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

12 th Congress of the European Hematology Association
dence of bulky disease was higher in pts with IPS 3-5 than in pts with
IPS 0,1. (23.3% vs 6.6% p50
was found in pts with IPS 3-5 comparing to the pts with IPS 0.1 (33.3%
vs 10% p50 found in pts with high IPS pointed out shorter
survival of those pts (40.86 m vs 64.4 m p3, bulky disease and ESR>50 are in risk of relapse and treatment failure,
and are eligible for the initial aggressive therapeutic approach.
1073
FLAG-IDA IN THE TREATMENT OF REFRACTORY/RELAPSED ACUTE LEUKEMIA: A SINGLE
INSTITUTIONAL STUDY
P. Carluccio, 1 D. Pastore, 1 A. Pannunzio, 1 A. Russo Rossi, 1 P. Lerario, 1
G. Spinosa, 1 M. Giannoccaro, 1 A.M. Mazzone, 1 M. Santodirocco, 2
V. Fesce, 2 C. Lubelli, 1 A. Liso, 2 V. Liso, 1 G. Specchia1 1 Hematology Section, BARI, Italy; 2 Hematology, FOGGIA, Italy
Background. Relapsed or refractory adult acute myeloid leukaemia
(AML) have a poor prognosis. The strategy for treating this patients is
through reinduction chemotherapy followed by allogeneic stem cell
transplantation, provided that the toxicity of the salvage regimen is
acceptable. High or intermediate dose cytarabine has been reported to
be effective in the salvage treatment of AML; addition of the purine
analogue fludarabine to cytarabine increases the rate of accumulation of
cytarabine in leukemic blasts and the response to chemotherapy may be
improved by addition of idarubicin, an anthracycline that is less susceptible
to multidrug resistance Aims. Based on these consideration, we
evaluated the efficacy and the toxicity of FLAG-IDA in a series of 78
refractory/relapsed AML. Patients and Methods. Fifty-two patients (66%)
were in first relapse and 26 (34%) were refractory to conventional
chemotherapy. The patient group included 44 men and 34 female with
a median age of 43 years (range 15-63). All patients were treated with
fludarabine (30 mg/m 2 iv for 5 days), cytarabine (2 gr/m 2 iv for 5 days),
idarubicin (10 mg/m 2 iv for 3 days) and G-CSF (5 mcg/Kg/day subcutaneous
24 h after completing chemotherapy and until neutrophil regeneration).
Results. The overall CR rate was 55% (43 of 78): 31 of 52 (59%)
in relapsed and 12 of 26 (46%) in refractory patients; there were 5 of 78
(6%) deaths during therapy: 2 due to cerebral haemorrhage and 3 due
to infection. In patients achieving remission, the median time to reach
absolute neutrophil count (ANC) more than 0.5×10 9 /L and 1×10 9 /L was
21 (range 16-26) and 24 days (range 20-28) from the start of chemotherapy,
respectively. Platelets level of more than 20 ×10 9 /L and 100 ×10 9 /L
were achieved in a median time of 24 (range 19-26) and 32 days (range
28-39) days, respectively. Fever more than 38.5°C was observed in 63 of
78 patients (80%): 45 (71%) had fever of unknown origin and 18 (29%)
documented infections. Nonhematological side effects, consisting mainly
of mucositis (60/78 or 76%) and transient liver toxicity increase (30/78
or 38%). All 43 patients who achieved CR received a second course
with FLAG-IDA, and 18 received allogeneic stem cell transplantation, 8
patients received autologous stem cell transplantation, 9 were junged
unable to receive any further therapy, and 8 refused other therapy. The
median overall survival (OS) for all 78 patients was 6 months (range 3-
62); for the 43 responders patients, the disease free survival (DFS) and
OS were 9 (range 4-62) and 11 (range 7-62) months, respectively; the 18
patients who received allogeneic transplantation had a DFS of 13 (range
7-62) months. Summary. In our experience, FLAG-IDA is a well-tolerated
regimen in refractory/relapsed AML with a CR rate of 55%; the toxicity
of this treatment is acceptable, enabling the patients who achieved
CR to receive further treatment, including transplantation procedures.
1074
POLYMORPHISMS OF DNA REPAIR AND DETOXIFICATION GENES IN B-CELL CHRONIC
LYMPHOCYTIC LEUKAEMIA
C. Ganster, 1 J. Neesen, 1 U. Jaeger, 2 H. Esterbauer, 3 C. Mannhalter, 3
C. Fonatsch1 1 Department of Medical Genetics, MUW, VIENNA, Austria; 2 Department of
Internal Medicine I, MUW, VIENNA, Austria; 3 KIMCL, MUW, VIENNA,
Austria
B-cell chronic lymphocytic leukemia (CLL) is the most common type
of leukemia in adults in the Western World. As its clinical course is highly
variable, prognostic factors for disease progression such as particular
cytogenetic abnormalities, the mutational status of the immunoglobulin
heavy chain (IgH) genes, LPL, or CD38 expression, have been identified.
However, a convincing prediction of disease progression can not
396 | haematologica/the hematology journal | 2007; 92(s1)
be made in early stages of the disease. Further prognostic factors would
be helpful for meaningful prediction of disease progression. There is
evidence that multiple low-penetrance genetic factors, including genetic
polymorphisms, predispose to CLL or modify its clinical course. The
aim of this study was to identify such allelic variants of genes, primarily
concentrating on DNA repair and detoxification genes. We studied the
distribution of 50 polymorphisms in 500 CLL-patients and 500 control
persons using PCR amplification followed by restriction enzyme digestion.
Whereas for most polymorphisms an association with CLL could
be excluded, the risk of the development of CLL increased with the
number of high-risk alleles in the DNA base excision repair gene XRCC1
and in a combined analysis on alleles in XRCC1 and the detoxification
gene CYP1B1. Further investigations are now under way to proof the relevance
of these polymorphisms in the clinical course of CLL and its
putative significance for CLL in combination with other prognostic factors.
The results of this study will lead to new insights into the etiology
of CLL and may help to predict disease progression.
1075
THRESHOLDS OF IRON TOXICITY IN PATIENTS OF MYELODYSPLASTIC SYNDROMES
H. Brummendorf, 1 P. Nielsen, 1 N. Kroeger, 1 R. Grosse, 1 J. Matt, 2
R. Engelhardt, 1 O. Leismann, 2 C. Bokemeyer, 1 R. Fischer, 1 A. Zander, 1
T. Brummendorf1 1 University Hospital Eppendorf, HAMBURG, Germany; 2 Novartis Pharma
GmbH, NÜRNBERG, Germany
Background. Patients with myelodysplasia (MDS), osteomyelofibrosis
(OMF), or severe aplastic anemia (SAA) suffer from ineffective erythropoiesis
due to pancytopenia, which is often treated with red blood cell
transfusion. Especially in low-risk patients with mean survival times of
> 5 years (MDS-RA, -RARS, -5q-), potentially toxic levels of liver iron
concentration (LIC) can be reached. Aims. Although, the 2005 consensus
of Nagasaki gave recommendations for chelation treatment based on
a wide range of ferritin levels, there is still no evidence based agreement
about the initiation of chelation treatment in these patients. Moreover,
ferritin levels can vary independently from the true iron stores as
assessed by LIC. Therefore, we aimed to establish a relationship
between LIC and ferritin in the patients of the myelodysplasia syndrome.
Methods. In the present study, a total of 67 transfused patients
with MDS (n=20, age: 17-75 y), OMF (n=4, age: 48-68 y), SAA (n=43,
age: 5-64 y) were measured by SQUID biomagnetic liver susceptometry
(BLS) and their liver and spleen volumes were scanned by sonography
at the Hamburg biosusceptometer. Less than 50% were treated
with DFO. LIC (µg/g-liver wet weight, conversion factor of about 6 for
µg/g-dry weight) and volume data were retrospectively analyzed in
comparison to ferritin values. Results. LIC values ranged from 149 to
8404 with a median value of 2705 µg/g-liver, while serum ferritin (SF)
concentrations were between 500 and 10396 µg/l with a median ratio
of SF/LIC = 0.9 [(µg/L)/(µg/g-liver)] (range: 0.4 to 5.2). The Spearman
rank correlation between SF and LIC was found to be highly significant
(RS=0.80, p 2700 µg/g-liver (Angelucci
et al. Blood 2002; 100:17-21) within 60 months and significant cardiac
iron levels have been observed for LIC > 3300 µg/g-liver (Jensen et al.
Blood 2003; 101:4632-9). These thresholds were exceeded by 51% and
39% of our patients for hepatic fibrosis progression and for cardiac iron
toxicity, respectively. The total body iron burden is even higher as more
than 50% of the patients had hepatomegaly (median hepatomegaly factor:
1.2 of normal). Summary/Conclusions. A liver iron concentration of
about 3000 µg/g-liver or 18 mg/g-dry weight has to be seen as the latest
intervention threshold for chelation treatment as MDS patients are
affected by more than one risk factor. A more secure intervention threshold
would be a LIC of 1000 µg/g-liver or 4 - 6 mg/g-dry weight, corresponding
with a ferritin level of 900 µg/L for transfused MDS patients.
Such a LIC value is not exceeded by most of the heterozygous hereditary
hemochromatosis subjects and is normally well tolerated without
treatment during their life-time.