Transcript The Experiences of Siblings of Patients with Fanconi`s

Fanconi’s Anemia:
Research in Another Form of
Community
Sadie P. Hutson, PhD, RN, WHNP
Department of Family/Community Nursing
ETSU College of Nursing
Fanconi’s Anemia (FA) is a model for
studies of individuals within families
facing chronic illness and an inherited
predisposition to cancer.
History: Guido Fanconi
 Fanconi Anemia (Fanconi
pancytopenia syndrome):
1927 - 3 brothers with
pancytopenia and physical
abnormalities,
“perniziosiforme”
 Fanconi Syndrome (renal
Fanconi syndrome): 1936 –
Ricketts, growth
retardation, proteinuria,
glucosuria, and proximal
renal tubular acidosis
Alter, FA101 (2006)
FA Background
• Fanconi’s Anemia
– ~1400 cases in literature
– Median survival >30 years (SCT)
– Aplastic anemia
– Acute myeloid leukemia (AML)
– Early onset solid tumors
*
Fanconi’s Anemia (FA) - Definition
• Autosomal
recessive
• Physical findings
• Aplastic anemia
• Leukemia
• Solid tumors
• Genetic instability
• DNA repair defect
• >12 genes
• More to come
Alter, FA101 (2006)
Fanconi’s Anemia
Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan DG, Oski FA, eds. Hematology of Infancy and
Childhood, 4th ed. Philadelphia, PA: W.B. Saunders, Inc., 1993: pp. 216-316.)
*
FA: Physical Findings Part 1
Finding
Skin – pigmented and/or
café au lait
Short stature
Upper limbs - radii, thumbs
Abnormal gonads, male
Head
Eyes
Renal
% of Patients
55
51
43
32
26
23
21
Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan DG, Oski FA, eds. Hematology of Infancy and
Childhood, 4th ed. Philadelphia, PA: W.B. Saunders, Inc., 1993: pp. 216-316.)
FA: Physical Findings Part 2
Finding
Low birth weight (<5 ½ lbs)
Developmental delay
Ears, hearing
Lower limbs
Cardiopulmonary
Gastrointestinal
No findings
Short and/or skin only
% of Patients
11
11
9
8
6
5
25
11
Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan DG, Oski FA, eds. Hematology of Infancy and
Childhood, 4th ed. Philadelphia, PA: W.B. Saunders, Inc., 1993: pp. 216-316.)
Autosomal Recessive Inheritance
FA Laboratory Findings
•
•
•
•
Low blood counts (pancytopenia)
Large red cells (macrocytosis)
Increased fetal hemoglobin
Increased chromosome breakage in
lymphocytes or fibroblasts cultured with
DNA crosslinking agents such as
diepoxybutane (DEB) or mitomycin C
(MMC)
Alter, FA101 (2006)
FANC Genes
C
D1 D2 E F
G
B
I J
L
M
A
Faivre L, Guardiola P, Lewis C, et al: Association of complementation group and mutation type with clinical outcome in fanconi
anemia. European Fanconi Anemia Research Group. Blood 2000 Dec 15; 96(13): 4064-70
FA: Complications
•
•
•
•
Acute Leukemia
Myelodysplastic Syndrome
Solid Tumors
Liver tumors
FA Neoplastic Complications
Cumulative
Risk**
40 %
Max. Age,
Yrs
30
MDS
50 %
45
Liver
45 %
50
Solid Tumor*
75 %
45
Complication
AML
*Primarily oropharynx, gynecologic, esophagus
Rosenberg PS, Greene MH, Alter BP: Cancer incidence in persons with Fanconi anemia. Blood 2003 Feb 1; 101(3):6.
Rosenberg PS, Socie G, Alter BP, Gluckman E: Risk of head and neck squamous cell cancer and death in patients with
Fanconi anemia who did and did not receive transplants. Blood 2005 Jan 1; 105(1): 67-73
FA Literature: Types of Solid Tumors
Tumor
Number
Tumor
Number
HNSCC
31
Lung
3
Esophagus
9
Lymphoma
2
Vulva/anus
12
Stomach
3
Cervix
3
Colon
1
Brain
13
Osteogenic
1
Skin
6
Retinoblastoma
1
Urogenital
10
Neuroblastoma
1
Breast
4
100 cancers in 86 patients
FA and Solid Tumors
• FA diagnosis preceding tumors
• Cumulative incidence of cancer is 75%
by age 45.
• Cancer diagnosis preceding FA
diagnosis
• Magnitude of the contribution of FA to
“young, atypical” cancer patients is
unknown.
Preimplantation Genetic Diagnosis
Alter, FA101 (2006)
FA Summary 1
• Patients with FA have a high risk of
malignancies (tumors and leukemia)
• These patients lack the usual risk factors
seen in the general population
• BMT increases the risk of oral cancers,
beginning after 5 years
• Leukemia may recur long after BMT
Alter, FA101 (2006)
FA Summary 2
• “Older” patients who present with
cancer may be diagnosed with FA after
the cancer, or may never know they
have FA
• “Younger” patients with cancer may
present very young; they too may never
be diagnosed as FA
Alter, FA101 (2006)
FA and Community
• Community- A group of people with
diverse characteristics who are linked by
social ties, share common perspectives,
and engage in joint action in geographical
locations or settings (MacQueen et al.,
2001)
• Culture as a part of community
*
FA as a Culture
• A rare disease of distinct and common features
• Given the genetic basis of the disease, families as a
whole (thorough shared experiences) make up a larger
culture.
• Families are unified through the US and Canadian-based
family support organizations
– These organizations publicize cutting edge research and clinical
knowledge related to FA
– Support groups online and at summer camps
– Sponsor the majority of activities in the US related to FA
– Organizations protect their members from researchers, media, etc.
• Gaining the trust of the families is rarely ever
accomplished unless the individual has a good rapport
with the family support organizations
Current Research Studies with FA
Families
• IBMFS NCI Protocol 02-C-0052
– www.marrowfailure.cancer.gov
• Sibling Sub-Study- Protocol 02-C-0052
• Utilization of SCT in FA
Sibling Study
• Rationale
– Sibling relationships are important
– Serious childhood illness places great
demands on family life
– Siblings of children with serious childhood
illness experience emotional and behavioral
problems
– Little is known about the experiences of
families with an inherited predisposition to
cancer
Research Question
What is the experience of siblings
of patients with Fanconi’s Anemia?
Study Design
Qualitative descriptive approach
– Comprehensive summary of events
– Enhances understanding of what it is like to
experience a particular situation
Methodology: Protocol
• The Sibling Study was
a sub-study of a
National Cancer
Institute (NCI) protocol
• Etiologic Investigation
of Cancer Susceptibility
in Inherited Bone
Marrow Failure
Syndromes (IBMFS)
Informants
• 7 siblings in 5 families enrolled in NCI
IBMFS protocol
• 3 females; 4 males
• Ages 11-21 years
• White, non-Hispanic
• Average yearly household income of
parents >$80,000 (4/5 families)
• All informants living in the US
• Family Case Study
Data Collection and Analysis
• In-depth semi-structured interviews, in
home communities of informants
– Average length: 1.5 hours
– Audio-taped, transcribed verbatim
– Follow-up interview; Follow-up email
Qualitative
Content Analysis
Codes
Categories
Themes
Major Themes of the Sibling
Experience
•
•
•
•
Containment
Invisibility
Worry
Despair
Containment
“Everyone is born with a mixed bag of [sic] Pandora’s
Box, if you will. You’ve just got to make sure you keep
the snap of that lid shut...guess that’s your only option,
all this vile [stuff] is coming out of the box and you’ve
got to deal with it. (16-21)”
• Meaning of FA
• Parental silence
Invisibility
“I kind of felt like I fell through the cracks a little bit, for a
little while. I think I was in some ways left to fend for
myself. It was really kind of a long process with me
ignoring everything. Just going about my feeling with it or
dealing with it…” (11-15)
•
•
•
•
People-pleasing
Being busy
Caretaking and protecting
Staying under the radar
Worry
“I'm worried about what my friends will say
about my family. I worry that some of them are
acting really strange. You worry if they are
going to reject you or like ignore you for a
long period of time.” (11-15)
•
•
•
•
Friends’ perceptions of the family
Future plans and being successful
Worries about the ill brother or sister
FA effect on siblings’ own families
Despair
“Well,
sometimes we are happy because nothing goes wrong.
And sometimes [my sister] doesn’t go to the hospital for a while,
because she doesn’t need platelets or blood or white cells.
Sometimes we are happy, but that is kind of for a short period of
time, because she always gets a chemical reaction. It’s kind of
sad. (Tearful). (11-15)”
•
•
•
•
Sadness
Jealousy
Loneliness and abandonment
Uncertainty
Summary of Major Findings
• Siblings need psychosocial attention
• Siblings need to be involved from the time
of diagnosis, especially BMT donors
• Findings may be generalizeable to other
severe chronic childhood illness
• Health care system must recognize
“unaffected” family members as individuals
in need of care
Utilization of Stem Cell Transplantation for
Fanconi’s Anemia: A Survey of the Patients
in the US and Canada
SCT Survey Background
• Allogeneic stem cell transplantation (SCT) is
currently the only available treatment option that
can cure aplastic anemia and prevent leukemia
in FA patients.
• The 10-year probability of survival following an
HLA-matched sibling donor transplant is greater
than 60% BUT
• There is only a 44% probability of 10-year
survival for patients receiving alternative donor
transplants
• Current survival results seem to be improving,
but the follow-up time is shorter
SCT Study Purpose
• The purpose of this study is to survey those families
who are members of the FARF and Fanconi Canada
to:
– gain a clearer understanding of the components
of the decision-making process with regard to
SCT in FA;
– understand the relation of prior therapies to the
decision for and outcome of SCT; and
– explore the post-transplant cancer incidence.
Study Objectives
• To survey families who are members of the FARF and Fanconi
Canada in order to explore:
1. The number of patients for whom SCT was considered;
2. The number who chose SCT;
– The number of HLA-matched sibling donor transplants;
– The number of alternative donor transplants;
3. The reasons why SCT was not utilized;
4. The role of the potential risk of post-transplant cancer on the
decision regarding SCT;
5. How SCT decisions may have evolved over time in the context of
changing perceived risks;
6. Who was influential in making the final decision about SCT;
7. The role of assisted reproductive technologies (i.e. PGD) in making
SCT a treatment option;
8. The number of patients who were first treated with ATG +
cyclosporine (CSA) and the outcome of subsequent treatment with
androgens or SCT; and
9. Neoplastic outcomes post-transplant.
SCT Survey Hypotheses & Methods
1. The perceived risks of adverse outcomes influence the
utilization of SCT.
2. Certain prior therapies may impact on the outcome of
SCT.
•
•
•
•
2-phase self-report survey targeting adult patients with
FA, mothers, fathers, and significant others/spouses
FARF & Fanconi Canada as sponsors
Investigators blinded to the mailing lists
Study funding by the Clinical Genetics Branch, NCI
SCT Survey Progress to Date
• Surveys mailed in Canada on
November 27, 2006
• Surveys mailed in the US on
November 28, 2006
• Point person at CGB batching and
scanning surveys
• Database development in progress
• Phase 2 mailing targeted for January
8, 2007
Long Term Studies Needed for FA
– 1. Consider expanding sibling study to other
IBMFS diseases of childhood; collaborate with
other scholars (Dr. Sally Kinsey-Leeds, UK);
– 2. Design studies leading to clinical
interventions;
– 3. Role of PGD and psychosocial implications
for families and children, especially donors for
children who did not survive transplant; and
– 4. Psychosocial consequences of genetic
information: creating a new “patient”
*
Making Linkages
• ETSU- dedication to serving vulnerable
populations
• Importance of furthering research
infrastructure (Appalachian Center for
Translational Research In Disparate
Populations)
• National Institute of Nursing Researchresearch priorities
*
In Closing...
• Research Goals
– To develop connections within
and among the academic and
clinical settings, and collaborate
within interdisciplinary teams;
– To make meaningful contributions
to expand the reach of the
nursing discipline, build science
and improve the clinical care of
patients with inherited cancer
predisposition syndromes
Acknowledgments
• Drs. Blanche P Alter, Mark H Greene, and the entire CGB staff.
• Westat IBMFS Study Team
• T32 Institutional NRSA in Psychosocial Oncology
• NCI CRTA Pre-doctoral Fellowship
• American Cancer Society Doctoral Degree Scholarship in Cancer
Nursing
• Clinical Genetics Branch, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
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ETSU Center for Nursing Research
Fanconi Anemia Research Fund
Fanconi Canada
Camp Sunshine (Maine)
Patients and families participating in our research