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

previously reported, a single course of DAC-7 induction resulted in 17%
higher CR rate compared to the DA-7 treatment (p=0,0008). The difference
was particularly pronounced in patients: aged >40 years and with
initial WBC >100×10 9 /L. In the latter subgroup also the overall CR rate
(achieved after entire induction program) was higher in the DAC-7 arm
(71% vs. 43%). [Leukemia 2004;18:989-97] In the present report we analyzed
seven-year long-term outcome (median follow-up 5 yrs) in the
whole study population and in subgroups stratified according to age,
initial WBC, cytogenetics, sex, FAB subtype, and preceding myelodysplasia.
In the whole group the overall survival (OS) rate equaled 29,5%
for DAC-7 and 24% for DA-7 arm (p=NS) and leukemia free survivall
(LFS) 30% vs. 28% (p=NS), respectively. Of note, in patients aged >40
years, the therapy containing cladribine was associated with improved
OS (26% vs. 14,5%, p=0.03), and LFS (28% for DAC-7 vs. 18,5% for DA-
7, p=0.02). Other subgroup analyses revealed higher probability of the
OS in patients with initial WBC ≤50 G/L assigned to DAC-7 compared
to DA-7 arm (32% vs. 20,5%, p=0.04). The LFS rate equaled 35% and
27% (p=NS), respectively. In women receiving DAC-7 induction therapy
in comparison with those treated in arm without 2-CdA reached
higher OS: 29% vs. 19,5%, p=0,03, respectively. LFS in these subgroups
was comparable: 25% vs. 22%, p=NS, respectively. We conclude that
addition of cladribine to induction and consolidation therapy of AML
improves long-term outcome in patients: older than 40 y, as well as in
those with high tumour burden. The better outcome in older patients
results mainly from reduced risk of relapse, whether that in cases with
high WBC seems to be linked to a higher CR rate.
0492
INFANT LEUKEMIAS: TRANSIENT MYELOPROLIFERATIVE SYNDROMES IN CHILDREN
WITH TRISOMY 21 MOSAIC
K. Reinhardt, 1 A. Pekrun, 2 A. Sauerbrey, 3 D. Reinhardt1 1 Hannover Medical School, HANNOVER; 2 Prof.-Hess Kinderklinik, BREMEN;
3 Helios-Klinikum Children's Hospital, ERFURT, Germany
Introduction. Children with Down syndrome have a 10- to 20-fold
increased risk of leukemia and a 10%-incidence of transient myeloproliferative
disorders (TMD). TMD may also occur in neonates without
any stigmata of Down syndrome but with trisomy 21 mosaic. About 20-
30% of DS-neonates with TMD developed myeloid leukemia of Down
syndrome (ML-DS) during the first 4 years of life. TMD blasts are indistinguishable
from ML-DS blasts in both morphology and immunophenotyping.
In almost all patients with TMD or myeloid leukemia of
Down syndrome mutations in exon2 or exon3 or the hematological transcription
factor GATA1, leading to a truncated GATA1s, have been
detected. Materials and Methods. We performed polymerase chain reaction
(PCR) on exons 2 and 3 using primers that flanked each of the exons.
DNA sequencing was done directly on purified PCR products. Each identified
mutation was confirmed using sense and anti-sense primers.
Patients. All three children were mature newborns without any obvious
stigmata of Down syndrome. The clinical symptoms of leukemia
occurred within the first weeks of life. Due to typical morphology and
immunophenotype of the leukemic blasts (CD34/CD117/CD13/CD33/
CD7/CD56/CD36/CD42b), a TMD was considered and no intensive
anti-leukemic treatment initiated. Detection of GATA1 mutations in all
children and the karyotyping of fibroblasts and hematopoietic cells,
which revealed trisomy 21 mosaic, confirm the diagnosis of TMD. Due
to clinical symptoms caused by the TMD, two children were treated
with low-dose cytarabine (1 to 1.5 mg/KBW). All infants experienced
complete remission within 6 weeks. During follow-up no evidence of
relapse or development of a myeloid leukemia of Down syndrome was
observed. Results. Table 1.
Table 1.
Patient Sex/Age Symptoms WBC/µL Blasts DNA Mutation Consequence
diagnosis (BM) source
P.M. F/5 weeks Leukemia cutis 74,700 24% blasts IVS2+2 Splice mutant
anemia,
thrombocytopenia,
hepatosplenomegaly
T>C
K.V. M/0 Pulmonal 130,000 13% blasts 261 dup Stop codon
insufficiency,
hepatosplenomegaly
156-261 before Met84
A.S. M/6 weeks Anemia,
thrombocytopenia,
pericardiac effusion
40,600 65% smears 328 del 12 Splice mutant
Conclusions. In newborns and infants, diagnosed with acute megakaryoblastic
leukemia, the possibility of TMD and trisomy 21 mosaic should
12 th Congress of the European Hematology Association
be considered. Analysis of the GATA1 mutation should be performed to
prevent overtreatment. If clinical symptoms due to TMD occur, lowdose
cytarabine is recommended. Due to the possible risk of developing
myeloid leukemia, close follow-ups should be performed.
0493
CLAG-M IS HIGHLY EFFECTIVE SALVAGE REGIMEN IN PATIENTS WITH RELAPSED AND
REFRACTORY ACUTE MYELOID LEUKEMIA. THE FINAL RESULTS OF MULTICENTER PHASE
II STUDY OF THE POLISH ADULT LEUKEMIA GROUP (PALG)
A. Wierzbowska, 1 T. Robak, 1 A. Pluta, 1 E. Wawrzyniak, 1
J. Holowiecki, 2 S. Kyrcz-Krzemien, 2 S. Grosicki, 2 A. Skotnicki, 2
B. Piatkowska-Jakubas, 2 K. Kuliczkowski, 2 M. Kielbinski, 2
A. Wrzesien-Kus1 1 2 Copernicus Memorial Hospital, LODZ; Department of Hematology, KATOW-
ICE, Poland
Objectives. Cladribine (2-CdA) in addition to cytosine-arabinoside (Ara-
C) increases the accumulation of Ara-C-5’ triphosphate which is responsible
for the cytotoxic effect in leukemic blasts. Our preliminary results
have suggested that addition of Mitoxantron (MIT) to 2-CdA, Ara-C
and granulocyte colony-stimulating factor (G-CSF) CLAG-M improves
the treatment results in refractory/relapsed patients with acute myeloid
leukemia (AML). In this cooperative phase II study we evaluated the
efficacy and toxicity of salvage regimen CLAG-M in refractory/relapsed
AML patients with poor risk. Materials and Methods. The patients were
qualified to high risk group if they represent: i) primary refractory AML,
ii) AML in first relapse with duration of complete remission (CR)