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

12 th Congress of the European Hematology Association
Table 1.
Time to alemtuzumab after fludarabine was 6.3 months. Detection of
MRD was performed by four-color flow cytometry with this antibody
combination (CD43/CD23/CD19/CD5, CD20/CD79b/CD19/CD5 and
kappa/lambda/CD45/CD19) Results. 1.-12/19 (60.3%) patients treated
after CR with MRD positive cleared MRD and 2/6 patients with PR
achieved RC with MRD positive. Responses lasted 6-9 months untill
MRD detectable again in PB and 4 patients remain MRD negative after
19.2 months follow-up (range 16-24). 2.- Most common toxicity was
transient injection site skin reaction (grade 1-2 in 60%, grade >2: 7%).
Other toxicities: fever (grade 1-2:60%), asthenia/fatigue (grade 1:20%),
bilirrubin>2.5 normal range (1 pt), anemia and thrombocytopenia (grade
1: 1pt), neutropenia (grade >2: 3 pts). Alemtuzumab was holded in 2 pts
(grade 4 neutropenia and severe skin reaction) 3.- Cytomegalocirus
(CMV) reactivation ocurred in 7 pts (28%), being early reactivation
(within 2 months after alemtuzumab) in 6/7 pts. Half of these pts (14%)
had symptoms of CMV infection. No episodes of pneumonitis was
observed. Other infectious complications: c. jejunii diarrhea (1 pt) and
febrile episodes resolved with antimicrobial (2 pts). 1 patient developed
sepsis. 4.- Exitus ocurred in 2 pts (disease progression and sepsis). Conclusions.
Alemtuzumab is highly effective in clearing leukemia cells from
PB/BM, with responses lasting over 6-9 months in most patients. This
results support possible role for maintenance with alemtuzumab in this
subset of patients, but needs to be addressed with further studies. Infection
is the most common cause of morbidity in patients treated with
alemtuzumab. Subcutaneous administration offers better toxicity profile
compared to intravenous route resulting in a major number of pts eligible
for this treatment.
1091
CHILDREN AND ADOLESCENT ACUTE LYMPHOBLASTIC LEUKEMIA TUNISIA
M. Elloumi, L. Aissaoui, M. Laatiri, T. Souissi, A. Khelif, B. Meddeb
Hematology, SFAX, Tunisia
Introduction. The prognostic factors in acute lymphoblastic leukemias
(ALL) are better and better clarified, which allows to individualise different
risk groups and to better adapt the treatments. That is the case of
the last version of the OERTC protocol (88951) which we adopted (with
certain modifications) in Tunisia. We present in this paper the feasibility
of this protocol, the evolution and the survival of the patients treated
according to it. Patients and Methods. Our study is retrospective. It concerns
the patients aged 2 to 20 years, treated since 2000 according to the
modified version of the OERTC 588951 protocol. The latter comprises
3 risk groups: 1) mean risk 1 (MR1) : B type LAL , WBC < 100 000/ mm3 , without t(9,22) nor t(4,11) , corticosensitive, and with complete remission
after one course of chemotherapy; 2) mean risk 2 (MR2), the same
parameters, with WBC > 100 000 and/or phenotype T. 3) High risk
(HR) : one of the following criteria : t (9,22), t (4,11), cortico resistance,
no CR after one courseof chemotherapy. A leaflet was designed to contain
the data of diagnosis, evolution and survival. Statistical analysis
used are the chi 2 test for studying the correlations, the Kaplan Meier
method for studying the survival, and the Long-rank test for comparing
the survival curves. Results. 133 patients are recorded (2000-2003) : 57 are
female, 76 male (sex ratio: 1,33), mean age : 9 years , 46% are older than
402 | haematologica/the hematology journal | 2007; 92(s1)
10 years, WBC > 50 000 in 33% of the cases ; 75% are of cytological type
L1 ; 63% are of the B phenotype, caryotype is abnormal in 47% of the
cases, with isolated hyperdiploidy in 8% , and structural anomalies in
the remaining cases ; a Philadelphia chromosome is present in 3% of the
cases. The frequencies of the 3 risk groups 1,2,3 are : 47% , 27% and
26% respectively. A complete remission (CR) is obtained in 123 patients
(92,5%), with 6% deaths during induction treatment , and 1,5% failure.
A relapse occurred in 26% of the cases. Global survival rate at 3 years
for all patients is 63%, with 73%, 58% and 47% for MR1, MR2, and
MR3 respectively. The prognostic value was cheked for the following
parameters: age (< or > 10 years), sex, presence or absence of tumoral
syndrome, WBC number (< ou > 50 000/mm 3 ), cytological type, phenotype,
and risk group. Are of good prognosis: the age (< 10 years) (p=
0,0003), the Hb level < 10 g/dL (p=0,0028), the platelet number : < 50
000/mm 3 (p= 0,025) and the risk group MR1 (p= 0,048). Comments. Our
series is characterized by an elevated number of hyperleucocytic and T
phenotype forms. The number of deaths during induction is high as
compared with the numbers reported in western countries. The number
of relapses is also high. Although the overall survival in this study is
quite superior to that reported in precedent Tunisian studies, but it
remains lower than that reported in recent western publications. This
difference is most clear in the HR group; in which bone marrow allografting
in first CR should be indicated whenever the patient has a familial
HL-A identical donor.
1092
DNA HYPERPLOIDY IS ASSOCIATED WITH BOTH HIGH PLASMA CELL PERCENTAGE
& HIGH β2 MICROGLOBULIN AND IMPAIRS SURVIVAL IN MYELOMA PATIENTS TREATED
WITH OR WITHOUT TRANSPLANTATION
K. Dalva, E.A. Soydan, M. Kizil, P. Topcuoglu, F. Gungor, B. Atasoy,
M. Beksac
Ankara University School of Medicine, ANKARA, Turkey
Introduction. Chromosomal hyperdiploidy (HD) is the most frequent
cytogenetic abnormality in myeloma. HD can be defined by conventional
cytogenetics,FISH or flow cytometry(FC). DNA content has
been reported by three groups (Tafuri A 1991, J.San Miguel 1996, Mayo
group 2006 ). HD has been associated with favourable, poor or standard
risk. Proliferating plasma cells (PC) can also be quantitated by
FC. Aim: In this prospective study we aimed to analyze the influence
of immunophenotypic phenotypes, DNA content, S phase percentage
of PC in addition to ISS, age and 13q del (FISH) on clinical outcome.
All multiple myeloma patients diagnosed at our center between 2004-
2006 (M/F: 58/32, median age: 60, IgG/A/light: 53/17/11, lambda/kappa:
27/54, B2M: 3.8mg/dL, albumin: 3.4 mg/dL) were included. Patients
received VAD(n=53) or MP (n=3) chemotherapy and subsequent autologous
stem cell transplantation (n=22). Thalidomide frontline (n:4) or
second line (n=21) was also given. Bone marrow aspirates, collected at
diagnosis, was used for separation of PC with CD138 positive beads
(Clinimacs; Milteny Biotech,UK). The panel for immunophenotyping
consisted of CD38, CD138, CD56, CD19, CD28, CD44, CD45,
CD117, CD33, CD34, kappa and lambda. Upon enrichment of CD138 +
PCs, DNA was stained using the DNA prep reagent kit (Beckman
Coulter, USA) . Results. S phase fraction was: median 16% (1-58). DNA
content analysis revealed normal diploidy(n:27 ) and HD(n:56) . Comparison
of HD vs non-HD revealed: similar ISS stage, albumin, S
phase% but higher PC% (12% vs 5%, p=0.05), more patients with
>3.5 B2MG (p=0.064), male gender (M/F: 39/17 p: 0.114 ) and a tendency
for advanced stages (p=0.06) in the HD group.There were more
patients expressing CD 19 or CD44 or CD28 in the non-HD (p= 0.048,
0.024, 0.01, respectively). Response was similar between HD and Non-
HD (21/37 vs 14/22) with a tendency for better response in 13qdelpatients
(3/9 vs 25/41). Cox-regression analysis revealed a positive correlation
between B2MG and S phase(p= 0.046) B2MG values was higher
on HP group (p=0.039), >15% S phase was associated with a tendency
for advanced ISS stages (p: 0.127). Kaplan Meier analysis
revealed better OS with non-HD (p= 0.004) but not S phase