Publications by authors named "Piotr Smolewski"

117 Publications

Advances in the pharmacotherapeutic options for primary nodal peripheral T-cell lymphoma.

Expert Opin Pharmacother 2021 Feb 18:1-13. Epub 2021 Feb 18.

Copernicus Memorial Hospital , Lodz. Poland.

Introduction: Peripheral T cell lymphomas (PTCL) are a group of heterogenous hematologic malignancies derived from post-thymic T lymphocytes and mature NK cells. Conventional chemotherapy does not guarantee a good outcome.

Areas Covered: The article summarizes recent investigational therapies and their mechanism of action, as well as the pharmacological properties, clinical activity, and toxicity of new agents in the treatment of primary nodal PTCLs. The review scrutinized papers included in the MEDLINE (PubMed) database between 2010 and October 2020. These were supplemented with a manual search of conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association, and American Society of Clinical Oncology. Further relevant publications were obtained by reviewing the references from the chosen articles.

Expert Opinion: PTCLs have proved difficult to treat and investigate because of their rarity. Studies of aggressive lymphoma, including a small proportion of T-cell lymphomas, found that any benefit from intensified traditional chemotherapy in patients with PTCL is accompanied by increased toxicity. However, the management of PTCL is beginning to change dramatically, thanks to the use of more sophisticated agents targeting the mechanisms of disease development.
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http://dx.doi.org/10.1080/14656566.2021.1882997DOI Listing
February 2021

Current Treatment of Refractory/Relapsed Chronic Lymphocytic Leukemia: A Focus on Novel Drugs.

Acta Haematol 2020 Nov 25:1-15. Epub 2020 Nov 25.

Department of Hematology, Medical University of Lodz, and Copernicus Memorial Hospital, Lodz, Poland,

Recently, the use of novel targeted drugs has changed the treatment paradigms in chronic lymphocytic leukemia (CLL). Among the several drugs used for the management of relapsed/refractory (R/R) CLL, Bruton tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphatidylinositol 3-kinase inhibitors (idelalisib and duvelisib), B-cell lymphoma 2 inhibitor (venetoclax), and novel CD20 monoclonal antibodies have demonstrated the greatest improvements in survival among R/R CLL patients. However, patients with relapsed but asymptomatic CLL do not need immediate alternative treatment and should be observed until evident sign of progression. Among available approved treatments, venetoclax + rituximab for 24 months or ibrutinib as continuous therapy is recommended. Another, less recommended, option is idelalisib in combination with rituximab. The correct treatment selection depends on the type of prior therapy, response to previous treatment and side effects, presence of comorbidities, and the risk of drug toxicity. Allogeneic hematopoietic stem cell transplantation and investigational therapies such as chimeric antigen receptor-T-cell therapy are promising treatment options for high-risk patients, including those progressing after 1 or more targeted therapies. The present review discusses current treatment strategies for patients with R/R CLL.
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http://dx.doi.org/10.1159/000510768DOI Listing
November 2020

The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients.

Cancers (Basel) 2020 Sep 9;12(9). Epub 2020 Sep 9.

Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland.

Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84-1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.
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http://dx.doi.org/10.3390/cancers12092569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565855PMC
September 2020

Efficacy and safety of idelalisib for the treatment of indolent B-cell malignancies.

Expert Opin Pharmacother 2020 Oct 20;21(15):1915-1926. Epub 2020 Jul 20.

Department of Experimental Hematology, Medical University of Lodz , Lodz, Poland.

Introduction: The outcome of patients with lymphoid malignancies has markedly improved in recent years due to the implementation of new therapeutic options. Chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphomas (NHL) are characterized by the activation of the phosphatidylinositol 3-kinase (PI3 K) pathway B-cell receptor signaling. The PI3 K delta (PI3 Kδ) p110δ isoform inhibitor, idelalisib, showed high anti-tumor activity in this group of tumors. It was the first agent from a new class of isoform-specific inhibitors to receive regulatory approvals for the treatment of refractory/relapsed CLL, as well as small lymphocytic lymphoma and follicular lymphoma.

Areas Covered: In this paper, the authors provide a comprehensive overview of the activity and safety profile of idelalisib and other, newly developed PI3 K inhibitors in patients with indolent B-cell malignancies.

Expert Opinion: Idelalisib is a very potent anti-lymphoma agent in CLL and other NHL. However, there are some limitations of its broad clinical use according to some important side effects observed during treatment. Consequently, the development of new PI3 K inhibitors, which will be highly active and possess better safety profiles are warranted.
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http://dx.doi.org/10.1080/14656566.2020.1791083DOI Listing
October 2020

Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib.

Mediators Inflamm 2020 6;2020:1835836. Epub 2020 Jun 6.

Department of Hematology, Medical University of Lodz, Poland.

The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1 and lower levels of MIP-1 and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin < 10 g/dl compared to those without anemia. The levels of IL-8, MIP-1, and TNF- were significantly higher in patients with renal insufficiency. Only MIP-1 was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed.
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http://dx.doi.org/10.1155/2020/1835836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294367PMC
June 2020

Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study.

Blood 2020 03;135(10):735-742

Research and Clinical Innovation, Antoine-Lacassagne Cancer Centre, Nice, France.

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2-) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2- patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).
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http://dx.doi.org/10.1182/blood.2019003127DOI Listing
March 2020

Roux-en-Y gastric bypass as a cure of iatrogenic - steroid induced diabetes.

Pol Przegl Chir 2019 Jan;91(5):38-40

Katedra i Klinika Chirurgii Ogólnej i Transplantacyjnej, Uniwersytecki Szpital Kliniczny im. N. Barlickiego w Łodzi, Polska.

Background: Steroid-induced diabetes (SIDM) is a frequently found clinical condition since steroid-based therapies continue to be widely used in hospital and ambulatory care. Recommended optimal treatment of SIDM includes similar glucose lowering strategies as in type 2 diabetes. This typical management cannot cure the disease, it can only control blood glucose. Recently, bariatric surgery has emerged as an effective treatment for type 2 diabetes mellitus. However, up to now, the usefulness of bariatric surgery in treatment of SIDM has not been evaluated.

Case Report: A 49-year-old female oncologic patient with steroid induced diabetes was referred for surgical treatment to the Department of General and Transplant Surgery in November 2009. Six years earlier, she underwent successful oncologic treatment with cladribine and high doses of steroids due to hairy cell leukemia. Finally complete hematologic remission with normalization of morphology and reduction of spleen size has been obtained. Prior to steroid treatment, blood glucose and urine examinations were within normal range. The patient was non-obese and had no family history of diabetes. Nevertheless, the patient developed diabetes secondary to corticosteroid therapy, poorly controlled by oral hypoglycemic agent (acarbosum), successfully converted to insulin therapy. Upon admission to the Department of General and Transplant Surgery, the patient was treated with 58 units of insulin per day. The patient was scheduled for Roux-en-Y gastric bypass (RYGB). Insulin was withdrawn immediately after the surgery and within six months after the surgery, plasma glucose and glycated hemoglobin (HbA1c-5.5%) levels reached and remained within normal range. Currently, eight years after surgery, body weight and BMI are 80 kg and 27.68 kg/m2, respectively. Plasma glucose and glycated hemoglobin are also normal. Importantly, from an oncological point of view, the patient has remained in continuous complete remission since October 2003.

Conclusions: Our report is the first to our knowledge describing the effect of gastric bypass surgery on SIDM in a patient with prior hematologic malignancy. It proves that surgically altered anatomy of the small intestine improves glucose homeostasis previously disturbed with pro-diabetic medication.
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http://dx.doi.org/10.5604/01.3001.0012.8271DOI Listing
January 2019

Clinical management of mantle cell lymphoma in the elderly.

Expert Opin Pharmacother 2019 Oct 2;20(15):1893-1905. Epub 2019 Aug 2.

Department of Hematology, Medical University of Lodz , Lodz , Poland.

: Mantle cell lymphoma (MCL) is a disease with an indolent histology, but mostly aggressive clinical course. While treatment can yield more promising results in younger patients, the disease is most diagnosed at a median age of approximately 70 years, and treatment in this group still presents a major challenge for oncohematologists. Unfortunately, due to comorbidities and poorer general status, the implementation of intensive treatment approaches with the cytarabine-based regimens and autologous stem cell transplantation is generally not possible, and the disease remains incurable, especially in elderly patients. : In this paper, the authors discuss the therapeutic options available for older patients with MCL in the first line and relapsed/refractory settings, indicating new therapeutic options, which may achieve longer remissions and overall survival. : Although great progress has been made in the treatment of MCL in recent years, there remains a need for new treatment lines which can allow improved patient outcomes. Novel agents targeting altered the signal transduction pathways in MCL cells may offer more promise than traditional chemotherapy or immunochemotherapy and are currently being tested in clinical trials.
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http://dx.doi.org/10.1080/14656566.2019.1642871DOI Listing
October 2019

Hodgkin lymphoma transformation of chronic lymphocytic leukemia-A real life data from the Polish Lymphoma Research Group.

Hematol Oncol 2019 Oct 14;37(4):383-391. Epub 2019 Jun 14.

Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.

Richter transformation (RT) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to Hodgkin lymphoma (HL) is a rare and unexpected event in the course of the disease and data on this phenomenon is still limited. To better understand the clinical and histological characteristics and the outcomes of HL variant of RT (HvRS) the Polish Lymphoma Research Group performed a nationwide survey which identified 22 patients with histologically proven HvRS diagnosed between 2002 and 2016. There were 16 (73%) males. The median age at CLL/SLL and HvRS diagnosis was 59 (39-77) and 64 (40-77) years, respectively. The median interval between CLL/SLL and HvRS diagnosis was 38 months (range: 0-187). All patients had an advanced stage HL, and majority, 17 (77%), presented with B symptoms. The predominant subtypes of HL were nodular sclerosis (12; 55%) and mixed cellularity (9; 41%). Eighteen patients received non-palliative treatment, including 13 who received driamycin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen first line. Objective response was: 50%, with 33% complete remissions (61% and 46% for ABVD, respectively). Median overall survival reached 13.3 months (95% CI, 3.7-NA). The only adverse prognostic factor for survival was a higher number (≤1 versus ≥2) of prior lines of treatment given for CLL/SLL with HR 3.57 (95% CI, 1.16-10.92). We conclude, HvRS harbors a poor prognosis, especially in patients heavily pretreated for CLL/SLL. Response to standard first-line anti-HL chemotherapy is unsatisfactory, and new agents should be tested to improve the outcome.
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http://dx.doi.org/10.1002/hon.2624DOI Listing
October 2019

Mantle cell lymphoma: therapeutic options in transplant-ineligible patients.

Leuk Lymphoma 2019 11 25;60(11):2622-2634. Epub 2019 Apr 25.

Department of Medicine III, University Hospital Ludwig Maximilians University, Munich, Germany.

Management of patients with newly diagnosed mantle cell lymphoma (MCL) depends on the age and fitness of the patient. For younger patients, the commonly accepted standard of care is a high-dose cytarabine-based induction chemotherapy followed by autologous stem cell transplantation (ASCT). In newly diagnosed patients with MCL ineligible for intensive therapy and ASCT, the standard-of-care has generally been R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), followed by rituximab, maintenance. In recent years, bendamustine-based therapy has been increasingly adopted for older MCL patients and more recently, vincristine has been replaced by bortezomib in the R-CHOP combination as VR-CAP for previously untreated patients. Novel targeted agents now offer more promise than traditional chemotherapy or immunochemotherapy for both previously treated and untreated disease, and should also improve outcomes for older MCL patients. Here, we review standard therapies currently in use and novel agents that may soon be available for MCL patients and particularly for those unsuitable for ASCT.
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http://dx.doi.org/10.1080/10428194.2019.1605511DOI Listing
November 2019

Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders.

Expert Opin Investig Drugs 2019 May 13;28(5):421-433. Epub 2019 Apr 13.

a Department of Experimental Hematology , Medical University of Lodz , Lodz , Poland.

Introduction: Ixazomib is a new, orally administered, reversible proteasome inhibitor which is under investigation for the treatment of refractory/relapsed multiple myeloma (MM), systemic light chain amyloidosis (AL) and Waldenström macroglobulinemia (WM). Areas covered: This article covers the mechanism of action, pharmacology and clinical trial results of ixazomib while under investigation for the treatment of various lymphoproliferative disorders. We examine the findings from several phase 3 clinical trials (i) the pivotal TOURMALINE-MM1 study investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone; (ii) the TOURMALINE-MM3 study investigating ixazomib versus placebo as a maintenance therapy in newly diagnosed MM following induction therapy and autologous stem cell transplantation; (iii) the TOURMALINE-MM2 study investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM; and (iv) TOURMALINE-AL1 investigating ixazomib plus dexamethasone in patients with relapsed/refractory AL amyloidosis. Finally, we explore early phase clinical studies of this agent in Waldenström macroglobulinemia. Expert opinion: A key advantage of ixazomib is that it could allow an efficacious treatment approach to MM and other lymphoproliferative disorders through a convenient oral administration route. Ixazomib could soon be used in combination treatment regimens, but more work is necessary to define the place of this agent going forward.
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http://dx.doi.org/10.1080/13543784.2019.1596258DOI Listing
May 2019

Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells.

Int J Mol Sci 2018 Dec 10;19(12). Epub 2018 Dec 10.

Faculty of Medicine, Lazarski University, 02-662 Warsaw, Poland.

An epigenetic component, especially aberrant DNA methylation pattern, has been shown to be frequently involved in sporadic breast cancer development. A growing body of literature demonstrates that combination of agents, i.e. nucleoside analogues with dietary phytochemicals, may provide enhanced therapeutic effects in epigenetic reprogramming of cancer cells. Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine, ClF), a second-generation 2'-deoxyadenosine analogue, has numerous anti-cancer effects, including potential capacity to regulate epigenetic processes. Our present study is the first to investigate the combinatorial effects of ClF (used at IC concentration) with epigallocatechin-3-gallate (EGCG, tea catechin) or genistein (soy phytoestrogen), at physiological concentrations, on breast cancer cell growth, apoptosis, and epigenetic regulation of retinoic acid receptor beta () transcriptional activity. In MCF7 and MDA-MB-231 cells, promoter methylation and expression of , modifiers of DNA methylation reaction (, , ), and potential regulator of transcription, , were estimated using methylation-sensitive restriction analysis (MSRA) and quantitative real-time polymerase chain reaction (qPCR), respectively. The combinatorial exposures synergistically or additively inhibited the growth and induced apoptosis of breast cancer cells, followed by hypomethylation with concomitant multiple increase in , , and transcript levels. Taken together, our results demonstrate the ability of ClF-based combinations with polyphenols to promote cancer cell death and reactivate DNA methylation-silenced tumor suppressor genes in breast cancer cells with different invasive potential.
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http://dx.doi.org/10.3390/ijms19123970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321577PMC
December 2018

Immune Checkpoint Inhibitors to Treat Malignant Lymphomas.

J Immunol Res 2018 11;2018:1982423. Epub 2018 Apr 11.

Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.

Genetic and/or epigenetic changes provide antigen-derived diversity in neoplastic cells. Beside, these cells do not initiate immune response of host organisms. A variety of factors are responsible for the resistant to treatment, including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Immune system is controlled by several controlling mechanisms. Recently, a significant progress in hematologic treatment has been made; however, majority of diseases still remain incurable. Immunotherapy with checkpoint inhibitors has emerged as promising modality of antitumor treatment, showing marked response to several antigens, including cytotoxic T lymphocyte-associate protein-4 (CTLA-4) or programmed cell death 1 receptor (PD-1). In this review, we demonstrate actual knowledge on immune checkpoint function and its impact on development of new modality of antineoplastic treatment, using, for example, anti-CTLA-4 or PD-1/PD1 ligand (PD-L1) monoclonal antibodies in malignant lymphomas.
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http://dx.doi.org/10.1155/2018/1982423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925139PMC
October 2018

Rituximab, cladribine, and cyclophosphamide (RCC) induction with rituximab maintenance in chronic lymphocytic leukemia: PALG - CLL4 (ML21283) trial.

Eur J Haematol 2018 May 22;100(5):465-474. Epub 2018 Mar 22.

Department of Experimental Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland.

Objectives: PALG CLL4 is the first, randomized, phase IIIb study with rituximab, cladribine, and cyclophosphamide (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients.

Methods: The induction treatment consisted of 6 RCC cycles regimen. Patients with complete response (CR) or partial response (PR) after an induction phase were randomized into a maintenance arm with rituximab or an observational arm.

Results: In the intention-to-treat population, 97 patients completed the induction phase with an overall response rate (ORR) of 73.2% (CR 22.7%, PR 50.5%). Subsequently, 66 patients were randomized into the rituximab maintenance arm (n = 33) or the observational arm (n = 33). CR rates were 57.1% in the maintenance group vs 50% in the observational group. PFS was significantly longer in the rituximab maintenance vs the observational arm (P = .028). The multivariate Cox model indicated that del17p (P = .006) and elevated beta-2-microglobulin (P = .015) significantly increased the hazard ratio (HR) of progression, whereas the presence of CD38 (P = .013) significantly decreased it; maintenance therapy with rituximab (P < .0001) significantly decreased the HR of disease progression.

Conclusions: The study confirmed the high efficacy and acceptable safety profile of induction therapy with RCC and maintenance therapy with rituximab in previously untreated patients with CLL.
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http://dx.doi.org/10.1111/ejh.13042DOI Listing
May 2018

Investigational therapies targeting CD37 for the treatment of B-cell lymphoid malignancies.

Expert Opin Investig Drugs 2018 02 15;27(2):171-177. Epub 2018 Jan 15.

b Department of Hematology , Medical University of Lodz , Lodz , Poland.

Introduction: While chemotherapy still remains a cornerstone of oncologic therapy, immunotherapy with monoclonal antibodies has steadily improved the treatment strategy for several hematologic malignancies. New treatment options need to be developed for relapsed and refractory non-Hodgkin lymphoma (NHL) patients. Currently, novel agents targeting specific molecules on the surface of lymphoma cells, such as anti-CD37 antibodies, are under considerable investigation. Here we report on anti-CD37 targeting for the treatment of patients with B-cell NHL.

Areas Covered: CD37 seems to be the perfect therapeutic target in patients with NHL. The CD37 antigen is abundantly expressed in B-cells, but is absent on normal stem cells and plasma cells. It is hoped that anti-CD37 monoclonal antibodies will increase the efficacy and reduce toxicity in patients with both newly diagnosed and relapsed and refractory disease. Recent clinical trials have shown promising outcomes for these agents, administered both as monotherapy and in combination with standard chemotherapeutics.

Expert Opinion: The development of new therapeutic options might help to avoid cytotoxic chemotherapy entirely in some clinical settings. This article presents the latest state of the art on the new treatment strategies in NHL patients. It also discusses recently approved agents and available clinical trial data.
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http://dx.doi.org/10.1080/13543784.2018.1427730DOI Listing
February 2018

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma.

N Engl J Med 2018 01 10;378(4):331-344. Epub 2017 Dec 10.

From the University of British Columbia and the Department of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, Canada (J.M.C., K.J.S.); the Department of Hematology, Jagiellonian University, Krakow (W.J.), the Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw (E.L.-M.), the Department of Hematology and Transfusion Medicine, Center of Postgraduate Medical Education, Warsaw (E.L.-M.), the Department of Experimental Hematology, Medical University of Lodz, Lodz (P.S.), and the Department of Lymphoid Malignancy, the Maria Sklodowska-Curie Memorial Institute and Oncology Center, Warsaw (J.W.) - all in Poland; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (D.J.S., A.Y.); the Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN (S.M.A.); the Division of Hematology and Oncology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea (W.S.K.); Research Innovation and Statistics, Antoine-Lacassagne Cancer Center, Nice, France (A.G.); Petrov Research Institute of Oncology, St. Petersburg, Russia (S.A.); the Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen (Á.I.), and the Department of Hematology, National Institute of Oncology, Budapest (A.R.) - both in Hungary; the Department of Advanced Biomedical Science, Federico II University Hospital, Naples (M.P.), and the Institute of Hematology Seràgnoli, University of Bologna, Bologna (P.L.Z.) - both in Italy; the Department of Lymphoma and Myeloma, M.D. Anderson Cancer Center, Houston (Y.O.); John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ (T.F.); the Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis (N.L.B.); the Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA (R.C.); the Department of Hematology-Oncology, Barbara Ann Karmanos Cancer Center, Detroit (R.R.); Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Sutton (D.C.), and the Department of Medical Oncology, University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester (J.R.) - both in the United Kingdom; the Department of Clinical Development, Seattle Genetics, Bothell, WA (N.C.J., E.S.); and Oncology Clinical Research (J.S., H.A.J., D.H.) and Global Biostatistics (R.L.), Millennium Pharmaceuticals, Cambridge, MA.

Background: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma.

Methods: We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival.

Results: At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.

Conclusions: A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).
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http://dx.doi.org/10.1056/NEJMoa1708984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819601PMC
January 2018

Successful hemihepatectomy following chemotherapy for primary liver lymphoma: case report and review of literature.

Pol Przegl Chir 2017 Oct;89(5):54-58

Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Lodz, Poland.

Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of B-cell and T-cell neoplasms. Diffuse large B-cell lymphoma (DLBCL), the most common type of NHL, accounts for around 30-40% of NHL cases. However, primary hepatic location of NHLs is rare and constitutes 0.01% of all NHL cases. Due to this rarity and a lack of large randomized trails, it is still unclear what treatment should be used for primary hepatic DLBCLs. In this study, we report of a female patient with primary hepatic DLBCL who was successfully treated with neoadjuvant chemotherapy and surgery. We also shortly review the literature regarding surgical treatments for primary GI tract NHLs. Taking into account our experience and the current literature, surgical treatment with postoperative chemotherapy seems to be a feasible option for patients with focal primary hepatic DLBCLs.
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http://dx.doi.org/10.5604/01.3001.0010.5609DOI Listing
October 2017

The impact of agonists and antagonists of TLR3 and TLR9 on concentrations of IL-6, IL10 and sIL-2R in culture supernatants of peripheral blood mononuclear cells derived from patients with systemic lupus erythematosus.

Postepy Hig Med Dosw (Online) 2017 Oct;71(0):867-875

Department of Dermatology and Venereology, Medical University of Lodz, Poland.

Toll-like receptors (TLR), especially TLR3, 7 and 9, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). In our study blood was collected from 16 patients with SLE and from 8 healthy volunteers. Concentrations of IL-6, IL-10 and sIL-2R were measured by ELISA in mononuclear cell culture supernatant after 24 hours of stimulation by agonists and antagonists of TLR3 and 9 (for TLR3-poli I/C, resveratrol and for TLR9-ODN2006, IRS 945). Stimulation of TLR9 by ODN2006 led to an increase of IL-6 concentration in cell culture supernatants from the cells of healthy volunteers compared with unstimulated cells from controls. Inhibition of TLR3 activation by resveratrol caused a significantly lower concentration of IL-10 in cell culture supernatants derived from both patients and healthy donors. Moreover, resveratrol significantly decreased the level of IL-10 and sIL-2R in culture supernatants of cells derived from patients with active disease compared to the inactive stage. A positive correlation was also found between IL-6 concentration following ODN2006 administration and disease activity. In conclusions, our results indicate that TLRs play a role in the modulation of the inflammatory response in SLE patients. This suppressive action on IL-10 synthesis demonstrated by resveratrol suggests that it may be useful in SLE therapy.
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http://dx.doi.org/10.5604/01.3001.0010.5266DOI Listing
October 2017

Emerging antibody-drug conjugates for treating lymphoid malignancies.

Expert Opin Emerg Drugs 2017 09 28;22(3):259-273. Epub 2017 Aug 28.

a Department of Hematology , Medical University of Lodz , Lodz , Poland.

Introduction: Antibody-drug conjugates (ADC) are monoclonal antibodies (Mabs) attached to biologically active drugs through specialized chemical linkers. They deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. These agents should improve the potency of chemotherapy by increasing the accumulation of cytotoxic the drug within or near the neoplastic cells with reduced systemic effects. Areas covered: A literature review was conducted of the MEDLINE database PubMed for articles in English examining Mabs, B-cell receptor pathway inhibitors and immunomodulating drugs. Publications from 2000 through April 2017 were scrutinized. Conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: Newer ADCs show promise as treatment for several hematologic malignancies, especially lymphoma, multiple myeloma, and leukemia. However, definitive data from ongoing and future clinical trials will aid in better defining the status of these agents in the treatment of these diseases.
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http://dx.doi.org/10.1080/14728214.2017.1366447DOI Listing
September 2017

The discovery and development of romidepsin for the treatment of T-cell lymphoma.

Expert Opin Drug Discov 2017 08 22;12(8):859-873. Epub 2017 Jun 22.

b Department of Hematology , Medical University of Lodz , Lodz , Poland.

Introduction: Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively. Areas covered: This review summarizes the development of romidepsin, the mechanisms behind its antineoplastic action and its pharmacology. It also covers its pharmacokinetic and pharmacodynamic properties, as well as the preclinical and clinical data on its activity in T-cell lymphoma. Expert opinion: Since there are only few effective therapies available for T-cell lymphomas, romidepsin is a valuable option for relapsed/refractory patients with both CTCL and PTCL. It's also generally well tolerated, and gives potentially durable responses for patients with advanced and symptomatic disease. Combinations of romidepsin with other antineoplastic agents may also further improve drug response and outcomes in T-cell lymphoma.
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http://dx.doi.org/10.1080/17460441.2017.1341487DOI Listing
August 2017

The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia.

Tumour Biol 2017 Mar;39(3):1010428317694551

1 Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.

The SMAD proteins are responsible for transducing signals from activated transforming growth factor-beta. This is the first study assessing the expression of SMAD-1/8, SMAD-2/3, SMAD-4, and SMAD-7 in chronic lymphocytic leukemia cells with regard to their clinical significance and potential prognostic value. Overexpression of SMAD-1/8 was observed in 160 chronic lymphocytic leukemia patients compared to 42 healthy volunteers (p = 0.023) and was associated with a more progressive course of the disease (p = 0.016). Moreover, the high expression of SMAD-1/8 correlated with other, well-established prognostic factors, including clinical stage (p = 0.010) and lymphocyte doubling time (p = 0.021). The expression of SMAD-4 was lower in chronic lymphocytic leukemia patients compared with the control group (p = 0.003). Importantly, lower SMAD-4 levels correlated with longer progression-free survival (p = 0.009), progressive course of the disease (p = 0.002), advanced clinical stage (p = 0.0004), elevated beta-2-microglobulin and lactate dehydrogenase levels (p < 0.05), shorter lymphocyte doubling time (p = 0.009), and CD38 antigen expression (p = 0.039). In addition, lower SMAD-4 expression correlated with lower apoptotic index (p = 0.0007) and lower expression of receptors for vascular endothelial growth factors VEGFR-1 and VEGFR-2. A significant association was found between the low expression of inhibitory protein SMAD-7 and both zeta-chain-associated protein kinase 70-negative cells (p = 0.04) and lower apoptotic index (p = 0.004). No differences were observed in SMAD-2/3 expression. In conclusion, our results demonstrate a significant correlation between greater SMAD-1/8 and lower SMAD-4 expression in chronic lymphocytic leukemia cells, as well as more progressive outcome and poor prognosis. These data provide supporting evidence that the expression of SMAD proteins plays an important role in disease development and may be considered as a novel, biologic prognostic factor in this disease.
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http://dx.doi.org/10.1177/1010428317694551DOI Listing
March 2017

Innovation in non-Hodgkin lymphoma drug discovery: what needs to be done?

Expert Opin Drug Discov 2016 Nov 7;11(11):1033-1045. Epub 2016 Sep 7.

b Department of Hematology , Medical University of Lodz , Lodz , Poland.

Introduction: A new generation of anticancer agents called target drugs has been recently developed for the treatment of non-Hodgkin lymphomas. Current recovery rates in these diseases are up to 70% with immunotherapy based on the anti-CD20 monoclonal antibody combined with standard chemotherapeutics. However, there are still refractory or relapsed patients. Recently, several novel anti-lymphoma agents have been developed. Choosing the most effective personalized therapy still remains a crucial challenge in hematology. Areas covered: New drugs can specifically target malignant cells and inhibit cancer cell growth, proliferation and survival by specific interactions with one or more target proteins. Recent clinical studies have illustrated promising outcomes for novel drugs used as single agents and in combination with traditional therapeutics. In this article, the authors discuss novel targeted therapies with a promising outcome in NHL patients that are becoming integrated into treatment paradigms. Expert opinion: The development of new treatment options may help to avoid cytotoxic chemotherapy entirely in some clinical settings. Multicenter studies should be continued to investigate small agents and pathways inhibitors as this will enable us to enhance not only the duration of the treatment response but also the quality of the extended survival.
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http://dx.doi.org/10.1080/17460441.2016.1230095DOI Listing
November 2016

Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies.

Molecules 2016 Jul 30;21(8). Epub 2016 Jul 30.

Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland.

Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended.
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http://dx.doi.org/10.3390/molecules21080995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274336PMC
July 2016

Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays.

Anticancer Agents Med Chem 2017 ;17(1):102-114

Department of Clinical and Laboratory Genetics, Medical University of Lodz, Lodz, Poland.

Background: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment.

Objective: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier.

Method: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes.

Results: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and protein expression in CLL cells.

Conclusion: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.
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June 2017

[The latest recommendations on the use of new oral anticoagulants in routine practice].

Postepy Hig Med Dosw (Online) 2016 Feb 8;70:43-55. Epub 2016 Feb 8.

Zakład Hematologii Doświadczalnej Uniwersytet Medyczny w Łodzi.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC) including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.
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http://dx.doi.org/10.5604/17322693.1194114DOI Listing
February 2016

Immune checkpoints: Cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 in breast cancer surgery.

Oncol Lett 2015 Aug 4;10(2):1079-1086. Epub 2015 Jun 4.

Department of Experimental Hematology, Medical University of Łódź, Łódź 93-510, Poland.

Immune checkpoints refer to a plethora of inhibitory pathways built into the immune system, and recent studies have emphasized the role of these checkpoints in carcinogenesis. The aim of the present study was to evaluate two major immune checkpoints, the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), in the serum of 35 patients with stage I and II breast cancer. Serum concentrations of CTLA-4 and PD-1 were measured at three time points: i) Preoperatively; ii) during anesthesia following the harvesting of sentinel nodes (SNs); and iii) 24 h postoperatively. Control samples were obtained from 25 healthy, age-matched females. Assessment of CTLA-4 and PD-1 expression levels was conducted using flow cytometry. A statistically significant difference in PD-1 expression was identified between breast cancer patients preoperatively and healthy controls (26.31±11.87 vs. 12.72±8.15; P<0.0001). In addition, a statistically significant association was found between CTLA-4 and PD-1 levels prior to surgery (P=0.0084). In addition, CTLA-4 expression was associated with age (P=0.0453), with elevated levels of CTLA-4 detected in older breast cancer patients. Higher PD-1 expression levels were observed in T2 tumors compared with T1 tumors prior to surgery and intraoperatively; however, the differences were not statistically significant. Furthermore, a decrease in PD-1 levels was observed subsequent to harvesting SNs with metastasis, but not in SN-negative patients (P=0.05). A negative correlation was also observed between PD-1 expression and progesterone receptor (PR) status following surgery (P=0.024). These results provided a basis for further investigation of immune checkpoints in breast cancer. Breast cancer patients exhibit an altered profile of immune checkpoint markers, with higher concentrations of PD-1 observed in larger, PR-negative tumors.
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http://dx.doi.org/10.3892/ol.2015.3321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508983PMC
August 2015

Sulforaphane Alone and in Combination with Clofarabine Epigenetically Regulates the Expression of DNA Methylation-Silenced Tumour Suppressor Genes in Human Breast Cancer Cells.

J Nutrigenet Nutrigenomics 2015 ;8(2):91-101

Background/aim: Sporadic breast cancer is frequently associated with aberrant DNA methylation patterns that are reversible and responsive to environmental factors, including diet. In the present study, we investigated the effects of sulforaphane (SFN), a phytochemical from cruciferous vegetables, on the methylation and expression of PTEN and RARbeta2 tumour suppressor genes as well as on the expression of regulators of DNA methylation reaction, DNMT1 , p53 , and p21 , in MCF-7 and MDA-MB-231 human breast cancer cells with different invasive potential. We also evaluate the role of SFN epigenetic effects in support of therapy with clofarabine (ClF) that was recently shown to modulate the epigenome as well.

Methods: Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis and real-time PCR, respectively.

Results: In both MCF-7 and MDA-MB-231 cells, SFN at IC 50 (22 and 46 μ M , respectively) and a physiologically relevant 10 μ M concentration lead to hypomethylation of PTEN and RARbeta2 promoters with concomitant gene upregulation. The combination of SFN and ClF enhances these effects, resulting in an increase in cell growth arrest and apoptosis at a non-invasive breast cancer stage.

Conclusions: Our findings provide evidence that SFN activates DNA methylation-silenced tumour suppressor genes in breast cancer cells and may contribute to SFN-mediated support of therapy with an anti-cancer drug, ClF, increasing its applications in solid tumours.
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http://dx.doi.org/10.1159/000439111DOI Listing
June 2016

Treatment options for mantle cell lymphoma.

Expert Opin Pharmacother 2015 11;16(16):2497-507. Epub 2015 Sep 11.

b 2 Medical University of Lodz, Copernicus Memorial Hospital, Department of Hematology , ul. Ciołkowskiego 2, 93-510 Lodz, Poland

Introduction: In this article, we provide an accurate overview of both standard treatment option and novel promising therapeutics. Major impact is on novel agents now being tested in randomized clinical trials. While the initial data are promising, they may rapidly expand treatment options, change existing paradigms and further improve outcomes for mantle cell lymphoma (MCL) patients.

Areas Covered: MCL is a disease with indolent histology, but aggressive clinical course. However, for now, MCL remains incurable and the search for the most effective and tumor-specific treatment still represents a great challenge for oncohematologists. However, the implementation of chemotherapy together with the anti-CD20 antibody rituximab, as well as the growing use of autologous stem cell transplantation in first remission, have improved effects of treatment in MCL, including even some improvement in overall survival. Recently, treatment modalities for MCL have been expanded by strategies based on several biologically targeted agents, including m-TOR kinase or proteasome inhibitors and immunomodulatory agents, such as lenalidomide. B-cell receptor pathway inhibitors, such as ibrutinib and idelalisib, and histone deacetylase or cyclin-dependent kinase inhibitors have also shown promising activity in resistant or relapsed disease.

Expert Opinion: Although enormous progress was made in the treatment of MCL over the last year, the disease remains incurable. One chance for the significant life prolongation is intensive treatment with consolidative auto SCT. However, real progress may be afforded by developing the novel agents described in this article. In this way, MCL may soon become another potentially curable oncological malignancy.
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http://dx.doi.org/10.1517/14656566.2015.1087507DOI Listing
March 2016

Development of Anti-CD20 Antigen-Targeting Therapies for B-cell Lymphoproliferative Malignancies - The State of the Art.

Curr Drug Targets 2016 ;17(9):1072-82

Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Ciolkowskiego 2, 93-510 Lodz, Poland.

For decades, the available anticancer therapies were mostly based on nonspecific cytotoxic regimens. These cytostatic combinations, while effective in some subpopulations of patients, are often limited by extensive toxicity and/or development of tumor resistance. Although standard chemotherapy still remains a common therapeutic tool in the fight with cancer, immunotherapy increasingly revolutionizes treatment strategy for several hematologic malignancies. For a subset of patients with B-cell lymphoproliferative disease, the introduction of subsequently developed classes of anti-CD20 monoclonal antibodies (mAbs) has resulted in improved overall response rates and, to some extent, patient overall survival. Rituximab, the most thoroughly-explored chimeric mouse anti-human anti-CD20 mAb, has been widely and successfully introduced to oncohematology, but also to other fields of medicine, such as transfusiology or rheumatology. Currently, several new generation anti-CD20 mAbs are undergoing different stages of preclinical and clinical studies of assessment to further improve the outcome and overcome mechanisms of resistance. The nature of the direct mechanisms responsible for the anticancer properties of different classes of anti-CD20 mAbs is still not fully understood. This is reflected in different approaches during the investigation of novel anti-CD20 agents. So far, three classes of anti- CD20 mAb have been described. In this review, we focus on CD20 antigen-targeting therapies both currently available and undergoing preclinical or clinical investigation for B-cell lymphoproliferative malignancies.
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http://dx.doi.org/10.2174/1389450116666150907105306DOI Listing
September 2017

New mutation in hairy cell leukemia.

Blood 2015 Aug;126(8):930-1

MEDICAL UNIVERSITY OF LODZ.

In this issue of Blood, Dietrich et al make the first observation of the presence of deleterious CDKN1B mutation in 16% of patients with hairy cell leukemia (HCL). Furthermore, in the majority of patients, the CDKN1B mutation was clonal, suggesting that this mutation plays a role in the pathogenesis of HCL.
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http://dx.doi.org/10.1182/blood-2015-06-652065DOI Listing
August 2015