in some patients. PBSC mobilizing agents have recently been proved to improve the PBSC yield after a prior mobilization failure. Predictive parameters of mobilization failure allowing for a preemptive, more cost-effective use of such agents during the first mobilization attempt are still poorly defined, particularly during mobilization with chemotherapy + granulocyte colony-stimulating factor (G-CSF). We performed a retrospective analysis of a series of lymphoma patients who were candidates for ASCT, to identify factors influencing PBSC mobilization outcome. Premobilization parameters-age, histology, disease status, mobilizing protocol, and previous treatments-as well as white blood cell (WBC) and PBSC kinetics, markers potentially able to predict failure during the ongoing mobilization attempt, were analyzed in 415 consecutive mobilization procedures in 388 patients. We used chemotherapy + G-CSF in 411 (99%) of mobilization attempts and PBSC collection failed (<2 × 10(6) CD34+ PBSC/kg) in 13%. Multivariable analysis showed that only a low CD34+ PBSC count and CD34+ PBSC/WBC ratio, together with the use of nonplatinum-containing chemotherapy, independently predicted mobilization failure. Using these three parameters, we established a scoring system to predict risk of failure during mobilization ranging from 2 to 90%, thus allowing a selective use of a preemptive mobilization policy.
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http://dx.doi.org/10.1002/hon.2148DOI Listing
September 2015

Relapsing bloodstream infections during treatment of acute leukemia.

Ann Hematol 2014 May 28;93(5):785-90. Epub 2013 Nov 28.

Department of Hematology, Spedali Civili, 25123, Brescia, Italy,

Acute leukemia (AL) patients may experience more than one episode of bloodstream infection (BSI) caused by the same pathogen during the entire chemotherapy program. In order to identify factors influencing BSI recurrence (R-BSI) during subsequent phases of treatment, we analyzed all BSIs occurring to consecutively treated AL patients during a period of active epidemiologic surveillance at our institution between 2004 and 2011. Two hundred and fifty BSIs were observed in 138 patients receiving more than 1 cycle of chemotherapy. BSI due to the same pathogen recurred in 39/138 (28.3 %) patients. Gram-negative rods (GNRs) accounted for 59.6 % and Gram-positive cocci (GPCs) for 34.4 % of BSI. Four pathogens were involved in R-BSI: Escherichia coli, Pseudomonas aeruginosa, coagulase-negative staphylococci, and Streptococcus viridans. GNRs were significantly more frequent among R-BSI compared to non-relapsing BSI (nR-BSI) [69/94 (73.4 %) vs 70/156 (50.6 %), p < 0.0001]; in particular, E. coli accounted for 67 % of R-BSI vs 32.1 % of nR-BSI (p < 0.0001). Receiving more than four chemotherapy courses and having an extended spectrum β-lactamase (ESBL)-producing E. coli BSI at any time of treatment were significantly associated to R-BSI. A trend toward a higher mortality among R-BSI patients in comparison with nR-BSI was observed (17.9 and 7.1 %, respectively, p = 0.12). Among AL patients, R-BSI is a frequent phenomenon, which may contribute to the shift of epidemiology toward GNR and to a higher mortality. This should significantly impact the strategies of antibiotic prophylaxis and treatment in patients with AL.
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http://dx.doi.org/10.1007/s00277-013-1965-0DOI Listing
May 2014

Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era.

Am J Hematol 2014 Feb;89(2):119-24

Chair of Haematology, Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, 25100, Brescia, Italy.

Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01% (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα.
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http://dx.doi.org/10.1002/ajh.23593DOI Listing
February 2014

Stem cell mobilization in HIV seropositive patients with lymphoma.

Haematologica 2013 Nov 23;98(11):1762-8. Epub 2013 Aug 23.

High-dose chemotherapy with autologous peripheral blood stem cell rescue has been reported as feasible and effective in HIV-associated lymphoma. Although a sufficient number of stem cells seems achievable in most patients, there are cases of stem cell harvest failure. The aim of this study was to describe the mobilization policies used in HIV-associated lymphoma, evaluate the failure rate and identify factors influencing mobilization results. We analyzed 155 patients who underwent attempted stem cell mobilization at 10 European centers from 2000-2012. One hundred and twenty patients had non-Hodgkin lymphoma and 35 Hodgkin lymphoma; 31% had complete remission, 57% chemosensitive disease, 10% refractory disease, 2% untested relapse. Patients were mobilized with chemotherapy + G-CSF (86%) or G-CSF alone (14%); 73% of patients collected >2 and 48% >5 × 10(6) CD34(+) cells/kg. Low CD4+ count and refractory disease were associated with mobilization failure. Low CD4(+) count, low platelet count and mobilization with G-CSF correlated with lower probability to achieve >5 × 10(6) CD34(+) cells/kg, whereas cyclophosphamide ≥ 3 g/m(2) + G-CSF predicted higher collections. Circulating CD34(+) cells and CD34/WBC ratio were strongly associated with collection result. HIV infection alone should not preclude an attempt to obtain stem cells in candidates for autologous transplant as the results are comparable to the HIV-negative population.
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http://dx.doi.org/10.3324/haematol.2013.089052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815178PMC
November 2013

Treatment of chronic myeloid leukemia elderly patients in the tyrosine kinase inhibitor era.

Curr Cancer Drug Targets 2013 Sep;13(7):755-67

Chair of Hematology, Unit of Blood Diseases and Cell Therapies, University of Brescia - AO Spedali Civili Brescia, P.le Spedali Civili 1, 25100 Brescia, Italy.

The prevalence of chronic myeloid leukemia (CML) is expected to double in the next 15 years. The introduction of imatinib significantly changed the prognosis of CML, challenging the concept of a fatal disease. Nowdays, imatinib, nilotinib and dasatinib are registered for first-line treatment of CML patients in chronic phase (CP). Considering elderly patients, the most extensively studied TKI is imatinib, that induces a rate of cytogenetic and molecular responses comparable between the younger and the elderly patients. Once a CCgR with imatinib is achieved, the probability to be alive and disease free at 8 years is more than 80%. These results confirm that imatinib has to be considered the first-line treatment for the elderly and that the CCgR is the guide parameter for treatment modulation and the most solid marker of long term outcome. Nevertheless, older patients tolerate imatinib worse in comparison to the younger, and this causes a higher rate of therapy discontinuation and less adherence to chronic treatment. Thus, the toxic profile of each TKI is one of the most important factors driving the choice of the best drug. Another important factor is the potency of the TKI. Since nilotinib and dasatinib are more potent than imatinib in inducing cytogenetic and molecular responses, they could be preferred for increasing the proportion of patients who can achieve deeper molecular responses, allowing treatment discontinuation. This approach is intriguing, but it is still experimental. Another therapeutic strategy could be the identification of the minimal effective dose of TKI in order to maintain the CCgR, but also this approach is under clinical investigation.
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http://dx.doi.org/10.2174/15680096113139990090DOI Listing
September 2013

Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia.

Blood 2013 Jun 15;121(26):5138-44. Epub 2013 May 15.

Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, Brescia, Italy.

We report a study of an alternative treatment schedule of imatinib (IM) in chronic myeloid leukemia (CML). Seventy-six Philadelphia-positive (Ph+), BCR-ABL-positive patients aged 65 years or older who had been treated with IM for more than 2 years and who were in stable complete cytogenetic response (CCgR) and major molecular response (MMR) were enrolled in a single-arm study to test the effects of a policy of intermittent IM (INTERIM) therapy for 1 month on and 1 month off. With a minimum follow-up of 4 years, 13 patients (17%) lost CCgR and MMR and 14 (18%) lost MMR only. All these patients resumed continuous IM and all but one (lost to follow-up) regained CCgR and MMR. No patients progressed to accelerated or blastic phase or developed clonal chromosomal abnormalities in Ph+ cells or BCR-ABL mutations. In elderly Ph+ CML patients carefully selected for a stable CCgR (lasting >2 years), the policy of INTERIM treatment affected the markers of residual disease, but not the clinical outcomes (overall and progression-free survival). This trial was registered at www.clinicaltrials.gov as NCT 00858806.
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http://dx.doi.org/10.1182/blood-2013-01-480194DOI Listing
June 2013

Prospective phase II Study on 5-days azacitidine for treatment of symptomatic and/or erythropoietin unresponsive patients with low/INT-1-risk myelodysplastic syndromes.

Clin Cancer Res 2013 Jun 17;19(12):3297-308. Epub 2013 Apr 17.

Chair of Hematology, Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Brescia, Italy.

Purpose: This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response.

Experimental Design: The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles.

Results: Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3-4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses.

Conclusions: 5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-12-3540DOI Listing
June 2013

Profile of toll-like receptors on peripheral blood cells in relation to acute graft-versus-host disease after allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2013 Feb 26;19(2):227-34. Epub 2012 Sep 26.

Stem Cell Transplantation Unit, Department of Hematology, University of Brescia, Brescia, Italy.

Toll-like receptors (TLRs) play a key role in the cross-talk between the innate and adaptive immune systems. Previous studies investigating associations between certain TLRs and acute graft-versus-host disease (aGVHD) have reported contrasting results, and no studies relating aGVHD to the expression and function of all human TLRs together have been published to date. We prospectively evaluated the expression of 9 TLRs on T lymphocytes and monocytes by flow cytometry in relation to aGVHD in 34 patients. Induction of TNF-α, IL-4, IFN-γ, and monocyte chemotactic protein 1 on TLR activation was assessed by ELISA on cell supernatants. Nineteen patients developed aGVHD, at a median time of 28 days (range, 20-50 days) after transplantation. A 2-step multivariate analysis was performed using principal component analysis and multifactor analysis of variance. The levels of TLR-5 expression on monocytes and T lymphocytes were positively correlated to aGVHD (P = .01), whereas levels of TLR-1 and -9 were negative predictors (P = .03 and .01, respectively). This profile of TLR-1, -5, and -9 can promote an overall immunostimulatory/proinflammatory response. If our findings are confirmed by further studies, this TLR profile could be a useful biomarker of aGVHD.
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http://dx.doi.org/10.1016/j.bbmt.2012.09.013DOI Listing
February 2013

A simple prognostic scoring system for newly diagnosed cytogenetically normal acute myeloid leukemia: retrospective analysis of 530 patients.

Leuk Lymphoma 2011 Dec 12;52(12):2329-35. Epub 2011 Jul 12.

Chair of Hematology, Unit of Blood Disease and Cell Therapy, Spedali Civili Hospital, Brescia, Italy.

We retrospectively analyzed the data of 337 patients with cytogenetically normal (CN) acute myeloid leukemia (AML), aged ≤ 65 years (training set). A prognostic index score (PIS) was calculated by totaling the score derived from the regression coefficients of each clinical variable, significantly associated with prognosis by multivariate analysis. The variables that were independent prognostic factors for event-free survival (EFS) and overall survival (OS) in the training set were: age ≥ 50 years, secondary AML and white blood cell count (WBC) ≥ 20 × 10(9)/L. The patients of the training set were stratified into three groups: low-, intermediate- and high-risk. The median EFS was 25, 12 and 7 months in the low-, intermediate- and high-risk groups (p < 0.0001), respectively. The median OS was not reached in the low-risk group and was 19 and 10 months in the intermediate- and high-risk groups (p < 0.0001). This PIS was validated in a series of 193 patients with CN-AML. The median EFS was 66, 16, and 3 months (p < 0.0001) and the median OS was 66, 16, and 5 months in the three risk groups, respectively (p < 0.0001). This PIS may be useful for clinical decision-making in CN-AML and may be prospectively integrated with the newest biological markers which at present are not routinely assessed and need prognostic validation.
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http://dx.doi.org/10.3109/10428194.2011.596965DOI Listing
December 2011

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases.

Eur J Haematol 2008 Nov 19;81(5):354-63. Epub 2008 Aug 19.

Unit of Blood Diseases and Cell Therapies, University of Brescia, Brescia, Italy.

Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections.

Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients
Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation.

Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.
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http://dx.doi.org/10.1111/j.1600-0609.2008.01122.xDOI Listing
November 2008

The use of G-CSF during first line chemotherapy adversely affects the yield of PBSC mobilization in non-Hodgkin's lymphoma patients.

Adv Clin Path 2002 Jan;6(1):11-6

Chair and Division of Hematology, Bone Marrow Transplant Unit, Department of Medical and Morphological Research, University Hospital, Udine, Italy.

Regardless the mobilization procedure used there is a great variability from patient to patient in the yield of CD34 collections for autologous transplantation. We analyzed retrospectively our non-Hodgkin's lymphoma survey of 60 patients harvested with G-CSF alone after a unique first line chemotherapy; 67% of patients harvested a sufficient number of CD34+ cells during the first attempt of mobilization. The charachteristics of leukaphereses procedures were the same for all the patients. Sex, age, months from the end of chemo- or radio-therapy did not have a significance in influencing mobilization capability, while requirement of G-CSF during chemotherapy was statistically different from failures to successes: 16/20 (80%) of patients failing to reach the target of 2x10(6)/kg CD34+ cells had required G-CSF support during previous chemotherapy versus 18/40 (45%) in the successful group (p 0,005). Our observation supports the hypotesis that individual biological charachteristics of each patient are the most important factors in affecting mobilization capability, deserving further investigation: mobilization schedules tailored on a given patient would minimize the rate of failures, avoiding a second attempt of collection that implies additional economic expenses and negative consequences on the maintenance of dose intensity.
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January 2002

Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients.

Br J Haematol 2007 Jan;136(1):87-95

Chair of Haematology, Unit of Blood Diseases and Cell Therapies, University of Brescia, Brescia, Italy.

One hundred and six patients aged /= 6) vs. 75% among the MDR-Pgp-negative (neg(ve)) ones (MFI < 6) (P = 0.16). Conversely, in the controls, the CR rate was 44% among the MDR-Pgp-pos(ve) patients vs. 67% among the MDR-Pgp-neg(ve) ones (P = 0.02). The 4-year disease-free survival (DFS) and overall survival (OS) of MDR-Pgp-pos(ve) cases were significantly longer than those of MDR-Pgp-pos(ve) controls (DFS, 28.1% vs. 6.5%, P = 0.004; OS, 33.5% vs. 9.6%, P = 0.01). This difference was not found among the MDR-Pgp-neg(ve) patients. By univariate (P = 0.007) and multivariate (P = 0.007) analysis, the MDR-Pgp-pos(ve) phenotype was negatively correlated with CR and it emerged as the most important independent negative prognostic factor, after cytogenetics. Our study confirms the prognostic impact of the MDR phenotype in AML and strongly suggests fludarabine-based induction treatments as a promising strategy for MDR-Pgp-pos(ve) AML patients. In this setting of patients, large prospective randomised studies should be planned.
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http://dx.doi.org/10.1111/j.1365-2141.2006.06390.xDOI Listing
January 2007

Effect on survival of the development of late-onset non-infectious pulmonary complications after stem cell transplantation.

Haematologica 2006 Sep;91(9):1268-72

Division of Haematology, Transplantation Unit and Cellular Therapies Carlo Melzi, Department of Clinical and Morphological Research, University Hospital of Udine.

We evaluated the incidence, risk factors, and clinical outcome of late-onset non-infectious pulmonary complications (LONIPC) in 599 patients who underwent hematopoietic allogeneic stem cell transplantation (HSCT). The 2-year cumulative incidence of LONIPC was 10% among the 438 patients surviving more than 3 months after HSCT. Transplants from an unrelated donor and occurrence of extensive chronic graft-versus-host disease were the variables significantly associated with the development of LONIPC. The 5-year overall survival was significantly worse among patients with LONIPC than among those without (34% vs 65%, p=0.009). Causes of death were respiratory failure and infections. The relapse rate was similar in the two groups.
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September 2006

The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery.

Exp Hematol 2006 Mar;34(3):389-96

Division of Haematology and Blood and Bone Marrow Transplantation Unit "Carlo Melzi," Department of Clinical and Morphological Research, Udine, Italy.

Objective: Chronic graft-vs-host disease (GVHD) has certain similarities with autoimmune diseases and is associated with the development of various autoantibodies in some patients. In this study, we analyzed the occurrence of autoantibodies in 63 patients surviving longer than 3 months after an allogeneic haematopoietic stem cell transplantation (HSCT), with the aim of detecting a possible association between occurrence of autoantibodies and development of chronic GVHD and immune recovery after HSCT.

Patients And Methods: The patients were screened every 3 months for the occurrence of the following autoantibodies: anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-cardiolipin (ACLA), anti-liver-kidney microsomal (LKM), anti-DNA, anti-neutrophil cytoplasmatic (ANCA), and anti-thyroid antibodies. Peripheral blood immunophenotyping with anti-CD3, CD4, CD8, CD19, CD20, CD16, and CD56 antibodies was evaluated at the same intervals.

Results: Autoantibodies were not found in 18 patients (29%), at least in one screening in 29 patients (46%), and in all screenings in 16 patients (25%). ANA were found in 41 patients (65%), AMA in 4 (6%), ASMA in 4 (6%), ANCA in 7 (11%), ACLA in 1 (2%), anti-thyroid antibodies in 3 (5%), and anti-DNA in 2 (3%). More than one antibody occurred in 16/63 (25%) positive patients. ANA was significantly more frequent in patients with chronic GVHD and, among these, in those with the extensive form. The nucleolar pattern of immunofluorescence of ANA but not its titer was correlated with the extension of chronic GVHD. Patients who developed autoantibodies had higher CD20(+) cell blood counts than negative patients in the third month (p=0.006), ninth month (p=0.061), and twelfth month (p=0.043).

Conclusion: We conclude that patients with chronic GVHD, particularly those with an extensive involvement, were likely to develop autoantibodies and have a faster B-cell recovery, suggesting a role of B cells in the pathogenesis of chronic GVHD.
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http://dx.doi.org/10.1016/j.exphem.2005.12.011DOI Listing
March 2006

Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome.

Haematologica 2006 Feb;91(2):258-61

Division of Haematology, Dept. of Clinical and Morphological Research, University of Udine.

Scleroderma may be one of the most severe forms of chronic graft-versus-host disease (GVHD). We retrospectively evaluated its incidence, predictor variables and outcome in 133 patients who survived at least 4 months after allogeneic hematopoietic stem cell transplantation. The 5-year cumulative incidence was 15.5% in patients with chronic GVHD. The generalized form had a progressive course despite immunosuppressive therapy. Eosinophilia, autoimmune markers, and previous skin involvement by chronic GVHD with disorders of pigmentation were significantly associated with an increased probability of developing scleroderma.
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February 2006

Successful treatment of hematological and extramedullary relapse of MLL-positive acute lymphoblastic leukemia after bone marrow transplantation using donor leukocyte infusion.

Ann Hematol 2004 Oct 5;83(10):667-9. Epub 2004 Aug 5.

Low response rates (range: 0-33%) were reported in acute lymphoblastic leukemia (ALL) patients who relapsed after bone marrow transplantation (BMT) and received donor leukocyte infusions (DLI). We describe an ALL patient who presented with a relapse in blood, bone marrow, breast, and axillary nodes 3 months after BMT from an unrelated donor. She achieved a second hematological complete remission (CR) after chemotherapy, with persistence of MLL-AF4 transcript in the bone marrow. DLI induced a long-lasting molecular CR that persisted on day 630 of DLI and was associated with a grade III graft-versus-host disease, which was controlled by prednisone, cyclosporine, and infliximab. This case report suggests the existence of an important graft-versus-leukemia (GVL) effect in patients with ALL and adds evidence for the activity of DLI towards extrahematological recurrences and ALL patients carrying t(4;11).
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http://dx.doi.org/10.1007/s00277-004-0880-9DOI Listing
October 2004

Autologous stem cell transplantation for Hodgkin's lymphoma: results and prognostic factors in 51 high-risk patients.

Adv Clin Path 2002 Apr;6(2):77-85

Division of Haematology, Bone Marrow Transplant Unit, Department of Medical and Morphological Research, University Hospital, Udine, Italy.

Autologous stem cell transplantation (ASCT) is largely employed in primary resistant or recurrent Hodgkin's Lymphoma (HL), while its role early in the course of the disease is still controversial. Our purpose was to analyse the results of 51 high-risk HL patients autografted at our Institution and the role of possible prognostic risk factors for the outcome. Twelve (23.5%) patients were in complete remission at transplant and were transplanted as having an high risk disease; 20 (39.5%) patients were in partial response and 19 (37.0%) were transplanted as primary induction failure. At a median time of 38 (6-111) months from ASCT, 36 (70.5%) patients are alive in complete remission, 8 (15.5%) patients are alive with disease and 7 (14.0%) died for progression. Thirty out of 32 (94.0%) patients transplanted with responsive disease (either complete or partial response) are alive without disease. Six out of 19 (32.0%) patients transplanted with resistant disease are alive in complete remission. The overall survival of the entire population is 77.0% at 60 (14-151) months from diagnosis. Disease free survival of the 22 patients that achieved a complete remission after ASCT (16 in partial response and 6 with resistant disease) is 100%. In our experience, more than 90% of patients transplanted with responsive but high risk disease, seem achieving and maintaining a durable complete remission, and more than 30.0% of patients submitted to ASCT with refractory disease can be potentially rescued by transplant.
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April 2002
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