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  • 1
    In: British Journal of Haematology, Wiley, Vol. 191, No. 2 ( 2020-10), p. 263-268
    Abstract: Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity‐associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post‐menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord‐RBCs) or from adult donors (adult‐RBCs), depending on whether cord‐RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty‐three neonates survived until this age: 14 received no transfusions, two only cord‐RBCs, three only adult‐RBCs and four both RBC types. HbF levels in neonates transfused with cord‐RBCs were significantly higher than in neonates receiving adult‐RBCs ( P   〈  0·0001) or both RBC types ( P   〈  0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult‐RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10‐fold, whereas this effect was not evident if combined adult‐ and cord‐RBCs were evaluated. Overall, these data show that transfusing cord‐RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 2
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4490-4490
    Abstract: Background : The conditioning regimen for patients with myelolfibrosis undergoing an allogeneic HSCT is usually composed of a combination of fludarabine (FLU) with one alkylating agent, busulkfan (BU), thiotepa (THIO) or melphalan. In a recent prospective randomized study comparing BU-FLU versus THIO-FLU, the proportion of patients with full donor chimerism at 6 months, was respectively 63% and 65% (Patriarca et al, BBMT 2019). Aim of the study. Assess the rate of full donor chimerism in patients with myelofibrosis, after conditioning with one or two alkylating agents. Methods. We analyzed 113 patients with myelofibrosis, for whom chimerism data were available on day +30 . There were two groups: 35 patients were conditioned with either thiotepa-cyclophosphamide , thiotepa-fludarabine or busulfan-fludarabine (ONE-ALK), whereas 78 patients were prepared with thiotepa, busulfan, fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years, p=0.008), were less frequently splenectomized pre-HSCT (30% vs 54%, p=0.03), had more frequently intermediate-2/high DIPSS scores (89% vs 74%, p=0.04) , and had comparable transfusion burden pre-HSCT (p=0.7). Chimerism was assessed via STR (PowerFlex-Promega) Results. The proportion of patients with full donor chimerism on day +30 in the TBF vs the ONE-ALK group was 87% vs 51% (p=0.00002); on day +60 these figures were 93% vs 13% (p 〈 0.0001) and on day +90 , the figures were 90% vs 21% (p 〈 0.00001). Full donor chimerism on day+30 was achieved in 81% of patients with DIPSS int1 (n=16), 74% of patients with int2 DIPSS, and 70% of patients with high risk DIPSS (p=0.6). Acute GvHD grade II-IV occurred in 27% vs 37% of patients in the two groups (p=0.7), and moderate severe chronic GvHD in 20% and 21% (p=0.8). The 5 year cumulative incidence of relapse was 8% in the TBF group, versus 50% for the ONE-ALK group (p 〈 0.0001), whereas the CI of TRM was 25% vs 11% (p=0.1). The 5 year actuarial disease free survival (DFS) was respectively 65% for TBF and 38% for the ONE-ALK group (p=0.004). Complete chimerism day+30. When looking at whether patients had (n=84) or not (n=29) full donor chimerism on day +30, the CI of relapse was respectively 44% vs 15% (p=0.002), the CI of TRM 18% vs 15% (p=0.5), and the 5 year DFS 65% vs 32% (p=0.001). Conclusions. Early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis undergoing an allogeneic HSCT. The combination of 2 alkylating agents in the conditioning regimen, provides a significantly higher chance of achieving full donor chimerism on day+30, and thus long term disease control. Figure Disclosures Angelucci: Vertex Pharmaceuticals Incorporated, and CRISPR Therapeutics: Other: Partecipation in DMC; Roche: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; BlueBirdBio: Other: Local advisory board; Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Partecipation in DMC.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 3
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 57, No. 5 ( 2022-05), p. 837-839
    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: 2022
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  • 4
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 57, No. 4 ( 2022-04), p. 532-537
    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: 2022
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  • 5
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3566-3566
    Abstract: Introduction. The granulocyte transfusions (GTXs) are used to booster antimicrobial drugs in severely neutropenic hematological patients. However, the optimal GTX dose and the actual efficacy of this practice are debated. Methods. We retrospectively evaluated the infection-attributable mortality (IAM, i.e. the mortality at 30 days after the last GTX) in 84 consecutive patients with hematological malignancies receiving GTXs (January 2009- December 2014). The indications for GTXs were i) presence of absolute neutrophil count (ANC) 〈 0.5 x 10^9/l ii) fever with evidence of bacterial or fungal infections or symptoms of infections and iii) unresponsiveness to appropriate antimicrobial therapies for at least 48 hours. Results. Among 84 patients, 101 infectious episodes requiring GTXs were recorded (422 transfusions in total). Patients characteristics are summarized in Table I. Bacterial infections were documented in 94 episodes (Klebsiella pneumonia in 35 cases, Escherichia coli in 16 and Pseudomonas aeruginosa in 13), invasive fungal infections (IFI) in 34 cases (including 18 pulmonary aspergillosis and 14 candidemia); 8 cases were considered as FUO. The infection was mono-microbial in 60 cases and poly-microbial in 33. Sepsis occurred in 67 cases. The overall IAM was 26.7 % (27 deaths among 101 infective episodes). At univariate analysis we failed to detect statistical association between IAM and several evaluated variables, either patient-related (age, sex, diagnosis, status of disease, allo-HSCT, aplasia duration) or infection-related (bacterial infection or IFI, sepsis, XDR, G-SCF concurrent administration) or GTX-related (number of GTXs received, PMN /Kg/course, PMN/Kg/day of neutropenia). However, when we grouped patients according to the value of the median dose of PMN per transfusion, we found that patients receiving 1.5 - 3 x 10^8/kg (GTXs A) had a lower IAM than patients receiving less than 1.5 (GTXs B) or more than 3 x 10^8 /kg (GTXs C) (15,7%, 35,3% and 44,4%, for GTXs A, B and C, respectively, p=0,014 at chi-square test). The dose's cut off were derived from the Guide to the preparation, Use and Quality assurance of Blood Components of the European Committee on Blood Transfusion (16th Edition). If the analysis was carried out by pooling together GTXs B and C, the association between PMN dose and IAM was even more pronounced (p value =0.006 at Fisher test for GTXs A versus GTXs B+C). At Kaplan-Meier analysis, the median survival was 59 days for GTXs A-patients and 30 days for GTXs B+C-patients (p =0,010). When patients with bacterial of fungal infections were separately evaluated, the effect of PMN dose on IAM was confirmed in bacterial (n=54, p=0,008) but not in fungal (n=23, p=0,588) infections. We then introduced the PMN dose (GTXs A or GTXs B+C) in a Cox proportional-hazards regression model together with variables with p 〈 0.1 at univariate analysis (sepsis) or other clinically relevant factors (Allo-HSCT, age over 60 years, disease status categorized as onset/remission or relapse/resistance ). The PMN dose was the unique variable significantly associated with IAM (HR=3,0; 1,1-8,0 95% CI, p=0,020). Conclusions. These findings suggest that appropriate GTX doses can improve the post-infection survival of severely neutropenic hematological patients. Transfusion-related immunomodulation, leukostasis or transfusion-associated GVHD may underlie the detrimental effect of high PMN doses and deserve to be better explored. Table 1. Clinical characteristics of 84 patients treated with GTXs. A total of 101 courses were recorded. Characteristics Age (years, median value range) 46 (20-74) Male/Female 54/30 Underlying disease (n, %)Acute myeloid leukemiaLymphomaAcute lymphoblastic leukemiaMyelodysplastic syndromeMultiple myelomaChronic lymphocytic leukemia 63 (75%)12 (14%)5 (6%)2 (3%)1 (1%)1 (1%) Disease status at PMN transfusion (n, %)OnsetRelapse/resistanceComplete remission 49 (48,5%)41 (40.5%)11 (10.8%) Duration of neutropenia (days, median value, range) 18 (3-79) Site of infection (n, %)Sepsis LungBowelOthersMultiples (≥3 involved sites) 67 (66.3%)22 (21.9%)4 (3.9%)8 (7.9%)4 (4%) Allo-HSCTYes No 21(20.7)80(79.2) Transfusions per course (median value, range) 4 (1-14) PMN x 108/kg/course (median value, range) 8.78 (0.53-53.23) PMN x 108/kg/transfusion (median value, range) 2.11 (0.46-7.34) 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: 2015
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  • 6
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3332-3332
    Abstract: Background .There has been a decrease in the use of unrelated cord blood transplants (UCBT) in the past years: this is probably due to slow hematologic and immune recovery, resulting in a relatively high non relapse mortality (NRM). The addition of anti-thymocyte globulin (ATG) in the conditioning prevents graft versus host disease (GvHD) but makes immune recovery very slow. In addition there is a growing competition of unmanipulated haploidentical transplants. Aim of the study. We have opened a pilot study to test whether high dose post-transplant cyclophosphamide (PT-CY) would prevent GvHD but still allow for robust immune and hematologic recovery . Methods. We have grafted 10 patients with an unrelated CB unit and PT-CY. The conditioning regimen was thiotepa (10 mg/kg), busulfan 9.6 mg/kg and fludarabine 150 mg/m^2 (TBF). GvHD prophylaxis was cyclosporin (CSA) starting day 0 (3 mg/kg/day(i.v.), mycophenolate (MMF) 30 mg/kg starting day +1 (p.o) , and PT-CY 30 mg/kg days +3 and +5. The median patients' age was 58 (43-66), and the median weight was 75 kg (54-85) the diagnosis was AML in 8 patients, Ph'+ALL in one and RAEB in one patient; 6 patients were in remission and 4 had active disease. CB units. The HLA matching of the CB unit was 5/8 antigens/alleles (A,B,C,DRB1) in six patients, 4/8 in two and 2/8 in one. The median nucleated cell dose was 3.1x10^7/kg (range 1.8- 4.5). The ABO was mismatched in all 10 patients. Hematologic recovery: median time to neutrophils 0.5x10^9/l was day 23 days (range 17-27) and the median time to a platelet count of 20x10^9/L was 38 days (range 34-40). The median counts on day +50 were as follows: Hb 9,1 gr/dL (range 8.7-11.1), Neutrophils 2,3 x10e9/L (range 1-5), PLTs 56 x10e9/L (10-90). One patient failed to engraft and received a second transplant from an unrelated donor, which was successful. No patient developed pure red cell aplasia despite 9/10 being ABO major mismatched. CD4 recovery : the median CD4 count on day +50 was 74 /cmm (range 67-116) and on day +100 it was 111/cmm(range 100-136). CMV pre-emptive therapy occurred in 3/6 evaluable patients Outcome: two patients with advanced disease, died early of infections, within day +20. GvHD was seen in 1 patient as a transient rash. No patient was treated for GvHD. No patient developed chronic GvHD. No patient relapsed. Eight patients survive in remission, with a median follow up of 6 months, and a projected one year actuarial survival of 80%. Readmissions were extremely rare. Conclusions. These first 10 patients suggest that UCBT followed by PT-CY, CSA, MMF, as GvHD prophylaxis is feasible and leads to encouraging hematologic and immunologic recovery. We were particularly impressed with the lack of GvHD, the absence of relapses and the good quality of life. Figure 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: 2019
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  • 7
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2597-2597
    Abstract: We have previously demonstrated that clonal hemopoiesis in female ET patients was significantly associated to the risk of thrombosis. When data on JAK2 V617P mutation became available we aimed to evaluate the incidence of this mutation according to clonality status. Ninety-two female patients, median age 32 (19–65) with a diagnosis of ET according to PVSG criteria were studied for clonality with X-CIP, 83 patients were evaluable for endogenous erythroid colonies (EECs) growth and 44 patients were evaluable for JAK2 V617P mutation. Twenty episodes of thromboses (21.7%) were detected and they include splanchnic (11), CNS (5), limb (3) thromboses and pulmonary embolism (1). Thromboses were mainly detected at diagnosis. Thirthy-seven patients showed clonal hemopoiesis (40%), 27 had polyclonal hemopoiesis (29.5%) and 28 were considered uninterpretable due to constitutional skewing (30.5%). Thromboses were overrepresented in the monoclonal group in respect to the polyclonal one (15/37 vs 2/27, p=0.003). DNA for analysis of JAK2 V617P by allele-specific PCR was available for 44 of these patients. Thirty-two patients of 44 (73%) showed JAK2 V617P mutation; JAK2 V617P was found in 16/21 patients with monoclonal hemopoiesis (76%), in 9/13 in the polyclonal group (69%) and in 7/10 (70%) in patients with constitutional skewing. Thirteen of the 32 patients with JAK2 V617P mutation (41%) had thromboses while no thrombotic event was recorded in wild type patients (p=0.008); among the 13 patients with thrombosis and JAK2 V617P mutation, 9 (69%) had monoclonal hemopoiesis, 2 (15%) had polyclonal hemopoiesis, and 2 had constitutive skewing. Thus there was a significant increase in thrombotic events in patients with JAK2 V617P mutation and monoclonal hemopoiesis (p=0.04). JAK2 V617P mutation was also significantly associated to the presence of EECs (p=0.02); in fact 22/26 patients with EECs growth showed JAK2 mutation (85%). Finally when patients with splanchnic thromboses were analyzed 9/11 had a monoclonal X-CIP (81.8%) and 7 of them who were evaluable for JAK2 V617P mutation were invariably carriers of the mutation. Thus we confirm that X-CIP in young female ET is correlated to the risk of thrombosis. JAK2 V617P mutation is significantly associated to the development of thrombosis and is present in the vast majority of patients with monoclonal hemopoiesis. The mechanisms underlying monoclonal hemopoiesis in the absence of JAK2 V617P mutation are unclear, notwithstanding these patients are clinically characterized by both absence of EECs and thrombosis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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