12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
gy. There are not significant differences between different therapeutical
approaches in terms of the percentage of CR. IVIG and HDMP at 7.5
mg/Kg for 4 days seem to be the best treatments to reach as soon as possible
a safe platelet level ≥30×10 9 /L (3-6 days), and a CR (7-11 days).
Among NR (chronic) patients, seven have been splenectomized and only
3 reached a stable CR. We never observed a significant toxicity, nor
adverse events related to the treatment. Conclusions. Our experience
shows that there are no statistically significant differences in terms of CR
between the different treatments, even considering that more than 70%
of relapses and 39% of NR children can be cured with further treatments.
However, the main target of the treatment is to reach safe platelet
levels ≥30×10 9 /L as soon as possible to avoid life-threatening risks (spontaneous
bleeding and trauma for young children) or parent anxiety.
Therefore, IVIG (0,4 mg/kg) and HDMP (7,5 mg/kg/day) seem to be the
best options; the low costs of HDMP and its safety need to be considered.
The high percentage of CR after any kind of first line treatment,
let us to suppose that it is possible to obtain a spontaneous recovery in
the great majority of patients also without treatment. Therefore, the
extension of the 'wait and see' strategy for as many patients as possible
could be important. In children, in comparison to ITP adults, the splenectomy
cannot be considered an usual therapy and not always a successful
procedure.
0751
ITP INCIDENCE AND MORTALITY IN UK GENERAL PRACTICE RESEARCH DATABASE
J. Kaye, 1 M. Schoonen, 2 J. Fryzek2 1 2 Boston University, LEXINGTON, USA; Amgen, UXBRIDGE, United Kingdom
Background. ITP is an autoimmune disease characterized by low
platelet counts and an increased risk of bleeding. The epidemiology of
ITP in the UK has not been well characterized. The General Practice
Research Database (GPRD), which comprises computerized general
practice medical records for a population-based cohort of approximately
five million residents of the UK, provides an opportunity to quantify
the occurrence and outcomes of ITP in the general population. Aims.1.
Estimate the incidence of ITP in the UK; and 2. Estimate the survival of
patients with incident ITP compared to the population without ITP.
Methods. Incident cases of ITP during 1990-2005 were identified in the
GPRD and matched to comparison subjects by sex, year of birth, and
index date. Total person-time contributed by all subjects in the GPRD
population was used as the denominator for incidence calculations (with
censoring when patients developed ITP, transferred out of their practice,
or died). We analyzed changes in incidence over time using Poisson
regression. We estimated survival by the Kaplan-Meier method and
compared survival among incident ITP cases and their matched comparison
subjects using the log-rank test and proportional hazards regression.
Results. We identified 1,146 incident ITP cases and 5,715 matched comparison
subjects without ITP. The crude (average) incidence of ITP was
3.9/10 5 person-years (py). The incidence was 4.4/10 5 py in females and
3.4/10 5 in males. The incidence by age was bimodal with highest values
under 18 years and in the elderly. The age- and sex-adjusted incidence
of ITP increased an average 5% per year (cumulative increase approximately
two-fold during the 15-year study period). During a median 3.4
years of follow-up in the GPRD (interquartile range 1.5-6.0 years, maximum
15 years), 140 ITP cases (12.2%) and 482 comparison subjects
(8.4%) died (p=0.0001). The estimated survival for ITP cases at 5 years
was 87% (95% confidence interval [CI] 84-89%) and at 10 years was
78% (95% CI 74-82%). Adjusted for age and sex, the hazard ratio for
death associated with ITP was 1.6 (95% CI 1.3-1.9). Ninety-six percent
of deaths among ITP cases occurred in those older than 45 years. There
was no significant survival difference between males and females. Conclusions.
This study provides estimates of ITP incidence and mortality in
the UK. ITP incidence recorded by general practitioners has increased
substantially during the past 15 years. Further work is needed to determine
whether this reflects a true increase in the incidence of ITP in the
UK population, better detection, changing criteria for diagnosis,
increased recording by general practitioners, or a combination of factors.
Patients with ITP have approximately 60% higher mortality than sexand
age-matched comparison subjects without ITP. This increased risk
of death with ITP is largely concentrated in middle-aged and elderly
patients. We are extending our study to explore causes of death among
patients with ITP in the UK.
280 | haematologica/the hematology journal | 2007; 92(s1)
0752
A CASE OF AMEGAKARYOCYTIC THROMBOCYTOPENIA WITH RADIO-ULNAR SYNOSTOSIS
SYNDROME, SUCCESSFULLY TREATED WITH ALLOGENEIC BONE MARROW TRANSPLAN-
TATION
M. Sugita, Y. Yokokawa, H. Yoneyama, T. Kaneko
Tokyo Metropolitan Kiyose Childrens Hos, TOKYO, Japan
Background and Aims. Bone marrow failure syndromes can be associated
with abnormalities of skeletal defects. Since Thompson et al. (2000)
have described two families of amegakaryocytic thrombocytopenia
with radio-ulnar synostosis at first, which has been distinguishable from
other congenital hyporegenerative thrombocytopenic disease or syndromes
such as congenital amegakaryocytic thrombocytopenia, Fanconi’s
anaemia, thrombocytopenia and absent radii (TAR), and is said to
be associated with a point mutation in exon2 of HOXA11 gene. Currently,
stem cell transplantation is considered to be the only curative
approach. We describe the case of an 1-year old girl with amegakaryocytic
thrombocytopenia with radio-ulnar synostosis syndrome. Methods
and Results. The patient was born to parents of Japanese and presented
systemic petichiae at birth. Laboratory findings showed with leukocyte
count of 17.1×109 /L with no abnormal cells. The hemoglobin was
12.9 g/dL and the platelet count was 8.0×109 /L. She had clinodactylies
of the fifth digit on both hands and limited pronation and supination of
both upper extremities. A bone marrow at 3 days of age showed normocellular
marrow with the normal maturation of erythroid and
myeloid elements, but the absence of megakaryocytes and radiographic
examination revealed bilateral proximal radial-ulnar synostosis (Figure
1). To make sure the diagnosis, DNA sequence analysis was also performed
in search of HOXA11 mutation. With those findings, she was
diagnosed as having amegakaryocytic thrombocytopenia with radioulnar
synostosis syndrome. The platelet count remained bellow 1.0
×109 /L and pancytopenia progressed gradually at the age of 5-months.
At the age of 1-year and 6-months, she underwent allogeneic bone marrow
transplantation (allo-BMT) from an HLA-identical unrelated donor.
The Conditioning regimen consisted of total lymphoid irradiation, fludarabine,
cyclophosphamide and anti-thymocyte globulin. FK506 and
short-term methotrexate were used for graft-versus-host disease (GvHD)
prophylaxis. The number of infused nucleated cells was 6.9×108 /kg.
Time to achieve a granulocyte count > 0.5×109 /L and a platelet count >
50×109 /L was 16 days and 27 days, respectively. One month after BMT,
a bone marrow examination showed complete remission with 100%
donor type chimerism. During the course, she developed acute
GvHD(skin; grade II) and was treated with prednisolone, successfully.
A bone marrow examination continues to show complete remission
with follow-up of 9 months after allo-BMT. Conclusions. Allo-BMT from
an HLA-identical unrelated donor is a curative and suitable approach for
patients with amegakaryocytic thrombocytopenia with radio-ulnar synostosis,
who do not have HLA-identical sibling donors. In our case, the
point mutation in HOXA11 gene was not found, which may suggest
that there is a co-factor modulating HOXA11 expression and this case
is possibly a subtype of this syndrome. Careful clinical course watching
is required if another complications or the disease relapse will occur
again.
Figure 1. Forearm radiograph shows raio-ulnar synostosis.