Publications by authors named "Idanna Innocenti"

58 Publications

Non-overt disseminated intravascular coagulopathy associated with the first obinutuzumab administration in patients with chronic lymphocytic leukemia.

Hematol Oncol 2021 Jan 18. Epub 2021 Jan 18.

Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.

Infusion-related reactions are among the worst complications of obinutuzumab (G) administration and occur predominantly during the first infusion. We reported another adverse event related to the first G infusion, a subclinical coagulopathy. We retrospectively analyzed a cohort of 13 pts with chronic lymphocytic leukemia treated with a frontline G-chlorambucil regimen. Six pts developed non-overt disseminated intravascular coagulopathy (DIC) (46%) after the first administration of G. The coagulopathy was subclinical and self-limited in all pts, not requiring any intervention apart from the suspension of anticoagulant therapy in one pt. We observed a drop in the platelet count, an elevation of D-dimer levels, and an elongation of activated partial thromboplastin time. We found a significant difference in the platelet count between the pts with DIC and those withouts; in fact, all the six pts with non-overt DIC had a platelet count greater than 100 × 10 /L, while in the other group only one (p = 0.019). A trend towards a lower lymphocyte count and a higher CD20 expression was found in the pts with DIC. No other correlation between the DIC complication and the clinical or laboratory characteristics of the patients was found. The pathogenesis of the G-related non-overt DIC could be related to the consumption of the platelets after the lysis of lymphocytes, probably triggered by the damage associated molecular patterns. Despite its limitations, this study describes a new adverse event and identifies a specific subgroup of patients whose clinical management at the time of the infusion of G may need to be refined.
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http://dx.doi.org/10.1002/hon.2837DOI Listing
January 2021

Enhanced Expression of in B Cells of CLL Improves the Anti-Tumor Cytotoxic T Cell Response.

Cancers (Basel) 2021 Jan 12;13(2). Epub 2021 Jan 12.

Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.

The clinical progression of B cell chronic lymphocytic leukemia (CLL) is associated with immune cell dysfunction and a strong decrease of (), promoting the death of CLL cells. Here we investigated whether the reduction of impairs the immune response in CLL. We demonstrate that activated CD4+ T cells increase expression in CLL through CD40-CD40L signaling, which enhances the maturation and activity of cytotoxic T cells and, consequently, the apoptotic response of CLL cells. The cytotoxic response is facilitated by a depletion of the anti-inflammatory cytokine interleukin 10, targeted by . In vivo experiments in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice confirmed that promotes the apoptotic death of CLL cells only when functional T cells are restored. Overall, our findings suggest that the reinstatement of in CLL cells could be an exploitable adjuvant therapeutic option for the treatment of CLL.
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http://dx.doi.org/10.3390/cancers13020257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826592PMC
January 2021

Second haploidentical stem cell transplantation for primary graft failure.

Bone Marrow Transplant 2020 Dec 16. Epub 2020 Dec 16.

IRCCS Policlinico San Martino IST, Genova, Italy.

We report the outcome of 19 patients who experienced primary graft failure (PrGF) after a haploidentical (HAPLO), unmanipulated bone marrow transplant. The median age of patients was 52 years; the conditioning regimen of the first HAPLO transplant was either full dose total body irradiation (TBI) or fludarabine, busulfan, and thiotepa (TBF); PTCY was given to all patients together with cyclosporine and mycophenolate. All 19 patients with PrGF received a second HAPLO graft, at a median interval of 42 days (34-82) after HSCT, using the Baltimore protocol and G-CSF mobilized PB from the same (n = 13) or another HAPLO family donor (n = 6). GvHD prophylaxis was again PTCY-based; 14/19 patients had trilineage recovery (74%) and 1-year survival was 66%. Engraftment at second HAPLO was seen in 7/8 patient with, and in 5/7 patients without donor-specific antibodies (DSA). In a multivariate logistic regression analysis on the original group of 503 patients, there was a trend for a reduced dose of busulfan, to increase the risk of PrGF (p = 0.1). In conclusion, patients with PrGF following a HAPLO transplant, can be rescued with a second early HAPLO transplant, using the same or a different donor.
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http://dx.doi.org/10.1038/s41409-020-01183-9DOI Listing
December 2020

Efficacy of ibrutinib in late relapse chronic lymphocytic leukemia after allogeneic hematopoietic stem cell transplantation.

Hematol Oncol 2020 Nov 5. Epub 2020 Nov 5.

Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

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http://dx.doi.org/10.1002/hon.2826DOI Listing
November 2020

Days Alive Outside Hospital and Readmissions in Patients Undergoing Allogeneic Transplants from Identical Siblings or Alternative Donors.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020055. Epub 2020 Sep 1.

Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.

We have studied the number of days alive outside the Hospital (DAOH) and the number of readmissions within the first 100 days after transplant in 185 patients who received an allogeneic hemopoietic stem cell transplant (HSCT). The donors were matched siblings (SIB; n=61), or alternative donors (ALT; n=124). The median number of DAOH for SIB transplants (78 days, range 21-84) was significantly greater than DAOH for ALT donor grafts (73 days, range 2-87) (p=0.0003). Other positive predictors of DAOH were the use of reduced-intensity regimens (p=0.01), grade 0-I acute graft versus host disease (GvHD) (p=0.0006), and a comorbidity index equal or less than two (p=0.04). Fifty-one patients required readmission (22%), which was predicted by grade II-IV acute GvHD (p=0.009), higher comorbidity index (p=0.06), and ALT donors as compared to SIBS (p=0.08). The CI of readmission was 18% (95%CI 10-31) for SIB and 30% (95%CI 23-39) for ALT donor grafts. The non relapse mortality (NRM) for patients re-admitted was 25% (95%CI 15-43%), compared to 5% (95%CI 2-12%) for patients not readmitted (p=0.0001). In a multivariate analysis, readmission was the strongest predictor of non-relapse mortality (NRM) (HR 2.0) (p=0.0006) and survival (HR 3.4) (p<0.0001).

In Conclusion: ALT donor transplants have lower numbers of DAOH, as compared to SIB grafts, which implies longer stay in hospital and higher costs. Readmission to hospital within 100 days, is predicted by acute GvHD, comorbidity index, donor type, and has a significant strong impact on non-relapse mortality and survival.
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http://dx.doi.org/10.4084/MJHID.2020.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485463PMC
September 2020

SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation.

Transfus Apher Sci 2020 Dec 23;59(6):102881. Epub 2020 Jul 23.

Istituto di Ematologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy; Universita' Cattolica del Sacro Cuore, Rome, Italy; Clinica di Malattie Infettive, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life-threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.
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http://dx.doi.org/10.1016/j.transci.2020.102881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377729PMC
December 2020

Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia.

Haematologica 2020 07 30. Epub 2020 Jul 30.

Cinical and Experimental Hematology Unit, CRO, IRCCS, Aviano (PN), Italy.

The introduction of agents inhibiting the BCR-associated kinases such as ibrutinib has dramatically changed treatments algorithms of chronic lymphocytic leukaemia (CLL) as well as the role of different adverse prognosticators. We evaluated the efficacy of ibrutinib as single agent, in a real-life context, on 180 patients with CLL mostly pre-treated, recruited from three independent cohorts from Italy. Patients received 420 mg oral ibrutinib once daily until progression or occurrence of unacceptable side effects. Seventy-three patients discontinued ibrutinib for progression or for adverse events. NOTCH1 mutations (M) were correlated with a reduced redistribution lymphocytosis, calculated at 3 months on ibrutinib (p=0.022). Moreover, NOTCH1 mutated patients showed inferior nodal response at 6 months on ibrutinib compared to NOTCH1 wild type patients (p<0.0001). Significant shorter progression free survival (PFS) and overall survival (OS) were observed in NOTCH1 mutated patients (p=0.00002 and p=0.001). Interestingly, NOTCH1 M plus lower bax/bcl-2 ratio identified a CLL subset showing the worst PFS and OS (p=0.0002 and p=0.005). In multivariate analysis of PFS and OS, NOTCH1 M were confirmed an independent prognosticator (p=0.00006 and p=0.0039). In conclusion, NOTCH1 M are strongly associated with lower bax/bcl-2 ratio, consistent with a defective apoptosis, lower redistribution lymphocytosis and lower nodal shrinkage under ibrutinib treatment, this last responsible for partial responses, subsequent relapses, shorter PFS and OS. The therapeutic options for NOTCH1 mutated patients could be represented by either new small molecules combination approaches or from antibodies targeting NOTCH1.
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http://dx.doi.org/10.3324/haematol.2020.251488DOI Listing
July 2020

Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia.

Br J Haematol 2020 09 26;190(6):901-908. Epub 2020 Jul 26.

Department of Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4·8%), 149 (10%), 200 (13·2%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo-γ) and normal Ig levels (γ-normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment-free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels.
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http://dx.doi.org/10.1111/bjh.16975DOI Listing
September 2020

Front-Line Therapy for Elderly Chronic Lymphocytic Leukemia Patients: Bendamustine Plus Rituximab or Chlorambucil Plus Rituximab? Real-Life Retrospective Multicenter Study in the Lazio Region.

Front Oncol 2020 10;10:848. Epub 2020 Jun 10.

Institute of Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Previous studies investigated the efficacy and the safety of bendamustine (B) vs. chlorambucil (Chl) associated with rituximab (R) in fludarabine-ineligible patients with treated and untreated chronic lymphocytic leukemia (CLL). We conducted a retrospective multicenter study in the Lazio region to further evaluate and compare the efficacy and the toxicity of Chl-R and B-R regimen in CLL patients over the age of 65. We enrolled 192 untreated CLL patients: 111 treated with B-R and 81 with Chl-R. The overall response rates (ORR; 93.6% in B-R and 86.5% in Chl-R) were not statistically different between the two groups, such as progression-free survival (PFS), time to retreatment (TTR), and overall survival (OS). The B-R group showed a higher hematological ( = 0.007) and extra-hematological ( = 0.008) toxicity. When comparing the toxicities according to age, we noted that the extra-hematological toxicity was higher in patients over the age of 75 who were treated with B-R than those treated with Chl-R ( = 0.03). This retrospective study confirms the feasibility of B-R and Chl-R in elderly untreated CLL patients. Currently, patients who are over 75 and unfit are usually treated with Chl-R. This scheme allows achieving the same ORR, PFS, TTR, and OS when compared with B-R because of hematological and extra-hematological toxicities due to B, in which a greater dose reduction has been shown in comparison to Chl.
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http://dx.doi.org/10.3389/fonc.2020.00848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298101PMC
June 2020

The concomitance of lymphoma and breast carcinoma in the bone.

Ann Hematol 2020 Jun 7;99(6):1403-1404. Epub 2020 May 7.

Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.

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http://dx.doi.org/10.1007/s00277-020-04041-2DOI Listing
June 2020

CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression.

Blood 2020 04;135(15):1244-1254

Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.

CD49d is a remarkable prognostic biomarker of chronic lymphocytic leukemia (CLL). The cutoff value for the extensively validated 30% of positive CLL cells is able to separate CLL patients into 2 subgroups with different prognoses, but it does not consider the pattern of CD49d expression. In the present study, we analyzed a cohort of 1630 CLL samples and identified the presence of ∼20% of CLL cases (n = 313) characterized by a bimodal expression of CD49d, that is, concomitant presence of a CD49d+ subpopulation and a CD49d- subpopulation. At variance with the highly stable CD49d expression observed in CLL patients with a homogeneous pattern of CD49d expression, CD49d bimodal CLL showed a higher level of variability in sequential samples, and an increase in the CD49d+ subpopulation over time after therapy. The CD49d+ subpopulation from CD49d bimodal CLL displayed higher levels of proliferation compared with the CD49d- cells; and was more highly represented in the bone marrow compared with peripheral blood (PB), and in PB CLL subsets expressing the CXCR4dim/CD5bright phenotype, known to be enriched in proliferative cells. From a clinical standpoint, CLL patients with CD49d bimodal expression, regardless of whether the CD49d+ subpopulation exceeded the 30% cutoff or not, experienced clinical behavior similar to CD49d+ CLL, both in chemoimmunotherapy (n = 1522) and in ibrutinib (n = 158) settings. Altogether, these results suggest that CD49d can drive disease progression in CLL, and that the pattern of CD49d expression should also be considered to improve the prognostic impact of this biomarker in CLL.
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http://dx.doi.org/10.1182/blood.2019003179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228464PMC
April 2020

Genetic dynamics in untreated CLL patients with either stable or progressive disease: a longitudinal study.

J Hematol Oncol 2019 11 19;12(1):114. Epub 2019 Nov 19.

Unit of General Pathology, Center for Advanced Studies and Technology (CAST), University G. d'Annunzio Chieti-Pescara, Chieti, Italy.

Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome.
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http://dx.doi.org/10.1186/s13045-019-0802-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862808PMC
November 2019

Purging with chlorambucil to prevent infusion-related reaction before obinutuzumab administration: A monocentric pilot experience.

Hematol Oncol 2019 Dec 7;37(5):641-643. Epub 2019 Nov 7.

Institute of Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1002/hon.2684DOI Listing
December 2019

A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.

Haematologica 2020 06 3;105(6):1613-1620. Epub 2019 Oct 3.

Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia (CLL) developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count >32.0x10/microliter, 1 point. Low-, intermediate- and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144 / 395 / 540 / 322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage CLL, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemofree era.
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http://dx.doi.org/10.3324/haematol.2019.228171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271568PMC
June 2020

Peripheral Blood Hemopoietic Stem Cell Mobilization Regimens in POEMS Syndrome: A Retrospective Study at 2 Hematologic Italian Centers.

Biol Blood Marrow Transplant 2019 12 21;25(12):2514-2516. Epub 2019 Aug 21.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.

Autologous peripheral blood stem cell transplantation should be considered first-line therapy in young patients with POEMS. The best protocol to collect peripheral blood stem cells remains to be defined, because of the disease rarity and the heterogeneity of published case series. We collected clinical and laboratory data from 25 patients undergoing mobilization, of whom 11 were mobilized using cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) and 14 patients using G-CSF. The incidence of poor mobilization was low and not statistically different between the 2 groups. Both schemes (CY plus G-CSF versus G-CSF alone) were able to harvest a sufficient CD34 cell dose.
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http://dx.doi.org/10.1016/j.bbmt.2019.08.011DOI Listing
December 2019

Preoperative autologous blood donation in adult bone marrow donors: reappraisal of a single-centre experience.

Vox Sang 2019 Oct 11;114(7):762-768. Epub 2019 Aug 11.

Fondazione Policlinico A. Gemelli IRCCS, Roma, Italy.

To avoid risk for allogeneic transfusions in healthy bone marrow (BM) donors, 1-2 preoperative autologous blood donations (PAD) are usually collected before the BM harvest. We analysed the haematological parameters in BM donors before and after the harvest, to assess the efficacy of this practice in limiting the postharvest anaemia. Overall, 102 consecutive donors underwent BM harvest preceded by one (26 cases) or two PAD (76 cases), which were infused during BM collection. We analysed the parameters related to donors, PAD timing and BM graft characteristics. PAD induced a significant decrease in Hb (from 14·6 g/dl, IQ range 13·3-15·5 to12·9 g/dl, IQ range 11·8-13·9; P < 0·0001) in all donors, with a median Hb loss at day -1 of 10·9% (IQ range 6·8-14·2). The PAD-related Hb decrease was independent of sex or number of PAD, and was inversely related to the time elapsed from first or last PAD. In comparison with values recorded at day-1, BM harvest produced an additional Hb decrease, accounting for a median Hb loss of 18·9% (IQ range 14·9-24·4). Overall, in comparison with pre-PAD values, Hb levels at day +1 were reduced of 28·9% (IQ range 23·6-32·2), independently if donors had 1 or 2 PAD reinfused. In conclusion, these data show that two PAD do not carry any advantage over one PAD. An eventual benefit of PAD can be achieved only if an adequate interval between PAD and BM harvest elapses. Prospective randomized studies could be worth to establish if any role for PAD does exist in BM donors.
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http://dx.doi.org/10.1111/vox.12834DOI Listing
October 2019

Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12.

Cancers (Basel) 2019 Jun 26;11(7). Epub 2019 Jun 26.

Institute of Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy.

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The study included 487 treatment-naive CLL patients with +12 from 15 academic centers; diagnosed between January 2000 and July 2016; and 816 treatment-naïve patients with absence of Fluorescence In Situ Hybridization (FISH) abnormalities. A cohort of 250 patients with +12 CLL followed at a single US institution was used for external validation. In patients with +12; parameters associated with worse prognosis in the multivariate model were high Lactate DeHydrogenase (LDH) and β-2-microglobulin and unmutated immunoglobulin heavy-chain variable region gene (IGHV). CLL patients with +12 and high LDH levels showed a shorter Progression-Free-Survival (PFS) (30 months vs. 65 months; p < 0.001), Treatment-Free-Survival (TFS) (33 months vs. 69 months; p < 0.001), Overall Survival (OS) (131 months vs. 181 months; p < 0.001) and greater CLL-related mortality (29% vs. 11% at 10 years; p < 0.001) when compared with +12 CLL patients with normal LDH levels. The same differences were observed in the validation cohort. These data suggest that serum LDH levels can predict PFS; TFS; OS and CLL-specific survival in CLL patients with +12.
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http://dx.doi.org/10.3390/cancers11070896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678692PMC
June 2019

Remission of acquired von Willebrand syndrome in a patient with chronic lymphocytic leukemia treated with venetoclax.

Leuk Lymphoma 2019 12 20;60(12):3078-3080. Epub 2019 May 20.

Institute of Hematology, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1080/10428194.2019.1612063DOI Listing
December 2019

HNRNPL Restrains Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia.

Cancers (Basel) 2019 Apr 23;11(4). Epub 2019 Apr 23.

Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.

Aneuploidy and overexpression of () characterize most solid and hematological malignancies. We recently demonstrated that sustains aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of downregulates spindle checkpoint proteins as the mitotic checkpoint serine/threonine kinase budding uninhibited by benzimidazoles 1 (BUB1), the centromere protein F (CENPF) and the zw10 kinetochore protein (ZW10), compromising the chromosome alignment at the metaphase plate and leading to aneuploidy in daughter cells. Here we show that the heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to the polymorphic marker D2S1888 at the 3'UTR of gene, impairs the targeting, and restores BUB1 expression in chronic lymphocytic leukemia. This mechanism occurs at advanced passages of cell transformation and allows the expansion of more favorable clones. Our findings have revealed, at least in part, the molecular mechanisms behind the chromosomal stabilization of cell lines and the concept that, to survive, tumor cells cannot continuously change their genetic heritage but need to stabilize the most suitable karyotype.
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http://dx.doi.org/10.3390/cancers11040575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520824PMC
April 2019

Unrelated cord blood transplantation and post-transplant cyclophosphamide.

Haematologica 2019 02 20;104(2):e77-e78. Epub 2018 Dec 20.

Istituto di Ematologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Universita' Cattolica, Rome, Italy.

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http://dx.doi.org/10.3324/haematol.2018.202598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355502PMC
February 2019

CD200 included in a 4-marker modified Matutes score provides optimal sensitivity and specificity for the diagnosis of chronic lymphocytic leukaemia.

Hematol Oncol 2018 Mar 30. Epub 2018 Mar 30.

CEINGE-Biotecnologie Avanzate s.c.a.r.l., "Federico II" University, Naples, Italy.

CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin superfamily, has been shown to have a differential expression in B-cell neoplasms. Here, we retrospectively assessed the diagnostic relevance of CD200 on 427 patients with B-cell chronic neoplasms in leukemic phase (median age, 69 y; range, 35-97 y). The final diagnosis based on the investigator's assessment was chronic lymphocytic leukaemia (CLL) in 75% of cases and non-CLL in 25% of cases. Sensitivity and specificity for the diagnosis of CLL (vs non-CLL) were calculated for the following markers: CD200, CD5, CD22, CD23, CD79b, FMC7, and SmIg. CD23 was the only marker without a statistically significant difference between the investigator assessment and the flowcytometric analysis. The other markers were unable-when individually evaluated-to discriminate between CLL and non-CLL, requiring the integration into a scoring system. The modified score no. 1 (addition of CD200) showed superimposable sensitivity and specificity compared with the Matutes score. The substitution of CD79b (modified score no. 2), surface membrane immunoglobulins (SmIg) (modified score no. 3), and CD79b and FMC7 (modified score no. 4) with CD200 showed that only the modified score no. 4 had both higher sensitivity and higher specificity compared with standard Matutes score. In conclusion, this work defines a simplified score, compared with the classical Matutes score, for the differential diagnosis of chronic B-cell leukaemia-which only requires 4 markers instead of 5 (CD5, CD23, CD200, and SmIg).
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http://dx.doi.org/10.1002/hon.2510DOI Listing
March 2018

Clinical, pathological, and biological characterization of Richter syndrome developing after ibrutinib treatment for relapsed chronic lymphocytic leukemia.

Hematol Oncol 2018 Feb 27. Epub 2018 Feb 27.

Institue of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy.

Richter syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a diffuse large B-cell lymphoma, is a rare complication of patients treated with chemo-immunotherapy. Richter syndrome might be both clonally related or unrelated to the underlying CLL and often showed mutations of the TP53 and NOTCH1 genes. Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation. The clinical picture, pathology, and genetics of Richter transformation after IBR treatment are largely unknown. Here, we report 2 cases of Richter transformation after Ibrutinib treatment. As just reported by previous report, Richter syndrome developing after ibrutinib therapy lacked resistance mutations of the BTK and PLCG2 genes, which are clonally related to the pre-existent CLL phase representing transformation from CLL. Richter syndrome after ibrutinib seems to have some peculiar clinical findings as the bone marrow predilection, severe hypercalcemia, and a more aggressive outcome.
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http://dx.doi.org/10.1002/hon.2502DOI Listing
February 2018

Ibrutinib does not affect ristocetin-induced platelet aggregation evaluated by light transmission aggregometry in chronic lymphocytic leukemia patients.

Haematologica 2018 03 14;103(3):e119-e122. Epub 2017 Dec 14.

Servizio Malattie Emorragiche e Trombotiche, Polo Oncologia ed Ematologia, Istituto di Medicina Interna, Rome, Italy

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http://dx.doi.org/10.3324/haematol.2017.179044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830396PMC
March 2018