Family Newsletter #53 - Fanconi Anemia Research Fund

28 Pages·2013·3.24 MB·English

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A semi-annual publication of the Fanconi Anemia Research Fund, Inc.
Participants Find Inspiration and Excitement
at Annual Symposium
Eleven sessions over four days facilitated two exciting special
included the ever-popular FA 101, sessions on the first full day of the
an introduction to the medicine and meeting. The first session, Bone
S biology of Fanconi anemia designed Marrow Transplantation: Point/
y for those new to FA treatment Counterpoint in the Landscape of
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and research as well as long- Change, explored questions vital to
p time veterans. Forty-six scientists patients and families considering
o presented abstracts in sessions transplant (see article on page 9).
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such as Drug and Small Molecule In the second session, The Pursuit
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u Therapeutics; FA Protein Structure of Stem Cell Expansion, panelists
m and Function; Genome Engineering discussed the latest findings in
and Stem Cells; and Carcinogenesis hematopoietic stem cell expansion
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and Human Papillomavirus. and the therapeutic significance for
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An additional 52 abstracts on a people with FA (see article, page
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wide range of related topics were 5). Both sessions generated great
s Grover C. Bagby, MD, receives
presented as posters. interest among participants and led
Lifetime Achievement Award
Jakub Tolar, MD, PhD, University Dave Frohnmayer, cofounder of the
The 24th Annual Fanconi of Minnesota, Minneapolis, continued on page 2
Anemia Research Fund Scientific
Symposium, held last September
in Denver, Colo., was attended by
175 scientists, clinicians, and family
representatives from 15 countries.
INSIDE
Symposium News ..............1-11
Science and Medical News ...12
Adults with FA Meeting ..13-16
Family News ...................17-21
Fundraising ....................22-25
News From the Fund .....26-27 Twenty-four adults with FA came together at the Fund’s Meeting for
Adults with FA in Austin, Texas. See related articles starting on page 13.
Symposium Overview Scientific Advisory Board since its inception in 1989,
received the Fund’s Lifetime Achievement Award. A
continued from page 1
founding director of the OHSU Knight Cancer Institute
and hematologist for more than 35 years, Dr. Bagby
has focused on FA research for the past 25 years. He
was saluted for his passionate curiosity, dedication to
inquiry and superb organizational and leadership skills.
In accepting the award, Dr. Bagby told the old parable
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about a group of blind men each touching one part of
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an elephant to learn what it is like. In the story, the man
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who feels the elephant’s side says it is like a wall, the
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man who feels the tail says it is like a rope, and so on.
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The moral of the story is, as Dr. Bagby told the gathered
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researchers and clinicians, “we need each other.”
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Participant evaluations attested to the meeting’s value.
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Fund, to pronounce, “This was the single best day in One participant wrote, “It is of utmost importance for
translational research in the history of the Symposia.” FA researchers to attend this annual symposium, not
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The annual Symposium gala dinner was again a moving only for the scientific value but for the approach to real
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w celebration illustrating for all in attendance how much
s has been accomplished and how much work remains. “The single best day in translational
Ken Atkinson, MD, a parent and active fundraiser, spoke
research in the history of the
about his family’s experience with FA. Two of Ken and
Symposia.” – Dave Frohnmayer
his wife, Jeanne’s, four children had FA. Their daughter
Kendall succumbed to complications of FA at age 20 and
their son, Taylor, passed away at age 18. Ken and Jeanne problems of FA families.” Another noted, “This meeting
founded the Kendall and Taylor Atkinson Foundation; has become my top priority. While emphasizing rigorous
daughters Allison Adams and Whitney Langlois founded basic research, clinical progress, and honest scientific
Kaps for Kendall. Both organizations raise funds for FA exchange, it reminds the community each year that FA
research and family support. families do not have the luxury of time.” Finally, “I loved
Grover Bagby, MD, Oregon Health & Science this meeting! You seem to have figured out how to keep
University, Portland, Ore. and chair of the Fund’s it balanced and exciting.”
Testing Service for FA Patients
Testing for Potentially For more information, contact:
Teresa Kennedy, Director of Family Support Services
Beneficial Cancer Therapy
Fanconi Anemia Research Fund, Inc.
The Knight Diagnostic Laboratories at Oregon
Phone: [phone] or
Health & Science University have recently made
1-888-FANCONI (888-326-2664)
available new molecular tumor tissue tests designed Email: [email protected]
to identify potential treatment targets in cancer
and to predict the likelihood of benefit for patients Or contact:
treated with the latest therapeutics. Christopher Corless, MD, PhD, Medical Director
OHSU Dept. of Pathology (mailcode L113)
This new testing is available at 3181 SW Sam Jackson Park Road
Portland, OR 97239
NO CHARGE to FA patients.
Phone: [phone]
Email: [email protected]
2 Family Newsletter #53
Presentations Highlight Aldehyde Research
A majority of ALDH2 or FANCD2 alone, when exposed to an
researchers at aldehyde. Interestingly, this seems to be a feature of the
the Scientific HSC’s only, since more mature and specialized blood
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Symposium progenitor cells do not show more damage.
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commented that the Juan Garaycoechea, PhD student at the MRC, did
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role of aldehydes experiments with mice deficient in both ALDH2 and
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in the Fanconi FANCD2. These mice had a strong predisposition to
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anemia pathway leukemia and developmental abnormalities, as previously
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is an exciting demonstrated by Frederic Langevin, PhD. They also
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area for further show a large decrease in the number of HSCs compared
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research, since it may more fully explain why Fanconi to normal mice. Furthermore, those double mutant mice
anemia patients develop bone marrow failure, congenital that do not develop leukemia go on to develop bone
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anomalies and cancer. Aldehydes also provide a new marrow failure, caused by an accumulation of DNA
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target to develop small molecule therapies to improve damage in the blood stem cells. Researchers conclude w
these problems. that endogenously generated aldehydes are a potent s
Aldehydes are highly reactive substances that can source of DNA damage that is repaired by the Fanconi
injure cells, particularly if they react with DNA in a DNA repair pathway.
way that FA cells cannot repair. A common example is Asuka Hira, MD, Kyoto University, Japan presented
formaldehyde. her lab’s analysis of Japanese FA patients who are
Some of the aldehydes that can harm cells are ALDH2 deficient. Approximately 50% of the Japanese
endogenous or formed within the body as a result of population are normally ALDH2 deficient. Hira’s
normal metabolism, such as the processing of alcohols, work supports the hypothesis that aldehydes are toxic
amino acids, lipids, etc. Some are from outside the body
or exogenous, like a number of drugs and environmental Aldehydes are highly reactive
agents, including the ethanol found in alcoholic substances that can injure cells,
beverages we drink.
particularly if they react with DNA in
To prevent aldehydes from causing damage, they are
a way that FA cells cannot repair.
first broken down by the cell, using enzymes called
“aldehyde dehydrogenases.” If the aldehyde persists
and causes DNA damage, the working Fanconi anemia to HSCs, and the FA pathway is counteracting this
pathway repairs it. With a defect in an FA gene, damage damage. The researchers determined that 23 of 55
to cells will accumulate. FA patients had one ALDH2 mutated gene allele, 2
had both ALDH2 mutated gene alleles, and 30 were
Aldehydes and Bone Marrow Failure
normal for both alleles. The two homozygous cases
Researchers at the laboratory of K.J. Patel, MD,
were both gravely ill. In all 25 cases where the patients
PhD, MRC Laboratory of Molecular Biology,
were deficient in at least one of the ALDH2 alleles,
Cambridge, UK, are conducting research to explain
bone marrow failure was strongly accelerated, but the
the relationship between aldehydes and bone marrow
deficiency did not affect the development of MDS or
failure in FA. Gerry Crossan, PhD, presented work
leukemia. Both FA patients with an ALDH2 mutation
showing that the identity of the enzyme responsible
and those with normal ALDH2 experienced the same
for aldehyde detoxification for hematopoietic stem
rates of developing MDS or leukemia. Interestingly,
cells (HSCs) is the aldehyde dehydrogenase ALDH2.
body weight at birth and number of physical anomalies
HSCs that lack both ALDH2 and FANCD2 genes
were not significantly affected by the lack of ALDH2.
are much more damaged than those lacking either
continued on page 2
Family Newsletter #53 3
Aldehyde Research Aldehydes and Cancer
Leslie Ann Cruz, PhD, from Daria Mochly-
continued from page 7
Rosen’s laboratory at Stanford University, Stanford,
Aldehydes and Developmental Defects Cal., presented a poster, which described the work
Nina Oberbeck, from the MRC, presented her work of Che-Hong Chen, PhD and her attempts to find
on mice embryos. By examining different genetic small molecules that can reduce DNA damage and
combinations of mothers and embryos, she concluded development of cancer associated with aldehydes.
that the mother’s ability to break down aldehydes Acetaldehyde is an aldehyde produced after alcohol
S determined the existence of DNA damage in the embryo ingestion. The researchers used an alcohol intoxication
y and the embryo’s subsequent developmental defects. The model in mice treated with Alda-1 (a small molecule
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work also showed that the placenta did not protect the activator of ALDH2) and Alda-89 (a small molecule
p embryo by breaking down these aldehydes and therefore activator of ALDH3, which is another aldehyde
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did not protect the embryo from DNA damage. dehydrogenase). They found that acetaldehyde
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These findings open areas for further exploration. For breakdown with Alda-89/Alda-1 treatment was
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u example, could developmental defects in FA be reduced significantly better compared to Alda-1 treatment alone.
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by drugs like cysteamine that mitigate the damaging Since ALDH3 is normally expressed in the mouth and
effects of aldehydes? Could a pregnant mother’s complete esophagus, where many of the solid tumors associated
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abstinence from alcohol or observance of a low-fat diet with exposure to aldehydes occur, their next studies
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w reduce her endogenous production of aldehydes and will be to determine whether recruiting ALDH3 to
s therefore reduce defects? metabolize toxic aldehydes reduces upper aero-digestive
cancer risk in rats and mice.
TALENS: A New Gene Editing Technique
Mark Osborn, PhD, correction of the mutated DNA to normal DNA.
University of Minnesota, One of the most powerful gene editing reagents,
Minneapolis, states that called “transcription activator like effector nucleases”
achieving the goal of or TALENS, functions as “molecular scissors.” TALEN
developing the optimal gene proteins exist in nature and are used by bacteria to alter
therapy approach for FA is “the the gene expression of the plant species they colonize.
highest priority in my lab.”
Gene therapy holds great The end result is the permanent
promise for treating numerous
correction of the mutated DNA
diseases. This therapy often
to normal DNA.
relies on a viral delivery
system to transport genetic material into cells. A critical
limitation of this strategy is that the virus transporting Research specialists at Iowa State University, Ames,
the therapeutic gene can integrate into a location in the Iowa and the University of Minnesota, Minneapolis,
patient’s genome that causes harm, such as cancer. re-engineered these proteins to generate highly specific
In contrast, gene editing specifically targets a tools for gene correction in human disease. A group at
typographical error in the DNA code for replacement the University of Minnesota has shown the ability of
with the normal sequence. Molecular “scalpels” can be TALENS to correct the human FANCC gene. This work
designed that preferentially excise the damaged DNA. provides proof of concept for TALENS in FA therapies.
The “wound” is sutured using a powerful and highly As the TALEN and gene therapy fields converge to define
accurate cellular repair pathway called homologous the optimal gene therapy approach, a new therapeutic
recombination. The end result is the permanent tool will become available to the FA community.
4 Family Newsletter #53
The Pursuit of Stem Cell Expansion
Fully functional blood infection and is a critical barrier to successful outcome,
stem cells can now be according to Colleen Delaney, MD, Fred Hutchinson
expanded in culture, Cancer Research Center, Seattle. Dr. Delaney described
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an approach that could a study to determine if cord blood cells, expanded in the
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revolutionize stem cell laboratory, could hasten the time to engraftment. Twenty
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transplants and eventually non-FA patients received partially matched double
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gene therapy. cord blood transplants. They were first infused with
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Jakub Tolar, MD, PhD, unmanipulated cells and, after four hours, were given
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University of Minnesota, cord blood stem cells expanded in the laboratory. Time
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Minneapolis, noted that a to engraftment (defined as an ANC >500) was 12 days,
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general rule of blood and instead of a median of 25 days without cell expansion.
marrow transplant is that “the higher the number of N
immunologically-matched hematopoietic stem cells
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Stem cell expansion could
(HSCs) available from the donor, the better for the w
patient’s engraftment and outcome.” HSCs are required change the field of transplant as s
in relatively high numbers on the day of transplant for
we know it.
the graft to take permanently. In umbilical cord blood
transplants, however, the number of stem cells is limited.
Researchers in the laboratory of Hans-Peter Kiem, Anthony Boitano, PhD, Genomics Institute of the
MD, University of Washington, Seattle, have tested use Novartis Research Foundation, San Diego, stated that
of expanded stem cells in a nonhuman primate model researchers at his center have identified a molecule
and observed very rapid neutrophil engraftment. After (SR1) that creates a 17-fold increase in the number of
transplant, two of three animals did not require any red functional HSCs. Using these manipulated cells, phase
blood cell or platelet transfusions. one/two clinical trials are underway for non-FA patients.
The significant delay in white cell recovery following Dr. Tolar concluded that these advances will “change
cord blood transplants leads to an increased risk of the field of transplant as we know it.”
Effectiveness of HPV Vaccines in Individuals with FA
No published studies have determined if individuals One FA patient, studied both three and five years after
with FA inoculated with a human papillomavirus (HPV) vaccination, consistently exhibited titers in the normal
vaccine have mounted sufficient antibodies against HPV. range. Dr. Alter concludes that for most FA patients,
Blanche Alter, MD, MPH, National Cancer Institute, Gardasil provides protection against HPV similar to
Rockville, Md., has now determined the post-vaccine what is achieved in non-FA individuals.
“titer” level for ten FA patients vaccinated with Gardasil.
Titers measure the relative amount of protective For most FA patients, Gardasil
antibodies mounted in response to a vaccine. Of these provides protection against HPV
ten patients, nine had sufficient titers. One male, seven
similar to what is achieved in non-FA
years post-transplant, had low titers.
individuals.
Family Newsletter #53 5
HPV Not Detected in FA Head and Neck Cancers
in Two Small Studies
oropharyngeal cancers, and four were vulvar/vaginal
cancers. The only cancer positive for HPV was one of the
four gynecological cancers.
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Laboratory findings of Susanne Wells, PhD, Cincinnati
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Children’s Hospital Medical Center, Cincinnati, OH,
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and Maura Gillison, MD, PhD, Ohio State University,
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Columbus, Ohio were similar to those from NCI. Of 10
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cancers studied, nine of nine FA head and neck cancers
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HPV positive.
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Blanche Alter, MD, MPH; Susanne Wells, PhD
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potentially causing cancers affecting FA patients is still a affecting FA patients is still a major
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major unresolved controversy. Two recent reports, based
unresolved controversy.
on extremely small numbers of FA patients, suggested that
HPV might play a role in gynecological cancers, but these
studies did not detect HPV in the head and neck squamous Studies consistently show that HPV is often implicated
cell carcinomas (HNSCCs) from these FA patients. in gynecological cancers in women with FA, but that
Blanche Alter, MD, MPH, National Cancer Institute, HPV alone cannot explain the high incidence of head
Rockville, Md., studied nine tumors from individuals and neck cancers in the FA population. Vaccination is
with FA. Three were cancers of the oral cavity, two were still recommended for all individuals with FA.
Mouse Studies Find a Higher Immune Response to
Gardasil than Cervarix in FA-deficient Mice
HPV plays a significant Health & Science University (OHSU), Portland, Ore.
role in causing certain Dr. Saldana presented the work of Jason Taylor, MD,
cancers in the general PhD and his investigators at OHSU at our fall 2012
population. It has been Symposium. Dr. Taylor found that FA-deficient mice,
implicated in some FA treated with Cervarix, mount far fewer antibodies
cancers as well. Two against HPV than non-FA (wild-type) mice. However,
commercially available both wild-type and FA-deficient mice mount a similar
vaccines, Cervarix and antibody response to Gardasil. These mouse studies
Gardasil, are highly suggest that Gardasil might be more effective than
effective in preventing HPV Cervarix in protecting FA patients from HPV.
infection in the general The ultimate test of the effectiveness of Cervarix and
population. Gardasil in preventing HPV in individuals with FA will
Mice deficient in Fancc provide an appropriate have to come from studies on humans, since mice and
preclinical model to test HPV vaccine response in FA, humans do not share an identical immune system.
according to Blachy Davila Saldana, MD, Oregon
6 Family Newsletter #53
Solid Tumors and FA
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David Kutler, MD; Robert Sclafani, PhD; Chantal Stoepker, MSc; Ian Mackenzie, DDS, PhD

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One-third of FA adult survivors will develop head A Novel Treatment with Resveratrol w
and neck squamous cell carcinomas (HNSCC), vulvar Robert Sclafani, PhD, University of Colorado, Aurora, s
cancers and other solid tumors by age 40. Not only does Colo., gave an exciting presentation on the effect the
the DNA repair defect characteristic of FA patients lead nutraceutical resveratrol can have in inhibiting and
to earlier onset of cancer, it compromises the patient’s perhaps eliminating cancer, particularly in FA patients.
response to many conventional chemotherapeutic agents. Resveratrol is found in many plants, including red grape
The following is a summary of some thought-provoking skins, peanuts and some berries.
presentations on prevention, early detection, and novel Previous animal studies on FA mice done by Marcus
approaches to treatment of tumors in FA patients. Grompe, MD’s group at the Oregon Health & Science
University, Portland, Ore., showed resveratrol caused no
HNSCC Treatment for Fanconi Anemia Patients
toxicity. Dr. Sclafani’s studies on cells from FA patients
in the IFAR
showed that resveratrol selectively stopped HNSCC
David Kutler, MD, Weill Cornell Medical
and ovarian cancer cells with no effect on normal cells.
Center, New York, presented his group’s study of the
Resveratrol achieves this by damaging cancer cell DNA
management and outcome of FA patients with HNSCC.
during the replication phase, thereby activating the body’s
Researchers studied patients enrolled in the International
own process to destroy damaged cells. This process is
Fanconi Anemia Registry (IFAR) who developed
actually enhanced by the DNA repair defect in FA cells.
HNSCC and were treated in the United States. The chart
Sclafani’s group is doing further experiments on FA
on page 8 summarizes their data.
HNSCC cells to test the hypothesis that resveratrol
FA patients have a high risk of developing aggressive
accomplishes its effect by partially slowing an enzyme
HNSCC at an early age. They can tolerate complex
used in DNA replication (called polymerase alpha) which
surgeries to treat the cancer, but careful post-operative
causes the DNA damage. Next, they will test cells where
care is needed. Their poor tolerance of radiation and
they have knocked out genes that they have previously
chemotherapy makes additional treatment difficult.
identified as potential resveratrol sensitizers to identify
However, radiation should be used for high-risk cancers
new pathways that could be targeted by drugs to enhance
because of the poor survival of these patients otherwise.
resveratrol’s effect.
Further study of FA patients’ response to various
Dr. Sclafani hopes resveratrol will eventually prove to
treatments should be initiated, to establish appropriate
be a safe, non-toxic and inexpensive compound to either
doses while limiting toxicity.
prevent and/or treat HNSCC in FA patients.
continued on page 8
Family Newsletter #53 7
Solid Tumors and FA
continued from page 7
Population of FA patients studied 25 with HNSCC; 12 male, 13 female
Age cancers developed Mean age of 33.5 years, range 15 to 48 years; median 30
Location of cancer Oral cavity 20; larynx 3; oropharynx 1; unknown 1.
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20% had tobacco and alcohol risk factors; 9 had prior bone marrow
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transplant
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HPV status of the tumor
s specimens HPV positive
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Surgery treatments
tions; no post-operative deaths

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e 12 received post-operative radiation therapy, average dose of 5278
Radiation management
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Toxicities from radiation High-grade mucositis 9/12; dysphagia 8/12; and pancytopenia 6/12;
only 4/12 survived
Survival 5-year overall survival was 27%, with a cause-specific survival of 41%
HNSCC Cell Lines as Tools to Develop Novel develop three ominous abilities: the ability to cause local
Treatments for FA Patients tumors, the ability to travel to distant tissue and cause
Chantal Stoepker, MSc and Johan de Winter, tumors (metastasis), and the ability to become resistant
PhD, Vrije Universiteit Medical Center, Amsterdam, to chemo- and radio-therapies. For this transformation
Netherlands, presented a poster describing how their called EMT (epithelial-mesenchymal transition) to occur,
group established three HNSCC cell lines from tissue the cell needs a signal from a protein produced in a
obtained from three FA patients who had squamous cell separate pathway called EGF (epidermal growth factor).
carcinoma (mouth mucosa FANC-A; floor of the mouth Mackenzie’s group concluded that if you can block
FANC-C ; and tongue FANC-L). These FA-HNSCC cell EGF, then the cells do not transform and cell death
lines will be used for the development of novel treatment follows. They examined how well three existing cancer
options, including more targeted therapies and perhaps treatments, Cetuximab (also known as Erbitux),
preventive treatments. Erlotinib and Tyrphostin could block EGF so that EMT
would not occur.
Therapeutic Resistance in Head and Neck Cancers
This specific targeting of particular cancer cells is a
Ian Mackenzie, DDS, PhD, Barts and The London
better way to treat FA patients for whom the side effects of
Medical School, London, presented his investigation of
DNA-damaging chemo- and radio-treatments are severe.
how some HNSCC cells lacking Fanconi gene function
S a v e t h e 25th Annual Fanconi Anemia Research Fund Scientific Symposium
D a t e !
October 24-27, 2013 • Hyatt Regency Houston
Houston, Texas • www.fanconi.org
8 Family Newsletter #53
Bone Marrow Transplantation: Point/Counterpoint
One of the most exciting sessions during the Scientific Symposium was a series of debates concerning decisions
and questions facing parents and individuals with FA. Experts with differing opinions gave a lively defense of their
positions. This thought-provoking exchange highlighted the difficulty families face in choosing the best treatment
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options. Larger patient numbers and improving data will help to clarify choices when facing a crucial crossroads.
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Should danazol be offered before patients with matched sibling donors. The protocol for m
transplant for bone marrow failure in FA? patients with alternative donors includes radiation. p
Minnesota has achieved impressive survival rates with o
YES
a conditioning regimen including total body irradiation s
Helmut Hanenberg, MD, Indiana University, i
(TBI) of 300 rads for patients with alternative donors. u
Indianapolis, made the case for offering danazol, a
The probability of survival is now 92% for patients m
very mild synthetic androgen, to a certain subset
with no prior history of transfusions or opportunistic
of FA patients. He acknowledged that those with N
infections.
myelodysplasia (MDS) or leukemia need to be e
Dr. MacMillan stated that both TBI and busulfan have
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transplanted immediately, but patients with a clinically
significant, but different, toxicities. TBI carries a risk for
milder disease and/or declining blood counts in the s
cataracts and hypothyroidism whereas busulfan can cause
absence of MDS or leukemia should be offered this
alopecia, veno-occlusive disease and hemorrhagic cystitis.
option. Danazol was well tolerated and did not show
Neither is more likely than the other to increase the risk
masculinizing side effects in a recent study of eight
of post-transplant malignancies.
patients with FA. Seven of these patients had a robust
In a trial of busulfan for nine patients with advanced
blood count response, some for several years. Danazol
disease, the toxicity rate was unacceptable, with the exception
can provide precious time to make decisions or find
of BRCA2 patients who tolerated this therapy well. The
an optimal donor. Some patients, perhaps as many as
standard of care at this center remains cyclophosphamide,
30%, may never need a stem cell transplant. If necessary,
fludarabine, TBI300 and thymic shielding.
patients can still go to transplant after danazol.
NO
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Farid Boulad, MD, Memorial Sloan-Kettering Cancer
Margaret MacMillan, MD, University of Minnesota,
Center, New York, stated that studies of non-FA patients
Minneapolis, stated that ten to twenty years ago patients
show two factors consistently associated with increased
wanted to buy time since transplant outcomes were so
risk of secondary malignancies post-transplant: graft-
uncertain. However, survival following bone marrow
versus-host disease and radiation. TBI is also associated
transplant has improved greatly and toxicity has decreased
with organ toxicity, growth impairment, gonadal
significantly. In most cases, there is no longer any need to
dysfunction and other post-transplant complications.
delay transplant by going on androgens, even androgens
Memorial Sloan-Kettering and other centers have
as mild as danazol. If there is an appropriate donor, the
reduced the risk of GvHD using T-cell depleted
downside of taking danazol is that patients might lose the
transplants. In an effort to reduce the risk of radiation
most optimal time to proceed to transplant.
toxicity post-transplant including the risk of secondary
malignancies, Dr. Boulad and others have initiated a
Should radiation be used in the
multi-center trial, substituting busulfan for radiation.
conditioning regimen for FA transplants?
To date, 27 patients have been treated on this protocol at
YES (with certain patients) four institutions. GvHD has been minimal (two patients
The answer depends primarily on the type of donor developed grade 1; one patient developed grade 2 GvHD).
available, according to Margaret MacMillan, MD, Twenty-three of the 27 patients are alive and well.
University of Minnesota, Minneapolis. Neither radiation Dr. Boulad asks: Why use radiation if there is an
nor busulfan is used at her center when transplanting alternative which leads to a comparable outcome?
Family Newsletter #53 9
Transplant Outcomes from Curitiba, Brazil
Carmem Bonfim, MD, are alive, one with active disease. Patients with cGvHD
Federal University of developed this complication much earlier and at a
Parana, Curitiba, Brazil, younger age than patients who did not have cGvHD.
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presented a follow-up of But three patients with cancer did not develop cGvHD.
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126 patients transplanted Dr Bonfim writes these poignant yet hopeful words:
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at her center from October “In the beginning, our poor patients (who didn’t have
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1983 to October 2009 who a chance to go to a dentist EVER) got diagnosed very
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survived two or more years late. Our country is big and they didn’t have money to
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i post-transplant. Today, 108 come back to our unit. Now we have family meetings;
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of these patients survive. we teach them how to take care of themselves and be
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Survival outcomes have their own advocates, and we are very clear about the

N improved dramatically in recent years: 73% of patients
e transplanted between 1983 – 2003 survived more than
Transplant survival outcomes
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have improved dramatically in
s from 2003 – 2009. The transplant regimen now
includes 60mg/kg cyclophosphamide; patients are not recent years.
given radiation or busulfan. In spite of these excellent
results, Dr. Bonfim expressed concern about the long-
term problems patients encounter post-transplant. ‘known’ cancer risks. Survival is MUCH, MUCH
Patients frequently experienced an increase in better after transplantation, but it can be even MUCH,
endocrine problems post-transplant. Chronic GvHD MUCH better if we try to prevent or detect cancer
(cGvHD), infections and malignancies were the most earlier. So, transplanted and non-transplanted patients
frequent causes of death. Eleven patients developed should ALWAYS take care, lifelong!”
squamous cell carcinoma of the tongue and only three
Long-term Follow-up of Patients After
Alternate Donor Transplants
Farid Boulad, MD, received 450 rads of TBI as part of the conditioning
Memorial Sloan-Kettering protocol, and three were conditioned with busulfan
Cancer Center, New York, followed by T-cell depletion. None of these long-term
discussed post-transplant patients developed chronic GvHD.
complications experienced One patient experienced a relapse of myelodysplastic
by a cohort of 21 patients syndrome three years post-transplant. Two patients
who had survived disease- developed squamous cell carcinoma, one of the vulvo-
free for at least one year, vaginal area (with dysplasia present pre-transplant) and
following an alternative one of the tongue. Cancers occurred 3.7 and 7.2 years
donor transplant. Patients post-transplant, at the ages of 27 and 28.
ranged in age from 4.5 to Eleven of the 21 patients, including four multiply
35 years. Eighteen patients transfused, had low-normal ferritin, while 10 patients
10 Family Newsletter #53