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Article ; Online: Treatment of older patients with mantle cell lymphoma in the era of novel agents.

Rozental, Alon / Jim, Heather S L / Extermann, Martine

2023 Volume 64, Issue 9, Page(s) 1514–1526

Abstract: Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin's lymphoma with a highly heterogeneous presentation that ranges from an indolent disease to an extremely aggressive one. Several clinical and biological prognostic markers can assist in determining ...

Abstract	Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin's lymphoma with a highly heterogeneous presentation that ranges from an indolent disease to an extremely aggressive one. Several clinical and biological prognostic markers can assist in determining the aggressiveness of the disease. Such as MIPI, Ki-67, and TP53, NOTCH1, and CDKN2A mutations. While aggressive chemoimmunotherapy regimens combining rituximab and cytarabine, followed by autologous stem-cell transplantation yield the most promising results, this treatment is too toxic for older patients. Several lower-intensity regimens have shown efficacy in older patients with reduced toxicity profiles. However, older relapsed/refractory patients have an extremely poor outcome. In the last several years, there is a major trend toward chemotherapy-free regimens, targeted therapies such as BTK, BCL-2 and PI3K inhibitors, and immunotherapies such as lenalidomide and CAR-T, which can provide a promising strategy for older patients. Herein we review the current therapies for older MCL patients, chemotherapy regimens, targeted therapies, and immunotherapies.
MeSH term(s)	Humans ; Adult ; Aged ; Lymphoma, Mantle-Cell/diagnosis ; Lymphoma, Mantle-Cell/drug therapy ; Phosphatidylinositol 3-Kinases ; Rituximab/therapeutic use ; Lenalidomide/therapeutic use ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Rituximab (4F4X42SYQ6) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2227748
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Book ; Online: Adversarial Generation and Encoding of Nested Texts

Rozental, Alon

2019

Abstract: In this paper we propose a new language model called AGENT, which stands for Adversarial Generation and Encoding of Nested Texts. AGENT is designed for encoding, generating and refining documents that consist of a long and coherent text, such as an ... ...

Abstract	In this paper we propose a new language model called AGENT, which stands for Adversarial Generation and Encoding of Nested Texts. AGENT is designed for encoding, generating and refining documents that consist of a long and coherent text, such as an entire book, provided they are hierarchically annotated (nested). i.e. divided into sentences, paragraphs and chapters. The core idea of our system is learning vector representations for each level of the text hierarchy (sentences, paragraphs, etc.), and train each such representation to perform 3 tasks: The task of reconstructing the sequence of vectors from a lower level that was used to create the representation, and generalized versions of the Masked Language Modeling (MLM) and "Next Sentence Prediction" tasks from BERT Devlin et al. [2018]. Additionally we present a new adversarial model for long text generation and suggest a way to improve the coherence of the generated text by traversing its vector representation tree.
Keywords	Computer Science - Computation and Language
Subject code	401
Publishing date	2019-06-01
Publishing country	us
Document type	Book ; Online
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Book ; Online: Amobee at SemEval-2019 Tasks 5 and 6

Rozental, Alon / Biton, Dadi

Multiple Choice CNN Over Contextual Embedding

2019

Abstract: This article describes Amobee's participation in "HatEval: Multilingual detection of hate speech against immigrants and women in Twitter" (task 5) and "OffensEval: Identifying and Categorizing Offensive Language in Social Media" (task 6). The goal of ... ...

Abstract	This article describes Amobee's participation in "HatEval: Multilingual detection of hate speech against immigrants and women in Twitter" (task 5) and "OffensEval: Identifying and Categorizing Offensive Language in Social Media" (task 6). The goal of task 5 was to detect hate speech targeted to women and immigrants. The goal of task 6 was to identify and categorized offensive language in social media, and identify offense target. We present a novel type of convolutional neural network called "Multiple Choice CNN" (MC-CNN) that we used over our newly developed contextual embedding, Rozental et al. (2019). For both tasks we used this architecture and achieved 4th place out of 69 participants with an F1 score of 0.53 in task 5, in task 6 achieved 2nd place (out of 75) in Sub-task B - automatic categorization of offense types (our model reached places 18/2/7 out of 103/75/65 for sub-tasks A, B and C respectively in task 6).
Keywords	Computer Science - Computation and Language
Subject code	004
Publishing date	2019-04-17
Publishing country	us
Document type	Book ; Online
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Article ; Online: R-CHOP compared to R-CHOP + X for newly diagnosed diffuse large B-cell lymphoma: a systematic review and meta-analysis.

Pasvolsky, Oren / Rozental, Alon / Raanani, Pia / Gafter-Gvili, Anat / Gurion, Ronit

Acta oncologica (Stockholm, Sweden)

2021 Volume 60, Issue 6, Page(s) 744–749

Abstract: Background: Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard of care first line treatment for diffuse large B-cell lymphoma (DLBCL), though outcomes remain suboptimal.: Methods: We performed a ... ...

Abstract	Background: Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard of care first line treatment for diffuse large B-cell lymphoma (DLBCL), though outcomes remain suboptimal. Methods: We performed a systemic review and meta-analysis of randomized controlled trials comparing the efficacy and safety of R-CHOP vs. R-CHOP + X (addition of another drug to R-CHOP) as first line treatment for DLBCL. We searched Cochrane Library, PubMed and conference proceedings up to September 2020. Results: Our search yielded ten trials including 4206 patients. The added drug was bortezomib or lenalidomide in three trials each, and gemcitabine, bevacizumab and ibrutinib, each drug in one trial. R-CHOP + X was associated with statistically significant improved disease control (HR 0.88, 95% CI 0.78-0.99). The point estimate was in favor of improved overall survival with R-CHOP + X (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.75-1.00), although this was not statistically significant. Subgroup analysis revealed improved disease control with the addition of lenalidomide and in patients younger than 60 years. R-CHOP + X was associated with an increase in serious adverse events and grade III/IV hematologic toxicity. Conclusion: The addition of another drug to frontline R-CHOP treatment for DLBCL did not result in a significant improvement in OS, although we did observe improved disease control compared to R-CHOP, perhaps most evident with the addition of lenalidomide. Yet, RCHOP + X was associated with an increased risk for serious and hematological adverse events. Further studies could reveal subgroups that would benefit most from augmentation of standard R-CHOP.
MeSH term(s)	Antibodies, Monoclonal, Murine-Derived/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Cyclophosphamide/adverse effects ; Doxorubicin/adverse effects ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Prednisone/adverse effects ; Rituximab/therapeutic use ; Vincristine/adverse effects
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2021-03-18
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	896449-x
ISSN	1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
ISSN (online)	1651-226X
ISSN	0349-652X ; 0284-186X ; 1100-1704
DOI	10.1080/0284186X.2021.1898048
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Article ; Online: Investigational venetoclax combination therapy in acute myeloid leukemia - a systematic review and meta-analysis.

Shimony, Shai / Rozental, Alon / Bewersdorf, Jan P / Goldberg, Aaron D / Stein, Eytan M / Grimshaw, Alyssa A / Stone, Richard M / DeAngelo, Daniel J / Wolach, Ofir / Stahl, Maximilian

Haematologica

2022 Volume 107, Issue 12, Page(s) 2955–2960

MeSH term(s)	Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Sulfonamides/therapeutic use ; Leukemia, Myeloid, Acute/drug therapy ; Combined Modality Therapy
Chemical Substances	venetoclax (N54AIC43PW) ; Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides
Language	English
Publishing date	2022-12-01
Publishing country	Italy
Document type	Meta-Analysis ; Systematic Review ; Letter
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281453
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Article ; Online: The role of maintenance therapy in patients with diffuse large B cell lymphoma: A systematic review and meta-analysis.

Rozental, Alon / Gafter-Gvili, Anat / Vidal, Liat / Raanani, Pia / Gurion, Ronit

Hematological oncology

2018 Volume 37, Issue 1, Page(s) 27–34

Abstract: Randomized trials of maintenance therapy (MT) in diffuse large B cell lymphoma (DLBCL) are inconclusive regarding its effect on overall survival (OS) and disease control. We aimed to examine the efficacy and safety of MT in this meta-analysis. Systematic ...

Abstract	Randomized trials of maintenance therapy (MT) in diffuse large B cell lymphoma (DLBCL) are inconclusive regarding its effect on overall survival (OS) and disease control. We aimed to examine the efficacy and safety of MT in this meta-analysis. Systematic review and meta-analysis of randomized controlled trials comparing MT with observation or placebo, in patients with DLBCL, who achieved complete response (CR) or partial response (PR) after first-line chemotherapy with or without rituximab. Primary outcome was OS. Secondary outcomes included relapse rate, disease control (defined as progression-free survival, event-free survival, or disease-free survival, as reported in the original trials), and safety. Our search yielded 14 trials including 5122 patients. Median age of patients was 49 to 70 years. Six trials included rituximab as the MT; three included Interferon alfa; other trials include thalidomide, lenalidomide, cyclophosphamide and prednisone, serine threonine kinase inhibitor enzastaurin, and mTOR inhibitor everolimus. MT did not improve OS compared to observation, OR 0.91, (95% CI 0.78-1.07). Results were the same in a subgroup analysis by the type of maintenance (rituximab vs other). MT did decreased relapse rate, RR 0.76 (95% CI 0.65-0.89) and improved disease control, OR 0.74 (95% CI 0.65-0.84). Disease control was significantly improved in the subgroup of studies evaluating rituximab as maintenance OR 0.61 (95% CI 0.47-0.79) and in the subgroup of R-CHOP induction studies OR 0.77 (95% CI 0.67-0.88). Serious or grade III/IV adverse events including neutropenia and infections were significantly more common in the maintenance arm, RR = 1.69 (95% CI 1.29-2.22). MT in patients with DLBCL achieving CR or PR after induction therapy did not affect OS, yet it decreased relapse rate and improved disease control at the cost of higher infection rate. Our data do not support routine administration of MT in patients with DLBCL.
MeSH term(s)	Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide ; Doxorubicin ; Female ; Humans ; Induction Chemotherapy ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; Maintenance Chemotherapy ; Male ; Prednisone ; Treatment Outcome ; Vincristine
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; R-CHOP protocol ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2018-10-08
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.2561
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Article ; Online: Clinico-pathologic and dynamic prognostic factors in sporadic and familial medullary thyroid carcinoma: an Israeli multi-center study.

Twito, Orit / Grozinsky-Glasberg, Simona / Levy, Sigal / Bachar, Gideon / Gross, David J / Benbassat, Carlos / Rozental, Alon / Hirsch, Dania

European journal of endocrinology

2019 Volume 181, Issue 1, Page(s) 13–21

Abstract: Objective: Multiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC ... ...

Abstract	Objective: Multiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC patients followed for long period are scarce. This study evaluated the association between baseline clinico-pathologic variables and response to initial treatment and short- and long-term disease outcomes in sporadic and familial MTC. Methods: Patients treated for MTC at four tertiary medical centers were retrospectively analyzed. Clinical and pathological data were collected. The outcomes measured included disease persistence 1 year after diagnosis, disease persistence at last follow-up, disease-related mortality (DRM) and all-cause mortality. Results: The study enrolled 193 patients (mean age: 48.9 ± 18.7, 44.7% males), of whom 18.1% were familial cases. The mean follow-up period was 10.1 ± 9.4 years (8.5 ± 8.1 in sporadic and 16.9 ± 11.6 in familial MTC). Disease persistence 1-year after diagnosis and at last follow-up was detected in 56.1 and 60.4% patients, respectively. All-cause and DRM were 28.5 and 12.6%, respectively. Extra-thyroidal extension (ETE) and distant metastases (DM) were associated with disease persistence at last follow-up. ETE and DM were also significantly associated with DRM. Complete remission 1 year after diagnosis had high correlation with no evidence of disease at last follow-up (Cramer's V measure of association 0.884, P < 0.001) and with 100% disease-specific survival (Cramer's V measure of association 0.38, P < 0.001). Conclusions: Apart from clinico-pathologic parameters, close correlation was found between 1-year status and long-term prognosis. These results underscore the importance of combining classical and dynamic factors for both sporadic and familial MTC prognostication and treatment decision making.
MeSH term(s)	Adolescent ; Adult ; Aged ; Carcinoma, Medullary/congenital ; Carcinoma, Medullary/mortality ; Carcinoma, Medullary/pathology ; Carcinoma, Medullary/therapy ; Carcinoma, Neuroendocrine/mortality ; Carcinoma, Neuroendocrine/pathology ; Carcinoma, Neuroendocrine/therapy ; Cause of Death ; Disease-Free Survival ; Female ; Humans ; Israel ; Male ; Middle Aged ; Mortality ; Multiple Endocrine Neoplasia Type 2a/mortality ; Multiple Endocrine Neoplasia Type 2a/pathology ; Multiple Endocrine Neoplasia Type 2a/therapy ; Neck Dissection ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Thyroid Neoplasms/mortality ; Thyroid Neoplasms/pathology ; Thyroid Neoplasms/therapy ; Thyroidectomy ; Tumor Burden ; Young Adult
Language	English
Publishing date	2019-05-03
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-18-1008
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Article ; Online: Prediction of life-threatening and disabling bleeding in patients with AML receiving intensive induction chemotherapy.

Blood advances

2022 Volume 6, Issue 9, Page(s) 2835–2846

Abstract: Bleeding in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy is multifactorial and contributes to early death. We sought to define the incidence and risk factors of grade 4 bleeding to support strategies for risk ... ...

Abstract	Bleeding in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy is multifactorial and contributes to early death. We sought to define the incidence and risk factors of grade 4 bleeding to support strategies for risk mitigation. Bleeding events were retrospectively assessed between day-14 and day +60 of induction treatment according to the World Health Organization (WHO) bleeding assessment scale, which includes grade 4 bleeding as fatal, life-threatening, retinal with visual impairment, or involving the central nervous system. Predictors were considered pretreatment or prior to grade 4 bleeding. Using multivariable competing-risk regression analysis with grade 4 bleeding as the primary outcome, we identified risk factors in the development cohort (n = 341), which were tested in an independent cohort (n = 143). Grade 4 bleeding occurred in 5.9% and 9.8% of patients in the development and validation cohort, respectively. Risk factors that were independently associated with grade 4 bleeding included baseline platelet count ≤40 × 109/L compared with >40 × 109/L, and baseline international normalized ratio of prothrombin time (PT-INR) >1.5 or 1.3 > 1.5 compared with ≤1.3. These variables were allocated points, which allowed for stratification of patients with low- and high-risk for grade 4 bleeding. Cumulative incidence of grade 4 bleeding at day+60 was significantly higher among patients with high- vs low-risk (development: 31 ± 7% vs 2 ± 1%; P < .001; validation: 25 ± 9% vs 7 ± 2%; P = .008). In both cohorts, high bleeding risk was associated with disseminated intravascular coagulation (DIC) and proliferative disease. We developed and validated a simple risk model for grade 4 bleeding, which enables the development of rational risk mitigation strategies to improve early mortality of intensive induction treatment.
MeSH term(s)	Disseminated Intravascular Coagulation ; Hemorrhage/epidemiology ; Hemorrhage/etiology ; Humans ; Induction Chemotherapy/adverse effects ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/drug therapy ; Retrospective Studies
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006166
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Article ; Online: Thrombosis, anticoagulation and outcomes in malignant superior vena cava syndrome.

Ratzon, Roy / Tamir, Shlomit / Friehmann, Tal / Livneh, Nir / Dudnik, Elizabeth / Rozental, Alon / Hamburger-Avnery, Orly / Pereg, David / Derazne, Estela / Brenner, Baruch / Raanani, Pia / Ten Cate, Hugo / Spectre, Galia / Leader, Avi

Journal of thrombosis and thrombolysis

2018 Volume 47, Issue 1, Page(s) 121–128

Abstract: Anticoagulation is often used in superior vena cava syndrome (SVCS) associated with cancer (i.e malignant SVCS), even without thrombosis, but its effect on outcomes has not been reported. We aimed to determine factors and outcomes associated with ... ...

Abstract	Anticoagulation is often used in superior vena cava syndrome (SVCS) associated with cancer (i.e malignant SVCS), even without thrombosis, but its effect on outcomes has not been reported. We aimed to determine factors and outcomes associated with thrombosis and anticoagulation in malignant SVCS. Patients with malignant SVCS diagnosed on computerized tomography (CT) were retrospectively included, indexed at diagnosis and followed for 6 months using medical records. The cohort included 183 patients with malignant SVCS of which 153 (84%) were symptomatic. Thirty of the 127 patients (24%) with a reviewable baseline CT had thrombosis of the SVC or tributaries at diagnosis. Patients with baseline thrombosis more often had symptomatic SVCS (p < 0.01). 70% (21/30) of patients with thrombosis and 52% (49/97) of those without thrombosis at baseline received anticoagulation, most often at therapeutic doses. Thrombosis occurred in 5/39 patients with anticoagulation (13%) compared to 2/18 (11%) of those without, during follow-up (p = 0.85). Anticoagulation was associated with a reduction in risk of SVC stent placement during follow-up that did not reach statistical significance (HR 0.47, 95% CI 0.2-1.13, p = 0.09). Major bleeding occurred in 7 (4%) patients, six of whom received anticoagulation (four therapeutic and two intermediate dose). Neither thrombosis nor anticoagulation affected survival. Anticoagulation is commonly used as primary prevention but its benefit remains to be proven. The role of reduced-dose anticoagulation in non-thrombotic malignant SVCS should be prospectively assessed.
MeSH term(s)	Adult ; Aged ; Anticoagulants/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; Stents ; Superior Vena Cava Syndrome/drug therapy ; Superior Vena Cava Syndrome/mortality ; Superior Vena Cava Syndrome/surgery ; Superior Vena Cava Syndrome/therapy ; Survival Analysis ; Thrombosis/prevention & control ; Tomography, X-Ray Computed ; Treatment Outcome
Chemical Substances	Anticoagulants
Language	English
Publishing date	2018-09-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-018-1747-6
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