FA Family News 9/02 - Fanconi Anemia Research Fund

24 Pages·2002·0.92 MB·English

FA F
AMILY
N
EWSLET TER
#32 A Semi-annual Publication of the Fanconi Anemia Research Fund, Inc. Fall 2002
The Breast Cancer
Gene, BRCA2, is an FA
Gene, FANCD1
In one of the most important FA
science developments of recent years,
researchers have discovered that one
of the FA genes is also a known can-
cer susceptibility gene.
The June 2002 issue of the jour-
nal Science printed an article entitled
“Biallelic Mutations of BRCA2Cause
Fanconi Anemia.”This article docu-
FA Family Meeting Returns to Camp Sunshine ments the discoveries made by the
continued on page 24
Forty-three FA families converged for our group. From all accounts,
on Camp Sunshine on the shores of they succeeded admirably.
HIGHLIGHTS
Sebago Lake, ME, for the 12th Families wasted no time renewing
Annual FA Family Meeting. Families old acquaintances and, for the new
who had attended the Family Meet- families, marveling that they were Clone with Chromosome 3
ing at Camp Sunshine in the mid- actually meeting other FA families. Abnormality Predicts MDS,
90s were delighted with the complete Camp Sunshine staff organized many AML in FA Patients..................2
renovation of the facility. A beautiful activities to help families get to know
John Wagner Reports on
new conference center which sym- one another, including hosting a ban-
Transplant Outcomes, Stresses
bolically welcomed young, teen, and quet for the parents, complete with
Importance of Timing..............3
adult FA family members with small, candlelight, white tablecloths, and
mid-size, and large doors provided an prime rib. A karaoke program topped Harris Reports on Transplant
excellent site for the scientific pro- off that particular evening. FA chil- Outcomes..................................3
gram as well as for the activities for dren and their siblings seemed to
the youngsters. Old-time families enjoy every minute of their activities, Preimplantation Genetic
Diagnosis....................................4
were delighted to find that the trailers which included arts and crafts, a
of years past had been replaced with sleepover, a masquerade ball, and a
Family News.................................10
sparkling new living units. Perhaps stage show. Families were also able to
most impressive, however, were the pay their respects to deceased FA
FA Regional Meeting .................18
volunteers who greeted families, family members during the Memorial
tuned into their needs, and did every- Balloon Release. A special lakeside Fundraising ..................................19
thing possible to make the Camp memorial service for Travis Massino
Sunshine experience a wonderful one continued on page 17
MEDICAL NEWS
Clone with Chromosome 3 Abnormality
Predicts MDS, AML in FA Patients
Wolfram Ebell, MD, of Hum- abnormality on chromosome 3.
boldt University, Berlin, stunned Unlike other clonal abnormalities in
many at the Family Meeting with the FA patients, this clone never disap-
news that a clone with a subtle pears, but becomes progressively
abnormality on chromosome 3 can more prevalent and often leads to
predict the evolution to myelodys- monosomy 7, a clone often associat-
plastic syndrome (MDS) or acute ed with AML. The risk of MDS or
myelogenous leukemia (AML) in FA AML is 90% for patients who exhibit
patients. This abnormality, character- this particular clone. Eighteen of 53
ized by duplicated material on chro- FA patients tested by a Berlin labora-
mosome 3, always appears in the tory were positive for this clone. This
same location on this chromosome. clone can be followed in the blood as
It is not detected by routine cytogen- well as in the bone marrow. Ebell
ics, but rather by a process called believes that the presence and
spectral karyotyping. More than half progression of this clone can help Wolfram Ebell, MD
of the patients considered normal on patients plan the timing of a bone
◆
a cytogenetics analysis had this marrow transplant.
FA Research Fund
Walsh Presents Gene Therapy Trial Update and Supports Work on
Plan for Future Trials Adult Stem Cells
Christopher Walsh, MD, Univer- identify additional sources of stem During the past year, FARF has
sity of North Carolina Gene Therapy cells and find better vectors to carry given two grants to the University of
Center, presented results of his gene the corrected gene into these cells. Minnesota to study the potential of
therapy trial for FA patients in FA-A. Walsh’s lab has developed several multipotent adult stem cells (MASC)
Four patients enrolled in this trial. new lentiviral vectors, which appear as a novel treatment for patients with
Two and a half years after gene to be far superior to his retroviral vec- FA. Drs. Catherine Verfaillie, Bruce
transfer, one patient has had a sig- tor. He has corrected the FA defect in Blazar and John Wagner are collabo-
nificant increase in the number of mice using these vectors. Based on rating on these studies.
peripheral blood cells carrying the this data, he has received approval MASC cells can be isolated from
FANCAgene. from the National Gene Vector Lab the bone marrow. They can be grown
Several factors have impeded the to manufacture these vectors for a in large quantities and can differenti-
success of this trial. Walsh used a clinical trial. He now needs approval ate into a variety of different cells and
retroviral vector to transport the cor- from the FDA to initiate a clinical tissues (e.g., liver, gut, lung). It is
rected gene into stem cells. This vec- trial. Walsh’s laboratory has also iden- conceivable that MASC cells could
tor can enter only dividing cells, thus tified a new population of cells that correct both the diseased bone
correcting a small proportion of stem act as hematopoietic stem cells. He is marrow and other tissues in an FA
cells. In addition, all FA patients, presently studying the potential of patient. These cells might help repair
despite age and blood counts, have these cells to expand after gene trans- damaged tissue following a bone
significantly fewer stem cells (10 to fer. By next year, Walsh hopes to have marrow transplant. It is possible that
100 times fewer) than the normal treated several FA patients in FA-A these cells might help prevent or treat
population. Walsh states we need to using this new approach.◆ cancer in FA patients.◆
2 FA Family Newsletter
John Wagner Reports on Transplant
Outcomes, Stresses Importance of Timing
Between April 1999 and April These patients should consider
2002, seven FA patients have under- androgen therapy, hemato-
gone matched sibling donor (MSD) poietic growth factors such as
transplant, and 36 patients have G-CSF, and transfusions.
undergone matched unrelated donor Patients with advanced MDS
(MUD) transplant at the University or leukemia should go to trans-
of Minnesota. Radiation has been plant since new approaches
Drs.Wagner, Harris, and Ebell respond to questions
eliminated as part of the protocol for may improve present outcomes.
from FA parents after their individual presentations.
MSD transplants; all seven MSD The University of Minne-
patients survive. sota has developed two new bone marrow transplant. Wagner
Of the 36 patients receiving unre- treatment protocols especially for stated that, with the use of fludara-
lated transplants, 25 were standard high-risk patients. See the article by bine, these might no longer be risk
risk patients. These patients had Wagner and Margaret MacMillan in factors. However, transfusions pose a
aplastic anemia or early myelodys- the Science Letterfor a detailed transplant risk when patients suffer
plastic syndrome (MDS). A patient description of these new approaches. iron overload. If iron levels are high,
with an abnormal clone but less than In the past, factors such as patients need to be on desferal.
5% blasts in the bone marrow is con- mosaicism, prior use of androgens, Wagner has found no evidence that
sidered standard risk. Patients were and blood transfusions appeared to physical malformations increase the
infection-free and under the age of decrease the likelihood of surviving a risk of transplantation.◆
18. Of these 25 patients, 81%
survive. In contrast, only 33% of
patients with high-risk disease, Harris Reports on Transplant Outcomes
defined as those with recurrent infec-
tions, poor organ function, or older Richard Harris, MD, Cincinnati Eight of 12 patients are alive, with
age, survive. For patients with Children’s Hospital, reported on bone follow-up from one to 35 months.
advanced MDS or acute myeloid marrow transplant outcomes at the Six of seven patients receiving PBSC
leukemia, only 20% survive. August Family Meeting. Twenty-nine are alive, and none experienced graft-
Given the promising outcomes patients received marrow from a versus-host disease (GVHD). Of the
for patients with matched sibling matched sibling donor. Patients re- 5 patients receiving bone marrow,
donors and for standard risk patients, ceived low-dose Cytoxan and thoraco- three experienced significant GVHD
Wagner believes that these patients abdominal irradiation (400 cGy). and two survive.
should go to transplant before the Follow-up is from one month to 13 Opportunistic infections were
development of leukemia, advanced years. Of 29 patients, 24 are alive; frequent, in spite of efforts to prevent
MDS or infection. This group of projected 5-year survival is 86%. this complication. Three patients
patients should consider transplanta- Harris reported on 12 alternative died of infection; one patient died of
tion before undergoing androgen (not a matched sibling) donor trans- pulmonary failure plus infection.
therapy. The transplant should be plants at Cincinnati utilizing their Based on his experience, Harris
considered (meaning that a donor new fludarabine-based regimen. The prefers PBSC to bone marrow. With
search should be initiated) when one preparative regimen consisted of low- PBSC he is able to harvest a very
of the following occurs: ANC consis- dose Cytoxan, total body irradiation large dose of stem cells, reducing the
tently below 1000; hemoglobin (450cGy), anti-thymocyte globulin risk of graft rejection. At his center,
below 10; platelets below 30,000. (ATG) and fludarabine. Six patients the PBSC collections can be more
However, patients with high-risk had been on androgen therapy. Seven thoroughly depleted of T-cells than
disease (recurrent infections, poor patients had a 6/6 match; 5 had a 5/6 bone marrow collections, thus reduc-
organ function or older age) should match. Five patients received bone ing the risk of GVHD and improv-
◆
delay transplant, with the hope that marrow; 7 received peripheral blood ing outcomes.
new therapies may become available. stem cells (PBSC).
Fall 2002 3
Preimplantation Genetic Diagnosis
Mark Hughes, MD, Wayne State stimulate her ovaries to produce FA families from complementation
University, spoke about Preimplanta- multiple eggs. The eggs are collected, groups A, C and G. Several mothers
tion Genetic Diagnosis (PGD) at our fertilized with the husband’s sperm, of FA children are pregnant with
Family Meeting. Researchers began and allowed to grow for three days, healthy fetuses and transplantation
to work on PGD 13 years ago, in dividing from one cell to 8 cells. matches.
response to the need to diagnose One cell is then removed from each Cost of this procedure depends
genetic diseases in fertilized eggs blastomere (pre-embryo), and tested greatly on the cost of in vitrofertiliza-
before a pregnancy occurred. This for HLA antigens and the absence of tion at a given clinic. These costs (per
procedure can also be used to test for the genetic disease. With FA, there attempt) vary from $11,000 in New
HLA antigens, thereby determining are 3 chances in 4 that a blastomere York City to $4,500 in some clinics
if a pregnancy might provide a will be free from FA, and 3 chances in the Midwest and Canada. Some
matched sibling donor for a later in 16 that any one blastomere will be health insurance companies have
transplant. Through the technologies free from FA and will be an HLA- begun covering the cost. Success of
of PGD and in vitrofertilization, matched donor for an FA sibling. PGD varies from one in vitroclinic
several thousand healthy babies have Hughes, working in collaboration to another, and parallels the success
been born. with Arleen Auerbach, PhD, The of that clinic’s in vitrofertilization
Fertile couples are sent to a clinic Rockefeller University, and John program for all couples. Most clinics
dealing with infertility problems. Wagner, MD, University of now have success rates between 45%
◆
The mother takes hormones, which Minnesota, has worked with many and 50% per IVF attempt.
FA and Cancer Researchers Request
Closely Linked Blood, Bone Marrow
Alan d’Andrea, MD, Dana-Farber Laboratory research is critical to
Cancer Institute, stated that by the development of new clinical tri-
focusing on FA, a rare disease, scien- als. Research depends on the avail-
tists will learn a great deal about ability of patient marrow and blood.
cancer in the general population. In At our recent family meeting, Chris
several respects, cancer cells resemble Walsh requested bone marrow sam-
FA cells. Under the microscope, can- ples, and John Wagner asked for
cer cells have a similar appearance to blood and bone marrow. If you are
FA cells. The chromosomes in cancer planning to do a routine CBC or
cells break and fuse back together in bone marrow aspiration in the near
the wrong places. Chromosomes in future, please seriously consider
FA cells also break and fuse inappro- gene, FANCD1. D’Andrea suspects donating a small additional sample
priately in response to DNA damage. that FA-D1 carriers with certain dis- for research. Contact one of these
D’Andrea believes that if we can find ease mutations have an increased risk labs for information on how to send
out what causes chromosomal breaks of developing cancer. a sample:
in FA, we would learn a great deal D’Andrea believes that the con-
Christopher Walsh
about what causes cancer in general. nection of FA with cancers in the
University of North Carolina
D’Andrea discovered two years general population will help speed
phone: [phone]
ago that the FA genes work directly FA research. A great deal is already
e-mail: [email protected]
with the breast cancer genes to repair known about the breast cancer sus-
DNA damage. Last June, he ceptibility genes; this knowledge now John Wagner, MD
announced the exciting discovery has direct relevance to FA. Drugs de- University of Minnesota
that the cancer susceptibility gene, signed to benefit FA patients should phone: [phone]
BRCA2, is also a Fanconi anemia help patients with some cancers.◆ e-mail: [email protected]
4 FA Family Newsletter
Hand and Arm Differences in FA
Scott H. Kozin, MD, of Shriners thumb (missing a stable base), the
Hospital for Children, Philadelphia, index finger can be moved to the
described the arm and thumb thumb position. The floating thumb
anomalies that affect many FA could be removed first or at the time
patients, and discussed therapies that of index finger transfer. This proce-
can improve the function of the dure is called pollicization. It is
hands and arms. In an FA patient, performed between 6 months and 2
the radius (a bone in the forearm) years of age, and requires a skilled
can be incompletely developed or surgeon who is comfortable with this
entirely missing. All patients with procedure. The success of polliciza-
this complication need treatment. tion depends upon the flexibility of
The initial treatment for the the index finger prior to surgery. A
absent radius is stretching, both by mobile index finger provides an
the therapist and the caregiver. excellent digit after transfer to the
Splints are used to maintain the hand thumb position. A stiff index finger
in a straight alignment. Without continued on page 23 Scott H. Kozin, MD
treatment, the hand will develop a
perpendicular relationship to the
forearm. In very young children,
stretching is usually recommended Transplant Results and Observations from our
every diaper change and is crucial to
Transplant Expert in Germany
the overall success of treatment.
In patients with a missing or
Wolfram Ebell, MD, of Humboldt University, Berlin, reported on 21 FA
incompletely developed radius, the
transplants at our recent Family Meeting. Ebell suspects that radiation
only substantial bone in the forearm
induces solid tumor malignancies in later years, so has eliminated it from his
is the ulna. Surgical treatment
conditioning protocol. Engraftment is achieved by using fludarabine, high
involves placing the wrist on top of
stem cell doses, T-cell antibodies, and low-dose busulfan.
the ulna. This process is usually per-
Eight patients received stem cells from matched sibling donors; 13 had
formed at about 1 year of age. Unfor-
alternate donors. Eleven patients had severe aplastic anemia, six patients had
tunately, while the initial results of
myelodysplastic syndrome, and 4 had leukemia at the time of transplant.
surgery can be impressive, it is diffi-
All 8 patients with matched sibling donors, and 7 of 13 with alternate
cult to maintain the correction. Stiff-
donors survive. Of the 6 who died, 3 died of infection and 3 of leukemia. Of
ness is also a possible complication.
the 11 patients with aplastic anemia, 10 survive. Of the 6 with MDS, 4
Recent efforts to improve outcomes
survive. Only one of 4 patients with AML survives.
include the use of an external fixator
to stretch the tissues prior to surgery. Ebell draws several conclusions from these results:
The external fixator has also been
• Radiation is not essential for matched sibling or alternate donor trans-
used to lengthen the forearm, usually
plants.
when the child is 8 to 15 years of age.
This is a difficult, lengthy process, • Toxicity with the present protocol is very low.
requiring much effort on the part of • Engraftment with the present protocol is acceptable.
the patient and family.
• Infections pose a considerable risk.
Thumb anomalies include
• If a patient has AML, chances for a successful transplant are greatly
missing, misshapen or extra thumbs.
reduced.
A thumb that is slightly smaller than
normal can be reconstructed to • Ebell believes that it is possible to go to transplant too early. Some patients
improve motion and use. If the will improve spontaneously. Ebell still recommends a trial of androgens
◆
thumb is missing or is a floating prior to BMT.
Fall 2002 5
Blanche Alter Helps New Families Understand FA;
Discusses Cancer Risk
Blanche Alter, MD, MPH, • FA patients experience a far Alter offered guidance on screen-
National Cancer Institute, presented greater risk of developing cancer ing for hematologic disease and for
two sessions at our Family Meeting compared to those in the general solid tumors. Patients should have
in August. New families benefited population. For example, the risk blood counts at least every 4 months,
greatly from her comprehensive for an FA patient to develop any and an annual bone marrow aspirate,
overview of this disease (see Science cancer was 50-fold; for solid biopsy, and cytogenetics (a study of
Letter,“FA 101”). Alter also tumors, it was 48-fold. When the chromosomes in dividing bone
addressed the sobering topic of FA analyzing cancers prevalent in FA marrow cells).
and cancer. This information is diffi- patients, the risks are even higher. Head and neck cancer screening
cult for all families to hear. However, includes an examination of the oral
• The types of cancer seen in FA
knowing the risks allows for appro- pharynx, the throat, and the region
patients are specific and unusual
priate screening and early interven- down to the vocal cords (this requires
(myeloid leukemia, liver tumors,
tion, with the hope of improving insertion of a flexible scope into a
head and neck cancer, esophageal
survival outcomes (see Science Letter, nostril and down the throat). Com-
cancer, and gynecologic cancer,
“Cancer in FA”). prehensive oral screening should be
especially vulvar cancer).
Alter presented data from two done annually, starting at age 10 in
• The maximum risk for AML is
sources: a review of 1300 reports of untransplanted patients, and within
age 16, and it appears to decline
FA in the medical literature, and an the year after transplant at any age.
in subsequent years. However, the
analysis of 145 responses to her Pilot Monitoring for gynecologic cancer
risk for solid tumors rises slowly
Study survey. Her findings include should begin at age 16 or earlier.
during childhood and then
the following: Skin examination should be done as
increases steeply, with no sign of
• FA patients who undergo trans- part of an annual physical. Pain,
reaching a plateau.
plant appear to develop oral can- sores, or lesions that persist for more
cer at an earlier age than non- • Myelodysplastic syndrome than a brief time should be brought
transplanted FA patients. In the (MDS) does not always progress to the attention of a physician.
literature, there are 12 reports of to AML in FA patients. Of 23 Patients on androgens (or who have
oral cancer following BMT, and patients in the Pilot Study with previously received androgens)
the median age of these patients is MDS, 19 did not develop should have an annual ultrasound of
21. This is younger than the leukemia. And five patients devel- the liver, as well as liver enzyme tests
median age of 28 years in the 26 oped leukemia without a previous 3-4 times per year.◆
diagnosis of MDS.
untransplanted FA patients with
oral cancer. The numbers are very
small but statistically significant.
The reasons for this observation
are not yet known.
• FA patients develop cancer at
much younger ages than those in
the general population. Median
age for developing leukemia is 14;
median age for solid tumors other
than those of the liver is 25. Liver
tumors can be benign (adenomas)
or malignant (hepatomas). Medi-
an age for developing either type
of liver tumor is 13, and is mostly
a complication of long-term
androgen usage. FA parents listen carefully to presentation of FA treatment and research findings.
6 FA Family Newsletter
Alter Receives Lifetime Achievement Award
At a banquet during the FA Fami- The inscription on the award
ly Meeting at Camp Sunshine, aptly describes Alter’s contributions:
Maine, Dave Frohnmayer, vice-presi-
With profound gratitude for pio-
dent of the FA Research Fund’s
neering greater understanding of Fan-
Board of Directors, presented
coni anemia and for tireless dedication
Blanche Alter, MD, MPH, with the
to helping FA patients and families
Fund’s Lifetime Achievement Award.
worldwide. Your gift of self as a
Alter, a cancer expert from the
resource to FA families and to the FA
National Cancer Institute, is only the
Research Fund as a teacher, physician,
second recipient of this honor. The
scientist, and friend has value beyond
award was presented with great fan-
measure.
fare and much appreciation. Teens
attending the Family Meeting Alter’s commitment to FA
marched into the auditorium to the patients and their families is well
tunes of O Canadaand The Star known and made the Family Meet-
Spangled Banner, bearing US and ing particularly appropriate as the
Canadian flags, in recognition of site of the presentation of this award.
both Alter’s country of birth and her The youngsters in attendance added
newly-acquired US citizenship. In their recognition to the Lifetime
presenting the award to Alter, Frohn- Achievement Award by presenting
mayer cited her exceptional accom- Dr. Alter with a colorful hand-made
Blanche Alter, MD, MPH receiving the
plishments and her unparalleled card bearing their handprints and
Fund’s Lifetime Achievement Award from
◆
dedication to her FA patients. their very best wishes. Dave Frohnmayer
Hormones and Fanconi Anemia
Susan R. Rose, Professor of these endocrinopathies may improve systematic baseline evaluation.
Endocrinology at Cincinnati Chil- growth, final height, and overall Growth should be monitored yearly;
dren’s Hospital Medical Center, dis- quality of life.” if growth rate continues to be slow,
cussed the importance of identifying During the past five months, endocrine tests should be repeated.
and treating endocrine problems in endocrinologists at Cincinnati Chil- When problems are identified, hor-
FA patients. Endocrinology is the dren’s Hospital Medical Center have mone therapy can help to optimize
◆
study of how hormone messages done endocrine testing in 12 FA chil- growth and promote good health.
interact in the body. Among other dren, in order to better understand
things, hormones affect growth and growth problems. Short stature was
development. identified in 58% of these children. Use of Logo
Many FA children have hormone Of this small study group, every
This is just a reminder to our FA
problems. The only large study on child had an endocrine deficiency.
families: please use our logo or
this subject was by Dr. Michael P. Either glucose intolerance (often a
letterhead only after you have
Wajnrajch and appeared in Pediatrics precursor to diabetes) or diabetes was
consulted the staff of the FA
2001; 107:744. This study of 54 identified in every child. Insulin Research Fund, and received their
patients revealed that 72% had levels were elevated in 63% of those approval. This is necessary to be
insulin resistance, 25% had glucose who were old enough to test. Abnor- sure our messages are accurate
intolerance, 46% had low growth mal thyroid tests were found in 83%; and consistent. It also helps to
hormone peak, and 36% had hypo- and low growth hormone peak was avoid legal complications. We are
thyroidism. Wajnrajch suggested identified in 62% of these patients. happy to collaborate on fundrais-
performing “endocrine evaluation in Rose recommends that all FA ers and mailings.
all FA children because correction of patients undergo a careful and
Fall 2002 7
Oral Cancer Precautions and Recommendations
Stephen Engroff, MD, DDS, Fel- progression to dysplasia, the lesion
low in Oral and Maxillofacial Oncol- needs to be removed. Surgical exci-
ogy at the University of Maryland sion, laser treatment, or photody-
Medical Center, reported on oral namic therapy can be effective. With
cancer at our recent Family Meeting. photodynamic therapy, the patient is
Engroff stated that 90% of oral can- given medication, which is taken up
cers are squamous cell carcinomas. rapidly in dividing cells. Light is
Treatment has become much more applied, which causes destruction of
successful in the early stage of this these lesions.
disease. Early-stage lesions (less than Malignant lesions must be
2 cm) have an 85-90% cure rate; removed. Today, there is no effective
stage 3-4 lesions have only a 20-30% chemotherapy for oral cancers. Radi-
cure rate. ation poses problems with salivation
Three types of premalignant con- and wound healing and is not ideal
ditions are implicated in oral cancers for FA patients. Surgical removal
of FA patients: remains the mainstay of treatment
Leukoplakia is the most common for oral squamous cell carcinomas in
premalignant condition. Engroff the FA population.
Grompe Wins E. Mead
defined leukoplakia as “a white patch Oral cancers can return rapidly
or plaque of oral mucosa that cannot and have a “field characterization,” Johnson Award
be rubbed off and cannot be charac- meaning that more than one spot is
Markus Grompe, MD, from Ore-
terized as any other disease.” In the often affected.
gon Health & Sciences University,
general population, depending on Engroff recommends aggressive
has been awarded the E. Mead John-
the site, up to 40% of leukoplakias screening to detect premalignant and
son Award for Excellence in Pediatric
will go on to become cancer within 5 malignant lesions as early as possible.
Research. This is the most prestigious
years. In FA, the percentage could be Specifically:
award given by the Pediatric Acade-
higher. • FA patients should undergo an
mic Society/Society for Pediatric
Mixed lesions are even more sus- oral examination upon diagnosis
Research. Grompe, a long-time
picious than leukoplakia. They are and every 3-4 months thereafter.
researcher into Fanconi anemia,
“thick and white, with associated red
• The dentist should be told that
recently isolated the FANCD2gene,
areas.”
the patient has FA and that FA
further contributing to the knowl-
Erythroplakia is a red patch of
patients are at high risk for oral
edge of the FA pathway. He also
oral mucosa. With erythroplakia, the
cancer.
manages the FA Cell Repository at
changes that have occurred in the
◆
• The entire oral cavity must be OHSU.
tissues of the mouth are more fre-
examined.
quently dysplasia, carcinoma in-situ
or frank carcinoma. A high percent • FA patients should be aggressive
of erythroplakias become malignant. in following up on suspicious-
Premalignant lesions should be appearing areas. Don’t just “wait
biopsied. Toluidine blue selectively and see.”
stains areas undergoing a higher rate
• FA patients should avoid behav-
of cell division, and can be helpful in
iors that increase the likelihood of
identifying the appropriate area for
oral cancers, such as drinking and
biopsy.
smoking.
There are several treatment
• Chinese green tea might reduce
options for premalignant and malig-
◆
the incidence of these cancers.
nant lesions. If biopsy of a premalig-
nant lesion shows thickening or
8 FA Family Newsletter
Comprehensive Care
Center Established
The Fanconi Anemia Compre-
hensive Care Center was established
at Cincinnati Children’s Hospital
Medical Center in January 2002.
The Center offers a weeklong clinical
assessment of FA patients and oppor-
tunities to participate in clinical
research studies. Research studies will
include gene therapy, blood and mar-
row transplantation, novel androgens
(oxandrolone), and endocrine evalua-
tions. Consultation will be available
on a wide range of specialties, includ-
Drs. D'Andrea and Joenje field questions from FA parents regarding the genetics of FA.
ing ear, nose and throat; orthopedics
and hand surgery; gastroenterology;
nephrology and urology; and dental. Hans Joenje Describes the Importance of
The Center is establishing an FA cell Molecular Diagnosis
repository of bone marrow, blood,
skin and tumor samples. Investiga- Hans Joenje, PhD, Free Universi- FANCG). It is therefore now possible
tors can apply to the Fanconi Anemia ty Medical Center, Amsterdam, The to do “molecular diagnosis,” i.e., the
Comprehensive Care Center for Netherlands, states that 95% of all determination of the defective gene
access to tissue samples and clinical FA patients have mutations in one of and the disease-causing mutations in
information. For questions, contact the seven known FA genes (FANCA, that gene, on the vast majority of FA
Robin Mueller, the FACCC coordi- FANCC, FANCD1 [BRCA1], patients. Some mutations are more
nator, at 513/636-3218 or email her FANCD2, FANCE, FANCF and severe than others. This knowledge
◆
at [email protected]. can help families and their physi-
cians devise an appropriate treatment
plan. Knowing which gene is defec-
Fanconi Anemia Comprehensive Care Program tive is essential for preimplantation
Established in Minnesota genetic diagnosis, access to gene
therapy trials, carrier detection, and
The University of Minnesota has University of Minnesota physi- earlier and more reliable prenatal
established the Fanconi Anemia cians have developed protocols that diagnosis. Knowing the specific
Comprehensive Care Program at have drastically improved outcomes disease mutations provides the great-
Fairview-University Medical Center, for patients undergoing BMT with est accuracy, and is most helpful
a treatment center for patients with unrelated donors. Scientists at the when making decisions concerning
FA.. Care is individually tailored to University of Minnesota continue to clinical care.
meet the unique needs of each fami- research ways to improve treatment Dr. Gerard Pals ([email protected])
ly. A wide range of services is provid- for FA patients. The focus of current at the Free University Medical
ed, including surgical correction of research efforts includes use of Center, Amsterdam, provides
congenital anomalies; bone marrow Preimplantation Genetic Diagnosis molecular diagnosis for all known
transplantation; hormone replace- to create a healthy HLA-matched FA genes. Joenje states the turn-
ment therapy to correct short stature, sibling donor; Multipotent Adult around time is 1-3 months, and the
thyroid insufficiency or diabetes; Stem Cell Therapy to treat tissues of price is reasonable. Patients for
cancer treatment; voice reconstruc- the body other than just the marrow; whom no mutations can be found
tion; and genetic counseling for and gene therapy.◆ are referred to the research division
◆
preimplantation genetic diagnosis. at no further cost.
Fall 2002 9
FAMILY NEWS
Surviving the First Year
By Carol Siniawski
A long time ago, I redefined to let go of things I truly cannot
“success” for myself. It was not about change. Letting go can sometimes be
whether Jake lived or died, as I very empowering. I have found peace
believed that was in hands bigger in sorting my troubles into these two
than mine. Instead I chose to define categories.
success by three things: 1) not having Jake packed a whole lot of living
any regrets, as Jake’s parent; 2) ensur- into his 10 years here on Earth. He
ing that Jake had a high quality of swam with dolphins, had a helicopter
life, regardless of how long I had ride over an active volcano, attended
him; and 3) always telling the truth, a Mass celebrated by Pope John Paul
even if it hurt. That definition served II, sat in the cockpit of the Raptor
me well while Jake was alive and and the Stealth, toured a Navy frigate
serves me well now that he has and Air Force One, rode in a Hum-
moved on to heaven. mer, was the Grand Marshal of a
Dr. Harris was incredibly patient parade, and so on. I cherish all the
with me and my 5 million questions. photos I took and the memories they
That was my way of ensuring I bring back. Jake inspired people to
wouldn’t have any regrets. I asked consider returning to the church,
questions when I wasn’t sure and giving more to charities and not
learned to trust my gut when it was taking life for granted. That was my
screaming at me. I learned how to 10-year-old son. I am so proud of
trust my son, when he was really him and how he handled his illness
speaking to me. And we talked a lot, with courage, grace and a smile.
about everything, conversations I Eventually, the complications
would never have had, if his life were from the transplant took over, and Jake Siniawski
not in grave danger. We would talk Jake was born into eternal life a few
about the decisions we needed to months short of his 11th birthday. that I loved him. He knew I was
make, the options, the possible out- Figuring how to get through the next proud of him. To some degree, all of
comes, his preferences. Jake was year without losing my mind was an that helped me get through the first
always part of the decision, for as entirely new task, and I was not year after his death.
long as I can remember. His body ready for it. We decided early on that we
was only 10 years old, but his mind I take comfort in knowing that I might as well dedicate some time and
matured at 4 times the normal rate. did my best. I have no regrets. I was energy to grieving, as it wouldn’t go
By the time we got to transplant, he successful, as I defined it all those away by itself. We decided to pay
had already learned that he could years ago. God’s plans for Jake were homage to Jake at every major event:
trust what I told him. not aligned with mine. But Jake holidays, birthdays, trips, hobbies,
Good thing I have my faith. I fell knew that whatever God had in store the simplest of family activities. We
away after he was diagnosed, but for him, He would take care of him hoped that, by investing the time this
eventually found my way back. I and never leave him. Jake also knew first year, maybe next year we could
have really clung to the Serenity that we’d all be together again some- enjoy the event again. It was all
Prayerover the years. It has helped day. We even agreed that Jake would painful. We had to learn how to deal
me focus on things I can change and save a seat for me. Jake died knowing continued on page 11
10 FA Family Newsletter