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Book Details
Abstract
The Editor of this publication is Dr Elise Olsen, Director of the Duke University Cutaneous Lymphoma Research and Treatment Center and professor of Dermatology and Oncology. In 2014, cutaneous lymphoma (CL) is considered a chronic, non-life threatening disease since the majority of patients are diagnosed at early stage, though progression to later stages does result in death from the disease. This issue covers T-cell and B-cell lymphomas, with content emphasis on Mycoides fungoides and Sezary syndrome, the two most common clinically encountered subtypes of CL. Pharmaceutical treatment of the disease is a part of each article and the issue uses the following Treatment outline: Mechanisms of action - Pharmacokinetics - Typical dosing - Response to therapy - Adverse effects - and Pearls to help management using the agent under discussion. Beyond Dermatologists, specialists who would find the information useful are Cancer specialists, Hematologists/Oncologists, Physician Assistants, Nurse Practitioners, and Pharmacists.
Some of the topics, written by the word's top experts in this disease, are: Overview of primary cutaneous lymphomas and the applicable staging and classification; Pathologic diagnosis of cutaneous lymphomas; in the section on Mycosis Fungoides and Sezary Syndrome, the clinician and researcher will find such topics as Skin directed medications; Phototherapy; Systemic retinoids; Interferons; HDAC inhibiotrs, Methotrexate and praletexate, along with other chemotherapeutic agents. Also, Bone marrow transplant; Diagnosis and management of CD30+ Lymphoproliferative disorders; and Diagnosis and management of primary cutaneous B cell lymphomas.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Cutaneous Lymphoma | i | ||
| Copyright\r | COii | ||
| Contributors | ii | ||
| CONSULTING EDITOR | ii | ||
| EDITOR | ii | ||
| AUTHORS | ii | ||
| Contents | iv | ||
| Erratum\r | iv | ||
| Preface: Cutaneous Lymphoma\r | iv | ||
| Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma\r | iv | ||
| Pathologic Diagnosis of Cutaneous Lymphomas\r | iv | ||
| Skin-Directed Therapies in Cutaneous T-Cell Lymphoma\r | iv | ||
| Phototherapy of Mycosis Fungoides\x0B | v | ||
| Radiation Therapy for Cutaneous T-Cell Lymphomas\r | v | ||
| The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma\r | v | ||
| The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma\r | v | ||
| Methotrexate and Pralatrexate\r | v | ||
| Histone Deacetylase Inhibitors for Cutaneous T-Cell Lymphoma\r | vi | ||
| Extracorporeal Photopheresis in the Treatment of Mycosis Fungoides and Sézary Syndrome\r | vi | ||
| Monoclonal Antibodies\r | vi | ||
| Other Chemotherapeutic Agents in Cutaneous T-Cell Lymphoma\r | vi | ||
| Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome\r | vii | ||
| Practical Management of CD30+ Lymphoproliferative Disorders\r | vii | ||
| Diagnosis and Management of Cutaneous B-Cell Lymphoma\r | vii | ||
| DERMATOLOGIC CLINICS\r | viii | ||
| FORTHCOMING ISSUES | viii | ||
| January 2016 | viii | ||
| April 2016 | viii | ||
| July 2016 | viii | ||
| RECENT ISSUES | viii | ||
| July 2015 | viii | ||
| April 2015 | viii | ||
| January 2015 | viii | ||
| Erratum | x | ||
| Preface:\rCutaneous Lymphoma | xii | ||
| Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma | 643 | ||
| Key points | 643 | ||
| INTRODUCTION | 643 | ||
| SUBTYPES AND EPIDEMIOLOGY OF CUTANEOUS LYMPHOMA | 643 | ||
| MYCOSIS FUNGOIDES AND SÉZARY SYNDROME | 645 | ||
| Diagnosis | 645 | ||
| Evaluation and Staging | 645 | ||
| Clinical assessment | 645 | ||
| Blood work | 646 | ||
| Radiology | 646 | ||
| Biopsies | 648 | ||
| Staging | 648 | ||
| Response Assessment | 649 | ||
| NON-MYCOSIS FUNGOIDES AND NON-SÉZARY SYNDROME CUTANEOUS T-CELL LYMPHOMAS | 650 | ||
| Incidence and Prognosis | 650 | ||
| Diagnosis | 650 | ||
| Evaluation | 650 | ||
| Clinical assessment | 650 | ||
| Blood work | 650 | ||
| Radiology | 650 | ||
| Biopsies | 650 | ||
| Staging | 650 | ||
| Response Assessment | 652 | ||
| CUTANEOUS B-CELL LYMPHOMAS | 653 | ||
| Incidence | 653 | ||
| Diagnosis | 653 | ||
| Evaluation | 653 | ||
| Clinical assessment | 653 | ||
| Blood work | 653 | ||
| Radiology | 653 | ||
| Biopsies | 653 | ||
| Staging | 653 | ||
| Response Assessment | 653 | ||
| SUMMARY | 653 | ||
| REFERENCES | 653 | ||
| Pathologic Diagnosis of Cutaneous Lymphomas | 655 | ||
| Key points | 655 | ||
| INTRODUCTION | 655 | ||
| Pathologic Approach | 655 | ||
| Phenotyping | 657 | ||
| Genotyping | 657 | ||
| CUTANEOUS T-CELL LYMPHOMAS | 657 | ||
| Mycosis Fungoides | 657 | ||
| Histology | 657 | ||
| Immunophenotype and clonality | 658 | ||
| Genetics | 658 | ||
| Differential diagnosis | 658 | ||
| Variants | 659 | ||
| Sézary Syndrome | 659 | ||
| Primary Cutaneous CD30-Positive Lymphoproliferative Disorders | 660 | ||
| Lymphomatoid Papulosis | 660 | ||
| Histology | 660 | ||
| Differential diagnosis | 662 | ||
| Primary Cutaneous Anaplastic Large T-Cell Lymphoma | 663 | ||
| Subcutaneous Panniculitis-Like T-Cell Lymphoma | 664 | ||
| Histology | 664 | ||
| Immunophenotype and clonality | 664 | ||
| Differential diagnosis | 664 | ||
| Cutaneous Peripheral T-Cell Lymphoma | 664 | ||
| Cutaneous CD4+- Small/Medium-Sized T-Cell Lymphoma | 664 | ||
| Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma | 665 | ||
| Cutaneous γ/δ T-Cell Lymphoma | 666 | ||
| Cutaneous Peripheral T-Cell Lymphoma, Unspecified | 667 | ||
| Extranodal Natural Killer-/T-Cell Lymphoma, Nasal Type | 667 | ||
| CUTANEOUS B-CELL LYMPHOMAS | 668 | ||
| Primary Cutaneous Marginal Zone Lymphoma | 668 | ||
| Histology | 668 | ||
| Immunophenotype and clonality | 670 | ||
| Genetics | 670 | ||
| Differential diagnosis | 670 | ||
| Primary Cutaneous Follicle Center Lymphoma | 671 | ||
| Histology | 671 | ||
| Immunophenotype and clonality | 671 | ||
| Genetics | 671 | ||
| Differential diagnosis | 671 | ||
| Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type | 672 | ||
| Histology | 672 | ||
| Immunophenotype and clonality | 672 | ||
| Genetics | 672 | ||
| Differential diagnosis | 672 | ||
| Primary Cutaneous Diffuse Large B-Cell Lymphoma-Other | 672 | ||
| Intravascular Large B-Cell Lymphoma | 673 | ||
| Epstein-Barr Virus–Associated B-Cell Lymphoproliferations | 673 | ||
| SUMMARY | 676 | ||
| REFERENCES | 676 | ||
| Skin-Directed Therapies in Cutaneous T-Cell Lymphoma | 683 | ||
| Key points | 683 | ||
| INTRODUCTION | 683 | ||
| TOPICAL THERAPIES | 683 | ||
| Emollients | 684 | ||
| Corticosteroids | 684 | ||
| TOPICAL CHEMOTHERAPEUTICS | 685 | ||
| Mechlorethamine | 685 | ||
| Carmustine | 689 | ||
| RETINOIDS | 690 | ||
| Bexarotene | 692 | ||
| Tazarotene | 692 | ||
| Alitretinoin | 692 | ||
| EMERGING TOPICAL THERAPIES | 692 | ||
| SUMMARY | 692 | ||
| REFERENCES | 693 | ||
| Phototherapy of Mycosis Fungoides | 697 | ||
| Key points | 697 | ||
| INTRODUCTION | 697 | ||
| ULTRAVIOLET B PHOTOTHERAPY IN MYCOSIS FUNGOIDES | 697 | ||
| Background | 697 | ||
| Radiation Therapy for Cutaneous T-Cell Lymphomas | 703 | ||
| Key points | 703 | ||
| INTRODUCTION | 703 | ||
| MYCOSIS FUNGOIDES | 703 | ||
| Local Radiation Therapy | 703 | ||
| Clinical applications of local radiation therapy | 704 | ||
| Minimal stage IA disease | 704 | ||
| Palliation of individual lesions | 704 | ||
| Palliation of nodal and visceral disease | 705 | ||
| Side effects | 705 | ||
| Technique and administration | 705 | ||
| Total Skin Electron Beam Therapy | 707 | ||
| Clinical indications | 707 | ||
| Early stage (T1) | 707 | ||
| Advanced stage (T2-T3) | 708 | ||
| Erythrodermic (T4) disease | 708 | ||
| Special circumstances with total skin electron beam therapy | 708 | ||
| Retreatment | 708 | ||
| Adjuvant therapies | 708 | ||
| Total skin electron beam therapy before stem cell transplant | 709 | ||
| Technique and administration | 709 | ||
| Dose | 709 | ||
| Side effects | 711 | ||
| PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA | 711 | ||
| REFERENCES | 712 | ||
| The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma | 715 | ||
| Key points | 715 | ||
| INTRODUCTION | 715 | ||
| RETINOIDS AND MECHANISM OF ACTION | 716 | ||
| RETINOIDS IN CUTANEOUS T-CELL LYMPHOMA | 717 | ||
| ADVERSE EFFECTS | 724 | ||
| SUMMARY | 726 | ||
| REFERENCES | 727 | ||
| The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma | 731 | ||
| Key points | 731 | ||
| INTRODUCTION | 731 | ||
| INTERFERON ALFA | 732 | ||
| Mechanism of Action | 732 | ||
| Pharmacokinetics | 732 | ||
| Typical Dosing | 733 | ||
| Response to Therapy | 734 | ||
| Interferon alfa alone | 734 | ||
| Interferon alfa in combination with psoralen plus ultraviolet light phototherapy | 737 | ||
| Interferon alfa in combination with oral retinoids | 738 | ||
| Interferon alfa in combination with extracorporeal photopheresis | 738 | ||
| Interferon alfa in combination with total skin electron beam therapy | 738 | ||
| Interferon alfa in combination with chemotherapeutics | 738 | ||
| Interferon alfa as part of multimodality treatment | 739 | ||
| Adverse Effects | 739 | ||
| INTERFERON GAMMA | 740 | ||
| Mechanism of Action | 740 | ||
| Pharmacokinetics and Dosing | 740 | ||
| Response to Therapy | 740 | ||
| Interferon gamma alone | 740 | ||
| Interferon gamma as part of combination treatment | 740 | ||
| Adverse Effects | 741 | ||
| INTERFERON BETA | 741 | ||
| TREATMENT PEARLS FOR PRESCRIBING PHYSICIANS | 741 | ||
| SUMMARY | 741 | ||
| REFERENCES | 742 | ||
| Methotrexate and Pralatrexate | 747 | ||
| Key points | 747 | ||
| INTRODUCTION | 747 | ||
| EMERGING CONCEPTS RELEVANT TO THE OPTIMAL USE OF FOLATE ANTAGONISTS | 747 | ||
| The Role of Folate Antagonists in the Epigenetic Regulation of Gene Expression | 747 | ||
| The Importance of Combination Therapy for Cancer | 748 | ||
| TREATMENT | 748 | ||
| Indications | 748 | ||
| Mechanism of Action | 748 | ||
| Pharmacokinetics | 749 | ||
| Typical Dosing | 750 | ||
| Response to Therapy | 750 | ||
| Methotrexate | 750 | ||
| Pralatrexate | 752 | ||
| Trimetrexate | 753 | ||
| Adverse Effects | 753 | ||
| PEARLS TO HELP MANAGEMENT USING METHOTREXATE AND PRALATREXATE | 753 | ||
| SUMMARY | 753 | ||
| REFERENCES | 753 | ||
| Histone Deacetylase Inhibitors for Cutaneous T-Cell Lymphoma | 757 | ||
| Key points | 757 | ||
| INTRODUCTION | 757 | ||
| MECHANISM OF ACTION OF HISTONE DEACETYLASE INHIBITORS | 757 | ||
| VORINOSTAT (ZOLINZA; SUBEROYLANILIDE HYDROXAMIC ACID) | 758 | ||
| ROMIDEPSIN (ISTODAR, DEPSIPEPTIDE, FK228) | 760 | ||
| BELINOSTAT (BELEODAQ; PXD101 MECHANISM OF ACTION) | 761 | ||
| PANOBINOSTAT (LBH-589, FARYDAK) | 762 | ||
| SUMMARY | 762 | ||
| ACKNOWLEDGMENTS | 762 | ||
| REFERENCES | 763 | ||
| Extracorporeal Photopheresis in the Treatment of Mycosis Fungoides and Sézary Syndrome | 765 | ||
| Key points | 765 | ||
| INTRODUCTION | 765 | ||
| HISTORICAL ASPECTS | 765 | ||
| MECHANISM OF ACTION | 766 | ||
| PHARMACOKINETICS | 767 | ||
| TYPICAL REGIMEN | 767 | ||
| RESPONSE TO THERAPY | 768 | ||
| EARLY STAGE MYCOSIS FUNGOIDES | 768 | ||
| TUMOR STAGE MYCOSIS FUNGOIDES | 769 | ||
| ERYTHRODERMIC MYCOSIS FUNGOIDES AND SÉZARY SYNDROME | 769 | ||
| EXTRACORPOREAL PHOTOPHERESIS AND ADJUNCTIVE THERAPIES | 770 | ||
| PREDICTORS OF RESPONSE | 771 | ||
| SURVIVAL | 771 | ||
| ADVERSE EFFECTS | 771 | ||
| PEARLS TO HELP THE MANAGEMENT OF PATIENTS WITH MYCOSIS FUNGOIDES/SÉZARY SYNDROME BEING TREATED WITH EXTRACORPOREAL PHOTOPHE ... | 772 | ||
| SUMMARY | 773 | ||
| REFERENCES | 773 | ||
| Monoclonal Antibodies | 777 | ||
| Key points | 777 | ||
| INTRODUCTION | 777 | ||
| ANTIBODIES CURRENTLY IN CLINICAL PRACTICE | 778 | ||
| Anti-CD52 | 778 | ||
| Anti-CD30 | 779 | ||
| Anti-CD25 | 780 | ||
| MONOCLONAL ANTIBODIES IN CLINICAL TRIALS | 781 | ||
| Anti-CD4 (Zanolimumab) | 781 | ||
| Anti–CC Chemokine Receptor 4 (Mogamulizumab) | 781 | ||
| Anti–Killer Cell Immunoglobulin-Like Receptor 3DL2 (IPH4102) | 782 | ||
| MONOCLONAL ANTIBODIES WITH POTENTIAL UTILITY IN CUTANEOUS LYMPHOMAS | 782 | ||
| LMB-2 | 782 | ||
| Checkpoint Blockade Inhibitors | 782 | ||
| Anti–cytotoxic T-lymphocyte antigen 4 (ipilimumab) | 782 | ||
| Programmed death-1 (nivolumab, pembrolizumab) | 783 | ||
| SUMMARY | 783 | ||
| REFERENCES | 783 | ||
| Other Chemotherapeutic Agents in Cutaneous T-Cell Lymphoma | 787 | ||
| Key points | 787 | ||
| INTRODUCTION | 787 | ||
| ANTIMETABOLITES | 787 | ||
| Purine Analogs/Antagonists | 787 | ||
| 6-Mercaptopurine | 791 | ||
| Fludarabine | 791 | ||
| Cladribine | 791 | ||
| Pentostatin | 791 | ||
| Pyrimidine Analogs/Antagonists | 792 | ||
| 5-Fluorouracil | 792 | ||
| Cytosine arabinoside | 792 | ||
| Gemcitabine | 792 | ||
| Antifolates | 793 | ||
| ALKYLATING AGENTS | 793 | ||
| Nitrogen Mustards | 793 | ||
| Mechlorethamine | 793 | ||
| Chlorambucil | 793 | ||
| Ifosfamide | 794 | ||
| Bendamustine | 794 | ||
| Cyclophosphamide | 794 | ||
| Melphalan | 794 | ||
| Lomustine | 794 | ||
| Nimustine | 795 | ||
| Nitrosoureas | 795 | ||
| Carmustine | 795 | ||
| Alkyl Sulfonates | 795 | ||
| Busulfan | 795 | ||
| Triazines | 795 | ||
| Dacarbazine | 795 | ||
| Temozolomide | 795 | ||
| Procarbazine | 795 | ||
| Ethylenimines | 795 | ||
| Thiotepa | 795 | ||
| Metal Salts | 795 | ||
| Carboplatin | 795 | ||
| Cisplatin | 795 | ||
| TOPOISOMERASE INHIBITORS | 795 | ||
| Anthracyclines | 795 | ||
| Doxorubicin and pegylated liposomal doxorubicin | 796 | ||
| Daunorubicin and liposomal daunorubicin | 796 | ||
| Epirubicin (Ellence) | 796 | ||
| Idrarubicin | 797 | ||
| Etoposide | 797 | ||
| INTERLEUKINS | 797 | ||
| Interleukin-2 | 797 | ||
| Interleukin-12 | 798 | ||
| PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS: FORODESINE | 798 | ||
| PROTEASOME INHIBITORS: BORTEZOMIB | 799 | ||
| MULTIAGENT CHEMOTHERAPY | 799 | ||
| SUMMARY | 799 | ||
| REFERENCES | 799 | ||
| Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome | 807 | ||
| Key points | 807 | ||
| INTRODUCTION | 807 | ||
| OVERVIEW OF HEMATOPOIETIC STEM CELL TRANSPLANT | 808 | ||
| STEM CELL SOURCES | 808 | ||
| DONOR SELECTION | 808 | ||
| CONDITIONING REGIMENS | 809 | ||
| COMPLICATIONS | 809 | ||
| GRAFT-VERSUS-LYMPHOMA EFFECT | 810 | ||
| AUTOLOGOUS STEM CELL TRANSPLANT FOR MYCOSIS FUNGOIDES AND SÉZARY SYNDROME | 810 | ||
| ALLOGENEIC STEM CELL TRANSPLANT FOR MYCOSIS FUNGOIDES AND SÉZARY SYNDROME | 811 | ||
| SUMMARY AND FUTURE DIRECTIONS | 815 | ||
| REFERENCES | 816 | ||
| Practical Management of CD30+ Lymphoproliferative Disorders | 819 | ||
| Key points | 819 | ||
| INTRODUCTION | 819 | ||
| LYMPHOMATOID PAPULOSIS | 820 | ||
| Treatment of Lymphomatoid Papulosis | 820 | ||
| Topical corticosteroids | 821 | ||
| Phototherapy | 821 | ||
| Methotrexate | 822 | ||
| Bexarotene | 822 | ||
| Interferon | 823 | ||
| Imiquimod | 823 | ||
| Topical nitrogen mustard | 823 | ||
| PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA | 823 | ||
| Treatment of Cutaneous Anaplastic Large Cell Lymphoma | 824 | ||
| Excision | 825 | ||
| Radiotherapy | 825 | ||
| Brentuximab vedotin | 825 | ||
| Methotrexate | 825 | ||
| Oral retinoids | 825 | ||
| Gemcitabine | 826 | ||
| Etoposide | 826 | ||
| Interferon | 826 | ||
| Imiquimod | 826 | ||
| Phototherapy | 826 | ||
| Combination therapies | 826 | ||
| MYCOSIS FUNGOIDES WITH LARGE CELL TRANSFORMATION | 826 | ||
| Treatment of Mycosis Fungoides with Large Cell Transformation | 827 | ||
| Pralatrexate | 827 | ||
| Gemcitabine | 828 | ||
| Pegylated liposomal doxorubicin | 828 | ||
| Brentuximab vedotin | 828 | ||
| Romidepsin | 828 | ||
| Bexarotene | 828 | ||
| Alemtuzumab | 828 | ||
| Allogeneic stem cell transplant | 829 | ||
| Combination therapies | 829 | ||
| SUMMARY/PEARLS | 829 | ||
| REFERENCES | 830 | ||
| Diagnosis and Management of Cutaneous B-cell Lymphoma | 835 | ||
| Key points | 835 | ||
| INTRODUCTION | 835 | ||
| DIAGNOSIS AND STAGING | 836 | ||
| PRIMARY CUTANEOUS FOLLICLE CENTER LYMPHOMA | 836 | ||
| EXTRANODAL MARGINAL ZONE LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID TISSUE | 836 | ||
| PRIMARY CUTANEOUS DIFFUSE LARGE B-CELL LYMPHOMA, LEG TYPE | 837 | ||
| OTHER B-CELL LYMPHOMAS THAT PRESENT IN SKIN | 837 | ||
| TREATMENT OF THE INDOLENT CUTANEOUS B-CELL LYMPHOMAS: PRIMARY CUTANEOUS FOLLICLE CENTER LYMPHOMA AND MUCOSA-ASSOCIATED LYMP ... | 837 | ||
| TREATMENT OF PRIMARY CUTANEOUS DIFFUSE LARGE B-CELL LYMPHOMA, LEG TYPE | 838 | ||
| SUMMARY | 838 | ||
| REFERENCES | 838 | ||
| Index | 841 |