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  • 1
    In: Blood, American Society of Hematology, Vol. 122, No. 25 ( 2013-12-12), p. 4111-4118
    Abstract: Efficacy of imatinib in steroid-refractory chronic GVHD was prospectively compared across 3 different response systems, with high agreement. Validity of quantitative-based assessment of response with NIH criteria was confirmed by its prognostic impact on long-term survival.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
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  • 2
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 50, No. 2 ( 2015-02), p. 282-288
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2004030-1
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  • 3
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4871-4871
    Abstract: Recipients of allogeneic hematopoietic stem cell transplant (HSCT) have been excluded from clinical trials of SARS-CoV-2 messenger RNA (mRNA) vaccines; however, since these patients are at higher risk of severe complications following infection, they have been given high priority in vaccination campaigns worldwide. In this prospective observational study, we evaluated the immunogenicity of two BNT162b2 (Pfizer-BioNTech) vaccine doses in allogeneic HSCT recipients compared to healthy controls. IgG antibodies to the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 were analyzed by SARS-CoV-2 IgG II Quant (Abbott, Ireland). The cutoff value of the test used in this study is 7.1 BAU/mL (Binding Antibody Unit/mL) and the results greater than 7.1 indicate that seroconversion has occurred, as recommended by the manufacturer. Peripheral blood samples were collected for immunological analysis at three timepoints: pre-vaccine baseline (w0, before the first BNT162b2 dose), week 3 (w3, before the second vaccine dose) and week 5 (w5, 2 weeks following the second dose). Patients older than 18 years who received BNT162b2 vaccine following an HSCT at seven Italian centers were included in the study. Enrolled patients received two successive doses (at 3-week interval) at a median of 15 months (range 2-141) after HSCT. Twenty-nine age-matched health care workers who were vaccinated with BNT162b2 were recruited as the control group. Among the 34 patients evaluable for serological response, three patients were excluded from the analysis as the baseline serology demonstrated previous natural SARS-CoV-2 infection. On w3, after the first vaccine dose 7/31 (23%) patients developed anti-S IgG antibodies as compared to 28/29 (97%) controls (p & lt;0.01). HSCT recipients showed lower antibody titers (median 1.8 BAU, range 0-481) as compared to healthy controls (median 118 BAU, range 6-1172, p & lt;0.01). In univariate analysis, transplant-to-vaccination interval ( & gt;12 months, p & lt;0.01), baseline CD4+ T cell count ( & gt;200/mm3, p=0.01), and CD4+CD45RA+ T naive cell count ( & gt;100/ mm3, p & lt;0.01) were significantly associated with antibody response after the first vaccine dose. On w5, after the second vaccine dose, 24/31 (77%) of the patients showed antibody response, as compared to 99% of healthy controls (p & lt;0.01); in fact, 71% of non-responders to the first dose developed IgG antibodies after vaccine boost (Figure 1). Median antibody titer after second dose was 350 BAU/ml (0-21.731). In univariate analysis, no significant association was found between patient characteristics and immunogenicity after vaccine boost. Adverse events were rare and modest. Nine percent of the patients reported mild local reactions after vaccine administration, including pain at the injection site and less commonly local erythema, local lymphadenopathy, or swelling; 35% of patients reported systemic adverse events, and all were mild. The most frequently reported systemic reactions included weakness (15%), headache (9%), and diarrhea (3%). In conclusion, in recipients of HSCT, a single dose of the BNT162b2 SARS-CoV-2 vaccine yielded poor efficacy, while immunogenicity increased significantly after vaccine boost at day 21 after the first dose. Patients who received vaccines beyond one year after transplant were more likely to mount anti-S IgG antibodies, which could be due to a broader immune reconstitution, as we observed an enhanced response to single BNT162b2 vaccine dose in patients with higher CD4+ T cell and particularly CD4+CD45RA+ naïve T cell counts. Figure 1 Figure 1. Disclosures Kordasti: Alexion: Honoraria; Celgene: Research Funding; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1659-1659
    Abstract: Reduced intensity allogeneic stem cell transplantation (RIC alloSCT) is a therapeutic option for poor risk relapsed chronic lymphocytic leukemia (CLL) and can lead to 50% of progression-free survivors. The aims of this study were: to assess the “molecular quality” of clinical remission after RIC alloSCT in CLL patients; to investigate whether molecular remission (MR) can correlate with a lower relapse risk; to understand the clinical role of molecular monitoring in post-transplant immunotherapy. Twenty-nine patients with a molecular marker (heavy chain gene immunoglobulin rearrangement, IgH) were monitored for minimal residual disease (MRD). All patients had a relapsed disease; 75% had an unmutated IgH; cytogenetic analysis was available in 13 patients at first relapse, and 5 of them (38%) showed a 17p deletion. Median age at transplant was 60 years (range, 44–69). Median number of previous chemotherapy was 3 (range, 1–6) and 29% of patients failed autologous transplant. Eleven patients (38%) were chemorefractory before transplant. The conditioning regimen included thiotepa-cyclophosphamide-fludarabine in HLA identical sibling transplants (n=21), and an in vivo T cell depletion in haploidentical and unrelated alloSCT (n=8). Molecular monitoring was performed by nested-PCR on bone marrow using CDR-2 and CDR-3-derived patient-specific primers. For real-time PCR a FR3-derived probe was used. Post-transplant samples were amplified including the pre-transplant sample as positive control, and ΔCT was calculated after normalization for GAPDH gene. Eight patients (28%) were PCR-negative: 4 of them (14%) have been always PCR-negative while 4 patients (14%) experienced a delayed clearance of MRD during the first year after transplant. All these patients are alive and in CR at the median follow-up of 24 months (range, 3–71). Seven patients (24%) showed a mixed pattern of PCR positivity and negativity: one patient died of secondary acute leukemia, another patient had a nodal relapse, the others are in CR at a median follow-up of 30 months (range, 6–60). Fourteen patients (48%) were always PCR-positive: 7 of them relapsed after a median time of 9 months (range, 3–12); 2 patients died of TRM in MR; 5 patients are alive and in CR after a median follow-up of 15 months (range, 3–24). Relapse risk was higher for PCR-positive patients compared to PCR-mixed/negative patients (p=0.014). Eighty percent of PCR-mixed/negative patients experienced GVHD compared to 43% of PCR-positive patients (p=0.06). In 5 PCR-positive patients real-time PCR was carried out. In 3 patients that did not relapse a decreasing tumor load was detected; these patients were affected by extensive chronic GVHD. In the other 2 patients after an initial reduction, the tumor load increased on day +300 and +270: both patients relapsed on days +420. In conclusion, in poor risk relapsed CLL clinical and molecular remission can be achieved in a sizeable fraction of patients after RIC alloSCT. Persistent PCR positivity correlates with a high incidence of relapse and requires novel treatments, while a mixed-PCR pattern can be observed without clinical relapse.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 875-875
    Abstract: Abstract 875 Conventional therapies and autologous stem cell transplantation lead to disappointing results in relapsed PTCL, therefore allo-SCT has been investigated in the last years. There are evidence supporting the existence of a “graft-versus-PTCL” effect, but the majority of the studies have a limited number of patients with a short follow-up. We conducted a retrospective analysis on 53 patients (pts) affected by relapsed/refractory PTCL who received a RIC regimen followed by allo-SCT. The main histopathological subtypes were PTCL-not otherwise specified (PTCL-NOS, n=24), anaplastic large-cell lymphoma (ALCL, n=11), and angioimmunoblastic (AILD, n=6). The remaining cases were rare subtypes (n=12). Median age was 47 years (range, 15-64 years). Patients were allografted from matched related siblings (n=34, 64%) or alternative donors (n=19, 36%). The majority of pts had chemosensitive disease (n=39, 74%), received allo-SCT more than 12 months from diagnosis (n=38, 72%) and were treated with only 1 or 2 lines of therapy before transplantation (n= 37, 70%). At last follow-up (median 49 months, range 6-118), 29 pts are alive (55%, 26 in CR) and 24 died [n=20 for disease progression, n=4 for non-relapse mortality (NRM)]. The majority of relapsing patients (20 of 25, 80%) died at median time of 7 months after allo-SCT. The crude cumulative incidence (CCI) of relapse was 32% and 50% at 6 months and at 4-year after allo-SCT. The CCI of relapse was influenced by status of disease [chemosensitive versus chemorefractory: 41% versus 77% at 4 years (p 〈 0.001)] and number of lines [≤ 2 versus 〉 2: 40% versus 70% at 4 years (p 〈 0.02)] received before allo-SCT and not by hystotype and time from diagnosis to allograft. The CCI of NRM were 4% and 10% at 6 months and 4-year, respectively; type of donor and previous auto had no significant impact on NRM. The CCI of acute (grade II-IV) and chronic GVHD were 21% and 44%, respectively. The 4-year OS and PFS were 50% (95% CI, 35% to 63%) and 47% (95% CI, 32% to 60%) for all the population, 62% (95% CI, 44% to 76%) and 15% (95% CI, 3% to 38%) as OS, 58% (95% CI, 40% to 72%) and 13% (95% CI, 1% to 41%)as PFS, for chemosensitive and chemorefractory pts, respectively. According to the histopathological subtypes, the OS and PFS were 42% and 40% for PTCL-NOS, 50% and 44% for ALCL, 67% and 80% for AILD, 58% and 48% for rare subtypes, respectively (p=ns). At multivariable analysis of OS and PFS, refractory disease prior to alloSCT and age more than 45 years were independent adverse prognostic factors [hazard ratio (HR)= 5.3, p 〈 0.001, HR=4.8, p 〈 0.003 for OS; HR=5.4, p 〈 0.0007, HR=2.7, p 〈 0.02 for PFS]. Six-teen pts received donor lymphocytes infusions (DLIs) for disease progression (n=12) or to accelerate immune reconstitution (n=4): 7 out of 12 responded to DLIs (n=3 CR, n=4 PR). In conclusion, our long-term data with a median 4-year follow-up shows that: i) only patients with chemosensitive had advantage from allo-SCT; ii) transplantation should be performed early because pts receiving less lines of therapy had a better outcome; iii) we did not observe a significant difference in outcome between the different histopathological subtypes; iv) response to DLI supports the notion of an immune mediated effect. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 808-808
    Abstract: Reduced intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) is associated with durable engraftment, low transplant-related mortality (TRM) and clinical remissions in hematologic malignancies. In addition, RIC followed by allograft is feasible also in patients who had failed previous autologous (auto) SCT. Here, we report the outcome of 118 lymphoma pts receiving RIC and allogeneic SCT from HLA-identical sibling donors. Histologic types included in the study were: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n=26), low-grade non-Hodgkin lymphoma (LG-NHL; n=24, 21 follicular NHL), high-grade NHL (HG-NHL, B cell n=28, T cell n=17), Hodgkin disease (HD; n=23). Median age was 50 years (range: 20–69). 47% of pts had refractory disease (46% CLL/SLL; 33% LG-NHL; 44% HG-NHL; 56% HD) and 48% have failed an auto SCT (15% CLL/SLL; 33% LG-NHL; 55% HG-NHL; 82% HD). All pts received debulkying chemotherapy followed by the same RIC regimen with thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. All pts engrafted. De-novo acute GVHD developed in 43% of pts and chronic GVHD in 45%. The 2-year TRM rate was 13% and was not influenced by previous auto SCT or hystological type. At a median follow-up of 20 months (range, 6–62 months), 91 pts (77%) are alive (n=69 CR, n=8 PR, n=14 with disease) and 27 died (23%) for disease (n=17) or TRM (n=10). The 2 years PFS rates for CLL/SLL, LG-NHL, HG-NHL, HD were 63%, 78%, 64%, 16%, respectively. Chemorefractory disease at time of SCT was associated with a worse 2-year PFS compared to chemosensitive disease (41% versus 74%, p 〈 0.001). There was a trend toward lower relapse risk for pts developing acute or chronic GVHD (37% versus 50%, p=0.2). The 2-year OS rates for CLL/SLL, LG-NHL, HG-NHL, HD were 77%, 90%, 76%, 56%, respectively. Chemosensitive disease had significant impact on OS (84% 2-year OS compared with 64% for chemorefractory patients; p 〈 0.007) as well the occurrence of chronic GVHD (87% versus 57%; p 〈 0.0059). Interestingly, previous auto SCT and age 〉 55 years did not influence OS. Among pts in clinical CR, 24 were suitable for PCR monitoring of residual disease and 17 pts (71%) are in continuous molecular remission. Our study indicates: 1) low TRM in a multicenter phase II study; 2) low risk of relapse and good survival rates in indolent lymphomas; 3) encouraging results in HG-NHL 4) disappointing results in HD
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 7
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Allogeneic stem cell transplantation from haploidentical donor using an unmanipulated graft and post-transplantation cyclophosphamide (PT-Cy) is growing. Haploidentical transplantation with PT-Cy showed a major activity in Hodgkin lymphoma (HL), reducing the relapse incidence. The most important predictive factor of survival and toxicity was disease status before transplantation, which was better in patients with well controlled disease. Methods We included 198 HL in complete (CR) or partial remission (PR) before transplantation. Sixty-five patients were transplanted from haploidentical donor and 133 from a HLA identical donor (both sibling and unrelated donors). Survival analysis was defined according to the EBMT criteria. Survival curves were generated by using Kaplan-Meier method and differences between groups were compared by the log rank test or by the log rank test for trend when appropriated. Results The PFS, OS, and RI were significantly better in patients in CR compared to PR (55% vs 29% p  = 0.001, 74% vs 55% p  = 0.03, 27% vs 55% p   〈   0.001, respectively). The 2-year PFS was significantly better for HAPLO than HLA-id (63% vs 37%, p  = 0.03), without difference in OS. The 1-year NRM was not different. The 2-year relapse incidence (RI) was lower in the HAPLO group (24% vs 44%, p  = 0.008). Patients in CR receiving haplo HSCT showed higher 2-year PFS and lower 2-year RI than those allografted with HLA-id donor (75% vs 47%, p   〈   0.001 and 11% vs 34%, p   〈  0.001, respectively). In multivariate analysis, donor type and disease status before transplantation were independent predictors of PFS as well as they predict the risk of relapse. Disease status at transplantation and age were independently associated to OS. Conclusions Nonetheless this is a retrospective study, limiting the wide applicability of results, data from this analysis suggest that HLA mismatch can induce a strong graft versus lymphoma effect leading to an enhanced PFS.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041352-X
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  • 8
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5138-5138
    Abstract: Previous autografting and older age are traditionally considered poor prognostic factors for patients receiving myeloablative conditioning followed by allogeneic stem cell transplantation (SCT). Reduced intensity conditioning (RIC) achieved a significant reduction of treatment related mortality, but the influence of previously described risk factors on the outcome of this new strategy has not been fully described. We have evaluated if age older than 55 years and a failed autologous transplantation could have an impact on transplant-related mortality (TRM) and graft versus host disease (GVHD) occurrence. One hundred and forty allogeneic SCTs from HLA-identical sibling donors were analyzed: all patients received the same conditioning (Thiotepa 10mg/Kg, Fludarabine 60 mg/ms and Cyclophosphamide 60 mg/kg and) and GVHD prophylaxis (cyclosporin 2mg/kg and short course methotrexate). Patients were divided in two cohorts according to age: 86 patients were younger and 54 older than 55 years (range 20–69). Main pre-transplant characteristics were fairly well distributed in both cohorts, in terms of: sex, mismatch donor/recipient, CMV status, previous autografting, disease status at transplant, type of disease (lymphoid vs myeloid), stem cell source and number of previous lines of chemotherapy ( 〈 2 vs ≥2). Four-year treatment related mortality (TRM) was 13% for younger group and 17% for the older one (p=0.3), while overall survival (OS) was 58% and 59%, respectively (p=0.9). By univariate and multivariate analysis no pretransplant risk factor examined was found as significantly negative predictor of TRM; in particular no significantly association was found between a previously failed autograft and TRM in the younger (p=0.8) and in the older cohort (p=0.1). Instead, looking at GVHD, we observed that the occurrence of grade III–IV aGVHD was associated with a significantly worse TRM in both young (p=0.008) and elderly patients (p=0.005); similarly, extensive cGVHD was a predictor for worse TRM if compared to limited cGVHD in younger (p=0.8) and older patients (p=0.03). Finally, a strong association between favourable outcome and the onset of limited cGVHD was observed not only if compared to patients with extensive cGVHD but even compared to patients who never showed any sign of cGVHD; in fact 4-year OS curve for younger patients with limited cGVHD was 80% vs 50% of patients with no cGVHD (p=0.03); the same applies for the older cohort (4-years OS of 100% vs 48%, respectively). Our results indicate that: RIC can be safely applied to patients over 50 years; the deleterious effect of a previous failed autoBMT has been minimized by the RIC program. Moreover, severe GVHD still has a maior impact on the outcome; otherwise limited cGVHD seems an effective immunotherapy in high risk patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
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  • 9
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 20, No. 6 ( 2014-06), p. 872-880
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 10
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 26, No. 4 ( 2020-04), p. 698-703
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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