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

characterized in 198 β thalassaemia alleles (98.01%). The distribution of
four mutations identified by RT-PCR in 83.6% of the thalassaemia chromosomes
was: [99 carriers of codon 39 (C--T); 34 of IVS-1-nt-110 (G--
A), 19 of IVS 1-nt-1 (G--A) and 17 of IVS 1-nt-6 (T--C)]. The remaining
8 mutations were represented in 33 alleles (16.4%) at frequencies ranging
between 7.1% and 0.5%. These molecular defects include the deletion
619 bp (7.1%), related with population with origin in India and Pakistan
and the mutations -28 (A--G) and IVS1-nt-2 (T--G) originating from
China detected in two Chinese carriers, the codon 41/42 (-TTCT) was
detected in a Tunisian woman and the mutation codon 8/9 (+G) previously
reported in Spain. This is the first report of three following β thalassaemia
mutations codon 51 (-C), codon 22 (G--T) and codon 24 (T--
A) in Spain, and the first description of novel mutation frameshift CD
20/21-TGGA in anywhere before. Conclusions. The distribution of the
mutations in Lanzarote is similar to found in Eastern Spain and Mediterranean
area. The important migratory flow received in Canary Islands
during last years may explain the emergence of mutations not reported
before in our area. The increasing incidence of β thalassaemia trait and
the information about the β thalassaemia mutations justifies the implementation
of screening of heterozygote carriers and prevention programs.
1149
FIRST CASE OF UPSHAW-SCHULMAN SYNDROME REVEALED AT EARLY ADULTHOOD
IN A PATIENT OF WHITE ARABIC NORTH AFRICAN HERITAGE
R. Jeddi, 1 N. Bougacha, 1 E. Gouider, 1 S. Donadel-Claeyssens, 2
L. Aissaoui, 1 R. Ben Amor, 1 K. Kacem, 1 R. Ben Lakhal, 1 H. Benabid, 1
Z. Belhadjali, 1 B. Meddeb1 1 2 Aziza Othmana Hospital, TUNIS, Tunisia; Centre Régional d’Hémophilie,
TOULOUSE, France
The congenital form of thrombotic thrombocytopenic purpura (TTP)
or Upshaw-Schulman Syndrome (USS) is a very rare but life-threatening
disease due to autosomal recessive severe deficiency of Von-Willebrand
factor-cleaving protease (ADAMTS 13).There’s a striking agedependent
clustering of the first TTP attack. Half of the patient suffered
from their first bout of TTP between the first day of life and the age of
about five years (early onset), while the other half remained asymptomatic
into early adulthood and suffered from a first acute TTP episode
at the age of 20-40 years (late onset). Symptoms in adults develop in association
with the stress of infection or pregnancy. We report herein a case
of an USS revealed at early adulthood, misdiagnosed initially as immune
thrombocytopenic purpura (ITP).A 17 year’s old man was admitted in
December 2002 in the Hematology department of Aziza Othmana University
Hospital of Tunis with pallor, epistaxis, skin petechiae and ecchymosis.He
has a sister (22 yr) with medical history of Rosai-Dorfman disease
diagnosed at the age of 2 yr. Laboratory studies showed: WBC=
13,000/mm 3 , regenerative anemia with hemoglobin level at 8,5g/dL and
thrombocytopenia with platelet count (Plt) at 21,000/mm 3 .Serum creatinine
and serum bilirubin was normal.Coombs test was negative.
Peripheral blood smear showed rare platelets and no schizocytes.Serology
for hepatitis B, C and for VIH were negative. Bone marrow aspiration
revealed increased number of megacaryocytes.The diagnosis of ITP
was considered and he received prednisone :1mg/kg/d leading to complete
correction of anemia and persistence of a mild thrombocytopenia
between 50,000 and 100,000/mm 3 despite discontinuation of corticotherapy.In
June 2005 he presented an episode of fever and diarrhea followed
by hemolytic crisis (Hb=7,7 g/dL) and severe thrombocytopenia
(Plt=13,000/mm 3 ), hyperbilirubinemia 107 µmol/L, and elevated
LDH=1095UI.Coombs test remained negative and schizocytes were
absent. This episode didn’t respond to scheduled cycle of Dexamethasone
20mg/m 2 /d1-d4,and the patient developed an ischemic cerebral
accident (August 2005) salvaged with Polyvalent Immunoglobulin
:1g/kg/d for 2 days and a plasmapheresis without plasma infusion leading
to normalization of Plt at 245,000 mm 3 .He remained in complete
response until developing another hemolytic crisis (Hb=8.7g/dL) and
acute renal failure :serum creatinine at 290 µmol/L in November
2006.Peripheral blood smear showed for the first time schizocytes
(16%). Assay for ADAMTS13 activity taken before plasma exchange
was 10 years (33,3%) and in females
(66,7%). Most received GS and/or IVIG, 3 were splenectomised.
Although the course of chronic ITP was generally mild, 15 (71,4%) had
some serious bleeding episodes, and 1 child died from ICH. Conclusions.
Annual incidence of acute ITP in our country is 4,0/100000 children
under 15 years (for chronic ITP it is 0,4/100000). Serious bleeding in
acute ITP is uncommon. Fatal ICH in our study (in a patient with chronic
ITP) is low (0,4%).
1151
RITUXIMAB FOR REFRACTORY IMMUNE THROMBOCYTOPENIC PURPURA: A SINGLE
CENTER EXPERIENCE
J. Arguiñano, Y. Burguete, M.A. Ardaiz, M.C. Mateos, M.C. Montoya,
M.J. Paloma, A.M. Redondo, I. Ezpeleta, M.A. Labaca, F.J. Oyarzábal
Hospital Virgen del Camino, PAMPLONA, Spain
Background. Refractory Immune Thrombocytopenic Purpura (ITP) is a
difficult disease to treat effectively, with a mortality approaching 10%
over 10 years. Rituximab is a chimeric monoclonal antibody targeting
CD20 antigen on neoplastic and normal B cells, approved for use in B cell
malignancies as well as rheumatoid arthritis. Its use in other autoimmune
diseases remains investigational. In ITP it has been used in several
scenarios, even as an splenectomy sparing strategy. Methods. We report
here our experience on eight patients treated with rituximab for refractory
ITP. The drug was used off label after informed consent. All patients
were refractory to steroids (at a maximum dose of 2 mg/kg of prednisone
per day) and intravenous immunoglobulins. Only one of the
patients had undergone splenectomy before the administration of rituximab.
Schedule of the drug was 375 mg/m2 weekly for a total of four doses.
A patient was considered to have reached a response when a platelet
count of at least 50×109 /L was achieved in the 120 days next to the first
rituximab administration, in the absence of bleeding symptoms and provided
no other effective therapy was administered in that period of time.
Results. Responses were achieved in six out of eight patients. Median
time to response was 38 days, ranging from 12 to 68 days. One of the
non-responding patients was rescued with splenectomy, while the other
one remains unresponsive. No significant side effects occurred with
rituximab administration, allowing an outpatient approach in three
patients. Four of the responding patients maintain normal platelet counts,
but follow-up is too short to state a median response. To date, the longest
response achieved has been 40 months in one patient. One of the two
patients who relapsed is responsive to steroids, requiring high doses to
maintain a safe platelet count. Summary. In our experience, rituximab is
a safe and effective therapy for refractory ITP, and can achieve long last-
haematologica/the hematology journal | 2007; 92(s1) | 423