Publications by authors named "Silvia Finotto"

18 Publications

  • Page 1 of 1

Complete remission of primary cutaneous anaplastic large cell lymphoma after a short course of brentuximab vedotin.

Mol Clin Oncol 2021 Jun 15;14(6):121. Epub 2021 Apr 15.

Unit of Dermatology, University of Padua, Padova I-35128, Italy.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30 lymphoproliferative disorder characterized by the development of lesions ranging from papules to large tumors. Most cases present as localized disease, however multifocal and generalized involvement of the skin can occur. Several treatments have been proposed for PCALCL; however a highly effective standard approach to multifocal disease has not yet been elucidated. The disease expression of CD30 antigen in at least 75% of the tumor makes it an optimal target for immunotherapy. The current study presents a case of a 62-year-old male referred to the University of Padua Dermatology Clinic complaining about nodular and ulcerated lesions involving the frontal area and scalp that were 8 cm in diameter. Doses of 180 mg brentuximab vedotin (BV), which is an antibody drug conjugate binding CD30 antigen, were administered every 21 days. A 75% decrease in dimensions after the first infusion and a complete remission after the second was observed. Disease response appeared to be dose-related and adverse reactions, in particular peripheral neuropathy, may be an effect of cumulative toxicity, meaning that treatment cycle reduction should be considered. Based on the present results, A high dose, short course of BV is recommended as a cost-effective approach for PCALCL. However, further studies are required to assess the efficacy and other potential advantages of this therapeutic regimen.
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http://dx.doi.org/10.3892/mco.2021.2283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082231PMC
June 2021

Older cancer patients and COVID-19 outbreak: Practical considerations and recommendations.

Cancer Med 2020 12 21;9(24):9193-9204. Epub 2020 Nov 21.

Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

Since the COVID-19 outbreak started, it has been affecting mainly older individuals. Among the most vulnerable older individuals are those with cancer. Many published guidelines and consensus papers deal with prioritizing cancer care. Given the lack of high-quality evidence for management of cancer in older patients also in normal times, it is even more stringent to provide some resources on how to avoid both undertreatment and overtreatment in this population, who as of now is twice challenged to death, due to both a greater risk of getting infected with COVID-19 as well as from cancer not adequately addressed and treated. We hereby discuss some general recommendations (implement triage procedures; perform geriatric assessment; carefully assess comorbidity; promote early integration of palliative care in oncology; acknowledge the role of caregivers; maintain active take in charge to avoid feeling of abandonment; mandate seasonal flu vaccination) and discuss practical suggestions for specific disease settings (early-stage and advanced-stage disease for solid tumors, and hematological malignancies). The manuscript provides resources on how to avoid both undertreatment and overtreatment in older patients with cancer, who as of now is twice challenged to death, due to both a greater risk of getting infected with COVID-19 as well as from cancer not adequately addressed and treated.
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http://dx.doi.org/10.1002/cam4.3517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774711PMC
December 2020

To Transplant or Not to Transplant During the SARS-CoV-2 Pandemic? That Is the Question.

Oncologist 2021 02 23;26(2):e336-e337. Epub 2020 Oct 23.

Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology (IOV), Istituto Ricerca Cura Carattere Scientifico, Padua, Italy.

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.
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http://dx.doi.org/10.1002/onco.13563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675713PMC
February 2021

Aggressive Merkel Cell Carcinoma After Janus Kinase Inhibitor Ruxolitinib for Polycythemia Vera.

In Vivo 2019 Sep-Oct;33(5):1667-1669

Dermatology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. It is highly aggressive and represents the second most common cause of skin cancer-related death. Ruxolitinib is an orally administered selective inhibitor of Janus associated kinases1 and 2, which is used in the management of patients with symptomatic myelofibrosis and polycythemia vera who are non-responders or intolerant to hydroxyurea. Herein, we report the case of a 47-year-old woman with a 14-year history of chronic myeloproliferative syndrome initially treated with hydroxyurea for 4 years. She was then enrolled in the Response trial and treated for 7 years with ruxolitinib subsequently developing an MCC. This report shows the possibility of development of MCC in patients treated with ruxolitinib. Periodic skin examination is indicated in patients who undergo ruxolitinib therapy, especially if they have a history of skin cancer; dermatologists and oncohematologists should be aware of this possibility in order to introduce appropriate preventive strategies.
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http://dx.doi.org/10.21873/invivo.11653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754986PMC
February 2020

A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi.

Biol Blood Marrow Transplant 2018 09 29;24(9):1814-1822. Epub 2018 May 29.

Oncologia Medica 1, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy.

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.
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http://dx.doi.org/10.1016/j.bbmt.2018.05.018DOI Listing
September 2018

Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi.

Lancet Haematol 2017 Jan 5;4(1):e15-e23. Epub 2016 Dec 5.

Hematology, Citta' della salute e della scienza University Hospital, Torino, Italy.

Background: The combination of rituximab, bendamustine, and cytarabine (R-BAC) was highly active in a pilot trial of mantle cell lymphoma, but its use was restricted by high haematological toxicity. We aimed to assess the efficacy and safety of an R-BAC regimen with low-dose cytarabine (RBAC500).

Methods: In this multicentre, phase 2 trial, we recruited previously untreated patients with an established histological diagnosis of mantle cell lymphoma from 29 Fondazione Italiana Linfomi centres in Italy. Patients had to be older than 65 years and fit according to the comprehensive geriatric assessment, or aged 60-65 years if they were ineligible for high-dose chemotherapy plus autologous stem-cell transplantation and were fit or unfit. All patients received RBAC500 (rituximab 375 mg/m on day 1, bendamustine 70 mg/m on days 2 and 3, and cytarabine 500 mg/m on days 2-4; all administered intravenously) every 4 weeks for up to six cycles. Primary endpoints were the proportion of patients achieving complete response at the end of treatment and toxicity, defined as the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity. All patients who started at least one cycle of RBAC500 were included in the primary and safety analyses. Using efficacy and toxicity as a composite primary endpoint, we considered the final conclusion positive if more than 28 of 57 patients achieve complete response and fewer than 18 of 57 patients report toxicities. This study is registered with EudraCT, number 2011-005739-23, and ClinicalTrials.gov, number NCT01662050, and is completed.

Findings: Between May 2, 2012, and Feb 25, 2014, we enrolled 57 patients (median age 71 years, IQR 67-75). 54 (95%) patients received at least four RBAC500 cycles (three discontinued because of toxicity), and 38 (67%) completed six cycles. Two (4%) had disease progression (one after the fourth cycle and one after the sixth cycle). All 52 (91%, lower limit of one-sided 95% CI 85%) remaining patients achieved complete response at the end of treatment. 23 (40%, upper limit of one-sided 95% CI 53%) of 57 patients had at least one episode of relevant toxicity. The most frequent grade 3-4 haematological toxicities were neutropenia (149 [49%] of 304 cycles) and thrombocytopenia (158 [52%]). Most treatment-related non-haematological adverse events were of grade 1-2, with the most frequent ones being fatigue (14 [25%] patients), nausea or vomiting (12 [21%]), and infusion-related reactions or tumour lysis syndrome (12 [21%]). 41 (72%) patients required a dose reduction. 12 patients died during the study, but no deaths were related to treatment.

Interpretation: RBAC500 is an effective treatment for elderly patients with mantle cell lymphoma and, despite not meeting our prespecified safety boundary, haematological toxicity was manageable with appropriate supportive care and dose reduction. Since maintenance therapy is not required, RBAC500 could be considered an option and should be studied in phase 3 trials.

Funding: Fondazione Italiana Linfomi and Mundipharma.
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http://dx.doi.org/10.1016/S2352-3026(16)30185-5DOI Listing
January 2017

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment.

World J Gastroenterol 2014 Aug;20(32):11054-61

Carlo Visco, Silvia Finotto, Department of Hematology and Cell Therapy, San Bortolo Hospital, 36100 Vicenza, Italy.

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.
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http://dx.doi.org/10.3748/wjg.v20.i32.11054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145748PMC
August 2014

Clinical significance of LAIR1 (CD305) as assessed by flow cytometry in a prospective series of patients with chronic lymphocytic leukemia.

Haematologica 2014 May 10;99(5):881-7. Epub 2014 Jan 10.

Most patients affected by chronic lymphocytic leukemia are diagnosed by flow cytometry. Several immunophenotypic markers have been identified as significant and independent prognostic variables, especially from retrospective cohorts. However, while attractive because their detection is inexpensive and feasible in most laboratories, only few have been validated by independent series. The expression of leukocyte-associated immunoglobulin-like receptor-1 (also known as LAIR1, LAIR-1 or CD305), an inhibitor of B-cell receptor-mediated signaling, has been reported to be lacking in high-risk chronic lymphocytic leukemia. However, its correlation with biological variables and its prognostic significance remain unknown. We investigated 311 consecutive patients, prospectively enrolled since 2007. Methods for studying patients were standardized and included clinical assessment, immunophenotype, fluorescence in situ hybridization, and status of immunoglobulin heavy chain variable region genes. Overall, 22.1% of patients had Binet stage B or C disease, 38.5% had unmutated immunoglobulin genes, 15.1% had high-risk cytogenetic abnormalities, 23.4% were CD38(+), 37.8% CD49d(+), and 59.8% LAIR1(+). Expression of LAIR1 was inversely related to that of CD38 (P=0.0005), but was not associated with CD49d expression (P=0.96). A significantly lower expression of LAIR1 was observed in patients with Binet stage B or C disease (P=0.023), and in the presence of high-risk cytogenetic abnormalities (P=0.048) or unmutated immunoglobulin heavy chain variable region genes (P<0.0001). At univariate analysis LAIR1(+) was significantly associated with longer time to first treatment (P=0.0002). This favorable effect of LAIR1(+) was confirmed by multivariate analysis (hazard ratio=2.1, P=0.03 for LAIR1). Our results indicate that LAIR1 expression is a reliable and inexpensive marker capable of independently predicting time to first treatment in newly diagnosed unselected patients with chronic lymphocytic leukemia.
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http://dx.doi.org/10.3324/haematol.2013.096362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008102PMC
May 2014

Autoimmune cytopenias in chronic lymphocytic leukemia at disease presentation in the modern treatment era: is stage C always stage C?

Leuk Lymphoma 2014 Jun 23;55(6):1261-5. Epub 2013 Sep 23.

Department of Hematology, S. Bortolo Hospital , Vicenza , Italy.

Abstract Anemia and thrombocytopenia at chronic lymphocytic leukemia (CLL) presentation have long been considered to be predictive of a poor prognosis, irrespective of the cause of cytopenia, yielding an advanced stage of the disease. We identified 86 patients with CLL who were diagnosed after year 2000 with Binet C disease at first presentation. Cytopenia was considered related to autoimmune conditions in 27 (31.3%; stage C "immune") or secondary to bone marrow failure in 59 (68.6%; stage C "infiltrative"). No difference in clinical characteristics, mutational status, cytogenetics, TP53 and NOTCH1 mutations was observed between stage C "immune" and "infiltrative." Patients with stage C "immune" had a trend toward a better overall survival than patients with stage C "infiltrative" (median 74 vs. 63 months), but the difference was not statistically significant (p = 0.30). This difference was not modified by adjustment for CLL tumor burden at presentation, and survival of stage C "immune" patients was significantly inferior compared to an unselected cohort of patients with stage A, but similar to stage B. Our findings suggest that autoimmune cytopenias at CLL diagnosis have a negative impact on patient outcome.
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http://dx.doi.org/10.3109/10428194.2013.834054DOI Listing
June 2014

B-cell receptor configuration and mutational analysis of patients with chronic lymphocytic leukaemia and trisomy 12 reveal recurrent molecular abnormalities.

Hematol Oncol 2014 Mar 17;32(1):22-30. Epub 2013 Jul 17.

Department of Hematology and Cell Therapy, S. Bortolo Hospital, Vicenza, Italy.

Trisomy 12 (+12) is the third most frequent cytogenetic aberration in chronic lymphocytic leukaemia (CLL) retrievable both as the sole chromosomal abnormality or in association with additional alterations. NOTCH1 mutations are known to be more prevalent among +12 patients, whereas mutations of FBXW7, a gene involved in NOTCH1 degradation, that lead to the constitutional activation of NOTCH1 have not been investigated in this setting. We analyzed a unicentric cohort of 44 +12 patients with CLL for mutations of TP53, NOTCH1 and FBXW7 genes, and we correlated them with B-cell receptor (BCR) configurations. FBXW7, TP53 and NOTCH1 mutations were identified in 4.5%, 6.8% and 18.2% of patients, respectively. FBXW7 and NOTCH1 mutations appeared in a mutually exclusive fashion, suggesting that both aberrations might affect the same biological pathway. We found that 44.1% of +12 CLL patients had stereotyped B-cell receptors, which is significantly higher than that observed in patients with CLL and no +12 (27%, p = 0.01). Subsets #1, #8, #10, #28 and #59 were the most represented stereotyped patterns, and IGHV4-39*01 was the gene configuration most commonly used. There was a significantly higher risk for Richter's syndrome (RS) transformation in patients with NOTCH1 or FBXW7 mutations, with four of the seven (57%) patients developing RS and characterized at least by one of the two abnormalities. These observations suggest that, similarly to the aberrations of NOTCH1, FBXW7 gene mutations may also result in cell proliferation and evasion from apoptosis in patients with +12 CLL. Together with the extremely high frequency of stereotyped BCRs and RS transformation, these abnormalities appear to cluster in these CLL patients with additional chromosome 12, suggesting a connection with the prognosis of the disease.
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http://dx.doi.org/10.1002/hon.2086DOI Listing
March 2014

Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia.

Am J Hematol 2013 Apr 28;88(4):277-82. Epub 2013 Feb 28.

Department of Hematology S. Bortolo Hospital, Vicenza, Italy.

The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV-mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials.
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http://dx.doi.org/10.1002/ajh.23396DOI Listing
April 2013

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia.

Am J Hematol 2013 Apr 28;88(4):289-93. Epub 2013 Feb 28.

Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.

Treatment of patients with B-cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B-cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m(2) , Day 1), plus bendamustine (70 mg/m(2) , days 1-2), and cytarabine (800 mg/m(2) , Day 1-3; R-BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high-risk R/R CLL. All patients (median age 60 years, range 53-74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy-chain variable region, and were heavily pretreated (1-5, median three previous lines). Overall, R-BAC was well tolerated with limited non-hematological toxicity. Major toxicities were transient Grade 3/4 neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow-up of 17 months, median progression-free survival was 16 months while median overall survival (OS) was not reached (1-year OS: 75 ± 13%). R-BAC is an active regimen in R/R heavily pretreated high-risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy.
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http://dx.doi.org/10.1002/ajh.23391DOI Listing
April 2013

Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation.

J Clin Oncol 2013 Apr 11;31(11):1442-9. Epub 2013 Feb 11.

Department of Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100 Vicenza, Italy.

Purpose: The combination of bendamustine (B) and rituximab (R) is efficacious, with favorable toxicity in mantle-cell lymphoma (MCL). In this phase II study, we combined cytarabine with R and B (R-BAC) in patients with MCL age ≥ 65 years who were previously untreated or relapsed or refractory (R/R) after one prior immunochemotherapy treatment.

Patients And Methods: In stage one, we established the maximum-tolerated dose (MTD) of cytarabine in R-BAC. In stage two, patients received R (375 mg/m(2) intravenously [IV] on day 1), B (70 mg/m(2) IV on days 2 and 3), and cytarabine (MTD IV on days 2 to 4) every 28 days for four to six cycles. The primary end point (overall response rate [ORR]) was evaluated by positron emission tomography. Secondary end points included safety, progression-free survival (PFS), response duration, and overall survival.

Results: Forty patients (median age, 70 years; 20 previously untreated patients) were enrolled; 93% had Ann Arbor stage III/IV disease; 49% had high Mantle Cell International Prognostic Index scores, with 15% blastoid histology. All R/R patients (35% refractory) had previously received R-containing regimens. The cytarabine MTD used in stage two was 800 mg/m(2), and R-BAC was well tolerated, with an 85% treatment completion rate. The major toxicity was transient grades 3 to 4 thrombocytopenia (87% of patients); febrile neutropenia occurred in 12%. The ORR was 100% (95% complete response [CR]) for previously untreated and 80% (70% CR) for R/R patients. The 2-year PFS rate (± standard deviation) was 95% ± 5% for untreated and 70% ± 10% for R/R patients.

Conclusion: R-BAC is well tolerated and active against MCL.
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http://dx.doi.org/10.1200/JCO.2012.45.9842DOI Listing
April 2013

Isolated erythrocytosis: study of 67 patients and identification of three novel germ-line mutations in the prolyl hydroxylase domain protein 2 (PHD2) gene.

Haematologica 2012 Jan 9;97(1):123-7. Epub 2011 Aug 9.

Department of Cellular Therapies and Haematology, San Bortolo Hospital, Vicenza, Italy.

The oxygen sensing pathway modulates erythropoietin expression. In normal cells, intracellular oxygen tensions are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins. PHD2 isozyme has a key role in tagging hypoxia-inducible factor (HIF)-α subunits for polyubiquitination and proteasomal degradation. Erythrocytosis-associated PHD2 mutations reduce hydroxylation of HIF-α. The investigation of 67 patients with isolated erythrocytosis, either sporadic or familial, allowed the identification of three novel mutations in the catalytic domain of the PHD2 protein. All new mutations are germ-line, heterozygous and missense, and code for a predicted full length mutant PHD2 protein. Identification of the disease-causing genes will be of critical importance for a better classification of familial and acquired erythrocytosis, offering additional insight into the erythropoietin regulating oxygen sensing pathway.
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http://dx.doi.org/10.3324/haematol.2010.039545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248940PMC
January 2012

Treatment outcome in a cohort of young patients with polycythemia vera.

Intern Emerg Med 2010 Oct 6;5(5):411-3. Epub 2010 Jul 6.

Department of Cell Therapy and Hematology, San Bortolo Hospital, Viale Rodolfi 37, Vicenza, Italy.

The treatment of polycythemia vera in young adults is challenging, requiring one to run a balance between the increased risk of vascular complications, if left untreated, versus the potential of promoting secondary leukemia/myelodysplasia or cancer, if actively managed with chemotherapy. We report the results of a 20-year retrospective analysis in a cohort of 30 young adults with PV (median age 37 years, range 19-45) treated exclusively with phlebotomy, aspirin and hydroxyurea only in case of vascular complications occurring in the presence of thrombocytosis (platelet count > 600 × 10(9)/L). With this approach, vascular complications were no higher than in other published series, and secondary leukemia/myelodysplasia or cancer was not observed during a follow-up of 14 years.
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http://dx.doi.org/10.1007/s11739-010-0429-yDOI Listing
October 2010

Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia.

Blood 2008 Aug 2;112(3):844-7. Epub 2008 Jun 2.

Unita Funzionale di Ematologia, Dipartimento di Area Critica Medico-Chirurgica, Università degli Studi, Florence, Italy.

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.
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http://dx.doi.org/10.1182/blood-2008-01-135897DOI Listing
August 2008