DOCSLIB.ORG

Mycosis Fungoides and Sézary Syndrome: Focus on The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mycosis Fungoides and Sézary Syndrome: Focus on The Anais Brasileiros de Dermatologia 2021;96(4):458---471 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br REVIEW Mycosis fungoides and Sézary syndrome: focus on the ଝ,ଝଝ current treatment scenario a,∗ a b José Antonio Sanches , Jade Cury-Martins , Rodrigo Martins Abreu , a c Denis Miyashiro , Juliana Pereira a Dermatology Clinic Division, Faculty of Medicine, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil b Medical Department, Private Institution, São Paulo, SP, Brazil c Hematology Clinic Division, Faculty of Medicine, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil Received 2 October 2020; accepted 6 December 2020 Available online 28 May 2021 Abstract Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative dis- KEYWORDS orders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides Lymphoma, T-cell, is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. cutaneous; Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from Mycosis fungoides; some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients Sezary syndrome; progress to advanced stages, with the development of skin tumors, extracutaneous spread and Therapeutics poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are pre- ferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome. © 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). ଝ How to cite this article: Sanches JA, Cury-Martins J, Abreu RM, Miyashiro D, Pereira J. Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario. An Bras Dermatol. 2021;96:458---71. ଝଝ Study conducted at the Dermatology Clinic Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. ∗ Corresponding author. E-mail: [email protected] (J.A. Sanches). https://doi.org/10.1016/j.abd.2020.12.007 0365-0596/© 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Anais Brasileiros de Dermatologia 2021;96(4):458---471 Introduction size of a small lymphocyte) surpassing > 25% of the dermal infiltrate or presenting microscopic nodules and is generally 3 associated with a worse prognosis. Primary cutaneous lymphomas are a heterogeneous group The clinical staging of MF and SS is based on the classi- of non-Hodgkin’s lymphomas that occur on the skin with- fication of cutaneous (T), lymph node (N), visceral (M) and out evidence of extracutaneous disease at the time of hematological (B) involvement (Tables 2 and 3). The TNMB diagnosis. They represent 19% of extranodal lymphomas, classification should include careful examination of the skin with an annual incidence in western countries of 1 case (paying attention to the scalp, palms, soles, and perineum), per 100,000 inhabitants/year. Primary cutaneous lymphomas biopsy(ies) of skin lesion(s), complete blood count with are classified by the World Health Organization - Euro- screening for Sézary cells, peripheral blood flow cytometry, pean Organization for Cancer Research and Treatment 2 biochemical tests and imaging studies. As HTLV-1 is endemic (WHO-EORTC) into Cutaneous T-Cell Lymphomas (CTCL) and in Brazil, screening for this retrovirus is mandatory for all Cutaneous B-Cell Lymphomas (CBCL). In the West, CTCLs patients with suspected or proven CTCL, to differentiate represent approximately 75% to 80% of all primary cutaneous 4 lymphomas.1,2 MF/SS from adult T-cell lymphoma/leukemia. CTCLs appear primarily on the skin and can progress to lymph nodes, blood and viscera. They are a het- Treatment options erogeneous group of tumors, with considerable variation regarding clinical presentation, as well as their histopatho- Most treatments available for MF/SS rarely induce long-term logical, immunophenotypic and prognostic characteristics. remission. Treatment responses might include the overall The updated classification is shown in Table 1, as well as the response rate (complete remission rate + partial remission 1 division according to their agressiveness. rate), complete remission, partial remission (remission of Indolent lymphomas usually have a chronic course with at least 50% of the disease burden), response duration, time frequent recurrences. The disease is generally considered until next treatment, progression-free survival, overall sur- incurable despite treatment, with a mean survival of 5 to vival, disease-specific survival and symptoms and quality 10 years. However, some patients can survive more than of life improvement (Tables 4 and 5). Both treatment and 20 years. Aggressive lymphomas progress faster when com- 6 prognosis vary according to the stages of the disease. pared to indolent forms and can lead to death in a few The treatment modalities can be divided into two groups: months.1 skin-directed therapies and systemic therapies. The treat- Mycosis fungoides (MF) is the most common type and ments can be done as monotherapy or combined therapy. accounts for 60% of CTCLs and almost 50% of all primary Skin-directed therapies include topical agents, photother- cutaneous lymphomas. Most patients are adults or elderly, 7 apy and radiotherapy. Systemic therapies include biological with a male to female ratio of 2:1, and a worldwide response modifiers, immunotherapies and chemotherapeu- incidence of approximately 5 --- 6 cases per million inhabi- 8 tic agents. For early-stage MF (stage Ia --- IIa), skin-directed tants/year. Sézary Syndrome (SS) is a rare leukemic variant therapies are the treatment of choice, aiming at control- of CTCL. This article will address the therapeutic possibili- ling the disease, improving symptoms and quality of life. In 1,2 ties for those two entities. refractory early-stage MF, late-stage MF (stage ≥ IIb) and SS, systemic treatment, combined or not with skin-directed therapy, is required. Treatment modalities are reviewed in Mycosis fungoides and Sézary syndrome this article. The approval and availability of drugs in the United MF is a non-Hodgkin’s mature T-cell lymphoma with a pri- States, Europe and Brazil are described in Tables 6 and 7*. mary presentation on the skin, but with potential secondary Extracorporeal photopheresis, narrow-band UVB photother- involvement of lymph nodes, blood and viscera. Skin lesions apy, psoralen-UVA (PUVA) photochemotherapy, and radio- include patches or plaques that may be localized or dis- therapy are more widely available. seminated, tumors and erythroderma. The course of MF is variable. In some patients the disease remains limited to the skin for many years, while in others, it may progress Skin-directed therapies more quickly to extracutaneous involvement, with a worse Topical drug therapies. prognosis. SS is an erythrodermic and pruritic form of CTCL, Corticosteroids. Topical corticosteroids are the most characterized by peripheral lymphadenopathy and the pres- widely used anti-inflammatory agents in dermatology. They ence of neoplastic T-cells with cerebriform nuclei (Sézary inhibit the binding of lymphocytes to the endothelium, cells), which are clonally related, in the skin, lymph nodes inhibit intercellular adhesion and induce apoptosis of neo- 2 and peripheral blood. plastic lymphoid cells. They are often formulated as cream, The histopathological analysis typically shows an epider- ointment, lotion or gel. According to the topical corti- motropic lymphoma of small to medium-sized lymphocytes costeroid and the formulation, the drug potency can be with cerebriform nuclei. The neoplastic cells have a mature stratified into seven classes: class I (super-high potency, T-cell phenotype, CD3+, CD4+, CD45RO+, CD8-, with variable e.g., 0.05% clobetasol propionate cream); class II (high 1 loss of CD7 expression. The CD30 molecule may eventually potency, e.g., 0.05% betamethasone dipropionate ointment; be expressed in neoplastic cells, but this expression seems class III (medium-high potency, e.g., 0.05% betamethasone to be more frequent and more intense in cases that show dipropionate cream); class IV (medium potency, e.g., 0.1% transformation to large cell lymphoma. The transformed triamcinolone acetonide cream); class V (lower-medium ≥ MF is defined by the presence of large cells ( 4-fold the potency, e.g., 0.1% betamethasone valerate cream), class 459 J.A. Sanches, J. Cury-Martins, R.M. Abreu et al. Table 1 Classification of T-cell lymphomas with primary cutaneous manifestations according to their clinical behavior, frequency 1 and disease-specific 5-year survival. Based on the WHO-EORTC guidelines. Clinical behavior Frequency (%) Disease-specific 5-year survival (%) Mycosis fungoides Indolent 39 88 Mycosis fungoides variants Folliculotropic mycosis fungoides Indolent 5 75 Pagetoid
Load more

Recommended publications
  • Bexarotene (Targretin) Capsules Reference Number: PA.CP.PHAR.75 Effective Date: 09/11 Revision Log Last Review Date: 04/18
    Clinical Policy: Bexarotene (Targretin) Capsules Reference Number: PA.CP.PHAR.75 Effective Date: 09/11 Revision Log Last Review Date: 04/18 Description The intent of the criteria is to ensure that patients follow selection elements established by Pennsylvania Health and Wellness ® clinical policy for bexarotene (Targretin®) capsules FDA Approved Indication(s) Targretin is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Policy/Criteria It is the policy of Pennsylvania Health and Wellness that Targretin is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Cutaneous T-Cell Lymphoma (must meet all): 1. Diagnosis of cutaneous T-cell lymphoma (CTCL) (see Appendix B for CTCL subtypes); 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Dose does not exceed 400mg/m2 daily; Approval duration: 6 months B. Other diagnoses/indications: Refer to PA.CP.PHAR.57 - Global Biopharm Policy. II. Continued Approval A. Cutaneous T-Cell Lymphoma (must meet all): 1. Currently receiving medication via Pennsylvania Health and Wellness benefit or member has previously met all initial approval criteria; or the Continuity of Care policy (PA.LTSS.PHAR.01) applies; 2. Member is responding positively to therapy; 3. Dose does not exceed 400mg/m2 daily; Approval duration: 6months B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via Pennsylvania Health and Wellness benefit and documentation supports positive response to therapy; or the Continuity of Care policy (PA.LTSS.PHAR.01) applies; Approval duration: Duration of request or 6 months (whichever is less); or 2.
    [Show full text]
  • Australian Public Assessment Report for Aminolevulinic Acid Hcl
    Australian Public Assessment Report for Aminolevulinic acid HCl Proprietary Product Name: Gliolan Sponsor: Specialised Therapeutics Australia Pty Ltd March 2014 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health, and is responsible for regulating medicines and medical devices. · The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website < http://www.tga.gov.au>. About AusPARs · An Australian Public Assessment Record (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations, and extensions of indications. · An AusPAR is a static document, in that it will provide information that relates to a submission at a particular point in time. · A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA.
    [Show full text]
  • Message from the President
    DermNewsletter of the American OsteopathicLine College of Dermatology Spring 2016 Vol. 32, No. 1 Message from the President Greetings from Houston, Texas - again! As President of the AOCD, I welcome you to another edition of DermLine. As I think about our recent past and the dramatic changes afoot, I recall Suzanne Sirota Rozenberg, DO, FAOCD, Past President of AOCD, commenting in the Spring 2014 edition of DermLine about the coming AOA/ACGME merger. As I stated previously, “Today, at this moment, we are living in yesterday’s future.” Our future has arrived. Because the AOA, along with the Accreditation Council for Graduate Medical Education and the American Association of Colleges of Osteopathic Medicine, have agreed to a single accreditation system for graduate medical education programs in the United States, our graduates of osteopathic institutions, along with graduates of allopathic medical schools will complete their residency and/or fellowship education in ACGME-accredited programs and demonstrate achievement of common milestones and competencies side-by-side. I hope you realize the power in the previous statement. Trained together, osteopathic and allopathic graduates will no longer be divided. Perhaps the most exciting news to share is the AAD vote that just passed last month. This has been a battle we have been fighting for generations. The vote suffered defeat in 2004 and 2010. On both occasions, a majority of the membership voted in favor, but the required two-thirds majority required to approve a change to the bylaws fell short. I was told I would never see this vote go through in my lifetime.
    [Show full text]
  • Evaluation of Melanocyte Loss in Mycosis Fungoides Using SOX10 Immunohistochemistry
    Article Evaluation of Melanocyte Loss in Mycosis Fungoides Using SOX10 Immunohistochemistry Cynthia Reyes Barron and Bruce R. Smoller * Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA; [email protected] * Correspondence: [email protected] Abstract: Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases; CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF. Citation: Barron, C.R.; Smoller, B.R. Evaluation of Melanocyte Loss in Keywords: mycosis fungoides; hypopigmented mycosis fungoides; SOX10; cutaneous T-cell lymphoma Mycosis Fungoides Using SOX10 Immunohistochemistry.
    [Show full text]
  • Primary Cutaneous Lymphoma: ESMO Clinical Recommendations for Diagnosis, Treatment and Follow-Up R
    Annals of Oncology 19 (Supplement 2): ii72–ii76, 2008 clinical recommendations doi:10.1093/annonc/mdn095 Primary cutaneous lymphoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up R. Dummer1 & M. Dreyling2 On behalf of the ESMO Guidelines Working Group* 1Department of Dermatology, University Hospital, Zu¨rich, Switzerland; 2Department of Medicine III, University Hospital Grosshadern, Munich, Germany introduction the quality of life due to their impact on skin appearance and annoying symptoms such as pruritus. In some cases they can Cutaneous lymphomas (CL) are the second most common already be disfiguring in early disease stages. In advanced stages, extranodal non-Hodgkin’s lymphomas. Their incidence is local skin problems are accompanied by systemic immune estimated at 1/100 000 yearly. Primary CL develop by definition suppression which results in an increased risk of infections and in the skin and remain confined to the skin for a long period of secondary malignancies. Some of the late-stage problems in time, while secondary CL reflect cutaneous spread from MF/SS patients might have been aggravated by earlier disseminated primary nodal or extranodal lymphomas. Primary therapeutic interventions, e.g. radiotherapy or phototherapy CL include a wide spectrum of clinically and histologically may contribute to mutations that increase the proliferative heterogeneous lymphoproliferative neoplasms: 75% of CL are and invasive capacity of the tumor cell populations. Cytotoxic cutaneous T-cell lymphomas (CTCL); 25% cutaneous B-cell drugs favor infectious complications. Most patients with lymphomas (CBCL); and a few percent other uncommon advanced disease may die due to secondary problems such as forms. CL and nodal or extracutaneous lymphomas with the infections.
    [Show full text]
  • Treatment of Pagetoid Reticulosis with Intensity Modulated Radiation Therapy Charles Mount Washington University School of Medicine in St
    Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 Treatment of pagetoid reticulosis with intensity modulated radiation therapy Charles Mount Washington University School of Medicine in St. Louis Daniel Ferraro Washington University School of Medicine in St. Louis Alejandro Gru Washington University School of Medicine in St. Louis Matthew rB adbury Washington University School of Medicine in St. Louis Lynn Cornelius Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Mount, Charles; Ferraro, Daniel; Gru, Alejandro; Bradbury, Matthew; Cornelius, Lynn; and Gay, Hiram, ,"Treatment of pagetoid reticulosis with intensity modulated radiation therapy." Dermatology Online Journal.20,10. (2014). https://digitalcommons.wustl.edu/open_access_pubs/5149 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Charles Mount, Daniel Ferraro, Alejandro Gru, Matthew Bradbury, Lynn Cornelius, and Hiram Gay This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/5149 Dermatology Online Journal UC Davis Peer Reviewed Title: Treatment of pagetoid reticulosis with intensity modulated radiation therapy Journal Issue: Dermatology Online Journal, 20(10) Author: Mount, Charles, Washington University in St. Louis Ferraro, Daniel, Washington University in St. Louis Gru, Alejandro, Washington University in St. Louis; The Ohio State University Bradbury, Matthew, Washington University in St. Louis Cornelius, Lynn, Washington University in St.
    [Show full text]
  • Other Alkylating Agents
    Anticancer agents The Alkylating agents The alkylating agents are the oldest group of cytostatic drugs. The first of them – mechlorethamine was introduced into therapy in 1949. The alkylating agents can contain one or two alkylating groups. In the body the alkylating agents may react with DNA, RNA and proteins, although their reaction with DNA is believed to be the most important. 1 • The primary target of DNA coross-linking agents is the actively dividing DNA molecule. • The DNA cross-linkers are all extremly reactive nucleophilic structures (+). • When encountered, the nucleophilic groups on various DNA bases (particularly, but not exclusively, the N7 of guaninę) readily attack the electrophilic drud, resulting in irreversible alkylation or complexation of the DNA base. • Some DNA alkylating agents, such as the nitrogen mustards and nitrosoureas, are bifunctional, meaning that one molecule of the drug can bind two distinct DNA bases. 2 • Most commonly, the alkylated bases are on different DNA molecules, and intrastrand DNA cross-linking through two guaninę N7 atoms results. • The DNA alkylating antineoplastics are not cel cycle specific, but they are more toxic to cells in the late G1 or S phases of the cycle. • This is a time when DNA unwinding and exposing its nucleotides, increasing the Chance that vulnerable DNA functional groups will encounter the nucleophilic antineoplastic drug and launch the nucleophilic attack that leads to its own destruction. • The DNA alkylators have a great capacity for inducing toth mutagenesis and carcinogenesis, they can promote caner in addition to treating it. 3 • Organometallic antineoplastics – Platinum coordination complexes, also cross-link DNA, and many do so by binding to adjacent guanine nucleotides, called disguanosine dinucleotides, on the single strand of DNA.
    [Show full text]
  • Metabolism and Pharmacokinetics of the Cyclin-Dependent Kinase Inhibitor R-Roscovitine in the Mouse
    Molecular Cancer Therapeutics 125 Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse Bernard P. Nutley,1 Florence I. Raynaud,1 COOH-R-roscovitine could be inhibited by replacement Stuart C. Wilson,1 Peter M. Fischer,2 of metabolically labile protons with deuterium. After 1 1 Angela Hayes, Phyllis M. Goddard, 60 minutes of incubation of R -roscovitine-d9 or Steven J. McClue,2 Michael Jarman,1 R-roscovitine with mouse liver microsomes, formation of 2 1 f David P. Lane, and Paul Workman COOH-R-roscovitine-d9 was decreased by 24% com- pared with the production of COOH-R-roscovitine. In 1 Cancer Research UK Centre for Cancer Therapeutics, Institute of addition, the levels of R-roscovitine-d remaining were Cancer Research, Surrey, United Kingdom and 2Cyclacel Ltd., 9 Dundee, United Kingdom 33% higher than those of R-roscovitine. However, formation of several minor R-roscovitine metabolites was enhanced with R-roscovitine-d9, suggesting that metabolic Abstract switching from the major carbinol oxidation pathway had occurred. Synthetic COOH-R-roscovitine and C8-oxo- R-roscovitine (seliciclib, CYC202) is a cyclin-dependent R-roscovitine were tested in functional cyclin-dependent kinase inhibitor currently in phase II clinical trials in patients kinase assays and shown to be less active than with cancer. Here, we describe its mouse metabolism and R-roscovitine, confirming that these metabolic reactions pharmacokinetics as well as the identification of the are deactivation pathways. [Mol Cancer Ther 2005; principal metabolites in hepatic microsomes, plasma, and 4(1):125–39] urine. Following microsomal incubation of R-roscovitine at 10 Ag/mL (28 Amol/L) for 60 minutes, 86.7% of the parent drug was metabolized and 60% of this loss was due to Introduction formation of one particular metabolite.
    [Show full text]
  • Nonpredictable Pharmacokinetic Behavior of High-Dose Cyclophosphamide in Combination with Cisplatin and 1,3-Bis(2-Chloroethyl)-1-Nitrosourea1
    Vol. 5, 747–751, April 1999 Clinical Cancer Research 747 Nonpredictable Pharmacokinetic Behavior of High-Dose Cyclophosphamide in Combination with Cisplatin and 1,3-Bis(2-chloroethyl)-1-nitrosourea1 Yago Nieto,2 Xuesheng Xu, Pablo J. Cagnoni, of the drug unpredictable from an initial measurement on Steve Matthes, Elizabeth J. Shpall, day 1. Thus, in this combination, measurement of levels of Scott I. Bearman, James Murphy, and parent CPA, with the objective of real-time therapeutic monitoring of this drug, is not informative. Roy B. Jones University of Colorado Bone Marrow Transplant Program [Y. N., P. J. C., S. M., E. J. S., S. I. B., R. B. J.] and Department of INTRODUCTION Biostatistics [X. X., J. M.], University of Colorado, Denver, Colorado HDC3 with stem cell support attempts to overcome cell 80262 resistance to standard-dose chemotherapy by exploiting the dose-response effects of combinations of antineoplastic drugs. ABSTRACT Considering the high potential for toxicity with HDC, ongoing research is pursuing the application of TDM to HDC. TDM Our objective was to assess whether the total area prospectively adjusts for interindividual variability of concen- under the curve (AUC) of high-dose cyclophosphamide trations achieved after the first dose of a drug to a final target PK (CPA), combined with cisplatin and 1,3-bis(2-chloroethyl)- parameter. This strategy is based on two requirements: (a) the 1-nitrosourea, could be predicted from its AUC on the first knowledge that, for a particular drug, a certain PK parameter is day of treatment. We reviewed the AUC of CPA in 470 associated with either a toxic or a therapeutic pharmacodynamic patients who underwent pharmacokinetic monitoring of the effect; and (b) the demonstration that the drug’s PK behavior is drug.
    [Show full text]
  • Mycosis Fungoides and Sézary Syndrome: an Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy
    cancers Review Mycosis Fungoides and Sézary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy Nuria García-Díaz 1 , Miguel Ángel Piris 2,† , Pablo Luis Ortiz-Romero 3,† and José Pedro Vaqué 1,*,† 1 Molecular Biology Department, Universidad de Cantabria—Instituto de Investigación Marqués de Valdecilla, IDIVAL, 39011 Santander, Spain; [email protected] 2 Department of Pathology, Fundación Jiménez Díaz, CIBERONC, 28040 Madrid, Spain; [email protected] 3 Department of Dermatology, Hospital 12 de Octubre, Institute i+12, CIBERONC, Medical School, University Complutense, 28041 Madrid, Spain; [email protected] * Correspondence: [email protected] † Same contribution. Simple Summary: In the last few years, the field of cutaneous T-cell lymphomas has experienced major advances. In the context of an active translational and clinical research field, next-generation sequencing data have boosted our understanding of the main molecular mechanisms that govern the biology of these entities, thus enabling the development of novel tools for diagnosis and specific therapy. Here, we focus on mycosis fungoides and Sézary syndrome; we review essential aspects of their pathophysiology, provide a rational mechanistic interpretation of the genomic data, and discuss the current and upcoming therapies, including the potential crosstalk between genomic alterations Citation: García-Díaz, N.; Piris, M.Á.; and the microenvironment, offering opportunities for targeted therapies. Ortiz-Romero, P.L.; Vaqué, J.P. Mycosis Fungoides and Sézary Abstract: Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases Syndrome: An Integrative Review of that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority the Pathophysiology, Molecular of these lesions and have recently been the focus of extensive translational research.
    [Show full text]
  • Gene Therapy with Drug Resistance Genes
    Cancer Gene Therapy (2006) 13, 335–345 r 2006 Nature Publishing Group All rights reserved 0929-1903/06 $30.00 www.nature.com/cgt REVIEW Gene therapy with drug resistance genes M Zaboikin1, N Srinivasakumar1 and F Schuening Division of Hematology/Oncology, Department of Medicine, Vanderbilt University, Nashville, TN, USA A major side effect of cancer chemotherapy is myelosuppression. Expression of drug-resistance genes in hematopoietic stem cells (HSC) using gene transfer methodologies holds the promise of overcoming marrow toxicity in cancer chemotherapy. Adequate protection of marrow cells in cancer patients from myelotoxicity in this way would permit the use of escalating doses of chemotherapy for eradicating residual disease. A second use of drug-resistance genes is for coexpression with a therapeutic gene in HSCs to provide a selection advantage to gene-modified cells. In this review, we discuss several drug resistance genes, which are well suited for in vivo selection as well as other newer candidate genes with potential for use in this manner. Cancer Gene Therapy (2006) 13, 335–345. doi:10.1038/sj.cgt.7700912; published online 7 October 2005 Keywords: hematopoietic stem cell; chemoprotection; drug resistance; gene transfer Introduction increasing interest due to their demonstrated superiority to g-retroviral vectors for gene delivery into HSCs.4–7 Hematopoietic stem cells (HSCs) are defined by their Retroviral vectors have been shown to be effective in properties of self-renewal, pluripotency, and life-long correcting genetic disorders in small animal models such persistence following transplantation in the host. HSCs as mice. However, success has been meager in large are easily accessible and deliverable back to recipients by animals including humans.
    [Show full text]
  • A Patient's Guide to Understanding Cutaneous Lymphoma
    WELCOME! If you or someone close to you has been given a diagnosis of cutaneous lymphoma, you probably have many questions and concerns. Living with cutaneous lymphoma and the many changes that this diagnosis brings to your life can leave you feeling overwhelmed, confused and lonely. You may not even be sure about what kinds of questions to ask. This guide was created so you can find valuable information to help you understand the disease, learn about available treatments and how to find specialists, access support, and ways to live the best life you can with cutaneous lymphoma. The Cutaneous Lymphoma Foundation is dedicated to providing patients, caregivers and loved ones with programs and services designed to help, support and provide hope to people who are given a diagnosis of cutaneous lymphoma. We are here for you. You are not alone. You are part of a knowledgeable, caring, resourceful, and compassionate community, and we’re here to help you. Get in touch anytime. We hope to hear from you or meet you in person at one of our patient events. We wish you all the best in your journey. The Staff and Board of Directors of the Cutaneous Lymphoma Foundation A Patient’s Guide to Understanding Cutaneous Lymphoma ACKNOWLEDGMENTS This guide is an educational resource published by the Cutaneous Lymphoma The Cutaneous Lymphoma Foundation acknowledges and thanks the Foundation providing general information on cutaneous lymphoma. Publication individuals listed below who have given generously of their time and expertise. of this information is not intended to take the place of medical care or the advice We thank them for their contributions, editorial wisdom and advice, which have of your physician(s).
    [Show full text]