Fanconi Anemia: Guidelines for Diagnosis and Management

392 Pages·2009·2.46 MB·English

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Fanconi
Anemia
Guidelines for Diagnosis
and Management
Third Edition • 2008
Fanconi Anemia Research Fund, Inc.
We are deeply grateful
to the following generous donors,
who made this publication possible:
The Autzen Foundation
Pat and Stephanie Kilkenny
Phil and Penny Knight
Disclaimer
Information provided in this handbook about
medications, treatments or products should not be
construed as medical instruction or scientific
endorsement. Always consult your physician before
taking any action based on this information.
copyright© 1999; second edition 2003; third edition 2008
Fanconi Anemia
Guidelines for Diagnosis and Management
Third Edition • 2008
Editors: Mary Ellen Eiler, Dave Frohnmayer, JD,
Lynn Frohnmayer, MSW, Kim Larsen, and
Joyce Owen, PhD
Layout and Design: Melanie Fee
These guidelines for the clinical care of Fanconi anemia
(FA) were developed at a conference held April 10-11, 2008
in Chicago, Illinois. We owe a tremendous debt of gratitude
to Eva Guinan, MD, for serving as moderator of the confer-
ence, as she did for the consensus conferences for the first
two editions, and for her skill in helping the participants
arrive at consensus.
We would like to thank all the participants for donating their
time and expertise to develop these guidelines. The names
and contact information of all participants appear in the
Appendix.
These guidelines are posted on our website and are available
from:
Fanconi Anemia Research Fund, Inc.
1801 Willamette Street, Suite 200
Eugene, Oregon 97401
Phone: [phone] or 888-326-2664 (US only)
FAX: [phone]
E-mail: [email protected]
Website: www.fanconi.org
Material from this book may be reprinted with the permis-
sion of the Fanconi Anemia Research Fund, Inc.
iv Fanconi Anemia: Guidelines for Diagnosis and Management
The Fanconi Anemia Research Fund, Inc., was founded in 1989
to provide support to FA fami lies and to raise money for scient ific
research. The Fund publishes a newslet ter twice a year, sponsors
an annual family meeting, and provides resource identification
and counseling support to families. To aid research into FA, the
Fund gives grants to scientists and sponsors scientific conferences,
including an annual scientific symposium.
Board of Directors
Barry Rubenstein, JD, President
David Frohnmayer, JD, Vice President
Ruby Brockett, Secretary/Treasurer
Deane Marchbein, MD
Kevin S. McQueen
Peg Padden
Mark K. Pearl
Kevin Rogers
Robert D. Sacks
Michael L. Vangel
Peter H. von Hippel, PhD
Joyce L. Owen, PhD, Director Emeritus
Advisor to the Board
Lynn Frohnmayer, MSW
Staff
Jeanne Negley, Executive Director
Teresa Kennedy, Family Support Coordinator
Melanie Fee, Publications Coordinator
Kristi Keller, Administrative Assistant and Bookkeeper
Kim Larsen, Grant Writer and Conference Coordinator
Scientific Advisory Board
Grover C. Bagby, Jr., MD, Chair
Manuel Buchwald, PhD, OC, Emeritus
Joseph Califano, MD
Marc Coltrera, MD
Richard Gelinas, PhD
Eva Guinan, MD
Hans Joenje, PhD
Christopher Mathew, PhD
Stephen Meyn, MD, PhD
Raymond J. Monnat, Jr., MD
Elaine Ostrander, PhD
Bhuvanesh Singh, MD, PhD
Erich M. Sturgis, MD, MPH
Neal S. Young, MD
Table of Contents
Introduction ..................................................................7
Chapter 1: Clinical Management Checklist ................13
Chapter 2: Diagnostic Evaluation of FA
Blanche P. Alter, MD, MPH, FAAP ...........................33
Chapter 3: Treatment of Hematologic
Abnormalities in Fanconi Anemia
Akiko Shimamura, MD, PhD......................................49
Chapter 4: Gastrointestinal, Hepatic, and Nutritional
Problems in FA
Sarah Jane Schwarzenberg, MD and
Nada Yagizi, MD .........................................................76
Chapter 5: Hand and Arm Differences in FA
Scott H. Kozin, MD ....................................................97
Chapter 6: Gynecologic and Fertility Issues in
Female FA Patients
Pamela Stratton, MD, Rahel Ghebre, MD, and
Jill Huppert, MD, MPH ............................................121
Chapter 7: Endocrine Disorders in Fanconi Anemia
Susan R. Rose, MD, Anna Petryk, MD, and
Constantine A. Stratakis, MD ...................................134
Chapter 8: Hearing and Ear Abnormalities in
Fanconi Anemia
H. Jeffrey Kim, MD, FACS, Christopher Zalewski,
MA, and Carmen C. Brewer, PhD ............................165
Chapter 9: Matched Sibling Donor Hematopoietic
Stem Cell Transplantation
Farid Boulad, MD .....................................................178
vi Fanconi Anemia: Guidelines for Diagnosis and Management
Chapter 10: Unrelated Donor Hematopoietic
Stem Cell Transplantation
John E. Wagner, MD, Jakub Tolar, MD, K. Scott
Baker, MD, and Margaret L. MacMillan, MD ..........197
Chapter 11: Late Effects in Fanconi Anemia Patients
Post-Transplant
Margaret L. MacMillan, MD, K. Scott Baker, MD,
and John E. Wagner, MD ..........................................223
Chapter 12: Novel Treatment Options
Jakub Tolar, MD, PhD ..............................................236
Chapter 13: Head and Neck Squamous Cell
Carcinoma in Fanconi Anemia Patients
Bhuvanesh Singh, MD, PhD .....................................250
Chapter 14: The Adult FA Patient
Alfred Gillio, MD and Eva Guinan, MD ..................264
Chapter 15: Genetic Counseling
Heather Zierhut, MS, CGC, and edited by
Ann Carr, MS, CGC ..................................................275
Chapter 16: Psychosocial Issues
Nancy F. Cincotta, MSW, CCLS ..............................291
Chapter 17: A Mother’s Perspective: The Grieving
Process and the Physician’s Role
Lynn Frohnmayer, MSW ..........................................307
Appendix: Participants and Contributors ................317
Glossary ....................................................................331
Index .........................................................................372
Introduction
This edition of guidelines for the care of patients with
Fanconi anemia is the result of a Consensus Conference
held by the Fanconi Anemia Research Fund in Chicago,
Illinois on April 11 and 12, 2008. It is intended as a
complete replacement for earlier versions published in
1999 and 2003. Our audience is physicians who provide
primary care for FA patients, and patients and families
who wish to secure optimal treatment through medical
understanding, consultation and appropriate referral.
These guidelines begin with a comprehensive checklist
for physicians and medical specialists and diagnostic
criteria. Subsequent chapters examine more specific
issues faced by the FA patient. The guidelines conclude
with important psychosocial considerations that bear
upon the well-being of the patient and extended family.
Where possible, the guidelines rely on evidence-based
medicine. Where adequate data are lacking because of
limitations of numbers, time frame or present knowl-
edge, the consensus of expert opinion underlies the rec-
ommendations. All chapters have been peer-reviewed
and speak to the state of best practices as of the date
of each chapter. To avoid being excessively prescrip-
tive, the title of this book has been changed deliberately
from “Standards” to “Guidelines.” From the discussions
at the Consensus Conference, the authors realize that
a more robust clinical database must be developed to
gather additional evidence upon which to base recom-
mendations.
FA-related science has advanced significantly in the five
years since the last publication in 2003:
8 Fanconi Anemia: Guidelines for Diagnosis and Management
• At least 13 FA genes now have been identified.
The understanding of interactions among molec-
ular pathways has become increasingly complex
and sophisticated. Genotype determination and
mutation analysis for each patient bear directly
on the appropriateness of some treatment
choices.
• Phenotypic and genotypic predictors of the
natural history and outcome of the disease are
beginning to emerge.
• The identification of BRCA2 and other FA
genes linked to breast cancer susceptibility has
brought an influx of new scientific talent and
interest to the field of FA research. The rele-
vance of these findings to heterozygotes is being
evaluated.
• The introduction of fludarabine (Fludara) into
FA hematopoietic stem cell transplantation
protocols has continued to produce dramatic
improvements in patient outcomes. As a conse-
quence, stem cell transplantation from unrelated
or mismatched donors is a realistic treatment
option for increasing numbers of FA patients.
• A growing cohort of post-transplant adult FA
survivors presents new medical surveillance and
treatment issues.
• The availability of preimplantation genetic diag-
nosis (PGD) for FA and for HLA determination
provides a potential parental choice for secur-
ing an HLA-matched umbilical cord stem cell
transplantation.
Introduction 9
• Evaluation of adult FA patients reveals a striking
and ominous incidence of squamous cell carci-
nomas (SCC), especially of the head and neck
and gynecological tract. This underscores the
need for continuous monitoring and more effec-
tive treatment options throughout the patient’s
lifetime.
General Considerations
The Consensus Conference was guided by the follow-
ing general considerations that form the underlying
basis for more specific recommendations.
FA is a very rare genetic disorder.
• Accuracy in diagnosis is crucial and requires
sophisticated expertise.
• The mode of inheritance is important for fur-
ther genetic testing of siblings; finding matched
donors; identification of genotype for purpose
of predicting onset of symptoms and conse-
quences; family planning (including PGD); and
genetic counseling to the family.
• Expertise in FA treatment is highly specialized
and to date is concentrated only in a few, criti-
cally important centers. Many patients do not
have access to such expertise locally, but the use
of referral networks and provider cooperation
should help provide adequate care.
FA is a complex and chronic disorder.
• Well-orchestrated multidisciplinary care across
several medical and surgical specialties is
typically required for adequate monitoring and
treatment.