1. No category

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Hematologic Abnormalities in Fanconi Anemia: An International Fanconi
Anemia Registry Study
By Anna Butturini, Robert Peter Gale, Peter C. Verlander, Barbara Adler-Brecher,
Alfred P. Gillio, and Arleen D. Auerbach
We analyzed data from 388 subjects with Fanconi anemia
reported to the International Fanconi
Anemia
Registry
(IFAR). Of those, 332 developed hematologic abnormalities
at a median age of 7 years (range,
birth to 31 years). Actuarial
riskof developing hematopoietic abnormalities was 98%
(95% confidence interval, 93% to 99%) by 40 years of age.
Commonhematologicabnormalities
were thrombocytopenia and pancytopenia. Thesewere often associated with
decreased bone marrow (BM) cellularity (75%of cases studied). Clonal cytogenetic abnormalities developedin 23 of 68
persons with BM failure who had adequate studies. Actuarial
risk of clonal cytogenetic abnormalities during BM failure
was 67% (47%to 87%) by 30 years of age. Fifty-nine subjects
developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML
of age. Risk was higher in
was 52% (37%to 67%) by 40 years
persons with than in those without a prior clonal cytogenetic
abnormality (3% 10% to 9%1 Y 35% [O% to 79961; P = .006).
One hundred twenty persons died of hematologic causes
including BM failure, MDS or AML and treatment related
complications.Actuarialrisk
of death from hematologic
causes was 81% (67% to 90%) by 40 years of age.
0 1994 by The American Societyof Hematology.
F
all cases, diagnosis was confirmed by DEB testing performed at The
Rockefeller University. Registration into the IFAR was usually at
the time of DEB testing and included information on congenital and
hematologic abnormalities. In persons with hematologic abnormalities, an attempt was made to obtain results of prior laboratory studies.
The frequency and completeness of hematologic studies were not
prospectively defined. Follow-up data were collected by different
modalities. In about 30% of cases, physicians sent reports of some
or all hematologic studies. In about 10% of cases, hematologic studies were performed on one or more occasions at The Rockefeller
University Hospital or affiliated institutions. Comprehensive attempts to obtain follow-up data were made in 1989 and in 1993 by
sending physicians of all living subjects detailed follow-up forms.
Response rates were about 75% in 1989 and 50% in 1993.
Definition of abnormalities. Hematologic abnormalities were defined as follows: thrombocytopenia, platelets less than 1 0 0 X IOy/
L, anemia, hemoglobin (Hb) less than 10 g/dL and neutropenia,
neutrophils less than 1 X 10y/L. Pancytopenia wasdefinedasan
abnormality in two or three blood cell lineages. Less severe decreases
in blood cells and alterations inredblood cell mean corpuscular
volume (MCV) and fetal Hb (HbF) were noted, butnot scored
as abnormalities. Decreases in blood cell levels from concomitant
nonhematologic diseases were also not scored as abnormalities.
Myelodysplastic syndrome (MDS) is a known complication of
Fanconi anemia.8,9Diagnosis of MDS usually does not require increased bonemarrow (BM) myeloid blasts. However, because of
interobserver variability in the diagnosis of MDS and the lack of
central review of BM, we defined as MDS only those cases with
5% to 30% myeloid blasts in the BM or 5% to 20%myeloid blasts
in the blood. BMs with myelodysplastic features but with less than
5% myeloid blasts were noted but not scored as MDS. Acute myelogenous leukemia (AML) was defined as greater than 30% myeloid
blasts in the BM or greater than 20% myeloid blasts in the blood.
MDS and AMLwere considered the initial hematologic abnormality
when they were diagnosed within 6 months from first detection of
thrombocytopenia or pancytopenia.
In this analysis, unless otherwise specified, we use the term BM
failure to indicate hematologic abnormalities other than MDS or
AML regardless of BM cellularity or whether these were diagnosed
by BM studies or not.
Cytogenetic abnormalities were termed clonal when 2 2 metaphases had the same or a related abnormality. Cytogenetic studies
showing only normal metaphases were considered adequate unless
reported as inadequate by the referring laboratory or physician.
Statistical analysis. Actuarial risk of hematologic events and
death was calculated by life-table analysis.’’ Univariate analysis was
performed by the Mantel-Cox test.” Multivariate statistical models
ANCON1 ANEMIA is an autosomal recessive disease
characterized by aplastic anemia and congenital abnormalities.’ Hypersensitivity to DNA cross-linking agents, like
diepoxybutane (DEB), is often used as a diagnostic test.’
DEB testing allows diagnosis of Fanconi anemia in persons
with diverse clinical features including those without clinically detectable congenital abn~rmalities.~
Complementation studies suggest that the genetic bases
of Fanconi anemia are heterogeneo~s.~.~
Abnormalities in at
least four genes, defined by complementation groups A, B,
C, and D, result in increased DNA cross-linking sensitivity’
that characterizes Fanconi anemia. Group C complementing
gene (FACC) was recently cloned! Mutation analysis suggests a correlation between genetic and clinical features in
persons with abnormalities in this gene.7
Although hematologic abnormalities are common in persons with Fanconi a ~ ~ e m i atheir
, ~ , ~natural history is uncertain. Most studies are of small numbers of subjects with brief
follow-up. We analyzed hematologic abnormalities in 388
persons with Fanconi anemia reported to the International
Fanconi Anemia Registry (IFAR).
MATERIALS ANDMETHODS
Registry characteristics. The F A R was established in 1982 to
study clinical features of persons with Fanconi anemia.’.’’ In almost
From the Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; the Department of Medicine, UCLA
School of Medicine, Los Angeles, CA: and the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.
Submitted May 10, 1993; accepted May 3, 1994.
Supported in part by Grants No. HL 32987 (to A.D.A.)and RR
00102 from the National Institutes of Health (to A.D.A.)and grants
from the Center for Advanced Research in Leukemia (to A.B.).
R.P.G. is the Wald Foundation Scholar in biomedical communications.
Address reprint requests to Anna Butturini, MD, Department of
Pediatrics, Division of Hematology and Oncology, University of
Parma, viale Gramsci 14, 43100 Parma, Italy.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
“advertisement” in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
0 1994 by The American Society of Hematology.
0006-4971/94/8405-0032$3.00/0
1650
Blood, Vol 84, No 5 (September l ) , 1994: pp 1650-1655
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ABNORMALITIES
HEMATOLOGIC
IN FANCONI ANEMIA
1651
Table 1. Actuarial Risk (95% confidence interval) of Hematoloaic Abnormalities in Fanconi Anemia
interval
N*
10 yrs
20 yrs
From birth
Hematologic abnormalities
Clonal cytogenetic abnormalities
MDS/AML
Deatht
488
68
388
332
73% (67-78)
15% (6-25)
7% (4-10)
16% (13-21)
93% (89-96)
37% (21-56)
27% (20-35)
45% (38-54)
97% (94-98)
67% (47-87)
43% (30-44)
65% (54-75)
From detection of hematologic abnormality
Clonal cytogenetic abnormalities
MDS/AML
Deatht
68
311
332
42% (25-60)
22% ( 14-31)
45% (30-53)
81% (63-96)
48% (35-60)
80% (59-92)
91% (75-100)
70% (62-79)
86% (74-95)
30 yrs
40 yrs
98% (93-99)
-
52% (37-67)
81% (67-90)
Number at risk.
t Death caused by hematologic abnormality.
were obtained by thestepwise step-up Cox proportional hazard
technique using the BMDP ~rogram.’~
Variablesconsideredweresex
and age at DEB testing.
The relationship between clonal cytogenetic abnormalities during
BM failure and successive development of MDS or AML was analyzed byFisherexacttest
andby life-table analysis.” Life-table
analysis was performed by entering subjects at the time of the first
cytogenetic study except asfollows. Subjects in whom first detection
of a clonal cytogeneticabnormality and diagnosis of MDS or AML
were coincident were excluded. Persons with
2 2 cytogenetic studies
inwhom . z 1 studies showed a clonal abnormality detected before
developing MDS or AML were entered into the life-table analysis
at the time of the clonal abnormality.
Statistical analyses were performed with and without censoring
persons who received BM or cord blood cell transplants at the time
of transplant. Results were similar in each case. Consequently,data
shown are the resultsof analyses performed withoutcensoringtransplant recipients at time of transplant unless otherwise specified.
RESULTS
Subject characteristics. 388 subjects were registered between 1982 and 1992. Of those, 205 were male and 183
female. Median age at DEB testing and registration was 6
years (range, birth to 36 years). In 328 persons, diagnosis
of Fanconi anemia was suspected because of congenital and/
or hematologic abnormalities. The remaining 60 persons
were siblings of probands. Additional details are p~blished.~
Median follow-up was 5 years (0to 10 years) from DEB
testing and 6 years (0to 36 years) from first detection of a
hematologic abnormality. Median age of subjects at the last
observation or death was 1 1 years (1 month to 41 years).
Median number of blood studies per subject per year of
known hematologic abnormality was 0.7 (0.1 to 11). Median
number of BM studies per subject per year of known hematologic abnormality was 0.1 (0to 3).
Initialhematologicabnormalities.
Hematologic abnormalities were detected in 332 persons. In 274 persons, these
were present at the time of DEB testing. In 58 others, these
were detected a median of 3 years (1 to 13 years) after DEB
testing. Median age at detection of a hematologic abnormality was 7 years (birth to 31 years). Actuarial risk of developing a hematologic abnormality by 40 years of age was
98% (95% confidence interval, 93% to 99%) (Table 1, Fig
1 ).
Initial hematologic findings were diverse; 128 persons
(38%) presented with thrombocytopenia, 176 (53%) with
pancytopenia, 13 with MDS, 7 with AML, 6 with anemia,
1 with acute lymphoblastic leukemia (ALL) and 1 with neutropenia. Platelets were higher (50[20 to 981 v 35 [2 to 651
X lo9 L; P < .001) and age at diagnosis younger (5 years
[birth to 17 years] v 8 years [birth to 31 years]; P = .009)
in persons presenting with thrombocytopenia than in those
presenting with pancytopenia. MCV was increased in 189
of 191 evaluable persons and HbF in all 79 studied persons.
BM studies at first detection of a hematologic abnormality
were reported in 168 persons; 125 (75%) showed reduced
BM cellularity, 22 (13%) normal or increased cellularity, 20
(12%) MDS or A M L , and 1 ALL.
Disease
evolution.
Of 128 persons presenting with
thrombocytopenia, 62 progressed to pancytopenia after a median of 3 years (3 months to 15 years). Actuarial risk of
progression to pancytopenia was 84%(72%to 92%)20 years
after thrombocytopenia was first detected.
risk ot
hematologic
abnormality
100 n-
80
+-
N of want8
1
I
BO n -
40 2 -
20 4!
-
k
6
6
l
II;
l o
20
I
10
lt::
40
16
20
26
30
36
40
yearn
Fig 1. Hematologic abnormality. Line indicates the actuarial risk
of hematologic abnormalities by years of age in the 388 patients
represent 95% confidence interval).
with Fanconi anemia. (Error bars
Histogram indicates age distribution recorded as number of events
over 5-year intervals (U, probands; M, siblings).
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BUTTURlNl ET AL
1652
risk of
MDSlAML
N of events
t
t
25 20
5 15 10
30
35
40
years
Fig 2. MDS/AML. Lineindicates the actuarial risk of MDS/AML
by years of agein the 388 patients with Fanconi anemia. Histogram
indicates age distribution (0.MDSlAML developing in persons with
prior BM failure; m, MDS/AML diagnosed as first hematologicabnormality).
Of the 3 l 1 persons with BM failure, 39 developed MDS
or AML after a median of 9 years (1 to 17 years) from
detection of a hematologic abnormality. Actuarial risk of
developing MDS or AML was 48% (35% to 60%) 20 years
after BM failure was detected.
Persons with BM failure received diverse treatments including androgens, corticosteroids, hematopoietic growth
factors and transfusions. Fifty-eight persons received BM or
umbilical cord blood cell transplants from HLA identical
siblings or alternative donors. Because treatment wasnot
given in a prescribed way and treatment modalities evolved
over several years, no attempt was made to analyze the impact of treatment on disease evolution or survival.
MDS and AML. 34 persons developed MDSand25
AML, including 10 with prior MDS. Medianage at detection
of MDS or AML was 13 years ( l month to32 years). Actuarial risk of developing MDS or AML by 40 years of age was
52% (37% to 67%) (Table 1, Fig 2).
In 20 persons, MDS or AML was the first hematologic
abnormality detected. In the other 39 cases, MDS or AML
developed after BM failure. Age at diagnosis of leukemia
was significantly younger in persons without than those with
prior BM failure (7 years [ l month to 20 years] v 17 years
[6 to 32 years]; P < ,0001) (Fig 2). Age at detection of first
hematologic abnormality did not differ significantly between
these groups (7 years [ 1 month to 20 years] v 9 years [ 1
month to 30 years]).
Eight of 34 persons with MDS received a BM transplant,
and therefore, were unevaluable for disease evolution. Of
the remaining 26 persons, 10 progressed to AML after a
median of 2.5 years (0.5 to 7 years), 9 of the remaining 16
died of hematologic complications after a median of 2 years
(0.5 to 6 years), and 7 are alive at a median of 1 year (1
month to 10 years) after diagnosis of MDS.
Five of 35 persons with AML (10 with prior MDS) received transplants, and therefore, were unevaluable for dis-
ease evolution. Of the remaining 30 persons, 26 died within 3
months from diagnosis of AML with BM aplasia or resistant
leukemia, and 1 has been followed-up lessthan 3 months.
In 3 persons, treatment decreased BM myeloblasts to less
than 5%; 2 had persistent myelodysplastic BM and clonal
cytogenetic abnormalities and died of infection after 1 and
2 years. The third subject had hypoplastic BM withonly
normal metaphases for 9 years until dying of hepatocellular
carcinoma.
Survival. 135 of the 388 persons with Fanconi anemia
died at a median age of 13 years (1 month to 40 years). In
the 332 persons with hematologic abnormalities, there were
129 deaths; 120 deaths were directly or indirectly caused by
hematologic abnormalities and 9 were from other causes,
including 6 from cancers other than leukemia.
Of 120 deaths from hematologic abnormalities, 49 were
from BM failure, 37 from treatment-related complications
after transplant and 34 from MDS or AML. Actuarial risk
of death from a hematologic cause by 40 years of age was
81% (67%to 90%) (Table l and Fig 3). Median interval
from onset of a hematologic abnormality to death was 7
years (1 month to 35 years). Actuarial risk of death after 20
years from first detection of hematologic abnormalities was
80% (59% to 92%). Censoring the 71 persons who received
transplants at the time of transplant did notsignificantly
affect these results.
BM cytogenetics. Cytogenetic studies were performed
one or more times on BM samples from 105 persons. Some
of these data are p~blished.'~
Eighty-eight persons were studied during BM failure. Cytogenetic studies were performed
a median of 5 years (0 to 20 years) after detection of a
hematologic abnormality. In 85 persons there was no report
of myelodysplasia in a concurrent histologic study; 3 were
reported to have myelodysplasia with less than 5% myeloblasts.
Adequate cytogenetic studies were obtained in 68 persons:
45 (66%) had only normal metaphases and 23 (34%), clonal
riak of
N of events
death
I
6
20 15 10
25
30
35
150
40
years
Fig 3. Death from hematologicabnormalities. Line indicates actuarial risk of death from hematologicabnormalitiesby years of age in
the 332 persons with Fanconi anemia who developed hematologic
abnormalities. Histogram indicates age distribution.
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HEMATOLOGIC ABNORMALITIES IN FANCONI ANEMIA
1653
N of cases
l4
l"---"--bone marrow lailure
Fig 4. Cytogenetic abnormalities in persons with
Fanconi anemia and some marrow failure, MDS, or
AML. Bars show frequency of chromosome abnormalities [numerical and structural).
=Leukemia
1 2 3 4 5 6 7 8 9 10 11 12 1314 15 16 17 18 19 20 21 22
cytogenetic abnormalities on 2 1 study. Results of cytogenetic analysesaresummarizedinFig
4. Studiesshowing
only normal metaphases were performed in younger persons
(median age 9years[2
to 27years] v 16 years[3to
32
years]; P < ,0001) and earlier after detection of hematologic
abnormalities (2 years [0 to 24 years] v 7 years [0 to 20
years]; P = ,004) thanthose showingclonalcytogenetic
abnormalities. Actuarial risk ofdeveloping clonalabnormali30 years of age and 81%
ties was 67% (47% to 87%) by
(62% to 95%) by 20 years from detection of a hematologic
abnormality (Table 1).
Of 68 persons with adequate cytogenetic studies, 7 developed AML or MDSincluding 1 of 45 (2%) with only normal
metaphases and 6 of 23 (26%) with clonal cytogeneticabnormalities (P = . O M ) . Actuarialrisk of developing MDS or
AML within3 years from cytogenetic analysisinpersons
with BM failure and only normal metaphases was 3% (0%
to 9%) versus 35% (0% to 79%) in persons with BM failure
and clonal cytogenetic abnormalities (P = .006).
Clonal cytogenetic abnormalities were oftendetected in
close temporal proximity to the diagnosis of MDS or AML
(median 5 months [ l to 15 months]). To determine whether
prior knowledge of clonal cytogeneticabnormalities was predictive of leukemia development, we considered leukemia
risk in cases where either a normal or abnormal study was
reported 2 6 months before diagnosis of MDS or AML. Of
three leukemia cases meeting these criteria, two had prior
clonal
cytogenetic
abnormalities
(intervals
12 and 15
months) and one did not (interval 6 months). These cases
are too few for further analysis.
Evolution of clonalcytogenetic abnormalities wasanalyzed in persons who had BM cytogenetic studies on two or
more occasions. Eight persons had
2 2 studies during BM
failure. Two with onlynormal metaphases in the initial study
subsequently developed clonal cytogenetic abnormalities.
Six others with clonal cytogenetic abnormalitiesin the initial
study had the same abnormality on retesting.
Five other subjects were studied during BM f d u r e and
x
Y
Chromosome
after developing MDS or AML (TabIe 2). Three who had
only normal metaphases during BMfailure developed clonal
abnormalities after progressing to leukemia. The other two
had thesameor
related clonal abnormalities duringBM
failure and after developing leukemia.
Twenty-three persons were studied after developing MDS
or AML. All had at least one study showing clonal cytogenetic abnormalities. Loss of chromosome 7 or rearrangement
or loss of 7q and rearrangements of lp36 and 1q24-34 were
similarly detected in persons with BM and MDS or AML;
rearrangements of 11q22-25 were more frequent in persons
with MDS or AML (Fig 4).
Sibship. We analyzed hematologicabnormalitiesand
outcome in 106 members of 46 affected sibships.
Hematologic abnormalities weredetected in all 46 probands and 40 siblings. Median age at detection of hematologic abnormalities in probands was X years(0.5 to29).
Table 2. B M Cytogenetic Analyses in Persons Studied During B M
Failure and After Development of MDS or AML
UPN
Age
(yrs)
412-1
14
15
16
378-1 BMF
8
15
Status
Cytogenetics
BMF
BMF
MDS
46XY
46XY
46XY [151,47XY,+21 151
46XX
46XX. "-21, t(3;11)(q27;q21) [31/46XX, t(3;11;21)
[l1 (q27;qZl;pll) [l1
46XY
45XY. -7
46XY. de1(7q)(q22;q36)
46XY, de1(7q)(q22;q36) [131/46XY, de16(~23),
de1(7q)(q22;q36) [51
46XX
46XX [91/46XX, t(l;?)(p36:?) [ I l l
46XX, t(l;?)(p36:?) [81/46XX, t(1;6)(qZI;p21) I101
AML
187-1 BMF
6
MDS
8
390-1 30
BMF
31
MDS
44-2
8
9
10
BMF
BMF
MDS
Abbreviations: UPN, unique patient number;
failure.
EMF, bone marrow
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1654
BUTTURlNl ET AL
Actuarial risk of developing a hematologic abnormality by
40 years of age was 100%. Median age at detection of hematologic abnormalities in siblings was9 years (0.6 to 27
years). Actuarial risk of developing a hematologic abnormality by 40 years of age was 83% (71% to 92%).
Age at detection of hematologic abnormalities in probands
and siblings was correlated (R, 0.72; P = .0006). However,
there was no concordance for the type of first hematologic
abnormality within affected sibships. Also, development of
leukemia or death in one member of a sibship did not increase the risk of leukemia or death in the other siblings.
5
20
15
...............................
*
.
30 y
25
.3 *
MDSlAML
9........... clonal cytogenetic abnormality
...............
7
bone marrow failure
DISCUSSION
We used an observational database of 388 subjects with
Fanconi anemia most of whose diagnosis was confirmed by
DEB
Although large numbers of subjects and long
follow-up make this database unique in analyzing hematologic abnormalities of Fanconi anemia, there are potential
limitations. One is possible selective reporting. Another is
that there was no prospectively defined study design; frequency and extent of hematologic testing were determined
by the participating physicians even after subjects were registered. A third consideration is completeness and accuracy
of data reporting; no audits of reporting centers were performed. Certainty of our conclusions could be increased by
a prospective study. However, this would require substantial
numbers of subjects and a long observation period.
Our study indicates that most persons with Fanconi anemia develop a hematologic abnormality; actuarial risk was
98% (93% to 99%) at 40 years of age. Whether the few
older persons currently without hematologic abnormalities
will eventually develop them is unknown. A 50 year old with
Fanconi anemia dying without ever developing hematologic
abnormalities is reported (E. Gordon-Smith, personal communication, September 1993).
Our study indicates an actuarial risk of developing MDS
and/or AML of 52% (37% to 67%) at 40 years of age. This
exceeds the 15% rate cited in
most
This difference
is not surprising because prior estimates were based on small
sample sizes and were not actuarial. It should be emphasized
that our study may underestimate risk of developing MDS
and/or AML because of the relatively strict definitions we
used and because of nonprospective testing and ascertainment of hematologic data.
An interesting problem in Fanconi anemia is the relationship betweenthe different hematologic features. Data we
review suggest that thrombocytopenia and pancytopenia are
phases of a single process. For example, persons presenting
with thrombocytopenia were younger than those presenting
with pancytopenia. Also, most persons with thrombocytopenia had multilineage abnormalities, as shown by elevated
HbF and macrocytosis. The actuarial probability of progression to pancytopenia was 84% (72% to 92%) after 20 years.
A similar problem is the relationship between BM failure
and leukemia (Fig 5). In our study, the most striking data
suggesting that BM failure is a phase of leukemia development is the 67% [47% to 87%] actuarial risk of developing
clonal cytogenetic abnormality during BM failure by 30
years of age. Most of these clonal cytogenetic abnormalities
10
7
l
birth
5
10
15
20
25
30
35
40y
Fig 5. Chronology of hematdogie e v ~ t in
s person8 with Fmconi
anemia. Black arrows indicatethe 50th (Urus, 26th to 75th) percentile
actuarial risk of hematologic events by years of age.
Dotted scale
indicates interval from first detection of BM failure. White arrows
indicate the 50th (- - - -, 25th to 75th) percontila actuarial risk of
hematologic eventsby interval from first detection
of a hematologic
abnormality. *75th pamentile riskof MDSlAML not yet reached.
were similar to those reported in MDS and therapy-linked
AML in persons without Fanconi anemia,I5 developed late
in the course of hematologic disease and persisted when
leukemia developed. Also, in two subjects, the same clonal
cytogenetic abnormality was detected during BM failure and
leukemia. When we analyzed the association between detection of clonal cytogenetic abnormalities during BM failure
and subsequent risk of developing MDS or AML, we found
an increase in leukemia risk in persons with these abnormalities compared with those with only normal metaphases. Because our strategy of analysis excluded cases where clonal
cytogenetic abnormalities and leukemia diagnosis were concurrent, our results may underestimate the risk of leukemia
in persons with these abnormalities.
Controversy regarding the relationship between BM failure and leukemia in Fanconi anemia is similar to that regarding the relationship between aplastic anemia and leukemia
in otherwise normal per~ons.’~~’’
Although cytogenetic abnormalities are rare,’* some data suggest a substantial incidence of clonal hematopoiesis in persons with aplastic anemia.19.20 Also, some studies suggest an increased risk of
leukemia in persons who recover from aplastic anemia.zl.22
What is still uncertain is whether detection of clonal hematopoiesis during aplastic anemia increases leukemia risk. Experimental data link development of clonal hematopoiesis in
aplastic anemia to decreased stem cells rather than leuken~ia.’~
Fanconi anemia is an interesting model of leukemia development. Because many persons with Fanconi anemia will
develop MDS andor AML if they survive sufficiently long,
it is reasonable to regard the Fanconi anemia genotype as
‘ ‘preleukemia.” The subsequent development of hematologic abnormalities might occur as a direct consequence of
absence of the Fanconi gene product or because of an interaction of this abnormality with other intrinsic or extrinsic potentially leukemogenic factors.
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HEMATOLOGICABNORMALITIES IN FANCONIANEMIA
ACKNOWLEDGMENT
We thank physicians reporting data to the F A R and Drs Kathy
Sobicinsky, Kenneth Lange, and Glen Heller for help with statistical
analyses.
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From www.bloodjournal.org by guest on December 29, 2014. For personal use only.
1994 84: 1650-1655
Hematologic abnormalities in Fanconi anemia: an International
Fanconi Anemia Registry study [see comments]
A Butturini, RP Gale, PC Verlander, B Adler-Brecher, AP Gillio and AD Auerbach
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