Publications by authors named "Maria Stefania De Propris"

64 Publications

Correction to: Pre-emptive use of Sorafenib combined with DLI post HSCT in AML FLT3+: a single center experience.

Bone Marrow Transplant 2021 Feb 26. Epub 2021 Feb 26.

Haematology, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1038/s41409-021-01242-9DOI Listing
February 2021

Pre-emptive use of Sorafenib combined with DLI post HSCT in AML FLT3+: a single center experience.

Bone Marrow Transplant 2021 Jan 29. Epub 2021 Jan 29.

Haematology, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1038/s41409-020-01174-wDOI Listing
January 2021

Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial.

Am J Hematol 2021 Mar 29;96(3):292-301. Epub 2020 Dec 29.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD <10 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.
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http://dx.doi.org/10.1002/ajh.26066DOI Listing
March 2021

Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults.

N Engl J Med 2020 10;383(17):1613-1623

From the Division of Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome (R.F., A.V., L.E., M.-C.P., M.C., M.-S.D.P., M.V., S.C.), Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Data Center, Fondazione GIMEMA Franco Mandelli Onlus (A.P., M.V.), and the Department of Molecular Medicine, Sapienza University of Rome (A.G.), Rome, the Hematology Unit, Ospedale dell'Angelo and Ospedale SS Giovanni e Paolo, Venice (R.B., P.V., A.M.), the Division of Hematology, Cardarelli Hospital, Naples (F. Ferrara), the Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara (M.L.), Division of Hematology and Bone Marrow Transplantation, Ospedali Riuniti Villa Sofia Cervello, Palermo (F. Fabbiano), the Department of Medicine, Section of Hematology, University of Verona, Verona (M.B.), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano (N.F.), and the Department of Oncology-Hematology, University of Milan (A.R.), Milan, the Department of Hematology, Ospedale Civile, Pescara (P.D.B.), and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (A.R.) - all in Italy.

Background: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.

Methods: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.

Results: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an deletion plus additional genetic aberrations ( or , , or both [i.e., ]). mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).

Conclusions: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.).
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http://dx.doi.org/10.1056/NEJMoa2016272DOI Listing
October 2020

Human herpesvirus-8-positive primary effusion lymphoma in HIV-negative patients: Single institution case series with a multidisciplinary characterization.

Cancer Cytopathol 2021 Jan 10;129(1):62-74. Epub 2020 Sep 10.

Department of Radiological, Oncological and Pathological Sciences, Sapienza University, Rome, Italy.

Background: Primary effusion lymphoma (PEL) is a very rare non-Hodgkin lymphoma caused by human herpesvirus-8 (HHV8) that grows in liquid phase within body cavities. The diagnosis of PEL is based on cytology but requires confirmatory ancillary tests. PEL occurs mainly in association with HIV infection. This study describes 9 cases of PEL in HIV-negative patients and compares their characteristics with 10 HIV-associated cases of PEL diagnosed at a single institution in Italy between 1995 and 2019.

Methods: Clinical records were reviewed for demographic data, comorbidities, laboratory abnormalities, and outcome. PEL samples were evaluated for cytomorphology, immunophenotype, immunoglobulin (IG)/T cell receptor (TR) rearrangements, and HHV8 and Epstein-Barr virus (EBV) viral loads in effusion supernatants.

Results: HIV-unrelated PEL occurred in 8 elderly patients (7 men, 1 woman) and 1 young adult with primary antibody deficiency. Cytology revealed HHV8-positive lymphoma cells lacking B/T cell antigens and exhibiting 2 cell patterns (polymorphous or monotonous). IG was clonally rearranged in all cases; aberrant TRG occurred in 2 cases. Effusion supernatants had more than 10 HHV8 DNA copies per mL and variable loads of EBV DNA. Compared with HIV-associated PEL, the HIV-negative cohort was characterized by older age, less frequent association with Kaposi sarcoma and/or multicentric Castleman disease, comparable but less abnormal laboratory parameters, and a nonsignificant survival benefit. PEL cases with low apoptosis were associated with better prognosis.

Conclusion: To the best of our knowledge, our case series of HIV-unrelated PEL is the largest thus far, expands the spectrum of cytological findings, and supports the need for a multidisciplinary approach in the diagnostic workup.
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http://dx.doi.org/10.1002/cncy.22344DOI Listing
January 2021

ROR1 is an accurate and reliable marker of minimal residual disease in chronic lymphocytic leukaemia.

Br J Haematol 2020 09 24;190(6):e346-e349. Epub 2020 Jun 24.

Hematology, Department of Translational and Precision Medicine, "Sapienza" University, Rome, Italy.

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http://dx.doi.org/10.1111/bjh.16910DOI Listing
September 2020

Very late acute myeloid leukemia relapse: clinical features, treatment and outcome.

Leuk Lymphoma 2020 Jan 16:1-4. Epub 2020 Jan 16.

Hematology, Department of Translational and Precision Medicine, 'Sapienza' University, Rome, Italy.

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http://dx.doi.org/10.1080/10428194.2020.1713320DOI Listing
January 2020

Minimal Residual Disease in Chronic Lymphocytic Leukemia: A New Goal?

Front Oncol 2019 29;9:689. Epub 2019 Aug 29.

Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

In chronic lymphocytic leukemia (CLL), there is a growing interest for minimal residual disease (MRD) monitoring, due to the availability of drug combinations capable of unprecedented complete clinical responses. The standardized and most commonly applied methods to assess MRD in CLL are based on flow cytometry (FCM) and, to a lesser extent, real-time quantitative PCR (RQ-PCR) with allele-specific oligonucleotide (ASO) primers of immunoglobulin heavy chain genes (IgH). Promising results are being obtained using droplet digital PCR (ddPCR) and next generation sequencing (NGS)-based approaches, with some advantages and a potential higher sensitivity compared to the standardized methodologies. Plasma cell-free DNA can also be explored as a more precise measure of residual disease from all different compartments, including the lymph nodes. From a clinical point of view, CLL MRD quantification has proven an independent prognostic marker of progression-free survival (PFS) and overall survival (OS) after chemoimmunotherapy as well as after allogeneic transplantation. In the era of mechanism-driven drugs, the paradigms of CLL treatment are being revolutionized, challenging the use of chemoimmunotherapy even in first-line. The continuous administration of ibrutinib single agent has led to prolonged PFS and OS in relapsed/refractory and treatment naïve CLL, including those with deletion/mutation or unmutated genes, though the clinical responses are rarely complete. More recently, chemo-free combinations of venetoclax+rituximab, venetoclax+obinutuzumab or ibrutinib+venetoclax have been shown capable of inducing undetectable MRD in the bone marrow, opening the way to protocols exploring a MRD-based duration of treatment, aiming at disease eradication. Thus, beside a durable disease control desirable particularly for older patients and/or for those with comorbidities, a MRD-negative complete remission is becoming a realistic prospect for CLL patients in an attempt to obtain a long-lasting eradication and possibly cure of the disease. Here we discuss the standardized and innovative technical approaches for MRD detection in CLL, the clinical impact of MRD monitoring in chemoimmunotherapy and chemo-free trials and the future clinical implications of MRD monitoring in CLL patients outside of clinical trials.
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http://dx.doi.org/10.3389/fonc.2019.00689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727319PMC
August 2019

Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study.

Ann Hematol 2019 May 13;98(5):1083-1093. Epub 2019 Mar 13.

CEINGE Biotecnologie Avanzate, Naples, Italy.

In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p < 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large (> 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.
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http://dx.doi.org/10.1007/s00277-019-03644-8DOI Listing
May 2019

Autologous stem cell transplant in acute lymphoblastic leukemia: prognostic impact of pre-transplant minimal residual disease.

Leuk Lymphoma 2019 01 26;60(1):274-276. Epub 2018 Jun 26.

a Department of Cellular Biotechnologies and Hematology , 'Sapienza' University , Rome , Italy.

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http://dx.doi.org/10.1080/10428194.2018.1468895DOI Listing
January 2019

Lymphomatoid granulomatosis and large granular lymphocyte leukemia, a rare association of two lymphoproliferative disorders.

Leuk Lymphoma 2018 11 23;59(11):2715-2718. Epub 2018 Feb 23.

a Department of Hematology , Cellular Biotechnologies and Hematology, University of Rome , Rome , Italy.

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http://dx.doi.org/10.1080/10428194.2018.1439583DOI Listing
November 2018

Very late relapse in a patient with acute promyelocytic leukemia (APL) rescued with a chemotherapy-free protocol.

Leuk Lymphoma 2017 04 23;58(4):999-1001. Epub 2016 Sep 23.

a Department of Cellular Biotechnologies and Hematology , 'Sapienza', University , Rome , Italy.

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http://dx.doi.org/10.1080/10428194.2016.1222377DOI Listing
April 2017

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia.

Hematol Oncol 2017 Dec 12;35(4):804-809. Epub 2016 Jul 12.

Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFβ-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 10 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.
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http://dx.doi.org/10.1002/hon.2331DOI Listing
December 2017

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications.

Haematologica 2016 08 5;101(8):941-50. Epub 2016 May 5.

Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy

Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways.
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http://dx.doi.org/10.3324/haematol.2015.139410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967573PMC
August 2016

CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities.

Leuk Res 2016 Feb 23;41:36-42. Epub 2015 Dec 23.

Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy. Electronic address:

Background: A deregulated CRLF2 (d-CRLF2) expression was described in B-cell acute lymphoblastic leukemia without recurrent fusion genes (B-NEG ALL). While the role of d-CRLF2 in children has been extensively described, little is known about its role and impact in adult ALL.

Methods: Expression levels of CRLF2 were evaluated by quantitative real-time PCR in 102 newly-diagnosed adult B-NEG ALL and correlated with the clinico-biological characteristics and outcome. Incidence and clinical impact of the P2RY8/CRLF2 transcript was also assessed.

Results: High CRLF2 levels, as continuous variable, were significantly associated with hyperleucocytosis (p=0.0002) and thrombocytopenia (p=0.005); when a cut-point at ΔCt≤8 was applied, 35 cases (34.3%), mostly males (80%), proved positive for CRLF2 expression. High CRLF2 levels, as continuous or categorical variable, were associated with a worse disease-free (p=0.003 and p=0.015) and overall survival (p=0.017 and 0.0038). Furthermore, when CRLF2 was analyzed as a categorical variable, a high statistical association was found with IKZF1 deletion and mutations in the JAK/STAT pathway (p=0.001 and p<0.0001, respectively). Finally, the P2RY8/CRLF2 transcript, identified in 8/102 patients (7.8%), was associated with a poor outcome.

Conclusions: In adult B-NEG ALL, high CRLF2 expression is associated with distinct clinico-biological features and an unfavourable prognosis in both univariate and multivariate analysis; similarly, P2RY8/CRLF2 positivity correlates with a poor outcome. The quantification of CRLF2 is an important prognostic marker in adult B-lineage ALL without known genetic lesions.
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http://dx.doi.org/10.1016/j.leukres.2015.11.018DOI Listing
February 2016

Inter- and intra-patient clonal and subclonal heterogeneity of chronic lymphocytic leukaemia: evidences from circulating and lymph nodal compartments.

Br J Haematol 2016 Feb 24;172(3):371-383. Epub 2015 Nov 24.

Division of Haematology, Department of Cellular Biotechnologies and Haematology, Sapienza University, Rome, Italy.

Whole exome sequencing and copy number aberration (CNA) analysis were performed on cells taken from peripheral blood (PB) and lymph nodes (LN) of patients with chronic lymphocytic leukaemia (CLL). Of 64 non-silent somatic mutations, 54 (84·4%) were clonal in both compartments, 3 (4·7%) were PB-specific and 7 (10·9%) were LN-specific. Most of the LN- or PB-specific mutations were subclonal in the other corresponding compartment (variant frequency 0·5-5·3%). Of 41 CNAs, 27 (65·8%) were shared by both compartments and 7 (17·1%) were LN- or PB-specific. Overall, 6 of 9 cases (66·7%) showed genomic differences between the compartments. At subsequent relapse, Case 10, with 6 LN-specific lesions, and Case 100, with 6 LN-specific and 8 PB-specific lesions, showed, in the PB, the clonal expansion of LN-derived lesions with an adverse impact: SF3B1 mutation, BIRC3 deletion, del8(p23·3-p11·1), del9(p24·3-p13·1) and gain 2(p25·3-p14). CLL shows an intra-patient clonal heterogeneity according to the disease compartment, with both LN and PB-specific mutations/CNAs. The LN microenvironment might contribute to the clonal selection of unfavourable lesions, as LN-derived mutations/CNAs can appear in the PB at relapse.
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http://dx.doi.org/10.1111/bjh.13859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732889PMC
February 2016

A case of lineage switch from B-cell acute lymphoblastic leukaemia to acute myeloid leukaemia. Role of subclonal/clonal gene mutations.

Br J Haematol 2016 08 12;174(4):648-51. Epub 2015 Oct 12.

Haematology, Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.

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http://dx.doi.org/10.1111/bjh.13800DOI Listing
August 2016

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy.

Am J Hematol 2015 Sep 14;90(9):E181-2. Epub 2015 Jul 14.

Division Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1002/ajh.24033DOI Listing
September 2015

Enteropathy-associated T-cell lymphoma in childhood: a case report and review of the literature.

Leuk Lymphoma 2015 9;56(9):2743-6. Epub 2015 Feb 9.

a Division of Hematology, Department of Biotechnologies and Hematology , "Sapienza" University of Rome , Rome , Italy.

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http://dx.doi.org/10.3109/10428194.2015.1009059DOI Listing
August 2016

A case of late isolated ovarian relapse of acute lymphoblastic leukemia after an allogeneic stem cell transplant.

Leuk Lymphoma 2015 May 5;56(5):1517-20. Epub 2014 Nov 5.

Department of Cellular Biotechnologies and Hematology, "Sapienza" University , Rome , Italy.

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http://dx.doi.org/10.3109/10428194.2014.956317DOI Listing
May 2015

Negative prognostic value of CD34 antigen also if expressed on a small population of acute promyelocytic leukemia cells.

Ann Hematol 2014 Nov 10;93(11):1819-23. Epub 2014 Jun 10.

Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy,

Potential clinical significance of CD34 expression in acute promyelocitic leukemia (APL) has not been deeply investigated. We hereby analyzed the clinico-biological features and treatment outcome of APL patients in relation to CD34 expression, even when expressed in a small subpopulation: 114 APL patients homogeneously treated with the AIDA schedule were included in the study and prognostic correlation with respect to CD34 expression, both when expressed in association with CD2 and as isolated expression (cutoff ≥2 to <10 % or ≥10 %), were investigated. CD34 was associated to CD2 in 30 patients and was isolated in 19 patients. When compared to the CD34-negative population, CD34/CD2 expression identified a subgroup with characteristic features: M3 variant subtype (26 vs 7 % in the negative group, p = 0.02), bcr3 transcript subtype (73 vs 32 %, p = 0.001), high risk according to the risk of relapse (66 vs 17 %, p = 0.002), high incidence of differentiation syndrome (26 vs 12 %, p = 0.01), lower overall survival (88 vs 95 %), and a significantly higher rate of relapse (22 vs 13.8 %, p = 0.05). We then evaluated the prognostic value of isolated CD34 expression: it was detected in nine patients with a cutoff of expression ≥10 % and in 10 patients with a cutoff ≥2 but <10 %. Isolated CD34 positivity identified a subgroup with a classic morphology (79 %), bcr1 prevalence (53 %), higher rate of relapse (37 vs 13.8 % in the negative group, p = 0.002), higher incidence of differentiation syndrome (55 vs 12 %, p = 0.03), and lower overall survival (60 vs 95 %, p = 0.001). The results of our study confirm that CD34/CD2 expression characterizes a subset of APL with a high WBC count and a variant morphological subtype, associated with an unfavorable clinical course. We also show that the isolated expression of CD34, even at a low cutoff, identifies a group of classic APL with a negative prognosis. Further studies aimed at identifying other molecular signatures in CD34-positive patients are needed in order to optimize the therapeutic strategy for this subset of patients.
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http://dx.doi.org/10.1007/s00277-014-2130-0DOI Listing
November 2014

Mediastinal isolated myeloid sarcoma: a single-institution experience.

Leuk Lymphoma 2015 Feb 4;56(2):539-41. Epub 2015 Feb 4.

Cellular Biotechnologies and Hematology, Sapienza University , Rome , Italy.

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http://dx.doi.org/10.3109/10428194.2014.914201DOI Listing
February 2015

Selective splenic artery embolization for the treatment of thrombocytopenia and hypersplenism in paroxysmal nocturnal hemoglobinuria.

J Hematol Oncol 2014 Mar 27;7:27. Epub 2014 Mar 27.

Division of Hematology, NYU School of Medicine, and the New York Harbor VA Medical Center, New York, NY, USA.

Background: PNH is associated with abdominal vein thrombosis, which can cause splenomegaly and hypersplenism. The combination of thrombosis, splenomegaly, and thrombocytopenia (TST) is challenging because anticoagulants are indicated but thrombocytopenia may increase the bleeding risk. Splenectomy could alleviate thrombocytopenia and reduce portal pressure, but it can cause post-operative thromboses and opportunistic infections. We therefore sought to determine whether selective splenic artery embolization (SSAE) is a safe and effective alternative to splenectomy for TST in patients with PNH.

Methods: Four patients with PNH and TST received successive rounds of SSAE. By targeting distal vessels for occlusion, we aimed to infarct approximately 1/3 of the spleen with each procedure.

Results: Three of 4 patients had an improvement in their platelet count, and 3 of 3 had major improvement in abdominal pain/discomfort. The one patient whose platelet count did not respond had developed marrow failure, and she did well with an allo-SCT. Post-procedure pain and fever were common and manageable; only one patient developed a loculated pleural effusion requiring drainage. One patient, who had had only a partial response to eculizumab, responded to SSAE not only with an improved platelet count, but also with an increase in hemoglobin level and decreased transfusion requirement.

Conclusions: These data indicate that SSAE can decrease spleen size and reverse hypersplenism, without exposing the patient to the complications of splenectomy. In addition, SSAE probably reduces the uptake of opsonised red cells in patients who have had a limited response to eculizumab, resulting in an improved quality of life for selected patients.
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http://dx.doi.org/10.1186/1756-8722-7-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984395PMC
March 2014

Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

Am J Hematol 2014 May 18;89(5):480-6. Epub 2014 Feb 18.

Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.
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http://dx.doi.org/10.1002/ajh.23668DOI Listing
May 2014

Rituximab in previously treated primary immune thrombocytopenia patients: evaluation of short- and long-term efficacy and safety.

Acta Haematol 2014 19;132(1):24-9. Epub 2013 Dec 19.

Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University of Rome, Rome, Italy.

The anti-CD20 chimeric monoclonal antibody rituximab has been effectively used in the treatment of patients with primary immune thrombocytopenia (pITP). We retrospectively evaluated 19 patients affected by pITP resistant to 2 or more lines of therapy who were treated with rituximab. Nine of the 19 patients showed an initial response (47.4%). The sustained response rate was 31.6% (6/19). The median follow-up of the patients was 53.2 months (range 9.2-92.9). Disease-free survival at 48 months was 62.2%. Following rituximab treatment, a proportion of patients (42%) recovered a normal B lymphocyte number. During the follow-up, no opportunistic or severe infectious complications were observed. These data confirm, over a long period of observation, the efficacy and safety of rituximab treatment in the management of patients with resistant pITP.
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http://dx.doi.org/10.1159/000355650DOI Listing
September 2014

Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute promyelocytic leukemia patients.

Leuk Res 2014 Feb 18;38(2):194-7. Epub 2013 Nov 18.

Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

Limited information is available on the relationship between expression of some additional aberrant phenotypic features and outcome of acute promyelocytic leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and CD56 expression, and their prognostic value in a large series of APL patients. One hundred and fourteen adult patients consecutively diagnosed with PML/RARα-positive APL and homogeneously treated with the AIDA induction schedule at a single institution were included in the study. Twelve (10.5%) and 9 (8%) of the 114 patients expressed CD15 and CD56, respectively. CD15 expression identified a subset of patients with a classic morphologic subtype (92%), a prevalent association with a bcr1 expression (67%) with an unexpectedly higher frequency of relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56 expression was detected only in patients with a classic morphologic subtype, a prevalent bcr3 expression (67%), high incidence of differentiation syndrome (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04) and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the negative prognostic value of CD56 and we show that the same applies also to cases expressing CD15. These aberrant markers may be considered for the refinement of risk-adapted therapeutic strategies in APL patients.
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http://dx.doi.org/10.1016/j.leukres.2013.11.008DOI Listing
February 2014