DOCSLIB.ORG

The Immunomodulatory Effects of Arsenic Trioxide in Autoimmunity and Alloreactivity Yishan Ye

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Immunomodulatory Effects of Arsenic Trioxide in Autoimmunity and Alloreactivity Yishan Ye The Immunomodulatory Effects of Arsenic Trioxide in Autoimmunity and Alloreactivity Yishan Ye To cite this version: Yishan Ye. The Immunomodulatory Effects of Arsenic Trioxide in Autoimmunity and Alloreactivity. Immunology. Sorbonne Université, 2019. English. NNT : 2019SORUS426. tel-03233559 HAL Id: tel-03233559 https://tel.archives-ouvertes.fr/tel-03233559 Submitted on 25 May 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Sorbonne Université Ecole doctorale 394: Physiologie, Physiopathologie et Thérapeutique Centre de recherche Saint Antoine / Equipe Mohty The Immunomodulatory Effects of Arsenic Trioxide in Autoimmunity and Alloreactivity Par Yishan YE Thèsededoctoratdebiologie Spécialité : Immunologie Dirigée par Mohamad Mohty Présentée et soutenue publiquement le 23 Mai 2019 Devant un jury composé de : AUCOUTURIER Pierre, PU-PH, Président du Jury BAZARBACHI Ali, Professeur, Rapporteur SAAS Philippe, Professeur, Rapporteur HERMINE Olivier, PU-PH, Examinateur MALARD Florent, MCU-PH, Co-directeur de thèse MOHTY Mohamad, PU-PH, Directeur de thèse 1 Acknowledgments First I would like to thank the jury members, Professor Pierre Aucouturier, Professor Ali Bazarbachi, Professor Philippe Saas, Professor Olivier Hermine for having accepted to evaluate my work. I can still remember the day in 2014 when I asked my distinguished guest from France, the president of the European Society for Blood and Marrow Transplantation, to write me a recommendation letter for a future PhD. The answer was ‘Perhaps you can come to my lab’, which opened the door to a long and fascinating journey. To Professor Mohty, despite tons of work that you are dealing with on a daily basis, you are always the first to respond to my requirements, and the first to congratulate me when something good happens. Your global vision, leadership nature, passion towards work, great care and patience for me make you a role model that I will always follow. Thank you Professor Mohty, with my greatest appreciation. To Dr. Florent Malard, you are really the most outstanding young physician scientist that I have ever had the privilege to meet. You are in charge of all the detailsofmy project, and always help me make correct choice when problem happens. It is my honor to have you, a man with sharp mind, accurate choice, impartial judgement as my co-director. Thank you Florent. To Dr. Béatrice Gaugler, you were the first person who gave me greetings during my first visit to the hospital, the moment that I will always remember. As the scientific leader of the lab, you offered me the first idea for my project, and later became the main body of this thesis. I can’t finish this thesis without the ideas, and the continuous and unselfish intellectual supports from you. Thank you Béatrice. To Dr. Laure Ricard and Dr. Nicolas Stocker, my greatest colleagues, for fighting together, for creating a really welcoming and harmonious atmosphere, for helping and encouraging me during the hard time of research. Thank you! To Prof. Arsène 2 Mekinian, for great support on the clinical samples and suggestions offered during my PhD study. Thank you! To Dr. Lama Siblany, an excellent start and I am sure that you will do great academic work in the near future. Good luck! Nevertherless, toDr. Charlotte Laurent, Mr. Maxime Tenon, Mr. Christophe de Vassoigne, and all the other people that I have had the chance to meet in the lab, thank you so much. To Dr. Baptiste Lamarthée, Mr. Frédéric de Vassoigne, and Dr. Ruoping Tang, you were the first who offered me, a nervous foreigner without any lab techniques, the warmest welcome and the orientation courses with great patience. Thank youso much. It is impossible to list all the people who have helped and supported me during the three years. France has become so warm and lovely because of you. To Prof. He Huang and all the colleagues in Hangzhou, for offering me the best clinical training, and continuous care during my PhD study. Thank you. To China Scholarship Council for the financial support. Finally, I would like to extend my most sincere thanks to my parents, my girlfriend, my friends, and all the other people who cared and supported me continuously, far away in China. Love you forever, and see you soon. 3 List of abbreviations ABT-199: chemical name of venetoclax G-CSF: granulocyte-colony stimulating aGVHD: acute graft-versus-host disease factor AHR: airway hyperresponsiveness GM-CSF: granulocyte-macrophage AP3: adapter protein-3 colony-stimulating factor APCs: antigen presenting cells GRFS: GVHD-free/relapse-free survival APL: acute promyelocytic leukemia GVHD: graft-versus-host disease As(III): trivalent arsenicals GVL: graft-versus-leukemia As2O3: arsenic trioxide H2O2: hydrogen peroxide ATG: antithymocyte globulin HEVs: high endothelial venules ATL: adult T-cell leukemia/lymphoma HLA: human leukocyte antigen ATRA: all-trans retinoic acid HMGB1: high mobility group box 1 BALF: broncho-alveolar lavage fluid HSC: hematopoietic stem cell BST2: bone marrow stromal antigen 2 HCT: hematopoietic cell transplantation BU: busulfan iAs: inorganic arsenic compounds cDC: conventional dendritic cell IBD: inflammatory bowel disease CDP: common DC progenitor ID2: Inhibitor Of DNA Binding 2 cGAMP: cyclic guanosine IDO: indoleamine 2,3-dioxygenase monophosphate-adenosine IFNAR: IFN-I receptor monophosphate IFN-I: type-I interferons CLP: common lymphoid precursor IKK: IĸB kinase CMP: common myeloid precursor IRF7: interferon regulatory factor 7 CNI: calcineurin inhibitor LAK: lymphokine activated killer CpG-ODN: CpG LAP: LC3-associated phagocytosis oligodeoxyribonucleotides LC3: microtubule-associated protein CsA: cyclosporine 1A/1B-light chain 3 G-CSF: granulocyte-colony stimulating LFA-1: Lymphocyte function-associated factor antigen 1 M-CSFR: macrophage Lin: lineage markers colony-stimulating factor receptor LMPP: lymphoid-primed multi-potent CX3CR1: CX3C chemokine receptor 1 progenitor CY: cyclophosphomide LP: lymphoid precursor DAMPs: damage-associated molecular LPS: lipopolysaccharide patterns MA: myeloablative DC: dendritic cell mAb: monoclonal antibodies EC50: half maximal effective MAPKs: mitogen-activated protein concentration kinases ER: endoplasmic reticulum MCMV: mouse cytomegalovirus FKBP12: FK506-binding protein 12 MDDC: monocyte derived dendritic cell Flt3L: Fms-like tyrosine kinase 3 ligand MDP: macrophage and DC precursor GC: glucocorticoid MHC: major histocompatibility complex GI: gastrointestinal tract miHA: minor histocompatibility antigen 4 miRNA: microRNA STAT3: signal transducer and activator MM: multiple myeloma of transcription 3 MMF: mycophenolate mofetil Syk: spleen tyrosine kinase MP: myeloid precursor TBI: total body irradiation mRNA: messenger RNA TCF4: transcription factor 4 mTOR: mammalian target of rapamycin Th: T helper cell MTX: methotrexate TLR: toll-like receptor MYD88: myeloid differentiation TNF: tumor necrosis factor primary response protein 88 Treg: regulatory T cell NaAsO2: sodium arsenite UPR: unfolded protein response NADPH: nicotinamide adenine dinucleotide phosphate NBs: nuclear bodies NETs: neutrophil extracellular traps Nf-κB: nuclear factor-κB NK cell: natural killer cell NOD: non-obese diabetic Nrf2: nuclear factor erythroid 2-related factor 2 NRM: non-relapse mortality PAMPs: pathogen-associated molecular patterns PBMC: peripheral blood mononuclear cell pDC: plasmacytoid dendritic cell PML: promyelocytic leukemia PTCy: posttransplantation cyclophosphomide RA: rheumatoid arthritis RARE: retinoic acid response elements RARα: retinoic acid receptor-α RIC: reduced-intensity conditioning RNS: reactive nitrogen species ROR: retinoic-related orphan receptor ROS: reactive oxygen species RXR: retinoid X receptor Sca-1: stem cells antigen-1 Siglec-H: sialic acid-binding immunoglobulin-like lectin H SLE: systemic lupus erythematosus SPF: specific pathogen-free SSc: systemic sclerosis 5 List of Figures Figure 1 . Reaction of vicinal sulfhydryl groups in a protein structure with trivalent arsenic (Emadi et al., Blood Rev, 2010)...............................................................10 Figure 2 . Dual targeting of PML-RARα and PML by As2O3 lead to APL cell differentiation and loss of self-renewal (de Thé., Nat Rev Cancer, 2018) .........11 Figure 3 . Diverse functions of As(III) on immune cells............................................. 15 Figure 4 . Mechanisms of action: As2O3 effects on CD4+ T cell............................... 20 Figure 5 . The proposed spectrum between pDC and cDC (Reizis, Immunity, 2019) 30 Figure 6 . Possible pathways of plasmacytoid dendritic cell development (modified from Shortman et al, Adv Immunol, 2013)..........................................................34 Figure 7 . Factors involved in pDC trafficking (modified from Swiecki et al,NatRev Immunol, 2015)....................................................................................................36 Figure 8 . TLR9 signaling (Swiecki et al, Nat Rev Immunol, 2015)........................... 40 Figure 9 . Cell-intrinsic and cooperative sensing
Load more

Recommended publications
  • Summary of Product Characteristics
    Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT NIPENT 10 mg powder for solution for injection, powder for solution for infusion 2 QUALITATIVE AND QUANTITATIVE COMPOSITION One vial contains 10 mg Pentostatin. When reconstituted (see Section 6.6), the resulting solution contains pentostatin 2 mg/ml. For a full list of excipients see section 6.1. 3 PHARMACEUTICAL FORM Powder for solution for injection, powder for solution for infusion. The vials contain a solid white to off-white cake or powder. The pH of reconstituted solution is 7.0 – 8.2. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Pentostatin is indicated as single agent therapy in the treatment of adult patients with hairy cell leukaemia. 4.2 Posology and method of administration Pentostatin is indicated for adult patients. Administration to patient It is recommended that patients receive hydration with 500 to 1,000 ml of 5% glucose only or 5% glucose in 0.18% or 0.9% saline or glucose 3.3% in 0.3% saline or 2.5% glucose in 0.45% saline or equivalent before pentostatin administration. An additional 500 ml of 5% glucose only or 5% glucose in 0.18% or 0.9% saline or 2.5% glucose in 0.45% saline or equivalent should be administered after pentostatin is given. The recommended dosage of pentostatin for the treatment of hairy cell leukaemia is 4 mg/m2 in a single administration every other week. Pentostatin may be given intravenously by bolus injection or diluted in a larger volume and given over 20 to 30 minutes.
    [Show full text]
  • Cyclophosphamide-Etoposide PO Ver
    Chemotherapy Protocol LYMPHOMA CYCLOPHOSPHAMIDE-ETOPOSIDE ORAL Regimen Lymphoma – Cyclophosphamide-Etoposide PO Indication Palliative treatment of malignant lymphoma Toxicity Drug Adverse Effect Cyclophosphamide Dysuria, haemorrragic cystitis (rare), taste disturbances Etoposide Alopecia, hyperbilirubinaemia The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Patients diagnosed with Hodgkin’s Lymphoma carry a lifelong risk of transfusion associated graft versus host disease (TA-GVHD). Where blood products are required these patients must receive only irradiated blood products for life. Local blood transfusion departments must be notified as soon as a diagnosis is made and the patient must be issued with an alert card to carry with them at all times. Monitoring Drugs FBC, LFTs and U&Es prior to day one of treatment Albumin prior to each cycle Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Version 1.1 (Jan 2015) Page 1 of 6 Lymphoma- Cyclophosphamide-Etoposide PO Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent.
    [Show full text]
  • Fludarabine Phosphate Powder for Solution for Injection Or Infusion
    For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory This package insert is continually updated. Please read carefully before using a new pack. Fludarabine Phosphate Powder for Solution for Injection or Infusion FLUDARA® NAME OF THE MEDICINAL PRODUCT Fludara 50 mg powder for solution for injection/infusion COMPOSITION Active ingredient: Each vial contains 50 mg fludarabine phosphate I.P. 1 ml of reconstituted solution for injection/infusion contains 25 mg fludarabine phosphate. Excipients: Mannitol, Sodium hydroxide (to adjust the pH to 7.7). INDICATIONS Fludara is indicated for the treatment of patients with B -cell chronic lymphocytic leukemia (CLL) who have not responded to at least one standard alkylating-agent containing regimen. DOSAGE AND METHOD OF ADMINISTRATION Method of administration Fludara must be administered only intravenously. No cases have been reported in which paravenously administered Fludara led to severe local adverse reactions. However, unintentional paravenous administration must be avoided. Dosage regimen Adults Fludara solution for injection/infusion should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. The recommended dose is 25 mg fludarabine phosphate/m² body surface given daily for 5 consecutive days every 28 days by the intravenous route. Each vial is to be made up in 2 ml water for injection. Each ml of the resulting solution for injection/infusion will contain 25 mg fludarabine phosphate (see section ‘Instructions for use/handling’). The required dose (calculated on the basis of the patient's body surface) is drawn up into a syringe. For intravenous bolus injection, this dose is further diluted into 10 ml of 0.9 % sodium chloride.
    [Show full text]
  • PEMD-91-12BR Off-Label Drugs: Initial Results of a National Survey
    11 1; -- __...._-----. ^.-- ______ -..._._ _.__ - _........ - t Ji Jo United States General Accounting Office Washington, D.C. 20648 Program Evaluation and Methodology Division B-242851 February 25,199l The Honorable Edward M. Kennedy Chairman, Committee on Labor and Human Resources United States Senate Dear Mr. Chairman: In September 1989, you asked us to conduct a study on reimbursement denials by health insurers for off-label drug use. As you know, the Food and Drug Administration designates the specific clinical indications for which a drug has been proven effective on a label insert for each approved drug, “Off-label” drug use occurs when physicians prescribe a drug for clinical indications other than those listed on the label. In response to your request, we surveyed a nationally representative sample of oncologists to determine: . the prevalence of off-label use of anticancer drugs by oncologists and how use varies by clinical, demographic, and geographic factors; l the extent to which third-party payers (for example, Medicare intermediaries, private health insurers) are denying payment for such use; and l whether the policies of third-party payers are influencing the treatment of cancer patients. We randomly selected 1,470 members of the American Society of Clinical Oncologists and sent them our survey in March 1990. The sam- pling was structured to ensure that our results would be generalizable both to the nation and to the 11 states with the largest number of oncologists. Our response rate was 56 percent, and a comparison of respondents to nonrespondents shows no noteworthy differences between the two groups.
    [Show full text]
  • Fludarabine Phosphate (NSC 312878) Infusions for the Treatment of Acute Leukemia: Phase I and Neuropathological Study1
    [CANCER RESEARCH 46, 5953-5958, November 1986] Fludarabine Phosphate (NSC 312878) Infusions for the Treatment of Acute Leukemia: Phase I and Neuropathological Study1 David R. Spriggs,2 Edward Stopa, Robert J. Mayer, William Schoene, and Donald W. Kufe3 Dana Farber Cancer Institute [D. R. S., R. J. M.. D. W. K.J and Department ofPathology, Brigham and Women 's Hospital [E. S., W. SJ, Boston, Massachusetts 0211S ABSTRACT a relationship between dose and lethargy. The schedule of drug administration in these studies was not a 5-day infusion. A Fludarabine phosphate (NSC 312878), an adenosine deaminase resist ant analogue of 9-/9-D-arabinofuranosyladenine, has entered clinical trials. single bolus was used in one study while the other used a single bolus followed by a 48-h infusion. Eleven patients with acute leukemia in relapse received 14 courses of fludarabine phosphate as a 5-day continuous infusion administered at Based on the myelosuppressive effects of fludarabine phos doses of 40 to 100 mg/m2/day. Toxicity was characterized by uniform phate in Phase I testing, we instituted a Phase I and II trial to myelosuppression, as well as occasional nausea, vomiting, and hepato- identify the toxicity and efficacy of fludarabine phosphate in toxicity. Three episodes of metabolic acidosis and lactic acidemia were the treatment of acute leukemia. The drug was administered as noted. In addition, three patients suffered neurotoxicity. Two of these a 5-day continuous infusion at a starting dose equivalent to the three patients had a severe neurotoxicity syndrome characterized by maximum tolerated dose reached in patients with solid tumors.
    [Show full text]
  • Arsenic Summary & Details: Greenfacts
    http://www.greenfacts.org/ Copyright © GreenFacts page 1/9 Scientific Facts on Source document: IPCS (2001) Arsenic Summary & Details: GreenFacts Level 2 - Details on Arsenic 1. What is arsenic?.............................................................................................................3 1.1 What are the properties of arsenic?...................................................................................3 1.2 How are arsenic levels measured?.....................................................................................3 2. Where does environmental arsenic come from?....................................................3 2.1 What are the natural sources of environmental arsenic?.......................................................3 2.2 What are the man-made sources of environmental arsenic?..................................................4 2.3 How is arsenic transported and distributed in the environment?............................................4 3. What are the levels of exposure to arsenic?...........................................................4 3.1 How much arsenic is there in the environment?..................................................................4 3.2 What levels of arsenic are found in living organisms?...........................................................5 3.3 What levels of arsenic are humans exposed to?..................................................................5 4. What happens to arsenic in the body?......................................................................6 4.1
    [Show full text]
  • Inhibition of Cyclophosphamide and Mitomycin C-Induced Sister Chromatid Exchanges in Mice by Vitamin C
    ICANCERRESEARCH46,2670-2674, June 19861 Inhibition of Cyclophosphamide and Mitomycin C-induced Sister Chromatid Exchanges in Mice by Vitamin C G. Krishna,' J. Nath, and T. Ong Natio,wilnstitutefor OccupationaiSafety and Health, Division ofRespiratory Disease Studies, Morgansown, West Virginia 26505-2888 fG. K., T. 0.], andDivision of PlantandSoil Sciences,West VirginiaUniversity,Morgantown,West Visijnia 265O6fJ.N.J ABSTRACF The research reported here was performed to determine the effect of ascorbic acid on SCEs induced by CPA and MMC in Ascorbic acid (vitamin C) is known to act as an antimutagen and in vivo and in vivo/in vitro conditions in bone marrow and anticarcinogen in several test systems. However, there is no report of its spleen cells of mice. Analysis of SCEs is a sensitive cytogenetic effect on carcinogen-induced chromosomal damage in vii'o in animals. technique for detecting cellular chromosomal damage (11). The present study was performed to determine whether or not ascorbic SCEs are visualized as reciprocal exchangesof staining inten acid affects sister ébromatidexchanges (SCEs) induced by cyclophos sities between sister chromatid arms in metaphase cells that phamide (CPA) and mitomycin C (MMC) in bone marrow and spleen cells in mice. The results indicate that ascorbic acid per se did not cause have replicated twice in the presenceof BrdUrd. a significantincreaseinSCEsin mice.However,increasingconcentra tions of ascorbic acid caused decreasing levels of CPA- and MMC induced SCEs in both cell types in rho. At the highest concentration of MATERIALS AND METHODS ascorbic acid, 6.68 gfkg, approximately 75 and 40% SCE inhibition in Animals. Male CD-I mice were purchased from Charles River Breed both cell types was noted for CPA and MMC, respectively.
    [Show full text]
  • Testicular Cancer Treatment Regimens
    Testicular Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. Note: All recommendations are category 2A unless otherwise indicated. uPrimary Chemotherapy for Germ Cell Tumors1 REGIMEN DOSING Preferred Regimens BEP (Bleomycin + Etoposide + Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya Cisplatin)2,a,b Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily Days 1,8,15 OR Days 2,9,16: Bleomycin 30 units IV over 10 minutes daily.
    [Show full text]
  • Prednisolone-Rituximab-Vincristine (Rpacebom)
    Chemotherapy Protocol LYMPHOMA BLEOMYCIN-CYCLOPHOSPHAMIDE-DOXORUBICIN-ETOPOSIDE-METHOTREXATE- PREDNISOLONE-RITUXIMAB-VINCRISTINE (RPACEBOM) Regimen Lymphoma – RPACEBOM-Bleomycin-Cyclophosphamide-Doxorubicin-Etoposide- Methotrexate-Prednisolone-Rituximab-Vincristine Indication CD20 Positive Non Hodgkin’s Lymphoma Toxicity Drug Adverse Effect Bleomycin Pulmonary toxicity, rigors, skin pigmentation, nail changes Cyclophosphamide Dysuria, haemorrragic cystitis (rare), taste disturbances Doxorubicin Cardiotoxicity, urinary discolouration (red) Etoposide Hypotension on rapid infusion, alopecia, hyperbilirubinaemia Methotrexate Stomatitis, conjunctivitis, renal toxicity Weight gain, GI disturbances, hyperglycaemia, CNS disturbances, Prednisolone cushingoid changes, glucose intolerance Severe cytokine release syndrome, increased incidence of Rituxumab infective complications, progressive multifocal leukoencephalopathy Vincristine Peripheral neuropathy, constipation, jaw pain The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Version 1.2 (Jan 2015) Page 1 of 16 Lymphoma- RPACEBOM-Bleomycin-Cyclophospham-Doxorubicin-Etoposide-Methotrexate-Prednisolone-Rituximab-Vincristine Monitoring Drugs FBC, LFTs and U&Es prior to day one and fifteen Albumin prior to each cycle Regular blood glucose monitoring Check hepatitis B status before starting treatment with rituximab The presence of a third fluid compartment e.g. ascites or renal failure may delay the clearance of methotrexate
    [Show full text]
  • Cancer Drug Pharmacology Table
    CANCER DRUG PHARMACOLOGY TABLE Cytotoxic Chemotherapy Drugs are classified according to the BC Cancer Drug Manual Monographs, unless otherwise specified (see asterisks). Subclassifications are in brackets where applicable. Alkylating Agents have reactive groups (usually alkyl) that attach to Antimetabolites are structural analogues of naturally occurring molecules DNA or RNA, leading to interruption in synthesis of DNA, RNA, or required for DNA and RNA synthesis. When substituted for the natural body proteins. substances, they disrupt DNA and RNA synthesis. bendamustine (nitrogen mustard) azacitidine (pyrimidine analogue) busulfan (alkyl sulfonate) capecitabine (pyrimidine analogue) carboplatin (platinum) cladribine (adenosine analogue) carmustine (nitrosurea) cytarabine (pyrimidine analogue) chlorambucil (nitrogen mustard) fludarabine (purine analogue) cisplatin (platinum) fluorouracil (pyrimidine analogue) cyclophosphamide (nitrogen mustard) gemcitabine (pyrimidine analogue) dacarbazine (triazine) mercaptopurine (purine analogue) estramustine (nitrogen mustard with 17-beta-estradiol) methotrexate (folate analogue) hydroxyurea pralatrexate (folate analogue) ifosfamide (nitrogen mustard) pemetrexed (folate analogue) lomustine (nitrosurea) pentostatin (purine analogue) mechlorethamine (nitrogen mustard) raltitrexed (folate analogue) melphalan (nitrogen mustard) thioguanine (purine analogue) oxaliplatin (platinum) trifluridine-tipiracil (pyrimidine analogue/thymidine phosphorylase procarbazine (triazine) inhibitor)
    [Show full text]
  • Fludarabine-Based Versus Chop-Like Regimens with Or Without Rituximab in Patients with Previously Untreated Indolent Lymphoma
    OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Fludarabine-based versus CHOP-like regimens with or without rituximab in patients with previously untreated indolent lymphoma: a retrospective analysis of safety and efficacy Xiao-xiao Xu1 Abstract: Fludarabine-based regimens and CHOP (doxorubicin, cyclophosphamide, vincristine, Bei Yan2 prednisone)-like regimens with or without rituximab are the most common treatment modalities Zhen-xing Wang3 for indolent lymphoma. However, there is no clear evidence to date about which chemotherapy Yong Yu1 regimen should be the proper initial treatment of indolent lymphoma. More recently, the use of Xiao-xiong Wu2 fludarabine has raised concerns due to its high number of toxicities, especially hematological Yi-zhuo Zhang1 toxicity and infectious complications. The present study aimed to retrospectively evaluate both the efficacy and the potential toxicities of the two main regimens (fludarabine-based and CHOP-like 1 Department of Hematology, Tianjin regimens) in patients with previously untreated indolent lymphoma. Among a total of 107 patients Medical University Cancer Institute and Hospital, Tianjin Key Laboratory assessed, 54 patients received fludarabine-based regimens (FLU arm) and 53 received CHOP or of Cancer Prevention and Therapy, CHOPE (doxorubicin, cyclophosphamide, vincristine, prednisone, or plus etoposide) regimens Tianjin, 2Department of Hematology, (CHOP arm). The results demonstrated that fludarabine-based regimens could induce significantly First Affiliated Hospital of Chinese People’s Liberation Army General improved progression-free survival (PFS) compared with CHOP-like regimens. However, the Hospital, Beijing, 3Department of FLU arm showed overall survival, complete response, and overall response rates similar to those Stomach Oncology, Tianjin Medical University Cancer Institute and of the CHOP arm.
    [Show full text]
  • Program Slides
    Living with Hairy Cell Leukemia Michael Grever, MD Professor Emeritus, Internal Medicine/Hematology The Ohio State University Columbus, OH Living with Hairy Cell Leukemia Introduction to Hairy Cell Leukemia Michael Grever, MD Professor Emeritus, Internal Medicine/Hematology The Ohio State University Columbus, OH Financial Disclosures M. Grever served on a data safety monitoring board for Ascerta Inc., as a consultant for Pharmacyclics Inc., and as a consultant for AstraZeneca. First Descriptions of Hairy Cell Leukemia Gosselin GR, Hanlon DG, Pease GL. Leukaemic Reticuloendotheliosis. Can Med Assoc J. 74(11):886- 91, 1956 Bouroncle BA, Wiseman BC, Doan CA. Leukemic Reticuloendotheliosis. Blood 13: 609-630, 1958 Dr. Bertha Bouroncle Typical hairy cells among red blood cells (Dr. Gerard Lozanski, OSU) Clinical Features of Hairy Cell Leukemia • Remarkable male predominance 4:1 • Median age 55 years • Symptoms related to fatigue and infection • Physical exam shows enlarged spleen • Low blood cell counts (“cytopenias”) • Diagnosis made by examination of blood and bone marrow • Flow cytometry is critical for the diagnosis • Characteristic markers: CD11c, CD25; CD103; CD123 Manifestations of Hairy Cell Leukemia • Fatigue and symptoms of anemia • Easy bruising or bleeding • Infection • Herpes zoster (shingles) • Autoimmune disorders such as vasculitis, rheumatoid- like arthritis, immune thrombocytopenia • Bone lesions Clinical Judgement in Treatment Decisions • Determine if diagnosis is correct (e.g., classic HCL is different disease than HCL variant). • While 10% patients with HCL do not require immediate treatment, they require close follow-up. • Patients with active infection should not receive cladribine, and require special treatment planning • Need to assess kidney function and history of hepatitis exposure before treatment • Bone marrow biopsies at initiation and following completion of therapy have value.
    [Show full text]