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

12 th Congress of the European Hematology Association
with a classical 3+7 chemotherapy (daunorubicin 30 to 45 mg/m 2 , Ara-
C 100 mg/m 2 ) (validation cohort). Results. 45 pts (38 MBC CML and 7
Ph+ AML) were included[(median age 53 years, (22-74); sex ratio 67%]
from 2001 to 2006 with a median follow-up of 3.9 years. 7 pts were
treated in cohort 1, 6 in cohort 2, 6+8 in cohort 3 and 18 in the validation
cohort. Haematological responses were observed in 31 pts (68.9%)
including 26 patients in CR (57.8%) and 5 patients in CP (chronic phase).
The rate of CR and CP was significantly higher in pts treated in cohorts
3 and in the validation cohort (21 CR, 2 CP, 8 failures) compared to
cohorts 1 and 2 (3 CR, 3 CP, 7 failures) (p=0,013) indicating a benefit of
combining standart chemotherapy and IM. After induction, a complete
cytogenetic response was observed in 13 pts (42%) including 4 of them
with a major molecular response. 5 pts (11%) died early during induction
due to disease progression (n=3), septicaemia (n=1) and following
splenectomy for haematoma (n=1). All responding pts had a neutrophil
recovery before day 45 (median 22 days). The median duration of grade
3-4 thrombocytopenia was 25.5 days. For pts with MBC CML (n=38),
response rate (CP and CR) was 63.1%. However, median survival and
DFS were 9.8 and 14.4 months respectively. Only pts who received allogeneic
stem cell transplantation (n=11) experienced a prolonged DFS
(not reached versus 10.9 months, p=0,01) and a trend in survival (65.9%
at 3 year). For pts with Ph+ AML (n=7), the CHR rate is 100% and median
survival and DFS were not reached. At 3 year, estimated survival and
DFS were 85.7%. 4 out of 7 Ph+ AML received allogeneic HSCT. Their
survival was +4.2, +6.5, +19.3 and+23.1 months compared to +43.6,
+17.9 and 4 months for non allografted patients. Conclusion. IM combined
with the classical 3+7 induction protocol produce 63.1% of
haematological remission in pts with MBC CML without significant
toxicity but only pts who received allogeneic HSCT experienced prolonged
DFS and survival. All our 7 pts with Ph+ AML obtained a CR and
long survivors were observed either after allogeneic HSCT or maintenance
with IM and chemotherapy.
0548
ALTERED BONE AND MINERAL METABOLISM IN CHRONIC PHASE CML PATIENTS
TREATED WITH IMATINIB
S. Jönsson, 1 Y.W. Wei, 2 B.O. Olsson, 1 D.M. Mellström, 1
H.W. Wadenvik1
1 2 Sahlgrenska Academy of Göteborg Univ., GOTHENBURG, Sweden; Shandong
University, Qilu Hospital, JINAN, P.R. of China
Background. Imatinib mesylate (Glivec ® , Gleevec) is the drug of choice
for most patients with chronic phase CML. It was recently suggested that
hypophosphatemia develops in imatinib treated patients as a consequence
of suppression of bone turnover and renal phosphate wasting. Aims. To
gain more information regarding the imatinib-associated hypophosphatemia
we analyzed bone and mineral metabolism in imatinib treated
CML patients and age and sex matched healthy individuals. Material. Eighteen
imatinib treated CML patients (11 males/7 females; mean age 60±11
(SD) years) and 19 helthy volunteers (11 males/8 females; mean age 58±12
(SD) years) were included. All CML patients were treated in first chronic
phase, targeting an imatinib dose of 400 mg q.d. At time of study, all
patients were in complete cytogenetic remission and the mean imatinib
treatment duration was 48±21 (SD) months.
Table 1.
204 | haematologica/the hematology journal | 2007; 92(s1)
Blood was collected in the morning, between 8-10 am, after a light
breakfast. All serum and plasma samples were stored frozen at -80°C
until analysis. Twenty-four hours urine collections, for determination of
Calcium and Phosphate excretion, were also obtained from all patients
and controls. Results. The results from the biochemical evaluation are given
the attached table. Results from bone density measurements (DEXA
and pQCT) are pending. Conclusions. The imatinib treated patients had
lower levels of 1,25-(OH)2 vitamin D, lower ionized Calcium, lower S-
Phosphate, lower S-Osteocalcin and increased S-Parathyroid hormone;
the changes were small but still statistically significant. These alterations
in mineral metabolism resemble those seen in hereditary, vitamin Ddependent
rickets type 1, i.e. a dysfunctional renal 1-OHase enzyme. It
is still unknown if the altered mineral metabolism has any clinically relevant
effect on the bone mineralization. Results from our DEXA and
pQCT measurements will be presented.
0549
IMATINIB 400 MG IN LOW SOKAL RISK CML PATIENTS IN EARLY CHRONIC PHASE:
RESULTS OF AN OBSERVATIONAL, MULTICENTRIC PROSPECTIVE TRIAL OF THE GIMEMA
CML WP
F. Castagnetti, 1 I Iacobucci, 1 F. Palandri, 1 G Marzocchi, 1 P Giannoulia, 1
M. Amabile, 1 T. Intermesoli, 2 M. Breccia, 3 F. Radaelli, 4 E Usala, 5
E Abruzzese, 6 F Pane, 7 G Saglio, 8 G. Martinelli, 1 M Baccarani, 1 G Rosti1 1 Institute of Hematology Seràgnoli, BOLOGNA; 2 Ospedali Riuniti, BERGAMO;
3 Chair of Hematology, Università La Sap, ROMA; 4 Chair of Hematology, Università
di Mila, MILANO; 5 Hematology Unit, Ospedale Businco, CAGLIARI;
6 Hematology Unit, Ospedale S. Eugenio, ROMA; 7 CEINGE - Università di
Napoli, NAPOLI; 8 Patologia Medica, Orbassano, TORINO, Italy
Background. Imatinib 400 mg (SD) is the established first line treatment
of chronic myeloid leukemia (CML) in chronic phase. The efficacy of
imatinib in early chronic phase has been demonstrated by phase 2 and
3 controlled trials like the IRIS study (Druker BJ et al NEJM 355:23, 2006).
Large multicentric studies aimed to evaluate the impact of imatinib 400
mg/daily outside strictly monitored frameworks are not yet available.
AIMS The GIMEMA (Gruppo Italiano Malattie Ematologiche dellAdulto)
CML Working Party opened in January, 2004, an observational study
(serial n. CML/023) to investigate the efficacy of imatinib SD in newly
diagnosed CML patients in chronic phase. Since response to treatment
is risk related and reporting on the cumulative response rate irrespective
of risk is confusing, we report the results obtained in low (Sokal) risk
patients. This allows a more suitable comparison with other published
series. METHODS Clinical and anagraphical data were collected through
a web-based system. Peripheral blood samples for quantitative molecular
analysis (RT-Q-PCR, Bcr-Abl/Abl x 100 - Taqman) were centralized
in Bologna. RESULTS Overall, between Jan 2004 and Jan 2006, 55 italian
centers enrolled 217 low Sokal risk newly diagnosed CML pts . Median
age was 50 yrs (range 18-84), 136 (63%) males and 81 (37%) females.
217 patients were evaluable for response at 3 months, 181 at 6 months
and 118 at 12 months. Median observation time is 12 months. At 6
months, 86% of evaluable cases obtained a complete cytogenetic
response (100% Ph-neg, CCgR). A major molecular response (MMolR)
defined as a Bcr-Abl/Abl x 100 ratio < 0.05%, was shown in 54% of
CCgR pts. At 12 months, the CCgR rate was 88% and the MMolR rate
in CCgR pts was 60%. With this short observation period, only 4 pts
(1,8%) progressed to accelerated/blastic phase.CONCLUSIONS 201 low
Sokal risk pts were enrolled in the IRIS trial: at 12 months CCgR and
MMolR (reduction of Bcr-Abl/Bcr ratio level > 3 logs) rates were 76%
and 66%, respectively (T. Hughes et al., NEJM 349:15, 2003). Our multicentric
study confirms and reinforce the results of the IRIS trial in the
same Sokal risk category, showing that imatinib is highly effective and
manageable outside of academical structures as well as in strictly monitored
trials. ACKNOWLEDGMENTS COFIN 2003, FIRB 2001, AIRC,
Fondazione del Monte di Bologna e Ravenna, European Leukemia Net,
BolognaAIL. Background. Imatinib 400 mg (SD) is the established first line
treatment of chronic myeloid leukemia (CML) in chronic phase. The
efficacy of imatinib in early chronic phase has been demonstrated by
phase 2 and 3 controlled trials like the IRIS study (Druker BJ et al NEJM
355:23, 2006). Large multicentric studies aimed to evaluate the impact
of imatinib 400 mg/daily outside strictly monitored frameworks are not
yet available. AIMS The GIMEMA (Gruppo Italiano Malattie Ematologiche
dellAdulto) CML Working Party opened in January, 2004, an
observational study (serial n. CML/023) to investigate the efficacy of
imatinib SD in newly diagnosed CML patients in chronic phase. Since
response to treatment is risk related and reporting on the cumulative
response rate irrespective of risk is confusing, we report the results