Cancer Consult: Expertise for Clinical Practice

I wholeheartedly extend my gratitude towards our cancer experts who contributed to this fabulous project. They have elegantly combined their invaluable experience with clinical data and attempted to solve some of the most challenging and controversial issues in malignant hematology, hematopoietic stem cell transplantation, and oncology. I must add that this project would not have been a visible reality without constant support and love from the Supreme Lord and my family—which includes (and always will) my patients. I trust that readers will enjoy our work and would provide con-structive feedback which should allow us to improve on subsequent editions.

Thank you kindly,Syed Ali Abutalib“I grow by that Hand which nurtures me”

I would like to thank my fabulous co-editor, Syed Abutalib, whose tireless efforts have made this book possible; the terrific contributors whose impressive chapters have created a publication of immense clinical value; the fantastic staff at Wiley Blackwell who have created this magnificent text; my wife (Tomes) and our wonderful children who have made it all worthwhile; and the patients I have had the genuine privilege and honor to meet and serve in my years of clinical practice.

Sincere regards,Maurie Markman

Cancer Consult: Expertise for Clinical Practice

Edited by

Syed A. Abutalib, MDAssistant DirectorHematology and Hematopoietic Cell TransplantationMidwestern Regional Medical Center;Cancer Treatment Centers of AmericaZion, IL, USA

Maurie Markman, MDSenior Vice President of Clinical AffairsNational Director of Medical OncologyCancer Treatment Centers of America;Clinical Professor of MedicineDrexel University College of MedicinePhiladelphia, PA, USA

Copyright © 2014 by John Wiley and Sons, Inc. All rights reserved

Published by John Wiley and Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Cancer Consult: Expertise for Clinical Practice / edited by Syed A. Abutalib, Maurie Markman. p. ; cm. Includes bibliographical references and index. ISBN 978-1-118-58921-2 (pbk. : alk. paper) I. Abutalib, Syed A., editor. II. Markman, Maurie, editor. [DNLM: 1. Neoplasms–Examination Questions. 2. Hematopoietic Stem Cell Transplantation–Examination Questions. 3. Leukemia–Examination Questions. 4. Medical Oncology–Examination Questions. QZ 18.2] RC266.5 616.99′40076–dc23

2014008386

Cover image: Two center images courtesy of Shaunagh McDermott and Michael A. Blake (Chapter 131), all other images courtesy of Carmen Barcena and Laurence de Leval (Chapter 38).

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

v

List of Contributors, x

Preface, xxi

Section 1 | Malignant Hematology and Hematopoietic Cell Transplantation

Part 1 | Acute Lymphoblastic Leukemia in Adults

1 Diagnosis of acute lymphoblastic leukemia, 5Frederick G. Behm, Agatha Bogard, Syed A. Abutalib, and Sujata S. Gaitonde

2 Prognostic markers and models in acute lymphoblastic leukemia, 18Dieter Hoelzer

3 Management of B-cell acute lymphoblastic leukemia, 22Hady Ghanem, Hagop Kantarjian, Nitin Jain, and Elias Jabbour

4 Management of T-cell acute lymphoblastic leukemia, 29Daniel J. DeAngelo

5 Minimal residual disease in acute lymphoblastic leukemia, 35Meir Wetzler

6 Hematopoietic cell transplantation in adult acute lymphoblastic leukemia, 40Netanel A. Horowitz and Jacob M. Rowe

Part 2 | Acute Myeloid Leukemia in Adults

7 Prognosis in acute myeloid leukemia: cytogenetics and beyond, 51Gordana Raca, Madina Sukhanova, and Lucy A. Godley

8 Induction therapy in acute myeloid leukemia, 58Tapan Kadia and Farhad Ravandi

9 Consolidation therapy in acute myeloid leukemia, 67Gregory K. Behbehani and Bruno C. Medeiros

10 Management of acute promyelocytic leukemia, 71Eytan M. Stein and Martin S. Tallman

11 Minimal residual disease in acute myeloid leukemia, 76Hans Beier Ommen, Line Nederby, Marie Toft-Petersen, Charlotte Guldborg Nyvold, and Peter Hokland

12 Relapsed and refractory acute myeloid leukemia, 82Stefan H. Faderl

13 Hematopoietic cell transplantation in acute myeloid leukemia, 89Antonio M. Jimenez and Stefan O. Ciurea

Part 3 | Myelodysplastic Syndromes and Related Disorders

14 Pitfalls in the diagnosis of myelodysplastic syndromes, 99Jay Yang, Gail Bentley, and Charles A. Schiffer

15 Cytogenetics and prognostic models in myelodysplastic syndromes, 106Uma Borate and Harry P. Erba

16 Management of myelodysplastic syndromes, 113Vu H. Duong, Alan F. List, and Rami S. Komrokji

17 Management of therapy-related myeloid neoplasms, 120Jagoda K. Jasielec and Richard A. Larson

18 Hematopoietic cell transplantation in myelodysplastic syndromes, 126Antonio Di Stasi, Armin Ghobadi, and Partow Kebriaei

19 Acquired aplastic anemia, 131Valeria Visconte and Ramon V. Tiu

Part 4 | Myeloproliferative Neoplasms

20 Diagnostic approach in myeloproliferative neoplasms, 137Ayalew Tefferi

21 Chronic myeloid leukemia: chronic phase, 142Jerald P. Radich

Contents

vi    |    Contents

22 Blast crisis of chronic myeloid leukemia, 147Michael J. Mauro

23 Chronic myeloid leukemia and pregnancy, 150Michael J. Mauro

24 Polycythemia vera, 152Constantine S. Tam and Srdan Verstovsek

25 Essential thrombocytosis, 156Paola Guglielmelli and Alessandro M. Vannucchi

26 Primary myelofibrosis, 162Ayalew Tefferi

27 Eosinophilic myeloproliferative disorders, 167Jason Gotlib

28 Chronic myelomonocytic leukemia, 176Mrinal M. Patnaik

29 Hematopoietic cell transplantation in chronic myeloid leukemia, 180Jerald P. Radich

30 Hematopoietic cell transplantation in primary myelofibrosis, 187Irum Khan and Damiano Rondelli

Part 5 | Chronic Lymphocytic and Other Leukemias

31 Prognostic markers and management of chronic lymphocytic leukemia, 195Courtney D. DiNardo and Susan O’Brien

32 Hematopoietic cell transplantation in chronic lymphocytic leukemia, 201Michael R. Bishop

33 Prolymphocytic leukemia, 207Claire Dearden

34 Hairy cell leukemia, 220Justin M. Watts and Martin S. Tallman

Part 6 | Hodgkin Lymphoma

35 Management of classical Hodgkin lymphoma, 229Kristen Sanfilippo and Nancy L. Bartlett

36 Nodular lymphocyte-predominant Hodgkin lymphoma, 235Dennis A. Eichenauer

37 Hematopoietic cell transplantation in Hodgkin lymphoma, 240Tsiporah Shore and Koen van Besien

Part 7 | Non-Hodgkin’s Lymphomas

38 Pitfalls in the diagnosis of non-Hodgkin’s lymphomas, 247Carmen Barcena and Laurence de Leval

39 Follicular lymphoma, 257Myron S. Czuczman

40 Diffuse large B-cell lymphoma, 263Andrew D. Zelenetz

41 Mantle cell lymphoma, 270Stephen Smith and John Sweetenham

42 Marginal zone lymphoma, 275Sarah Rutherford, Wayne Tam, and Peter Martin

43 Primary mediastinal large B-cell lymphoma, 282Pier Luigi Zinzani

44 Burkitt lymphoma, 286Mark Roschewski and Wyndham Wilson

45 Gray zone lymphoma, 290Caron A. Jacobson and Ann S. LaCasce

46 Transformed lymphoma, 295Stephane Doucet and Jane N. Winter

47 HIV-associated lymphoma, 304Kieron Dunleavy

48 Primary CNS lymphoma, 308Nicholas A. Blondin, Joachim M. Baehring, and Fred H. Hochberg

49 Primary cutaneous lymphoma, 316Thomas M. Habermann

50 Mycosis fungoides and Sézary syndrome, 323Stephane Dalle, Marie Perier-Muzet, Brigitte Balme, and Luc Thomas

51 Hematopoietic cell transplantation in indolent non-Hodgkin’s lymphoma, 327Saurabh Chhabra and Ginna G. Laport

52 Hematopoietic cell transplantation in diffuse large B-cell lymphoma, 332Syed A. Abutalib and Istvan Redei

53 Hematopoietic cell transplantation in T-cell non-Hodgkin’s lymphomas, 339Lori S. Muffly and Sonali M. Smith

Part 8 | Plasma Cell Neoplasms and Related Disorders

54 Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, 347Robert A. Kyle

Contents    |    vii

55 Risk stratification and response assessment in multiple myeloma and Waldenström’s macroglobulinemia, 352Silvia Gentili and Sagar Lonial

56 Treatment of multiple myeloma, 358Cindy Varga, Claudia Paba Prada, Kenneth Anderson, and Paul Richardson

57 Light-chain amyloidosis, 366David C. Seldin

58 Waldenström’s macroglobulinemia, 371Anita D’Souza and Morie A. Gertz

59 Autologous hematopoietic cell transplantation in multiple myeloma, 376Jean-Luc Harousseau and Mohamad Mohty

60 Allogeneic hematopoietic cell transplantation in multiple myeloma, 381Jasleen Randhawa, Veerpal Singh, and Parameswaran Hari

Part 9 | Special Issues in Hematology

61 Role of PET scan in lymphomas, 391Matthew A. Lunning and James O. Armitage

62 Radioimmunotherapy in lymphomas, 398Reem Karmali and Stephanie A. Gregory

63 Radiation oncology consultation for hematologic malignancies, 403Chris R. Kelsey and Leonard R. Prosnitz

Part 10 | Special Issues in Hematopoietic Cell Transplantation

64 Donor and graft selection in allogeneic hematopoietic cell transplantation, 411Jose Leonel Ochoa-Bayona and Claudio Anasetti

65 Preparative regimens in allogeneic hematopoietic cell transplantation for malignant hematological diseases, 417Robert J. Soiffer

66 T-cell depletion in allogeneic hematopoietic cell transplantation, 421Jenna D. Goldberg and Miguel-Angel Perales

67 Prevention and treatment of relapse following hematopoietic cell transplantation, 426Robert Chen, Sandra Thomas, and Stephen J. Forman

68 Acute graft-versus-host disease, 432Andrew C. Harris and John E. Levine

69 Chronic graft-versus-host disease, 438Carrie L. Kitko and Daniel R. Couriel

Section 2 | Oncology

Part 1 | Central Nervous System Tumors

70 Primary brain tumors, 449Barbara J. O’Brien and Mark R. Gilbert

71 Secondary brain and spinal cord tumors, 457Rimas V. Lukas, Patrik Gabikian, and Steven J. Chmura

Part 2 | Head and Neck Cancers and Thoracic Malignancies

72 Medical management of head and neck cancers, 467Tobenna Nwizu and David Adelstein

73 Endocrine malignancies, 476Ann W. Gramza

74 Methodological and practical challenges for personalized therapies in non-small-cell lung cancer, 480Ignacio I. Wistuba

75 Screening, staging, and stage I non-small-cell lung cancer, 486Tarek M. Mekhail

76 Stage II and III non-small-cell lung cancer, 493Grzegorz Korpanty and Natasha B. Leighl

77 Recurrent and metastatic non-small-cell lung cancer and novel targets, 500Evan Pisick and Ravi Salgia

78 Small-cell lung cancer, 503Stephen V. Liu and Glen J. Weiss

79 Mesothelioma, 506Christopher W. Towe and Harvey I. Pass

Part 3 | Breast Cancer

80 Immunohistochemistry testing and beyond in breast cancer, 515Alejandro A. Gru and D. Craig Allred

81 Prevention and adjuvant therapy in breast cancer, 523Faithlore P. Gardner and Edith A. Perez

82 Preoperative systemic therapy for breast cancer, 532Virginia Kaklamani and William J. Gradishar

83 Recurrent and metastatic breast cancer, 540Dennis L. Citrin

84 Special issues in the young and pregnant patient with breast cancer, 546Hatem A. Azim Jr. and Fedro A. Peccatori

viii    |    Contents

Part 4 | Gastrointestinal Oncology

85 Early-stage esophageal and stomach cancers, 555M. Naomi Horiba and Yixing Jiang

86 Metastatic esophagogastric cancer: controversies, consensus, and new targets, 562Geoffrey Y. Ku and David H. Ilson

87 Early-stage colorectal cancer, 567Vaibhav Sahai and Al B. Benson III

88 Recurrent and metastatic colorectal cancer: controversies, consensus, and new targets, 573Davendra Sohal and Robert J. Pelley

89 Pancreatic cancer, 581Katherine Van Loon and Margaret Tempero

90 Hepatobiliary cancer, 590Keith Stuart

91 Neuroendocrine tumors, 595Anya Litvak and Leonard Saltz

92 Transarterial liver-directed therapies in oncology, 601Divyesh G. Mehta and Jeffery Choh

93 Anal cancer, 606Rob Glynne Jones

Part 5 | Genitourinary Oncology

94 Renal cancer: tumor diversity, molecular taxonomy, and prognostic algorithms, 615Henry J. Conter and Eric Jonasch

95 Medical management of renal cancer, 621Gary R. MacVicar and Timothy M. Kuzel

96 Medical management of bladder cancer, 628Gary R. MacVicar and Timothy M. Kuzel

97 Prostate cancer: Screening, surveillance, prognostic algorithms and independent pathologic predictive parameters, 634Megan G. Lockyer and Thomas M. Wheeler

98 Medical management of prostate cancer, 638Elizabeth K. O’Donnell and Philip Kantoff

99 Germ cell tumors, 645Timothy Gilligan

Part 6 | Skin Malignancies

100 Medical management of melanoma, 653Ana M. Ciurea and Kim Margolin

101 Nonmelanoma skin cancers, 661Daniel Christiansen and Anna Sancho Clayton

PART 7 | Gynecological Malignancies

102 Ovarian cancer: neoadjuvant, adjuvant, and surgical issues, 669Alpa M. Nick and Robert L. Coleman

103 Ovarian cancer: second-line treatment strategies, 675Maurie Markman

104 Endometrial and cervical cancers, 681Maurie Markman

PART 8 | Sarcomas

105 Bone sarcomas, 689Nicole Larrier, William C. Eward, and Richard F. Riedel

106 Soft tissue sarcomas, 696Neeta Somaiah and Shreyaskumar Patel

PART 9 | Multidisciplinary Approach: Consultation with Surgical Oncology Team

107 Surgical aspects of head and neck cancers, 707Constance E.H. Teo and Randal S. Weber

108 Surgical aspects of thoracic malignancies, 711Albert S.Y. Chang, Thomas A. D’Amico, and David C. White

109 Surgical aspects of upper gastrointestinal cancers, 719Sabha Ganai and Mitchell C. Posner

110 Surgical aspects of pancreatic cancer, 723Amanda B. Cooper, Ching-Wei D. Tzeng, and Matthew H.G. Katz

111 Surgical aspects of hepatobiliary tumors, 729Subhasis Misra and Leonidas Koniaris

112 Surgical aspects of lower gastrointestinal cancers, 735Anthony J. Senagore

113 Surgical aspects of renal cancer, 739Michael E. Woods and Matthew C. Raynor

114 Surgical aspects of bladder cancer, 744Michael B. Williams

115 Surgical aspects of prostate cancer, 747Peter Pinto

116 Surgical aspects of melanoma, 754Thomas Velancia

Contents    |    ix

PART 10 | Multidisciplinary Approach: Consultation with Radiation Oncology Team

117 Radiotherapy for head and neck cancers, 761Shiyu Song

118 Radiotherapy for ductal carcinoma in situ (DCIS), 767Beryl McCormick

119 Radiotherapy for early-stage invasive breast cancer, 771Julia White

120 Radiotherapy for thoracic malignancies, 778Meredith E. Giuliani and Andrea Bezjak

121 Radiotherapy for gastrointestinal malignancies, 785Manisha Palta, Christopher Willett, and Brian Czito

122 Radiotherapy for genitourinary malignancies, 789Christina H. Chapman and Curtiland Deville

PART 11 | Hereditary Cancer Syndromes and Genetic Testing in Oncology

123 When to suspect hereditary cancer syndromes, 795Emily Dalton and Kathy Schneider

124 Hereditary breast cancer syndromes, 800Kathy Schneider and Emily Dalton

125 Genetic testing in gastrointestinal tumors, 804Kristen M. Shannon and Daniel C. Chung

126 Hereditary urogenital cancer syndromes, 810Melanie Corbman and Eric Fowler

PART 12 | Special Issues in Hematology and Oncology

127 Carcinoma of unknown primary (CUP), 817Isabella C. Glitza and Gauri R. Varadhachary

128 Geriatric oncology, 822Nayana Kamath and Supriya Gupta Mohile

129 Nuts and bolts of cancer immunotherapy, 826Christopher R. Heery and James L. Gulley

130 Controversies related to oncology clinical trial development, 831Elihu H. Estey

131 PET scan in oncology, 835Shaunagh McDermott and Michael A. Blake

132 Hematopoietic growth factors, 841LeAnn B. Norris, Jametta Magwood, and Charles L. Bennett

133 Anticoagulation issues in oncology, 844Steven M. Corsello and Jean Marie Connors

134 Symptom management and palliative care, 851Rony Dev and Eduardo D. Bruera

135 Metabolic and nutritional issues in oncology, 860Julia Fechtner, Carolyn Lammersfeld, Carol Ireton-Jones, and Pankaj Vashi

136 Bone-related issues in oncology, 867S. Mujtaba Rizvi, Helen Collins, and Alan Lipton

137 Integrative medicine in oncology, 872Weidong Lu and David S. Rosenthal

138 Naturopathic medicine in oncology, 879Christina M. Shannon, Tracey Thomas, and Shauna Birdsall

139 Anesthesiology consultation for localized cancer pain, 884Abed Rahman, Magdalena Anitescu, and Raed Rahman

140 Musculoskeletal care in oncology, 893James E. Rosenberg and Charles A. McDonald

141 Cancer survivorship and psychosocial issues in oncology, 896Jabeen Abutalib, Shahid Raza, and Laura Sunn

Index, 902Color plate section facing p.522

x

Jabeen Abutalib, MDMidwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Syed A. Abutalib, MDHematology and Hematopoietic Cell Transplantation, Midwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

David Adelstein, MD, FACPDepartment of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

D. Craig Allred, MDDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

Claudio Anasetti, MDBlood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA

Kenneth Anderson, MDJerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics;Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA, USA

Magdalena Anitescu, MD, PhDDepartment of Anesthesia & Critical Care, University of Chicago Medical Center, Chicago, IL, USA

James O. Armitage, MDUniversity of Nebraska Medical Center, Omaha, NE, USA

Hatem A. Azim Jr., MD, PhDBreast Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

Joachim M. Baehring, MD, DScDepartments of Neurology, Neurosurgery and Medicine, Yale University School of Medicine, New Haven, CT, USA

Brigitte Balme, MDPathology Unit, Lyon Sud Hospital, Claude Bernard Lyon 1 University, Pierre-Bénite, France

Carmen Barcena, MDInstitute of Pathology, University Hospital of Lausanne, Lausanne, Switzerland

Nancy L. Bartlett, MDDivision of Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

Gregory K. Behbehani, MD, PhDHematology and Oncology, Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, CA, USA

Frederick G. Behm, MDDepartment of Pathology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Charles L. Bennett, MD, PhD, MPPSouthern Network on Adverse Reactions (SONAR) of the South Carolina College of Pharmacy;Arnold School of Public Health of the University of South Carolina;William Jennings Bryan Dorn Veterans Administration Medical Center, Columbia, SC;Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

Al B. Benson III, MD, FACPDivision of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Gail Bentley, MDDepartment of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA

List of Contributors

List of Contributors | xi

Jeffery Choh, MDInterventional Radiology Department, Midwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Daniel Christiansen, MDDermatology Division, Vanderbilt Clinic, Vanderbilt University, Nashville, TN, USA

Daniel C. Chung, MDGastrointestinal Unit and GI Cancer Genetics Program, Cancer Center, Massachusetts General Hospital;Department of Medicine, Harvard Medical School, Boston, MA, USA

Dennis L. Citrin, MB, ChB, PhDMidwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Stefan O. Ciurea, MDStem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Ana M. Ciurea, MDDepartment of Dermatology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Anna Sancho Clayton, MDVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

Robert L. Coleman, MDClinical Research, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Helen Collins, MDAmgen Inc., Thousand Oaks, CA, USA

Jean Marie Connors, MDDepartment of Medicine, Hematology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Henry J. Conter, MDAssistant Professor, Dentistry, University of Western Ontario, London, ON, Canada

Amanda B. Cooper, MDDepartment of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Melanie Corbman, MS, LCGCGenetics/Oncology Clinic, Eastern Regional Medical Center, Cancer Treatment Centers of America, Philadelphia, PA, USA

Andrea Bezjak, MDCM, MSc, FRCPCDepartment of Radiation Oncology, University of Toronto, Princess Margaret Cancer Center, Toronto, ON, Canada

Shauna Birdsall, ND, FABNOWestern Regional Medical Center, Cancer Treatment Centers of America, Tulsa, OK, USA

Michael R. Bishop, MDHematopoietic Stem Cell Transplantation Program, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA

Michael A. Blake, MDDepartment of Abdominal Imaging, Massachusetts General Hospital, Boston, MA, USA

Nicholas A. Blondin, MDDepartment of Neurology, Yale University School of Medicine, New Haven, CT, USA

Agatha Bogard, MDDepartment of Pathology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Uma Borate, MD, MSDivision of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

Eduardo D. Bruera, MD, FAAHPMDepartment of Palliative Care and Rehabilitation Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Albert S.Y. Chang, MDSection of General Thoracic Surgery, Department of Surgery, Duke University Medical Center, Duke Raleigh Hospital, Raleigh, NC, USA

Christina H. Chapman, MDDepartment of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA

Robert Chen, MDDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Saurabh Chhabra, MDDivision of Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA

Steven J. Chmura, MD, PhDDepartment of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA

xii | List of Contributors

Antonio Di Stasi, MDDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Stephane Doucet, MDDepartment of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM Hospital), Montreal, QC, Canada

Anita D’Souza, MDDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

Kieron Dunleavy, MDNational Cancer Institute, Bethesda, MD, USA

Vu H. Duong, MDUniversity of Maryland Greenebaum Cancer Center, Baltimore, MD, USA

Dennis A. Eichenauer, MDFirst Department of Internal Medicine, University Hospital Cologne;German Hodgkin Study Group (GHSG), Cologne, Germany

Harry P. Erba, MD, PhDInternal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

Elihu H. Estey, MDUniversity of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA

William C. Eward, DVM, MDDepartment of Orthopedic Surgery, Section of Orthopedic Oncology, Duke Sarcoma Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

Stefan H. Faderl, MDDivision of Leukemia, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA

Julia Fechtner, RD, CSO, CNSCMidwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Stephen J. Forman, MDDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Eric Fowler, MS, LCGCGenetic Counseling, Outpatient Clinics, Midwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Steven M. Corsello, MDDepartment of Medical Oncology, Dana-Farber Cancer Institute;Harvard Medical School, Boston, MA, USA

Daniel R. Couriel, MDUniversity of Michigan Blood and Marrow Transplant Program, Ann Arbor, MI, USA

Brian Czito, MDDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

Myron S. Czuczman, MDRoswell Park Cancer Institute, Buffalo, NY, USA

Stephane Dalle, MD, PhDDermatology Unit, Lyon Sud Hospital, Claude Bernard Lyon 1 University, Pierre-Bénite, France

Emily Dalton, MS, CGCAmbry Genetics, Aliso Viego, CA, USA

Thomas A. D’Amico, MDSection of General Thoracic Surgery, Duke University Medical Center, Durham, NC, USA

Daniel J. DeAngelo, MD, PhDDepartment of Medical Oncology, Dana-Farber Cancer Institute;Department of Medicine, Harvard Medical School, Boston, MA, USA

Claire Dearden, MDDepartment of Haemato-Oncology, Royal Marsden NHS Foundation Trust, Sutton;Institute of Cancer Research, London, UK

Laurence de Leval, MD, PhDInstitute of Pathology, University Hospital of Lausanne, Lausanne, Switzerland

Rony Dev, MDDepartment of Symptom Control & Palliative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Curtiland Deville, MDDepartment of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Courtney D. DiNardo, MD, MSCEDepartment of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

List of Contributors | xiii

Lucy A. Godley, MD, PhDSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA

Jenna D. Goldberg, MDAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center;Weill Cornell Medical College, New York, NY, USA

Jason Gotlib, MD, MSStanford University School of Medicine / Stanford Cancer Institute, Stanford, CA, USA

William J. Gradishar, MDRobert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Ann W. Gramza, MDNIH/NCI Endocrine Oncology Branch, Bethesda, MD, USA

Stephanie A. Gregory, MD, FACPRush University Medical Center/Rush University, Chicago, IL, USA

Alejandro A. Gru, MDDepartment of Pathology, Ohio State University Wexner Medical Center, Columbus, OH, USA

Paola Guglielmelli, MDHematology Department, University of Florence, Florence, Italy

Charlotte Guldborg Nyvold, MS, PhDDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark

James L. Gulley, MD, PhD, FACPMedical Oncology Service, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Thomas M. Habermann, MDDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

Parameswaran Hari, MDMedical College of Wisconsin, Milwaukee, WI, USA

Jean-Luc Harousseau, MDUniversity of Nantes;Cancer Center René Gauducheau;Clinical Research Program, French National Cancer Institute, Nantes, France

Andrew C. Harris, MDBlood and Marrow Transplant Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

Patrik Gabikian, MDDepartment of Neurosurgery, Kaiser Foundation Hospital, Los Angeles, CA, USA

Sujata S. Gaitonde, MDDepartment of Pathology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Sabha Ganai, MD, PhDDepartment of Surgery, The University of Chicago Medicine, Chicago, IL, USA

Faithlore P. Gardner, MDDivision of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA

Silvia Gentili, MDClinica di Ematologia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy

Morie A. Gertz, MDDepartment of Medicine, Mayo Clinic, Rochester, MN, USA

Hady Ghanem, MDDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Armin Ghobadi, MDDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Mark R. Gilbert, MDDepartment of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Timothy Gilligan, MD, MSDepartments of Solid Tumor Oncology, Urology, and Inpatient Solid Tumor Oncology, Center for Ethics, Humanities and Spiritual Care, Taussig Cancer Institute, and Center for Excellence in Healthcare Communication, Cleveland Clinic, Cleveland, OH, USA

Meredith E. Giuliani, MD, MEd, FRCPCDepartment of Radiation Oncology, University of Toronto;Princess Margaret Cancer Center, Toronto, ON, Canada

Isabella C. Glitza, MDFellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Rob Glynne Jones, MBBSGastrointestinal & Colorectal Cancer, Mount Vernon Cancer Centre, Northwood, UK

xiv | List of Contributors

Eric Jonasch, MDDepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Tapan Kadia, MDDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Virginia Kaklamani, MDRobert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Nayana Kamath, MDUniversity of Rochester James P. Wilmot Cancer Center, Rochester, NY, USA

Hagop Kantarjian MDDepartment of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Philip Kantoff, MDDepartment of Medical Oncology, Solid Tumor Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute;Department of Medicine, Harvard Medical School, Boston, MA, USA

Reem Karmali, MDRush University Medical Center/Rush University, Chicago, IL, USA

Matthew H.G. Katz, MDDepartment of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Partow Kebriaei, MDDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Chris R. Kelsey, MDDepartment of Radiation Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

Irum Khan, MDUniversity of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Carrie L. Kitko, MDUniversity of Michigan Blood and Marrow Transplant Program, Ann Arbor, MI, USA

Rami S. Komrokji, MDH. Lee Moffitt Cancer Center, Tampa, FL, USA

Christopher R. Heery, MDLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Fred H. Hochberg, MDDepartment of Neurology, Harvard Medical School;Neurology, Massachusetts General Hospital, Boston, MA, USA

Dieter Hoelzer, MD, PhDDepartment of Medicine II, University Hospital, Frankfurt am Main, Germany

Peter Hokland, MD, DMScDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark

M. Naomi Horiba, MDMarlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

Netanel A. Horowitz, MDDepartment of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel

David H. Ilson, MD, PhDGastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Carol Ireton-Jones, PhD, RD, LD, CNSC, FASPEN, FANDDepartment of Nutrition, Cancer Treatment Centers of America, Dallas, TX, USA

Elias Jabbour, MDDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Caron A. Jacobson, MDDana-Farber Cancer Institute, Boston, MA, USA

Nitin Jain, MDDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Jagoda K. Jasielec, MDDepartment of Medicine, The University of Chicago, Chicago, IL, USA

Yixing Jiang, MD, PhDMarlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

Antonio M. Jimenez, MDStem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

List of Contributors | xv

Anya Litvak, MDDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Stephen V. Liu, MDNorris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, CA, USA

Megan G. Lockyer, MDDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

Sagar Lonial, MDDepartment of Hematology & Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA

Weidong Lu, MDDepartment of Medicine, Harvard Medical School; Osher Research Center, Harvard Medical School-Osher Institute; Chinese Herbal Medicine, New England School of Acupuncture;Zakim Center for Integrative Therapies, Dana-Farber Cancer Institute, Boston, MA, USA

Rimas V. Lukas, MDDepartment of Neurology, The University of Chicago, Chicago, IL, USA

Matthew A. Lunning, DOHematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, USA

Gary R. MacVicar, MDDivision of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Jametta Magwood, MPHSouthern Network on Adverse Reactions (SONAR) of the South Carolina College of Pharmacy;Arnold School of Public Health of the University of South Carolina;William Jennings Bryan Dorn Veterans Administration Medical Center, Columbia, SC;Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

Kim Margolin, MDUniversity of Washington, Seattle, WA, USA

Maurie Markman, MDCancer Treatment Centers of America;Drexel University College of Medicine, Philadelphia, PA, USA

Peter Martin, MDDivision of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA

Leonidas Koniaris, MDDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

Grzegorz Korpanty, MD, PhD, MRCPIDivision of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

Geoffrey Y. KuGastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Timothy M. Kuzel, MDDivision of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Robert A. Kyle, MDDepartment of Laboratory Medicine and Pathology, Mayo Medical School, Rochester, MN, USA

Ann S. LaCasce, MDDana-Farber/Partners CancerCare Hematology-Medical Oncology; Harvard Medical School, Boston, MA, USA

Carolyn Lammersfeld, MS, RD, CSO, CNSCIntegrative Medicine, Cancer Treatment Centers of America, Zion, IL, USA

Ginna G. Laport, MDDivision of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA, USA

Nicole Larrier, MS, MDDepartment of Radiation Oncology, Duke Sarcoma Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

Richard A. Larson, MDHematologic Malignancies Program, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA

Natasha B. Leighl, MD, MMSc, FRCPCDivision of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

John E. Levine, MDBlood and Marrow Transplant Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

Alan Lipton, MDPennsylvania State University, Hershey, PA, USA

Alan F. List, MDH. Lee Moffitt Cancer Center, Tampa, FL, USA

xvi | List of Contributors

LeAnn B. Norris, PharmDSouthern Network on Adverse Reactions (SONAR) of the South Carolina College of Pharmacy;Arnold School of Public Health of the University of South Carolina;William Jennings Bryan Dorn Veterans Administration Medical Center, Columbia, SC;Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

Tobenna Nwizu, MDDepartment of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

Barbara J. O’BrienDepartment of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Susan O’Brien, MDDepartment of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Jose Leonel Ochoa-Bayona, MDBlood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA

Elizabeth K. O’Donnell, MDDana-Farber Cancer Institute;Massachusetts General Hospital, Boston, MA, USA

Hans Beier Ommen, MD, PhDDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark

Claudia Paba Prada, MDJerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA

Manisha Palta, MDDepartment of Radiation Oncology, Duke Regional Hospital, Durham, NC, USA

Harvey I. Pass, MDDivision of Thoracic Surgery and Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York University, New York, NY, USA

Shreyaskumar Patel, MDDepartment of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Mrinal M. Patnaik, MBBSDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

Michael J. Mauro, MDMyeloproliferative Disorders Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Beryl McCormick, MD, FACRExternal Beam Radiotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Shaunagh McDermott, MB, BCh, FFR RCSIDepartment of Abdominal Imaging, Massachusetts General Hospital, Boston, MA, USA

Charles A. McDonald, MDWestern Regional Medical Center, Cancer Treatment Centers of America, Goodyear, AZ, USA

Bruno C. Medeiros, MDAssistant Professor of Medicine, Stanford University School of Medicine, Stanford, CA, USA

Divyesh G. Mehta, MDUniversity of Arizona College of Medicine;Division of Hematology Oncology, Maricopa Medical Center, Phoenix, AZ, USA

Tarek M. Mekhail, MDCancer Institute of Florida, Orlando, FL, USA

Subhasis Misra, MD, MS, FACCWSDivision of Surgical Oncology, Texas Tech University Health Sciences Center, Amarillo, TX, USA

Supriya Gupta Mohile, MDUniversity of Rochester James P. Wilmot Cancer Center, Rochester, NY, USA

Mohamad Mohty, MDHematology and Cellular Therapy Department, Saint-Antoine Hospital;University Pierre & Marie Curie, Paris, France

Lori S. Muffly, MDDepartment of Hematology/Oncology, The University of Chicago, Chicago, IL, USA

Line Nederby, MS, PhDDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark

Alpa M. Nick, MDDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

List of Contributors | xvii

Farhad Ravandi, MDDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Matthew C. Raynor, MDDivision of Urologic Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

Shahid Raza, MDClinical Research Specialist, Hollywood, FL, USA

Istvan Redei, MDHematology and Stem Cell Transplant, Cancer Treatment Centers of America, Zion, IL, USA

Paul Richardson, MDJerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA

Richard F. Riedel, MDDepartment of Internal Medicine, Division of Medical Oncology, Duke Sarcoma Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

S. Mujtaba Rizvi, MDPennsylvania State University, Hershey, PA, USA

Damiano Rondelli, MDDivision of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

Mark Roschewski, MDMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

James E. Rosenberg, MDCancer Treatment Centers of America, Zion, IL, USA

David S. Rosenthal, MDDepartment of Medicine, Harvard Medical School;Department of Faculty of Arts and Sciences, Harvard University;Zakim Center for Integrated Therapies, Dana-Farber Cancer Institute, Boston, MA, USA

Jacob M. Rowe, MDDepartment of Hematology and Bone Marrow Transplantation, Rambam Medical Center;Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa;Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel

Sarah Rutherford, MDDepartment of Medicine, Weill Cornell Medical College, New York, NY, USA

Fedro A. Peccatori, MD, PhDFertility and Procreation in Oncology Unit, Division of Gynecological Oncology, European Institute of Oncology, Milan, Italy

Robert J. Pelley, MDDirector of GI Oncology Program, Cleveland Clinic, OH, USA

Miguel-Angel Perales, MDAdult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center;Weill Cornell Medical College, New York, NY, USA

Edith A. Perez, MDDivision of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA

Marie Perier-MuzetUnit of Dermatoloy, Lyon Sud Hospital, Claude Bernard Lyon University, Pierre-Bénite, France

Peter Pinto, MDProstate Cancer Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Evan Pisick, MDCancer Treatment Centers of America, Zion, IL, USA

Mitchell C. Posner, MDDepartment of Surgery, The University of Chicago Medicine, Chicago, IL, USA

Leonard R. Prosnitz, MDDepartment of Radiation Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

Gordana Raca, MDLaboratory of Cancer Cytogenetics and Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA

Jerald P. Radich, MDFred Hutchinson Cancer Research Center, Seattle, WA, USA

Abed Rahman, MDDepartment of Pain Medicine, Cancer Treatment Centers of America, Zion, IL, USA

Raed Rahman, DODepartment of Pain Medicine, Cancer Treatment Centers of America, Zion, IL, USA

Jasleen Randhawa, MDMedical College of Wisconsin, Milwaukee, WI, USA

xviii | List of Contributors

Stephen Smith, MDDepartment of Internal Medicine, University of Washington, Seattle, WA, USA

Davendra Sohal, MD, MPHSolid Tumor Oncology, Taussig Cancer Institute and Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA

Robert J. Soiffer, MDHematologic Malignancies Department and Stem Cell/Bone Marrow Transplantation Program, Dana-Farber Cancer Institute;Department of Medicine, Harvard Medical School, Boston, MA, USA

Neeta Somaiah, MDDepartment of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Shiyu Song, MD, PhDDepartment of Radiation Oncology, Virginia Commonwealth University Health System, Richmond, VA, USA

Eytan M. Stein, MDLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Keith Stuart, MDTufts University School of Medicine, Boston, MA, USA

Madina Sukhanova, MDLaboratory of Cancer Cytogenetics, Department of Medicine, The University of Chicago, Chicago, IL, USA

Laura Sunn, MDConsultation-Liaison Psychiatry, Midwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

John Sweetenham, MDClinical Affairs, Huntsman Cancer Institute;Department of Medicine, University of Utah, Salt Lake City, UT, USA

Martin S. Tallman, MDLeukemia Service, Memorial Sloan Kettering Cancer Center;Weill Cornell Medical Center, New York, NY, USA

Constantine S. Tam, MBBS, MDDepartment of Hematology, Peter MacCallum Cancer Center, Melbourne, VIC, Australia

Wayne Tam, MDDepartment of Medicine, Weill Cornell Medical College, New York, NY, USA

Ayalew Tefferi, MDDivision of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

Vaibhav Sahai, MD, MSDivision of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Ravi Salgia, MD, PhDDepartments of Medicine, Pathology, and Dermatology;Chest Oncology and Thoracic Oncology Research Program andTranslational Research Program, The University of Chicago Medicine, Chicago, IL, USA

Leonard Saltz, MDGastrointestinal Oncology Service and Colorectal Oncology Section, Memorial Sloan Kettering CancerCenter, New York, NY, USA

Kristen Sanfilippo, MD, MPHSSiteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

Charles A. Schiffer, MDDepartment of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA

Kathy Schneider, MPHCancer Genetics and Prevention Program, Dana-Farber Cancer Institute, Boston, MA, USA

David C. Seldin MD, PhDDepartments of Medicine and Microbiology, Section of Hematology-Oncology and Amyloidosis Center, Boston University, Boston, MA, USA

Anthony J. Senagore, MD, MS, MBA, FACS, FACRSCentral Michigan University School of Medicine, Mount Pleasant, MI, USA

Christina M. Shannon, ND, FABNOCancer Treatment Centers of America, Zion, IL, USA

Kristen M. Shannon, MS, CGCCancer Center Genetics Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA

Tsiporah Shore, MDBone Marrow and Hematopoietic Stem Cell Transplant Program, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

Veerpal SinghFox Valley Hematology Oncology, Elgin, IL, USA

Sonali M. Smith, MDSection of Hematology/Oncology and Lymphoma Program, The University of Chicago, Chicago, IL, USA

List of Contributors | xix

Cindy Varga, MDJerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA

Pankaj Vashi, MDGastroenterology/Nutrition & Metabolic Support, Cancer Treatment Centers of America, Zion, IL, USA

Thomas Velancia, MDDepartment of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Srdan Verstovsek, MD, PhDLeukemia Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Valeria Visconte, PhDDepartment of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

Justin M. Watts, MDLeukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Randal S. Weber, MDDepartment of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Glen J. Weiss, MDCancer Treatment Centers of America, Goodyear, AZ; Translational Genomics Research Institute (TGen); University of Arizona College of Medicine, Phoenix, AZ, USA

Meir Wetzler, MD, FACPLeukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

Thomas M. Wheeler, MDDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

David C. White, MDSection of General Thoracic Surgery, Department of Surgery, Duke University Medical Center, Duke Raleigh Hospital, Raleigh, NC, USA

Julia White, MDDepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center–ArthurG. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA

Christopher Willett, MDDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

Margaret Tempero, MD, MPHUCSF Pancreas Center, Pancreas Cancer Program, and Division of Hematology and Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

Constance E.H. Teo, MBBS, MRCS (Edin), MMed

(Otorhinolaryngology)Department of Otolaryngology, Singapore General Hospital, Singapore

Luc Thomas, MD, PhDDermatology Unit, Lyon Sud Hospital, Claude Bernard Lyon 1 University, Pierre-Bénite, France

Sandra Thomas, PhDDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Tracey Thomas, NDCancer Treatment Centers of America, Zion, IL, USA

Ramon V. Tiu, MDDepartment of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

Marie Toft-Petersen, MDDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark

Christopher W. Towe, MDDepartment of Cardiothoracic Surgery, NYU Langone Medical Center, New York University, New York, NY, USA

Ching-Wei D. Tzeng, MDDepartment of Surgery, University of Kentucky, Lexington, KA, USA

Koen van Besien MD, PhDBone Marrow and Hematopoietic Stem Cell Transplant Program, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

Katherine Van Loon, MD, MPHHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

Alessandro M. Vannucchi, MDDipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy

Gauri R. Varadhachary, MDDepartment of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

xx | List of Contributors

Michael B. Williams, MD, MSDepartment of Urology, Eastern Virginia Medical School, Virginia Beach, VA, USA

Wyndham Wilson, MD, PhDMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Jane N. Winter, MDRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

Ignacio I. Wistuba, MDDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Michael E. Woods, MDDivision of Urologic Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

Jay Yang, MDDepartment of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA

Andrew D. Zelenetz, MD, PhDDepartment of Medicine and Lymphoma Service, Memorial Sloan Kettering Cancer Center;Weill-Cornell Medical Center, New York, NY, USA

Pier Luigi Zinzani, MD, PhDInstitute of Hematology “Seràgnoli,” University of Bologna, Bologna, Italy

xxi

Preface

It is commonplace in the oncology arena for patients to request a “second opinion.”

But it is equally usual for oncologists to discuss with a colleague a complex or unusual case, or a patient with serious comorbidities, to insure that a particular individual is given the greatest opportunity to experience the benefits of therapy while minimizing the risks of possible treat-ment-related harm. Such discussions occur both within a particular specialty (e.g., surgery, radiation, or medical oncology) and between various specialties.

And as cancer management becomes more multimodal in nature, with an increasing focus on both maximizing the opportunity for extended survival and at the same time optimizing quality of life, the requirement for essential communication between individual specialists with their own unique knowledge and experience of critically rele-vant components of care becomes ever more important.

It is with these thoughts in mind that the editors con-ceived of an oncology text that would focus on the “expert

perspectives” of oncology professionals. The intent was to have each individual book chapter be viewed as a “mini-consultation” provided by a specialist regarding a specific, highly clinically relevant issue in cancer management.

Considering the specific purpose and focus of the mate-rial presented, the book is written without detailed refer-ences (although a few selected readings are included at the end of each chapter). However, many of the authors have prepared a more extensive reference list, and the editors will be happy to email any reader the more detailed refer-ence lists for individual book chapters, if so requested.

The chapters that follow have been written by clinicians selected for their recognized clinical expertise and experi-ence. It is hoped that those reading this book will find the material of value in their own interactions with their patients.

Syed Abutalib and Maurie Markmancancerconsult@gmail.com

Malignant Hematology and Hematopoietic Cell Transplantation

SECTION 1

PART 1Acute Lymphoblastic Leukemia in Adults

5

Cancer Consult: Expertise for Clinical Practice, First Edition. Edited by Syed A. Abutalib and Maurie Markman.© 2014 John Wiley and Sons, Inc. Published 2014 by John Wiley and Sons, Inc.

Hematopathologists are often called on to clarify how they arrived at a diagnosis of acute lymphoblastic leukemia (ALL). This is frequently due to confusion regarding how to interpret unusual flow cytometry (FC) immunopheno-type or cytogenetic results. Occasionally, the diagnosis does not fit clinical findings, the clinical impression, or a referred diagnosis by another physician. The 2008 World Health Organization (WHO) classification provides good, general guidelines for the application of immunopheno-type, cytogenetic, and molecular genetic studies in the clas-sifications of these neoplasms. However, individual cases of acute leukemia may sit on the edge of these guidelines, resulting in questions if not confusion regarding the correct diagnosis. For example, the significance of aberrant expres-

sion of relatively lineage-specific markers by acute leuke-mia remains a confusing topic. On another front, the two most important factors that predict the favorable treatment response of a patient with ALL are cytogenetic and molecu-lar genetic findings and early response to treatment. These are most conveniently followed by minimal residual disease (MRD) studies that also pose additional questions, such as when the bone marrow of a patient in clinical remission has morphologically observable lymphoid-like blasts in the bone marrow. This chapter addresses some of these issues by way of case presentations. We tried to avoid presenting diagnostic and classification information that is readily available in the 2008 WHO and other texts as well as readily available online from many sources.

CHAPTER 1Diagnosis of acute lymphoblastic leukemiaFrederick G. Behm1, Agatha Bogard1, Syed A. Abutalib2, and Sujata S. Gaitonde1

1University of Illinois Hospital and Health Sciences System, Chicago, IL, USA2Midwestern Regional Medical Center, Cancer Treatment Centers of America, Zion, IL, USA

Case study 1.1

The first case involves a patient with a provisional diag-nosis of viral infection, but a review of a peripheral blood smear raises questions about the provided clinical diagnosis.

HistoryA 16-year-old male presents with fever and arthralgia. A complete blood count (CBC) shows anemia and elevated white blood cell (WBC) count with many atypical mononu-clear cells. The physician’s impression was a viral infection, and she refers the patient for hematology consult. Physical examination is significant for questionable splenomegaly and cervical lymphadenopathy. A repeat CBC shows a WBC of 56,000/μL normocytic anemia with hemoglobin (Hgb) of 8.5 g/dL and a platelet count of 128,000/μL. There is abso-

lute neutropenia. Peripheral blood and bone marrow aspi-rate smears are reviewed. The marrow was very difficult to aspirate and on examination consisted of peripheral blood and no marrow particles.

1.  Which of the following are possible diagnoses based on the clinical history, the CBC, and the cells shown in Figures 1.1 and 1.2? (Choose all that may apply)

A.  Reactive lymphocytosisB.  Large granular lymphocytic leukemia (LGLL)C.  Granular acute lymphoblastic leukemia (granular ALL)D.  Acute myeloid leukemia (AML)

The cells shown have features of blasts with a high nuclear-to-cytoplasmic ratio with finely dispersed nuclear

(Continued)

6    |    Acute Lymphoblastic Leukemia in Adults

chromatin. The presence of azurophilic cytoplasmic gran-ules raised the possibility of LGLL, AML, and an uncommon subtype of acute lymphoblastic leukemia (ALL) called gran-ular ALL. Large granular lymphocytes (LGLs) are a normal cell type in healthy individuals that may be of T- or NK-cell lineage. They have relatively large amounts of clear cyto-plasm with a few, small azurophilic granules; acentric nuclei; and no nucleoli. LGLL, a relatively rare chronic leukemia of LGL cells, may be confused with acute leukemia. Although patients with LGLL may present with neutropenia and/or thrombocytopenia, the WBC count is usually normal with relatively few leukemic lymphocytes. The leukemic cells of LGLL rarely replace normal hematopoietic elements at initial diagnosis. Reactive lymphocytes are frequently mis-taken for leukemic blasts in that they usually are large and frequently contain one or several nucleoli. However, they lack cytoplasmic granules and have intensely basophilic cytoplasm and dense, coarse nuclear chromatin. It would be unusual to see an abnormally high WBC count or normal marrow hematopoietic elements largely replaced by reactive lymphocytes. A rare exception may be a rare immune-com-promised individual with a viral infection.

The more pressing question is whether the cells pictured are myeloblasts of AML or lymphoblasts of granular ALL. An experienced morphologist may be able to distinguish between these two acute leukemias by their cytologic features but will always confirm the initial impression by additional laboratory studies. Cytochemical stains for mye-loperoxidase and Sudan black will differentiate between

these leukemias, but they have been replaced by more informative FC immunophenotype studies. We recommend that routine cytochemical studies of acute leukemia be abandoned.

The histograms of a flow cytometry immunophenotype study of the peripheral blood are shown in Figure 1.3.

2.  What is the lineage of the leukemia based on the studies shown in Figure 1.3?

A.  B-cellB.  T-cellC.  MyeloidD.  Mixed-lineage leukemia

The studies shown in Figure 1.3 contain sufficient infor-mation to differentiate AML from ALL. In our experience, the minimum number of markers to identify the lineage of over 95% of acute leukemias is shown Figure 1.4. These are markers that are lineage restricted in normal hematopoiesis and lymphopoiesis. However, many acute leukemias do not follow the norm, and they frequently express markers of another lineage. For example, many AML express lymphoid antigens, as discussed later. Well-versed hematologists will be familiar with these 10 lineage markers and their applica-tion and limitations in assignment of a cell lineage.

The blasts of the patient express B-associated surface CD19 and CD22 plus cytoplasmic CD79a, but not T-associated CD7 or cytoplasmic CD3 and no myeloperoxidase (MPO). By the criteria of the WHO classification of acute leukemia,

Figure 1.1 Peripheral blood smear. A monomorphous population of abnormal cells predominates in the peripheral blood. The insert shows azurophilic granules in the cytoplasm of several of these cells. Wright-Giemsa, 50×; insert, 63×. (Color plate 1.1)

Figure 1.2 Bone marrow core biopsy touch preparation. Touch imprints of the bone marrow core biopsy substituted for a suboptimal bone marrow aspirate specimen. The marrow is involved with the same abnormal cells present in the peripheral blood. The insert shows two cells containing azurophilic cytoplasmic granules. Wright-Giemsa, 63×; insert, 100×. (Color plate 1.2)