Publications by authors named "Anna Grazia Recchia"

74 Publications

Validation of the alternative international prognostic score-E (AIPS-E): analysis of binet stage a chronic lymphocytic patients enrolled into the O-CLL1-GISL protocol.

Eur J Haematol 2021 Mar 4. Epub 2021 Mar 4.

Hematology Unit AO of Cosenza, Cosenza, Italy.

Objectives: To validate the predictive value on time to first treatment (TTFT) of AIPS-E and IPS-E evaluated in an independent cohort of newly diagnosed and non-referred Binet stage A CLL patients enrolled in the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540).

Methods: A cohort of 292 newly diagnosed Binet A CLL cases has been enrolled in the study. Patients from several Italian Institutions were prospectively enrolled within 12 months of diagnosis into the O-CLL1-GISL protocol RESULTS: The majority of patients were male (62%); median age was 60.4 years, 102 cases (34.9%) showed unmutated IGHV genes, 8 cases (2.8) the presence of del(11q)/del(17p), 142 cases (48.6%) the presence of palpable lymph nodes and 146 cases (50%) and ALC >15x10 /l. After a median follow-up of 7.2 years, 130 patients underwent treatment. According to the AIPS-E, 96 patients were classified as low-risk, 128 as intermediate-risk, and 68 as high-risk. These groups showed significant differences in terms of TTFT. The C-statistic was 0.71 (P<0.0001) for predicting TTFT. According to IPS-E, 77 patients were classified as low-risk, 135 as intermediate-risk, and 80 as high-risk. These groups showed significant differences in terms of TTFT. The C-statistic was 0.705 (P<0.0001) for predicting TTFT.

Conclusions: Our data confirm an accurate prognostic utility of both AIPS-E and IPS-E at the individual patient level. These data may be useful for a precise stratification of early-stage patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.13614DOI Listing
March 2021

Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients.

Sci Rep 2020 10 28;10(1):18427. Epub 2020 Oct 28.

Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, 87100, Cosenza, Italy.

Chronic lymphocytic leukaemia (CLL) is characterised by a heterogeneous clinical course. Such heterogeneity is associated with a number of markers, including TP53 gene inactivation. While TP53 gene alterations determine resistance to chemotherapy, it is not clear whether they can influence early disease progression. To clarify this issue, TP53 mutations and deletions of the corresponding locus [del(17p)] were evaluated in 469 cases from the O-CLL1 observational study that recruited a cohort of clinically and molecularly characterised Binet stage A patients. Twenty-four cases harboured somatic TP53 mutations [accompanied by del(17p) in 9 cases], 2 patients had del(17p) only, and 5 patients had TP53 germ-line variants. While del(17p) with or without TP53 mutations was capable of significantly predicting the time to first treatment, a reliable measure of disease progression, TP53 mutations were not. This was true for cases with high or low variant allele frequency. The lack of predictive ability was independent of the functional features of the mutant P53 protein in terms of transactivation and dominant negative potential. TP53 mutations alone were more frequent in patients with mutated IGHV genes, whereas del(17p) was associated with the presence of adverse prognostic factors, including CD38 positivity, unmutated-IGHV gene status, and NOTCH1 mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-75364-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595214PMC
October 2020

TP53 dysfunction in chronic lymphocytic leukemia: clinical relevance in the era of B-cell receptors and BCL-2 inhibitors.

Expert Opin Investig Drugs 2020 Aug 27;29(8):869-880. Epub 2020 Jun 27.

Department of Experimental Medicine, University of Genoa , Genoa, Italy.

Introduction: Patients with dysfunction, assessed by del(17p) or mutations, respond poorly to chemo-immunotherapy and fare better with the new therapies (BCR and BCL-2 inhibitors); however, it is unclear whether their response is similar to that of patients without anomalies or whether there is currently an adequate determination of dysfunction.

Area Covered: A literature search was undertaken on clinical trials and real-world experience data on patients with dysfunction treated with different protocols. Moreover, data on the biological function and on the tests currently employed for its assessment were reviewed.

Expert Opinion: Although dysfunction has less negative influence on the new biological therapies, patients with these alterations, particularly those with biallelic inactivation of , have a worst outcome with these therapies than those without alterations. At present, a determination of , particularly with next generation sequencing (NGS) methodologies, may be sufficient for the identifications of the patients unsuitable for chemo-immunotherapy, although integration with del(17p) would be advisable. For the future, more extensive determinations of the status, including functional assays, may become part of the current armamentarium for a better patient stratification and treatment with newer protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13543784.2020.1783239DOI Listing
August 2020

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant.

Ann Hematol 2020 Feb 18;99(2):331-341. Epub 2019 Dec 18.

CNR-IFC, Rome, Italy.

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-019-03901-wDOI Listing
February 2020

An in-depth evaluation of acalabrutinib for the treatment of mantle-cell lymphoma.

Expert Opin Pharmacother 2020 Jan 18;21(1):29-38. Epub 2019 Nov 18.

Hematology and Oncology Department, Biotechnology Research Unit, Cosenza, Italy.

: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases.: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms 'mantle cell lymphoma' and 'acalabrutinib'.: Acalabrutinib has been approved for the treatment of relapsed/refractory (RR) MCL patients. To date, clinical trials have reported some adverse effects such as cardiac toxicity or atrial fibrillation. Acalabrutinib in combination with other drugs, either in chemo-containing or chemo-free schedules, represent a valid option for MCL. However, none of the treatment schedules containing BTK inhibitors have been shown to be curative in MCL. Acalabrutinib may ultimately represent an option for patients who are 'fit' and exhibit well-controlled disease, which often characterizes only a limited 'niche' among MCL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2019.1689959DOI Listing
January 2020

Quality of life outcomes in multiple myeloma patients: a summary of recent clinical trials.

Expert Rev Hematol 2019 08 3;12(8):665-684. Epub 2019 Jul 3.

f Hematology Unit, Department of Hemato-Oncology, Ospedale Annunziata , Cosenza , Italy.

: Management of multiple myeloma (MM) has improved over recent years. Health-related quality of life (HRQoL) data is becoming increasingly important, owing to improved survival outcomes. : The authors performed an expert review of the literature to identify evidence-based data available on HRQoL in frontline and relapsed/refractory MM (RRMM) patients. : De-novo patients should be informed that the HRQoL is expected to improve during first-line treatment with different degrees of possible deterioration during the first cycles. Achievement of a maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, HRQoL, and patient preferences. The same degree of improvement in HRQoL cannot be expected during conventional relapse treatments, where patients should be prepared only for stabilization of HRQoL. However, focusing attention only on measures such as toxicity may provide just a partial view of overall treatment effectiveness. Nonetheless, the authors believe the added value of taking into consideration the patient's perspectives and the importance of patient-reported outcomes in the evaluation of treatment effects should be considered mandatory. The incorporation of quality of life assessment into clinical and research practice has the potential of improving treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17474086.2019.1634541DOI Listing
August 2019

Challenge to Predict Mobilized Peripheral Blood Stem Cells on the Fourth Day of Granulocyte Colony-Stimulating Factor Treatment in Healthy Donors: Predictive Value of Basal CD34 Cell and Platelet Counts.

Biol Blood Marrow Transplant 2019 08 17;25(8):1586-1591. Epub 2019 Apr 17.

Institute of Clinical Physiology (IFC-CNR), Rome, Italy.

A longitudinal, prospective, observational, single-center cohort study on healthy donors was designed to identify predictors of CD34 cell mobilization on day 4 after granulocyte colony-stimulating factor (G-CSF) administration. As potential predictors of mobilization, age, sex, body weight, height, blood volume, WBC count, peripheral blood (PB) mononuclear cell count, platelet (Plt) count, and hematocrit and hemoglobin levels were considered. Two different evaluations of CD34 cell counts were determined for each donor: baseline (before G-CSF administration) and in PB on day 4 after G-CSF administration. One hundred twenty-two consecutive healthy donors with a median age of 47.5 years were enrolled. The median value of CD34 on day 4 was 43 cells/µL (interquartile range, 23 to 68), and 81.1% of donors had ≥20 cells/µL. Basal WBC count, Plt count, and CD34 were significantly higher for the subjects with CD34 levels over median values on day 4. A multivariate quartile regression analysis, adjusted by sex, age, basal CD34, and basal Plt count, showed a progressively stronger relationship between baseline CD34 and Plt levels and the CD34 levels on day 4. The basal CD34 cut-off level to predict the levels of CD34 on day 4 was either ≤2 cells/μL or ≥3 cells/μL and that of basal Plt count was ≤229 × 10/L or ≥230 × 10/L, respectively, to determine whether mobilization therapy should or should not be attempted. PB stem cell mobilization with G-CSF was highly effective on day 4, and herein we describe a model for predicting the probability of performing PB stem cell collection after a short course of G-CSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.04.011DOI Listing
August 2019

Lenalidomide for the treatment of mantle cell lymphoma.

Expert Opin Pharmacother 2019 Apr 4;20(5):487-494. Epub 2019 Jan 4.

b Biotechnology Research Unit, AO , Cosenza , Italy.

Introduction: Although a variety of therapeutic schemes for Mantle Cell Lymphoma (MCL) have been attempted, the clinical outcome of patients continues to be unsatisfactory especially among patients with a very high-risk profile and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel approaches, either by the use of biological agents in chemotherapy-free schedules or by integrating them with chemoimmunotherapy regimens. Areas covered: The efficacy of lenalidomide monotherapy and combination therapy established in clinical studies mainly involving relapsed/refractory MCL is reviewed. The mechanism of action of lenalidomide is also discussed. Furthermore, the current position of lenalidomide in the MCL treatment algorithm is debated. Expert opinion: Lenalidomide demonstrated high efficacy and tolerability in several clinical trials as well as in retrospective real-world reports, even in patients who relapsed or were resistant to bortezomib and ibrutinib. In 2013, lenalidomide was approved by the Food and Drug Administration (FDA) for relapsed/refractory MCL after two prior therapies including at least one prior treatment with bortezomib. However, the potential synergistic anti-neoplastic effects of lenalidomide in combination with other biological agents, i.e. ibrutinib and venetoclax, especially in the management of p53-mutated cases, still remain an open issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2018.1561865DOI Listing
April 2019

Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) refractory to standard therapies.

Transfus Apher Sci 2018 Apr 15;57(2):247-249. Epub 2018 Mar 15.

Hematology Unit, Department of Hemato-Oncology, Ospedale Annunziata, Cosenza, Italy.

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia, and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty percent of patients with autoimmune TTP experience one or multiple relapses. Patients with refractory TTP are currently managed by corticosteroids, twice-daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two cases of severe TTP, refractory to those standard agents. On the basis of the fact that in cases of severe TTP the classical complement pathway is activated, and that the alternative pathway is also involved, both patients underwent eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt hematological and organ system responses to the eculizumab and the recovery of plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients discontinued eculizumab, maintaining the response, emphasizes the possibility of its usefulness for limited treatment periods. In conclusion, the diagnostic and therapeutic algorithm in TTP appears complicated by increasing evidence of complement involvement and the eculizumab seems to be a potential agent for refractory patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2018.03.005DOI Listing
April 2018

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence.

Sci Transl Med 2018 02;10(428)

Hematology Unit, Department of Onco-Hematology, Azienda Ospedaliera (AO) of Cosenza, 87100 Cosenza, Italy.

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rβ1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rβ1 chain when cocultured with activated T cells or CD40L cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aal1571DOI Listing
February 2018

Venetoclax for the treatment of chronic lymphocytic leukemia.

Expert Opin Investig Drugs 2017 Nov 9;26(11):1307-1316. Epub 2017 Oct 9.

b Department of Hemato-Oncology , Unità di Ricerca Biotecnologica (URB) , Aprigliano , Italy.

Introduction: Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs. Expert opinion: Data from early clinical trials have shown that venetoclax, as a single agent, is highly effective for relapsed/refractory CLL patients, including those cases with high-risk features. Furthermore, venetoclax seems to be an appropriate option for patients who progress on B-cell receptor (BCR) pathway kinase inhibitors. Venetoclax is also safe, with the most common serious adverse events being neutropenia. The risk of tumor lysis syndrome (TLS) can be reduced by a slow dose ramp-up, careful monitoring, and adequate prophylaxis. Ongoing trials will further clarify the safety and efficacy of venetoclax in combination with other drugs in both relapsed/refractory and untreated CLL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13543784.2017.1386173DOI Listing
November 2017

Ponatinib-Induced Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant.

Chemotherapy 2017 16;62(6):353-356. Epub 2017 Aug 16.

Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib treatment was well tolerated and considered safe with easily manageable side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000477714DOI Listing
March 2018

Disappearance of Bone Marrow Fibrosis in a Patient with Chronic Myeloid Leukemia Treated with Dasatinib.

Chemotherapy 2017 26;62(6):350-352. Epub 2017 Jul 26.

Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.

We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy. Given the loss of major molecular response, we switched treatment to dasatinib 100 mg daily, observing a reduction in BCR-ABL transcript, a significant improvement of anemia, and a gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient maintains a complete cytogenetic response and a deep molecular response; the last bone biopsy confirmed the absence of fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000477796DOI Listing
March 2018

Basal CD34 Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony-Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study.

Biol Blood Marrow Transplant 2017 Jul 24;23(7):1215-1220. Epub 2017 Mar 24.

Hematology Unit, Department of Hemato-Oncology, Ospedale Annunziata, Cosenza, Italy; Unità di Ricerca Biotecnologica (URB), Aprigliano ASP Cosenza, Italy.

A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 cells on day 5 with emphasis on the predictive value of the basal CD34 cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/µL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 on day 5 using the baseline value of CD34 as the key predictor was performed. On crude analysis, a baseline value of CD34 ranging from .5 cells/µL to 1 cells/µL predicts a median value of 50 cells/µL on day 5; a value of 2 cells/µL predicts a median value of 70.7 cells/µL; a value of 3 cells/µL to 4 cells/µL predicts a median value of 91.3 cells/µL, and a value ≥ 5 predicts a median value of 112 cells/µL. In conclusion, the baseline PB CD34 cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2017.03.024DOI Listing
July 2017

Lenalidomide and low-dose dexamethasone (Rd) versus bortezomib, melphalan, prednisone (VMP) in elderly newly diagnosed multiple myeloma patients: A comparison of two prospective trials.

Am J Hematol 2017 Mar 23;92(3):244-250. Epub 2017 Jan 23.

Department of Onco-hematology, Hematology Unit, A.O. of Cosenza, Italy.

There are currently no direct head-to-head clinical trials evaluating bortezomib-melphalan-prednisone (VMP) versus lenalidomide and low-dose dexamethasone (Rd). VMP (257 cases) and Rd (222 cases) arms of two randomized phase III trials were employed to assess the treatment influence on outcome in untreated elderly MM patients. Progression free survival (PFS) and overall survival (OS) were the primary and secondary end-points, respectively, and were investigated according to treatments administered over a 60-months follow-up period. While VMP significantly reduced the disease progression rate between enrolment and 12 months of follow-up, no difference between the two schedules was found between 12 and 32 months. After 32 months, Rd-treated patients had a lower incidence of disease progression. A statistically significant higher OS rate was seen in the VMP arm, which was maintained after data adjustment for potential confounders. Both approaches showed acceptable toxicity profiles. The profound tumor reduction by VMP over Rd justifies the initial higher PFS rate in favor of the bortezomib schedule, while the Rd regimen overcomes this evident initial drawback in reducing the tumor burden by long-term drug administration, gaining a subsequent improved disease control. VMP is associated with a significant reduced risk of death. This study may help physicians make a more informed therapy choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.24621DOI Listing
March 2017

Pomalidomide in multiple myeloma.

Expert Opin Pharmacother 2017 02 26;18(2):133-137. Epub 2016 Dec 26.

a Dipartimento di Onco-Ematologia , Unità Operativa di Ematologia Azienda Ospedaliera di Cosenza , Cosenza , Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2016.1274973DOI Listing
February 2017

The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.

Am J Hematol 2016 Nov 8;91(11):1090-1095. Epub 2016 Aug 8.

Hematology Unit Department of Onco-Hematology, a.O. Of Cosenza, Cosenza, Italy.

The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL-IPI was originally developed to predict survival, we next investigated the optimal cut-off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n = 139), 1 (n = 90), and ≥ 2(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P < 0.0001.; C-statistic:c = 0.72; 95% CI:0.58-0.81). This optimized CLL-IPI scoring for TTFT was subsequently validated in an independent cohort of Binet A patients from the Mayo Clinic (n = 525). The ability of either original or optimized CLL-IPI to predict TTFT was equivalent to other prognostic models specifically designed for this endpoint (2011 MDACC score and O-CLL1 score). Although originally developed to predict suvival, the CLL-IPI is useful for predicting TTFT in early stage CLL patients. Am. J. Hematol. 91:1090-1095, 2016. © 2016 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072993PMC
http://dx.doi.org/10.1002/ajh.24493DOI Listing
November 2016

Panobinostat for the treatment of acute myelogenous leukemia.

Expert Opin Investig Drugs 2016 Sep 8;25(9):1117-31. Epub 2016 Aug 8.

e Department of Clinical and Experimental Medicine, Hematology Division , University of Pisa , Pisa , Italy.

Introduction: Therapeutic strategies in patients with acute myeloid leukemia (AML) have not changed significantly over the last decades. Appropriate strategies are ultimately driven by the assessment of patients' fitness to define suitability for intensive induction chemotherapy, which produces high initial remission rates but, increased likelihood of relapse. Old/unfit AML patients still represent an urgent and unmet therapeutic need. Epigenetic deregulation represents a strategic characteristic of AML pathophysiology whereby aberrant gene transcription provides an advantage to leukemic cell survival. Efforts to re-establish impaired epigenetic regulation include hypomethylating agents and histone deacetylase inhibitors (HDACi).

Areas Covered: The review discusses the underlying mechanisms leading to disruption of lysine acetyltransferases (KAT or HAT)/deacetylase (KDAC or HDAC) balance and the rationale for using the HDACi panobinostat (LBH-589) in AML.

Expert Opinion: Although panobinostat has produced significant results in myeloma, its efficacy remains limited in AML. Panobinostat exerts pleiotropic activity and lack of specificity, which likely contributes to its inadequate safety in elderly AML patients. Phase I-II trials, utilizing panobinostat associated with well-known chemotherapeutic agents are ongoing and combinations with other druggable targets may likely be evaluated in future trials. The clinical use of this HDACi in AML the near future does not appearing promising.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13543784.2016.1216971DOI Listing
September 2016

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

Clin Immunol 2016 Nov 16;172:52-60. Epub 2016 Jul 16.

Scientific Direction, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. Electronic address:

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Despite its indolent nature, CLL remains an incurable disease. Herein we aimed to monitor CLL disease engraftment and, progression/regression in a xenograft CLL mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Spleen contrast enhancement, quantified as percentage change in signal intensity upon USPIO administration, demonstrated a difference due to a reduced USPIO uptake, in the spleens of mice injected with CLL cells (NSG-CLL, n=71) compared to controls (NSG-CTR, n=17). These differences were statistically significant both after 2 and 4weeks from CLL cells injection. In addition comparison of mice treated with rituximab with untreated controls for changes in spleen iron uptake confirmed that it is possible to monitor treatment efficacy in this mouse model of CLL using USPIO-enhanced MRI. Further applications could include the preclinical in vivo monitoring of new therapies and the clinical evaluation of CLL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clim.2016.07.013DOI Listing
November 2016

Sorafenib for the treatment of multiple myeloma.

Expert Opin Investig Drugs 2016 Jun 6;25(6):743-9. Epub 2016 Apr 6.

a Hematology Unit , Azienda Ospedaliera di Cosenza , Cosenza , Italy.

Introduction: Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.

Areas Covered: In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed.

Expert Opinion: Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/13543784.2016.1169272DOI Listing
June 2016

Clinical Options in Relapsed or Refractory Hodgkin Lymphoma: An Updated Review.

J Immunol Res 2015 16;2015:968212. Epub 2015 Dec 16.

Biotechnology Research Unit, Azienda Sanitaria Provinciale di Cosenza, 87051 Aprigliano, Italy; Hematology Unit, Azienda Ospedaliera di Cosenza, 87100 Cosenza, Italy.

Hodgkin lymphoma (HL) is a potentially curable lymphoma, and modern therapy is expected to successfully cure more than 80% of the patients. Second-line salvage high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) have an established role in the management of refractory and relapsed HL, leading to long-lasting responses in approximately 50% of relapsed patients and a minority of refractory patients. Patients progressing after intensive treatments, such as auto-SCT, have a very poor outcome. Allogeneic SCT represents the only strategy with a curative potential for these patients; however, its role is controversial. Based on recent knowledge of HL pathology, biology, and immunology, antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints are currently explored. This review will discuss the clinical results regarding auto-SCT and allo-SCT as well as the current role of emerging new treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/968212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695673PMC
September 2016