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

12 th Congress of the European Hematology Association
1066
EVOLUTION OF PATIENTS WITH HODGKINS DISEASE STAGE I AND II AFTER RADIOTHERAPY
M. Badea, D. Badea, A. Genunche
Univ of Medicine and Pharmacy, CRAIOVA, Romania
Background. Patients with stage I and II Hodgkin’s disease and favorable
prognostic are treated with both chemotherapy and radiotherapy,
regimens with modified doses. Our study is retrospective and the purpose
is presenting the evolution of patients, from our center, with stage
I and II Hodgkin’s disease treated with radiotherapy alone. Material and
methods. The study contains 74 patients (median age 28±2,5 years) with
stage I and II Hodgkin’s disease treated with radiotherapy alone. The
study period was from 1984 to 1999. Results. 26 (35,1%) patients with
stage I and II Hodgkin’s disease treated with radiotherapy alone are
relapsed. The median age of this patients was 31 ±3 years. Relapse rate
varied according to the stage of the disease, stage IA and IIA representing
23,07% of the relapses (6 patients), stage IB and IIB representing
73,07% (19 patients) and stage IIIA 3,84% (1 patient). 21 patients
(80,7%) present early relapse. Disease free survival was 18±3 months.
The rest of 5 patients (19,2%) represents late relapses (over 3 years). 19
of the patients (73%) present relapse limited to nodal sites, and 7 patients
(27%) present extranodal relapse. Most of extranodal relapses are pulmonary
and are due to bulky mediastinal adenopathy. 61,5% (16
patients) of the total of relapses present tumors over 7 cm in diameter.
From 26 patients who relapsed, 14 patients (53,84%) present in-field
relapse, and in 12 patients (46,16%) the relapse occur outside the radiation
field. 17 cases (65,3%) occurred after localized radiotherapy, and
9 patients (34,6%) are relapsed after wide-field radiotherapy. Indifferent
to the type of relapse, the specific chemotherapy has re-induced the
complete remission in 92,3% of the patients and the durable responses
was in 86,3% of cases. Conclusions. Relapse rate in localized Hodgkin’s
disease treated with radiotherapy alone is 31,5%. Most of relapses are
early (80,7%) and they involved nodal sites. The relapse rate seems
influenced by the stage B of the disease, by the maximum tumor volume
and by the type of applied radiotherapy (local/extended). The sensitivity
to chemotherapy is for this patients is similar at the time of initial
therapy and salvage chemotherapy can achieve durable responses
and remissions in approximately 86,3 percent of these patients This
explains why, although the relapse rate for favorable prognosis stage I-
II Hodgkin’s disease is higher with radiotherapy alone compared to combined
with chemotherapy, survival is similar
1067
NO RELATIONSHIP BETWEEN THE JAK2V617F LOAD AT DIAGNOSIS AND THROMBOSIS
IN 57 PATIENTS WITH ESSENTIAL THROMBOCYTAEMIA
F. Girodon, 1 F. Dutrillaux, 1 V. Goussot, 1 E. Bergoin, 1 I. Janoray, 2
P.M. Carli, 2 M. Maynadié1 1 CHU Bocage, DIJON; 2 Registre des Hémopathies malignes, DIJON, France
Background. Essential Thrombocytaemia (ET) is a myeloproliferative
disorder (MPD) frequently complicated by thrombotic events. The
JAK2V617F mutation has been recently described as a risk factor to
develop thromboses along the clinical course of MPD. However, in most
of the studies, the JAK2V617F mutation was only qualitatively determined,
but the JAK2V617F load was not analysed. Aims. To evaluate
whether the JAK2V617F load at the time of diagnosis is associated with
thrombotic risk along the clinical course. Methods. Fifty-seven ET
patients (26 males and 31 females), with a median age at diagnosis of 54
years (range, 16-94) diagnosed according to the PVSG classification from
a population-based registry, were studied. Bone marrow smears at diagnosis
were scraped and DNA was isolated using the QIAamp DNA
Blood Mini kit (Qiagen, Courtaboeuf, France). The JAK2V617F was
determined using a sensitive, allele-specific, quantitative PCRs in genomic
DNA previously described. 1 Fifty patients were treated using cytoreductive
therapy and 39 received anti-platelet drugs. The median followup
duration was 69 months (2-203). Results. The JAK2V617F mutation
was observed in 43 patients (75%), with a median value of JAK2V617F
/ JAK2WT ratio of 20.2% (range, 2 to 85%). Patients were divided in 3
classes depending on the percentage of JAK2V617F:0% (n=15), 1-20.2%
(n=21), >20.2% (n=21). The percentage of patients with cardiovascular
risk factors was respectively 47%, 57% and 71% in these three classes.
Six (10%) patients had a prior history of thrombosis, mainly venous
thrombosis. There were 6 thrombotic events at the time of diagnosis in
6 different patients, and 22 thrombotic complications (12 arterial and 10
venous) in 14 different subjects during the follow-up. No difference in
thrombotic vascular events was noticed between the 3 classes, either for
394 | haematologica/the hematology journal | 2007; 92(s1)
arterial or venous thromboses. However, among the 4 patients with a
JAK2V617F load above 50%, three had thrombotic events during the
clinical course, without myelofibrosis evolution. Conclusions. No clear
association between the JAK2V617F / JAK2WT ratio and the risk of
thrombosis was observed in our patients. These results have to be confirmed
in a larger cohort, especially regarding very high JAK2V617F /
JAK2WT ratio.
Reference
1. Lippert E, Boissinot M, Kralovics R, Girodon F, Dobo I, Praloran V et al.
The JAK2-V617F mutation is frequently present at diagnosis in patients
with essential thrombocythemia and polycythemia vera. Blood 2006;
108:1865-7
1068
GEMTUZUMAB OZOGAMICIN WITH CYTARABINE AND MITOXANTRONE AS A THIRD LINE
TREATMENT IN A POOR PROGNOSIS GROUP OF ADULT ACUTE MYELOID LEUKEMIA
PATIENTS: A SINGLE CENTER EXPERIENCE
D. Pastore, P. Carluccio, S. Sibilla, M. Giannoccaro, G. Spinosa,
M. Casanova, N. Sgherza, R. Rizzi, A. Mestice, G. Specchia, V. Liso
Hematology Section, BARI, Italy
Background. Patients with refractory acute myeloid leukemia (AML)
after 2 courses of chemotherapy or in second relapse have very poor
prognosis. Most patients have already been exposed to intensive multiagent
chemotherapy and most reinduction regimens in current use cause
substantial toxicity; such patients are not always eligible for intensive
chemotherapy. Antibody-targeted chemotherapy is presumed to be less
toxic than conventional chemotherapy and has been developed for treatment
of CD33-positive AML. Aims. We conducted a study of GO combined
with mitoxantrone and cytarabine as third-line treatment in a
homogeneous poor prognosis group of 23 patients with refractory/relapsed
AML to evaluated the safety and toxicity of the drug in this
group of patients. Patients and Methods. Patients median age was 52
years (range 36-70); twelve patients were refractory after DCE (daunorubicin,
etoposide, and cytarabine) as first-line therapy and FLAG-IDA
(fludarabine, cytarabine, and idarubicin) as second line; eleven patients
were in second relapse and were treated with DCE at onset and with
FLAG-IDA in first relapse; this poor prognosis group was therefore homogeneous
as regards previous chemotherapy regimens. GO at a dosage of
3 mg/m2 was administered as a 2-h intravenous infusion on days 1 and
14, cytarabine at 100 mg/m2 on days 1-7 and mitoxantrone at 12 mg/m2 on days 1-3. Results. The overall complete remission rate was 5/23
(21.7%): 4 of 11 (36%) in second relapse and 1 of 12 (8.3%) in refractory
patients; CR and CRp were achieved in 2/23 (8.6%) and 3/23 (13%),
respectively; of these 5 responder patients one was in the favourable
cytogenetic group [t(8;21)] and 4 were in the intermediate (3 with normal
karyotypes and 1 with +8); no response was achieved in the poor
cytogenetic risk group. Four patients died during therapy (overall treatment-related
mortality 17.3%): two due to sepsis (P. aeruginosa), one to
cerebral haemorrhage and one to acute respiratory distress syndrome.
Baseline characteristics including age, type of AML, WBC count and
marrow blasts were not predictive of treatment in this study. Furthermore,
the CR/CRp rate after GO, cytarabine and mitoxantrone was not
influenced by CD33 positivity. All patients experienced profound neutropenia
(0.5×109L and 1×109 /L was 28
days (range 21-33) and 34 days (range 29-39), respectively. Grade III-IV
anemia and thrombocytopenia were observed in all cases; a grade I/II
bilirubin increase occurred in 5/23 cases (21.7%); grade I/II ALT/AST elevation
was documented in 3/23 cases (13%); grade I/II alkaline phosphatase
elevation was observed in 4/23 (17.3%) cases; no veno-occlusive
disease (VOD) occurred. The most common non-hematologic
adverse events were infusion-related allergic reactions (17/23 or 73.9%),
infection (5/23 or 21.7%) and febrile neutropenia (20/23 or 86.9%). Summary.
In our experience, the addition of GO to mitoxantrone and cytarabine
is feasible in refractory or second relapse acute myeloid leukemia
patients but yields a low response rate (21.7%) when used as a third line
treatment.