Publications by authors named "Alessandra Sperotto"

39 Publications

Haploidentical transplant after failure of a first allogeneic transplant: a long and winding road.

Eur J Haematol 2021 Mar 1. Epub 2021 Mar 1.

Division of Hematology and Bone Marrow Transplantation, Department of Medical Area, University of Udine, Italy.

In a recent manuscript entitled "Haploidentical transplant for patients with relapse after first allograft", Srour et al. reported on 29 patients that underwent an haploidentical transplantation (haplo-SCT) for relapse after a first allogeneic SCT for different hematological malignancies, mostly AML, with a 3-year overall survival (OS) of 40%. Moreover, they found that lower comorbidity index (HCT-CI) and lack of donor-specific anti-HLA antibodies were correlated with a significantly better outcome (3-year OS 60% in patients with HCT-CI < 3 and no detectable antibodies).
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http://dx.doi.org/10.1111/ejh.13611DOI Listing
March 2021

Feasibility and Predictive Performance of a Triage System for Patients with Cancer During the COVID-19 Pandemic.

Oncologist 2021 Feb 4. Epub 2021 Feb 4.

Department of Hematology, Santa Maria della Misericordia Hospital, Udine, Italy.

Background: Triage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID-19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting.

Materials And Methods: This retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID-19 pandemic (March 30 to April 30, 2020). A total of 3,923 triage procedures were performed, and data of 1,363 individual patients were reviewed.

Results: A self-report triage questionnaire identified 6% of triage-positive procedures, with a sensitivity of 66.7% (95% confidence interval [CI], 43.0%-85.4%), a specificity of 94.3% (95% CI, 93.5%-95.0%), and a positive predictive value of 5.9% (95% CI, 4.3%-8.0%) for the identification of patients who were not admitted to the hospital after medical review. Patients with thoracic cancer (odds ratio [OR], 1.69; 95% CI, 1.13-2.53, p = .01), younger age (OR, 1.52; 95% CI, 1.15-2.01, p < .01), and body temperature at admission ≥37°C (OR, 9.52; 95% CI, 5.44-16.6, p < .0001) had increased risk of positive triage. Direct hospital access was warranted to 93.5% of cases, a further 6% was accepted after medical evaluation, whereas 0.5% was refused at admission.

Conclusion: A self-report questionnaire has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. Differential diagnosis with tumor- or treatment-related symptoms is always required to avoid unnecessary treatment delays. Body temperature measurement improves the triage process's overall sensitivity, and widespread SARS-CoV-2 testing should be implemented to identify asymptomatic carriers.

Implications For Practice: This is the first study to provide data on the predictive performance of a triage system in the oncological setting during the coronavirus disease outbreak. A questionnaire-based triage has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms, and a differential diagnosis with tumor- or treatment-related symptoms is mandatory to avoid unnecessary treatment delays. Consequently, adequate recourses should be reallocated for a triage implementation in the oncological setting. Of note, body temperature measurement improves the overall sensitivity of the triage process, and widespread testing for SARS-CoV-2 infection should be implemented to identify asymptomatic carriers.
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http://dx.doi.org/10.1002/onco.13706DOI Listing
February 2021

Risk Factors and Outcome of Infection after Hematopoietic Stem Cell Transplantation.

J Clin Med 2020 Nov 16;9(11). Epub 2020 Nov 16.

Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy.

Patients who undergo hematopoietic stem cell transplants (HSCT) are at major risk of (CD) infection (CDI), the most common cause of nosocomial diarrhea. We conducted a retrospective study, which enrolled 481 patients who underwent autologous (220) or allogeneic HSCT (261) in a 5-year period, with the aim of identifying the incidence, risk factors and outcome of CDI between the start of conditioning and 100 days after HSCT. The overall cumulative incidence of CDI based upon clinical evidence was 5.4% (95% CI, 3.7% to 7.8%), without any significant difference between the two types of procedures. The median time between HSCT and CDI diagnosis was 12 days. Out of 26 patients, 19 (73%) with clinical and symptomatic evidence of CDI were positive also for enzymatic or molecular detection of toxigenic CD; in particular, in 5 out of 26 patients (19%) CD binary toxin was also detected. CDI diagnoses significantly increased in the period 2018-2019, since the introduction in the microbiology lab unit of the two-step diagnostic test based on GDH immunoenzymatic detection and toxin B/binary toxin/027 ribotype detection by real-time PCR. Via multivariate analysis, abdominal surgery within 10 years before HSCT ( = 0.002), antibiotic therapy within two months before HSCT ( = 0.000), HCV infection ( = 0.023) and occurrence of bacterial or fungal infections up to 100 days after HSCT ( = 0.003) were significantly associated with a higher risk of CDI development. The 26 patients were treated with first-line vancomycin (24) or fidaxomicine (2) and only 2 patients needed a second-line treatment, due to the persistence of stool positivity. No significant relationship was identified between CDI and the development of acute graft versus host disease (GVHD) after allogeneic HSCT. At a median follow-up of 25 months (range 1-65), the cumulative incidence of transplant related mortality (TRM) was 16.6% (95% CI 11.7% to 22.4%) and the 3-year overall survival (OS) was 67.0% (95% CI 61.9% to 71.6%). The development of CDI had no significant impact on TRM and OS, which were significantly impaired in the multivariate analysis by gastrointestinal and urogenital comorbidities, severe GVHD, previous infections or hospitalization within two months before HSCT, active disease at transplant and occurrence of infections after HSCT. We conclude that 20% of all episodes of diarrhea occurring up to 100 days after HSCT were related to toxigenic CD infection. Patients with a history of previous abdominal surgery or HCV infection, or those who had received broad spectrum parenteral antibacterial therapy were at major risk for CDI development. CDIs were successfully treated with vancomycin or fidaxomicin after auto-HSCT as well as after allo-HSCT.
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http://dx.doi.org/10.3390/jcm9113673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696044PMC
November 2020

Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Front Oncol 2020 15;10:572918. Epub 2020 Oct 15.

Ematologia, Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy.

We conducted a retrospective multicenter study including pediatric and adult patients with acute leukemia (AL) who received donor lymphocyte infusions (DLIs) after allogeneic hematopoietic stem cell transplantation (HCT) between January 1, 2010 and December 31, 2015, in order to determine the efficacy and toxicity of the immune treatment. Two hundred fifty-two patients, median age 45.1 years (1.6-73.4), were enrolled from 34 Italian transplant centers. The underlying disease was acute myeloid leukemia in 180 cases (71%). Donors were HLA identical or 1 locus mismatched sibling (40%), unrelated (40%), or haploidentical (20%). The first DLI was administered at a median time of 258 days (55-3,784) after HCT. The main indication for DLI was leukemia relapse (73%), followed by mixed chimerism (17%), and pre-emptive/prophylactic use (10%). Ninety-six patients (38%) received one single infusion, whereas 65 (26%), 42 (17%), and 49 patients (19%) received 2, 3, or ≥4 infusions, respectively, with a median of 31 days between two subsequent DLIs. Forty percent of evaluable patients received no treatment before the first DLI, whereas radiotherapy, conventional chemotherapy or targeted treatments were administered in 3, 39, and 18%, respectively. In informative patients, a few severe adverse events were reported: grade III-IV graft versus host disease (GVHD) (3%), grade III-IV hematological toxicity (11%), and DLI-related mortality (9%). Forty-six patients (18%) received a second HCT after a median of 232 days (32-1,390) from the first DLI. With a median follow-up of 461 days (2-3,255) after the first DLI, 1-, 3-, and 5- year overall survival (OS) of the whole group from start of DLI treatment was 55, 39, and 33%, respectively. In multivariate analysis, older recipient age, and transplants from haploidentical donors significantly reduced OS, whereas DLI for mixed chimerism or as pre-emptive/prophylactic treatment compared to DLI for AL relapse and a schedule including more than one DLI significantly prolonged OS. This GITMO survey confirms that DLI administration in absence of overt hematological relapse and multiple infusions are associated with a favorable outcome in AL patients. DLI from haploidentical donors had a poor outcome and may represent an area of further investigation.
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http://dx.doi.org/10.3389/fonc.2020.572918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593406PMC
October 2020

Gemtuzumab ozogamicin in acute myeloid leukemia: past, present and future.

Minerva Med 2020 Oct 21;111(5):395-410. Epub 2020 Sep 21.

Unit of Hematology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Forlì-Cesena, Italy.

After being in the therapeutic wilderness for several decades, acute myeloid leukemia has been recently thrust into the limelight with a series of drug approvals. Technical refinements in production, genetic manipulation and chemical modification of monoclonal antibodies led to growing interest in antibodies-based treatment strategies. Much of the focus of these efforts in acute myeloid leukemia has been on CD33 as a target. On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin for treatment of relapsed or refractory CD33+ acute myeloid leukemia. This signals a new chapter in the long and unusual story of gemtuzumab ozogamicin, which was the first antibody-drug conjugate approved for human use by the Food and Drug Administration. In this review we have analyzed the history of this drug which, among several mishaps, is experiencing a second youth and still represents a field to be further explored.
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http://dx.doi.org/10.23736/S0026-4806.20.07019-6DOI Listing
October 2020

Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy.

Blood Adv 2020 08;4(16):3900-3912

Department of Oncology/Hematology, Azienda Ospedaliera Universitaria (AOU) Città della Salute e della Scienza di Torino, Presidio Molinette, Turin, Italy.

Donor selection contributes to improve clinical outcomes of T-cell-replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.
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http://dx.doi.org/10.1182/bloodadvances.2020001620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448598PMC
August 2020

Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2017 Feb 4;23(2):333-339. Epub 2016 Nov 4.

Clinica Ematologica, Dipartimento di Scienze Sperimentali e Cliniche, Università di Udine, Udine, Italy.

The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count < .1 × 10/L). In multivariate analysis, allogeneic transplant and colonization with MDR GN bacteria at admission to the transplant unit were significantly associated with an increased risk of infection. Although we observed neither transplant-related mortality (TRM) nor deaths due to infections by MDR GN bacteria after autologous transplant, in the allogeneic setting a significant difference was reported in terms of overall survival (OS) and TRM between patients who developed infections and those who did not (1-year OS, 39% versus 68%; 1-year TRM, 42% versus 19%). In multivariate analysis, refractory disease and development of grades III to IV graft-versus-host disease (GVHD) were factors that affected both TRM and OS, whereas occurrence of infections by MDR GN pathogens significantly reduced OS. We conclude that eligibility to allogeneic HSCT in MDR GN bacteria carriers should be carefully evaluated together with all other factors that independently influence outcome (disease status, donor, and GVHD risk).
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http://dx.doi.org/10.1016/j.bbmt.2016.11.005DOI Listing
February 2017

ABCG2 overexpression in patients with acute myeloid leukemia: Impact on stem cell transplantation outcome.

Am J Hematol 2015 Sep 22;90(9):784-9. Epub 2015 Jul 22.

Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.

ABGG2 protein overexpression in acute myeloid leukemia (AML) has been associated with poor response to conventional chemotherapy and increased relapse risk. No data are available on the role of allogeneic stem cell transplantation (SCT) in reversing its negative prognostic role. We have reviewed the outcome of 142 patients with high risk AML who underwent allogeneic SCT in complete remission (n = 94) or with active disease (n = 48). Patients with ABCG2 overexpression at AML diagnosis have lower leukemia free survival (LFS) and increased cumulative incidence of relapse (CIR) compared with ABCG2- patients (5-year LFS 50% vs. 65%, P = 0.01; 5-year CIR 46% vs. 27%, P = 0.003). Five-year overall survival was not significantly different between ABCG2+ and ABCG2- patients (39% vs. 51%, P = 0.1). However, if we consider only disease-related deaths, ABCG2 maintains its negative role (64% vs. 78%, P = 0.018). The negative impact of ABCG2 overexpression was higher in patients undergoing SCT in CR compared with patients receiving transplant with active disease. Conditioning regimen did not abrogate the effect of ABCG2 overexpression, as CIR was higher in ABCG2+ patients receiving both myeloablative (44% vs. 22%, P = 0.018) or reduced intensity conditioning (50% vs. 32%, P = 0.03). In conclusion, ABCG2 overexpression at AML diagnosis identifies a subset of patients with poor outcome also after allogeneic SCT, mainly in terms of higher relapse rates. Prospective studies employing conditioning drugs or post-transplant strategies able to target ABCG2 are needed to maximize the curative potential of stem cell transplantation.
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http://dx.doi.org/10.1002/ajh.24084DOI Listing
September 2015

The role of positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in the evaluation of patients with multiple myeloma undergoing allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2015 Jun 6;21(6):1068-73. Epub 2015 Mar 6.

Hematology, DISM, University of Udine, Italy.

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.
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http://dx.doi.org/10.1016/j.bbmt.2015.03.001DOI Listing
June 2015

Brentuximab vedotin in combination with extended field radiotherapy as salvage treatment for primary refractory Hodgkin lymphoma.

Am J Hematol 2015 Apr 9;90(4):E73. Epub 2015 Mar 9.

Clinica Ematologica, Centro Trapianti E Terapie Cellulari "Carlo Melzi", DISM, Azienda Ospedaliera Universitaria S. Maria Misericordia, Udine, Italy.

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http://dx.doi.org/10.1002/ajh.23925DOI Listing
April 2015

Long lasting remission after haploidentical stem cell transplant and pre-emptive donor lymphocyte infusions in a patient with primary refractory Hodgkin lymphoma.

Leuk Lymphoma 2015 Apr 13;56(4):1129-31. Epub 2014 Aug 13.

Department of Hematology, Stem Cell Transplant Unit, DISM, University Hospital , Udine , Italy.

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http://dx.doi.org/10.3109/10428194.2014.946024DOI Listing
April 2015

Factors affecting outcome of allogeneic stem cell transplantation as salvage in patients with acute myeloid leukemia primary refractory to intensive induction therapy.

Am J Hematol 2014 Sep 19;89(9):933-4. Epub 2014 Jun 19.

Division of Hematology and Bone Marrow Transplantation, Department of Clinical and Experimental Medical Sciences, AOU Udine, Udine, Italy.

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http://dx.doi.org/10.1002/ajh.23769DOI Listing
September 2014

Bortezomib plus dexamethasone followed by escalating donor lymphocyte infusions for patients with multiple myeloma relapsing or progressing after allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2013 Mar 8;19(3):424-8. Epub 2012 Nov 8.

Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, Italy.

Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen-identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective.
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http://dx.doi.org/10.1016/j.bbmt.2012.10.032DOI Listing
March 2013

Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia.

Ann Hematol 2012 Dec 15;91(12):1937-43. Epub 2012 Aug 15.

Division of Hematology and Bone Marrow Transplantation & Department of Experimental and Clinical Medical Sciences, Azienda Ospedaliero-Universitaria di Udine, P.zzale S. M. Misericordia, 15, 33100 Udine, Italy.

We retrospectively analysed 78 patients with relapsed (n = 38), primary refractory (n = 34) or untreated (n = 6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47 %) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29 %). With a median follow-up time of 5 years, 13 of 78 patients (17 %) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58 %), infection in ten patients (16 %) and GVHD in six (9 %). One-year non-relapse mortality was 35 %. In multivariate analysis, performance status ≥80 % WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P = 0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.
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http://dx.doi.org/10.1007/s00277-012-1551-xDOI Listing
December 2012

Efficacy and safety of peripheral blood stem cell mobilization and collection: a single-center experience in 190 allogeneic donors.

Transfusion 2012 Nov 27;52(11):2387-94. Epub 2012 Mar 27.

Transfusion Medicine Department and the Clinic of Haematology, University Hospital of Udine, and the Department of Statistics, University of Udine, Udine, Italy.

Background: In the past two decades peripheral blood stem cells (PBSCs) have increasingly replaced marrow as stem cells source for allogeneic transplantation. The PBSC donation initially applied only to related donors; later, due to the safety of the procedure, it was extended to unrelated donors.

Study Design And Methods: We have retrospectively collected data regarding mobilization, collection, and short- and long-term follow-up of 190 consecutive donors, 174 related and 16 unrelated. All donors followed a standard protocol for mobilization and underwent at least one PBSC collection. Follow-up in related donors was performed every 4 months in the first year and then annually, with no time limits, while unrelated donors were monitored for 10 years.

Results: All 190 donors completed the established mobilization protocol. The mobilizing capacity was significantly greater in males and in donors less than 60 years old. No case of major toxicity by granulocyte-colony-stimulating factor was found, nor thromboembolic events. The total dose of CD34+/recipient (median 5.8×10(6)/kg recipient/body weight) was statistically correlated with age, CD34+ before and after mobilization, and collection efficiency. Compliance to follow-up was 66%, with a significant difference between related and unrelated (63% vs. 100%, p=0.03). During follow-up no significant abnormalities in hematologic variables or hematologic malignancies were reported.

Conclusion: Our study allowed us to define the PBSC donation as "a safe procedure for the donors," with short- and long-term effects limited to a small percentage of donors and "effective for the recipient," due to the dose of collected CD34+, adequate for transplantation in almost all recipients.
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http://dx.doi.org/10.1111/j.1537-2995.2012.03619.xDOI Listing
November 2012

Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability.

Biol Blood Marrow Transplant 2012 Apr 3;18(4):617-26. Epub 2011 Aug 3.

Hematology, Department of Experimental Clinical Medicine, Udine, Italy.

Allogeneic stem cell transplantation (allo-SCT) using reduced-intensity conditioning (RIC) is a feasible procedure in selected patients with relapsed multiple myeloma (MM), but its efficacy remains a matter of debate. The mortality and morbidity related to the procedure and the rather high relapse risk make the use of allo-SCT controversial. In addition, the availability of novel antimyeloma treatments, such as bortezomib and immunomodulatory agents, have made allo-SCT less appealing to clinicians. We investigated the role of RIC allo-SCT in patients with MM who relapsed after autologous stem cell transplantation and were then treated with a salvage therapy based on novel agents. This study was structured similarly to an intention-to-treat analysis and included only those patients who underwent HLA typing immediately after the relapse. Patients with a donor (donor group) and those without a suitable donor (no-donor group) were compared. A total of 169 consecutive patients were evaluated retrospectively in a multicenter study. Of these, 75 patients found a donor and 68 (91%) underwent RIC allo-SCT, including 24 from an HLA-identical sibling (35%) and 44 from an unrelated donor (65%). Seven patients with a donor did not undergo allo-SCT for progressive disease or concomitant severe comorbidities. The 2-year cumulative incidence of nonrelapse mortality was 22% in the donor group and 1% in the no-donor group (P < .0001). The 2-year progression-free survival (PFS) was 42% in the donor group and 18% in the no-donor group (P < .0001). The 2-year overall survival (OS) was 54% in the donor group and 53% in the no-donor group (P = .329). In multivariate analysis, lack of a donor was a significant unfavorable factor for PFS, but not for OS. Lack of chemosensitivity after salvage treatment and high-risk karyotype at diagnosis significantly shortened OS. In patients who underwent allo-SCT, the development of chronic graft-versus-host disease had a significant protective effect on OS. This study provides evidence for a significant PFS benefit of salvage treatment with novel drugs followed by RIC allo-SCT in patients with relapsed MM who have a suitable donor.
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http://dx.doi.org/10.1016/j.bbmt.2011.07.026DOI Listing
April 2012

Prognostic significance of delayed thrombocytopenia after allogeneic stem cell transplant.

Am J Hematol 2011 Sep 9;86(9):790-2. Epub 2011 Aug 9.

Clinica Ematologica, Centro Trapianti e Terapie Cellulari Carlo Melzi, DISM, Azienda Ospedaliero Universitaria S. M. Misericordia, 33100 Udine, Italy.

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http://dx.doi.org/10.1002/ajh.22086DOI Listing
September 2011

Outcome of allogeneic stem cell transplantation following reduced-intensity conditioninig regimen in patients with idiopathic myelofibrosis: the g.I.T.m.o. Experience.

Mediterr J Hematol Infect Dis 2010 May 8;2(2):e2010010. Epub 2010 May 8.

Division of Hematology and Cellular Therapies Unit 'Carlo Melzi', Dpt. of Morphological and Clinical Researches, University of Udine.

Background: Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for myelofibrosis (MI), though limited by a high rate of transplant-related mortality (TRM). In the present study we evaluate the outcome of MI patients undergoing an allogenic SCT after reduced intensity conditioning (RIC) regimens, and the impact of prognostic factors.

Design And Methods: Fifty two patients were transplanted in 26 Italian centres between 1998 and 2006. We analyzed the influence of patient and disease clinical features before SCT and of transplant procedures on TRM and overall survival (OS) by means of univariate and multivariate analyses.

Results: At SCT, median age was 52,5 years (32-68) and 89% of the patients had an intermediate or high Dupriez score. Conditioning regimens were based on fludarabine plus busulphan in 27% of patients, thiotepa plus cyclophosphamide in 46% and miscellaneous drug combinations in the other 27% of cases. Stem cells came from matched sibling donors for 75% of the patients and mismatched sibling or unrelated donors for the remaining 25%. The cumulative incidence of engraftment at day 90 after transplant was 83% (95% CI, 0.87-0.97). The estimated 1-year TRM was 30%. The estimated 3-year event-free-survival (EFS) and OS after hematopoietic SCT was 44% and 38% respectively. In multivariate analysis, an higher leukocyte count and circulating blasts in the peripheral blood before SCT significantly reduced EFS and OS respectively.

Interpretation And Conclusions: We conclude that the extension of the disease before transplantation based on the presence of circulating blasts and high leukocyte counts significantly affected the outcome after HSCT.
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http://dx.doi.org/10.4084/MJHID.2010.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033132PMC
May 2010

Clinical presentation, outcome and risk factors of late-onset non-infectious pulmonary complications after allogeneic stem cell transplantation.

Curr Stem Cell Res Ther 2009 May;4(2):161-7

Department of Morphological and Clinical Researches, University Hospital, Udine, Italy.

The term late-onset non-infectious pulmonary complications (LONIPCs) has been used to refer to events occurring later than 3 months after allogeneic hematopoietic stem transplant (HSCT), such as bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia, and lymphocytic or idiopathic interstitial pneumonia. The incidence of LONIPCs varies widely, ranging between 10% and 26%. Median time for LONIPC development is about 8-12 months after HSCT. Clinical symptoms may be insidious and non specific at the beginning and can be present in different types of infections. The diagnosis is made on the basis of thoracic high-resolution computed tomography and pulmonary function tests (PFT). It usually requires that standard cultures for infective agents on bronchoalveolar lavage are negative and is confirmed by transbronchial or lung biopsy, whenever possible. Total body irradiation and high doses of drugs used in the conditioning regimens, HLA disparity between donor and recipient, and chronic graft-versus-host disease (GVHD) are the main risk factors for LONIPCs. Since patients with LONIPCs have an increased risk of mortality because of infections or respiratory failure, pre- and post-transplant PFTs are strongly recommended in order to timely identify affected patients. The administration of antithymocyte globulin before unrelated donor transplants and slow taper of cyclosporine after transplant have been shown to prevent chronic GVHD and, therefore, the occurrence of LONIPCs.
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http://dx.doi.org/10.2174/157488809788167436DOI Listing
May 2009

Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

Haematologica 2008 Oct 25;93(10):1514-22. Epub 2008 Aug 25.

Division of Hematology and Cellular Therapies Unit Carlo Melzi, Department of Morphological and Medical Research, University of Udine, Udine, Italy.

Background: Allogeneic stem cell transplantation is a potentially curative treatment for myelofibrosis, although its use is limited by a high rate of transplant-related mortality. In this study, we evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors.

Design And Methods: One hundred patients were transplanted in 26 Italian centers between 1986 and 2006. We analyzed the influence of the patients' characteristics and the clinical features of their disease before stem cell transplantation and of transplant procedures on transplant-related mortality, overall survival, and relapse-free survival by means of univariate and multivariate analyses.

Results: The median age of the patients at the time of stem cell transplantation was 49 years (range, 21-68) and 90% of them had an intermediate or high Dupriez score. Forty-eight percent received a myeloablative conditioning regimen and 78% received stem cells from matched sibling donors. The cumulative incidence of engraftment at day 90 after transplant was 87% (95% CI, 0.87-0.97). The cumulative 1-year and 3-year incidences of transplant-related mortality were 35% and 43%, respectively. The estimated 3-year overall and relapse-free survival rates after stem cell transplantation were 42% and 35%, respectively. In multivariate analysis, negative predictors of transplant-related mortality were year of stem cell transplantation before 1995, unrelated donor, and a long interval between diagnosis and transplantation. There was a trend towards longer overall and relapse-free survival in patients receiving peripheral blood stem cells rather than bone marrow as the source of their graft (p=0.070 and p=0.077, respectively). The intensity of the conditioning regimen (myeloablative versus reduced intensity regimens) did not significantly influence the outcome.

Conclusions: We conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. We observed that a reduction in transplant-related mortality was associated with the choice of a matched sibling donor, whereas longer overall survival was associated with the use of peripheral blood as the source of stem cells.
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http://dx.doi.org/10.3324/haematol.12828DOI Listing
October 2008

Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib.

Leuk Res 2009 Jan 8;33(1):174-7. Epub 2008 May 8.

Division of Hematology and Bone Marrow Transplantation, Department of Medical and Morphological Researches, Azienda Ospedaliero-Universitaria, P.zzale S. M. Misericordia, 15, 33100 Udine, Italy.

Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation (SCT) is dismal. Immunotherapy with donor lymphocyte infusion (DLI) and imatinib are rarely and/or transiently effective. Here we describe the case of a patient with imatinib-resistant post-transplant relapse of ALL, who received a combination of standard dose nilotinib and monthly DLI infusion. Therapy was well tolerated and the patient achieved and maintained a complete molecular remission. Our case provides a rationale for the combined use of a second line tyrosine kinase inhibitor and DLI in the treatment of relapsed Ph+ ALL.
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http://dx.doi.org/10.1016/j.leukres.2008.03.031DOI Listing
January 2009

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

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

Infliximab treatment for steroid-refractory acute graft-versus-host disease.

Haematologica 2004 Nov;89(11):1352-9

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

Background And Objectives: Tumor necrosis factor a is one of the principal cytokines involved in the pathogenesis of acute graft-versus-host-disease (GVHD). Infliximab is an antibody to this cytokine.

Design And Methods: We performed a retrospective analysis to evaluate the activity of infliximab in 32 patients with severe steroid-refractory acute GVHD. The patients received a median of 3 weekly courses of infliximab. The main organs involved in the patients were skin (n=2) liver (n=1), bowel (n=19), liver and bowel at the same stage (n=10).

Results: Nineteen out 32 patients (59%) responded to infliximab with 6 (19%) complete and 13 (40%) partial responses. Age younger than 35 years, intestinal involvement and a longer time between hematopoietic stem cell transplantation and infliximab administration were factors predicting a favorable response. Infective episodes developed in 23/32 (72%) patients. All the 13 unresponsive patients died of GVHD shortly after infliximab. Thirteen of 19 responsive patients were alive at a median follow-up of 449 days (range 155-842) after infliximab, with no signs of chronic GVHD (n=5), limited (n=5) or extensive involvement (n=3). Six patients who responded subsequently died, one of chronic lung GVHD, the others of vascular complications or infections (2 fungal diseases).

Interpretation And Conclusions: We conclude that infliximab is active in the treatment of severe steroid-refractory acute GVHD, particularly when the intestine is involved. Infections commonly followed its administration. The clinical activity of infliximab and the possibility that it increases the risk of infections are worth investigating in prospective trials.
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November 2004

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