Publications by authors named "Valerio Maisano"

13 Publications

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Allogeneic stem cell transplantation in poor prognosis peripheral T-cell lymphoma: the impact of different donor type on outcome.

Bone Marrow Transplant 2020 Nov 15. Epub 2020 Nov 15.

Haematology Department, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.

We report the outcome of 68 patients with advanced peripheral T-cell lymphoma receiving transplantation from haploidentical or from conventional donors. The 4-year OS, PFS, 2-year cumulative incidence of relapse and 2-year GRFS was 75%, 70%, 21%, and 51%, respectively. Survival was not affected by donor type. The 2-year NRM was 9%, lower after related or haploidentical donor (21% vs 0% vs 7%; p = 0.06). Grade 2-4 aGVHD cumulative incidence was significantly different after transplantation from haploidentical vs matched sibling vs unrelated donor, and (24% vs 35% vs 58%, p = 0.024). The familial donor cohort was compared to the unrelated cohort. Familial donor induced less grade 2-4 aGVHD, with a trend to less grade 3-4 aGVHD or moderate-severe cGVHD. The OS and PFS were not different, while the relapse risk and NRM were reduced. Allo-SCT is highly effective in T-cell lymphoma, with low NRM and low relapse rate. The incidence of aGVHD was lower after haploidentical transplantation. Related donor may challenge unrelated transplant reducing the risk of relapse and NRM.
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http://dx.doi.org/10.1038/s41409-020-01133-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666822PMC
November 2020

Nonmyeloablative Conditioning Regimen before T Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Hodgkin and Non-Hodgkin Lymphomas.

Biol Blood Marrow Transplant 2020 12 19;26(12):2299-2305. Epub 2020 Aug 19.

Hematology Department, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a valid option in patients with refractory lymphomas. HLA haploidentical stem cell transplantation (haplo-SCT) expanded the accessibility to allogeneic hematopoietic cell transplantation. The aims of study were to retrospectively assess the toxicity and efficacy of haplo-SCT using nonmyeloablative conditioning in patients with advanced lymphoma. In total, 147 patients with advanced lymphoma at 2 partner institutions were included. Patients received a uniform nonmyeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis. The primary endpoints were progression-free survival (PFS), overall survival (OS), GVHD, nonrelapse mortality, and GVHD, relapse-free survival (GRFS). Median follow-up was 39 months (range, 6 to 114 months). The median age was 46 years (range, 19 to 71 years). Sixty-five percent of patients were in complete remission (CR) at transplantation. Cumulative incidence of grade II to IV acute GVHD was 30% (95% confidence interval [Cl], 23% to 38%). Two-year cumulative incidence of all grades of chronic GVHD was 13% (95% CI, 8% to 20%). Two-year cumulative incidence of disease relapse was 19% (95% CI, 14% to 27%), with a higher incidence in patients not being in CR at allo-HCT (CR versus not CR: 12% versus 33%, P = .006). Two-year PFS, OS, and GRFS were 66% (95% CI, 59-75), 73% (95% CI, 66-81), and 56% (95% CI, 48-65), respectively. Haplo-SCT with post-transplantation cyclophosphamide may be considered a valid option for patients with aggressive lymphoma and deserves further evaluation.
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http://dx.doi.org/10.1016/j.bbmt.2020.08.014DOI Listing
December 2020

Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma.

Blood Adv 2020 04;4(7):1242-1249

Department of Hematology, Humanitas Clinical and Research Center-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, Italy.

We report on 59 Hodgkin lymphoma patients undergoing haploidentical stem cell transplantation (SCT; haplo-SCT) with posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, comparing outcomes based on pretransplant exposure to checkpoint inhibitors (CPIs). Considering pretransplant characteristics, the 2 cohorts (CPI = 29 patients vs no-CPI = 30 patients) were similar, except for the number of prior lines of therapy (6 vs 4; P < .001). With a median follow-up of 26 months (range, 7.5-55 months), by univariate analysis, the 100-day cumulative incidence of grade 2-4 acute GVHD was 41% in the CPI group vs 33% in the no-CPI group (P = .456), whereas the 1-year cumulative incidence of moderate to severe chronic GVHD was 7% vs 8%, respectively (P = .673). In the CPI cohort, the 2-year cumulative incidence of relapse appeared lower compared with the no-CPI cohort (0 vs 20%; P = .054). No differences were observed in terms of overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) (at 2 years, 77% vs 71% [P = .599], 78% vs 53% [P = .066], and 15% vs 21% [P = .578], respectively). By multivariable analysis, CPI before SCT was an independent protective factor for PFS (hazard ratio [HR], 0.32; P = .037). Stable disease (SD)/progressive disease (PD) was an independent negative prognostic factor for both OS and PFS (HR, 14.3; P < .001 and HR, 14.1; P < .001, respectively) . In conclusion, CPI as a bridge to haplo-SCT seems to improve PFS, with no impact on toxicity profile.
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http://dx.doi.org/10.1182/bloodadvances.2019001336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160255PMC
April 2020

Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation.

Bone Marrow Transplant 2020 02 18;55(2):349-355. Epub 2019 Sep 18.

Department of Hematology, Institut Paoli-Calmettes, Marseille, France.

Posttransplant cyclophosphamide (PT-Cy) is an efficient GVHD prophylaxis but has not been extensively evaluated in mismatched unrelated donor (MMUD) allo-HSCT, for which antithymocyte globulin (ATG) is still considered as a standard. Thus, we evaluated the outcome of MMUD allo-HSCT with PT-Cy (n = 22) and performed a historical comparison with a control group receiving ATG (n = 40) in a single center experience. Compared with the ATG group, the risk of grade 2-4 acute GVHD was significantly lower in the PT-Cy group (HR = 0.12, 95% CI = [0.03-0.48], p = 0.002). No difference was observed in the cumulative incidence of chronic GVHD. The risk of both NRM and relapse was significantly lower in the PT-Cy group (NRM: HR = 0.05, 95% CI = [0.00-0.63], p = 0.021; relapse: HR = 0.31; 95% CI = [0.09-1.10], p = 0.07). Thus, we observed significantly better PFS (HR = 0.22, 95% CI = (0.07-0.65); p = 0.006), OS (HR = 0.24, 95% CI = (0.07-0.84); p = 0.026), and GRFS (HR = 0.37, 95% CI = (0.17-0.80); p = 0.011) in the PT-Cy group. We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT, resulting in a better outcome compared with standard prophylaxis using ATG. This suggests that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approach those observed after HLA matched allo-HSCT.
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http://dx.doi.org/10.1038/s41409-019-0682-2DOI Listing
February 2020

Peripheral Blood Stem Cells versus Bone Marrow for T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Hodgkin Lymphoma.

Biol Blood Marrow Transplant 2019 09 22;25(9):1810-1817. Epub 2019 May 22.

Bone Marrow Transplant Unit, Humanitas Clinical and Research Center, Rozzano, Italy.

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P = .405) and platelet (26 versus 26.5 days, P = .994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P = .761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR], .29; P = .006), PFS (HR, .38; P = .001), and GRFS (HR, .44; P = .020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant-specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.017DOI Listing
September 2019

Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients.

Biol Blood Marrow Transplant 2019 09 22;25(9):1803-1809. Epub 2019 May 22.

Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, Inserm U1068, UMR 7258, Marseille, France; Aix-Marseille University, UM 105, Marseille, France. Electronic address:

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.014DOI Listing
September 2019

Peripheral blood stem cell for haploidentical transplantation with post-transplant high dose cyclophosphamide: detailed analysis of 181 consecutive patients.

Bone Marrow Transplant 2019 11 19;54(11):1730-1737. Epub 2019 Mar 19.

Hematology Department, Institut Paoli Calmettes, Marseille, France.

While bone marrow (BM) grafts were initially used for T-replete HLA-haploidentical related donors transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), the use of peripheral blood stem cell (PBSC) remains debated. We thus conducted a detailed analysis evaluating the incidence, risk factors, and prevalence of GVHD after PBSC Haplo-SCT with PT-Cy. One hundred and eighty-one patients with hematological diseases were included. Median time for neutrophil and platelet recovery was 21 and 30 days, respectively. The cumulative incidence of grade 3-4 acute GVHD and severe chronic GVHD were 8% and 4%, respectively, approaching what was observed after BM Haplo-SCT. NRM at 2 years was 21%, and 41% of the non-relapse deaths were caused by GVHD. The cumulative incidence of relapse at 2 years was 17% in the whole cohort, and 13% among AML patients (n = 54), suggesting a high GVL effect. As surrogate markers for good quality of life, we observed a 2-year GVHD-relapse-free survival probability of 50% and found that 6% and 2% of disease-free patients at 2 years were still living with GVHD and immunosuppressive treatments, respectively. Haplo-SCT with PT-Cy using PBSC grafts results in low incidence GVHD and promising disease control, making PBSCs a valuable alternative to BM graft in this setting.
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http://dx.doi.org/10.1038/s41409-019-0500-xDOI Listing
November 2019

HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

Biol Blood Marrow Transplant 2018 07 12;24(7):1449-1454. Epub 2018 Feb 12.

Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Inserm U1068, CNRS UMR 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; UM 105, Aix-Marseille University, Marseille, France.

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML.
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http://dx.doi.org/10.1016/j.bbmt.2018.02.002DOI Listing
July 2018

Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity.

Turk J Haematol 2015 Jun;32(2):168-71

University of Messina Faculty of Medicine, Department of General Surgery and Oncology, Division of Hematology, Messina, Italy Phone: 0039 090 221 23 64 E-mail:

Imatinib mesylate is a small-molecule tyrosine kinase inhibitor (TKi) designed to target c-ABL and BCR-ABL, approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Adverse cutaneous reactions induced by imatinib are frequent, generally moderate, and dose-dependent. The aim of this work was to investigate the possible contribution of interleukin (IL)-33 and IL-31, cytokines involved in disorders associated with itching, in the pathogenesis of pruritus in a patient undergoing imatinib mesylate treatment. His IL-31 and IL-33 serum levels were significantly higher than in the control group (respectively 96.6 pg/mL vs. 7.623±7.681 pg/mL and 27.566 pg/mL vs. 6.170±7.060 pg/mL). In light of these findings, imatinib mesylate-related symptoms of dermatologic toxicities might be related to the release of IL-31 and IL-33. In particular, it is supposable that TKi usage could cause keratinocyte injury, the release of IL-33, and the consequent interaction with its receptor on mast cells that induces the secretion of several factors capable of causing skin manifestations, including IL-31, a known pruritus-inducing cytokine. This report, to the best of our knowledge, is the first work describing the possible involvement of the IL-31/IL-33 axis in the pathogenesis of skin side effects related to imatinib mesylate treatment.
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http://dx.doi.org/10.4274/tjh.2014.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451486PMC
June 2015

Castleman-Kojima disease (TAFRO syndrome) in a Caucasian patient: A rare case report and review of the literature.

Blood Cells Mol Dis 2015 Oct 25;55(3):206-7. Epub 2015 Jun 25.

Division of Hematology, Department of General Surgery, Oncology and Pathological Anatomy, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy.

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http://dx.doi.org/10.1016/j.bcmd.2015.06.013DOI Listing
October 2015

Vaccination of multiple myeloma: Current strategies and future prospects.

Crit Rev Oncol Hematol 2015 Nov 18;96(2):339-54. Epub 2015 Jun 18.

Division of Hematology, Department of General Surgery, Oncology and Pathological Anatomy-University of Messina, Messina, Italy.

Tumor immunotherapy holds great promise in controlling multiple myeloma (MM) and may provide an alternative treatment modality to conventional chemotherapy for MM patients. For this reason, a major area of investigation is the development of cancer vaccines to generate myeloma-specific immunity. Several antigens that are able to induce specific T-cell responses are involved in different critical mechanisms for cell differentiation, inhibition of apoptosis, demethylation and proliferation. Strategies under development include infusion of vaccine-primed and ex vivo expanded/costimulated autologous T cells after high-dose melphalan, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes, administration of dendritic cell/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. In addition, novel immunomodulatory drugs may synergize with immunotherapies. The task ahead is to evaluate these approaches in appropriate clinical settings, and to couple them with strategies to overcome mechanisms of immunoparesis as a means to induce more robust clinically significant immune responses.
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http://dx.doi.org/10.1016/j.critrevonc.2015.06.003DOI Listing
November 2015

Association of osteonecrosis of the jaws and POEMS syndrome in a patient assuming rituximab.

J Craniomaxillofac Surg 2014 Jun 22;42(4):279-82. Epub 2013 Jun 22.

Division of Hematology, Department of General Surgery and Oncology, AOU Policlinico G. Martino, Via Consolare Valeria, University of Messina, 98185 Messina, Italy.

POEMS syndrome, is a rare condition characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteinaemia, and skin lesions. We report a rare case of a patient affected by Waldenström macroglobulinemia, who developed POEMS syndrome and who presented at the time of diagnosis with oral manifestations of the lymphoma and an osteonecrosis of the jaw (ONJ) after rituximab treatment. Although the etiology of ONJ is not known, it is likely that several factors are at play, including endothelial cell damage, decreased angiogenesis, and microvascular compromise. Our patient was treated with rituximab for a long period, and recent studies have demonstrated the possibility that rituximab, a monoclonal antibody directed against the CD20 can exert part of its anti-tumor action, through its action on angiogenesis. Although our report does not allow identification of rituximab as a new risk factor for the onset of the ONJ, further studies seem necessary to exclude a role of the antibody in the alterations of angiogenesis that could lead to the development of the syndrome after rituximab treatment.
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http://dx.doi.org/10.1016/j.jcms.2013.05.014DOI Listing
June 2014