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

12 th Congress of the European Hematology Association
of the patients are female and median age at diagnosis was 50 years for
males and 53 years for females. Using the New CML Score the proportion
of low-risk patients varies between 34-53% (high risk: 5-23%)
among the participating study groups. First analyses of outcome data
indicate that the results of the IRIS trial can be reproduced. Having
excluded patients with less than 20 evaluated metaphases or with FISH,
72.3% of 535 patients treated with imatinib 400 mg with or without comedication
had a complete cytogenetic response up to month 12 compared
to 69.0% of the IRIS study. Summary and Conclusions. With more
countries participating and longer observation times, the European CML
Registry promises to provide highly interesting data.
0663
STABLE MOLECULAR REMISSION IN CHRONIC MYELOID LEUKEMIA PATIENTS MAIN-
TAINED WITH LOWER DOSES OF IMATINIB MESYLATE BECAUSE OF INTOLERANCE
A.M. Carella, 1 E. Lerma, 2 A.G. Congiu, 2 S. Biasco, 2 G. Catania, 2
S. Nati, 2 R. Vimercati, 2 M. Spriano, 2 M. Risso, 2 E. Rossi2 1 2 S.Martino Hospital, GENOVA; Hematology 1, S. Martino Hospital, GEN-
OVA, Italy
Imatinib mesylate (IM) has became the standard of care for chronic
myeloid leukaemia (CML) patients but it is unclear whether this therapy
can be discontinued in patients with undetectable BCR-ABL transcripts
by RQ-PCR and whether IM can cure CML. Between 2000 and
2005, 60 CML patients were treated with IM in our department. Twenty-seven
patients were in late chronic phase refractory to interferon-α
and 33 were newly diagnosed chronic phase patients. Forty-five (75%)
patients achieved complete cytogenetic remission (CCyR) and in 11
(25%) patients BCR-ABL transcripts became undetectable by RQ-PCR.
In this report, we want to address the question if the reduction of standard
dosage of IM in CML patients with undetectable residual disease
by RQ-PCR may impair their outcome. We describe the clinical history
of 4 CML patients where the IM treatment was tapered to a lower
dosage due to intolerance after those patients had achieved a molecular
remission documented by RQ-PCR. The median follow-up from the
beginning of IM therapy was 45 months (33-59). The median duration
of undetectable transcripts levels by RQ-PCR on IM 200 mg daily was
18 months (3-36). At the time of this report, all patients are in molecular
remission. We hypothesize that in IM intolerant CML patients in
molecular remission the compound dosage might be safely reduced to
a lower other than standard dose without to lose the response. In these
cases, the amount of leukemic transcripts is low and lower doses might
control the disease. Those patients should be monitored closely because
the selection of resistant clones after prolonged IM exposure and the
emergence of Philadelphia-negative clones with secondary cytogenetic
abnormalities could be a matter of concern. However, it is important to
underline that the probability to develop drug resistance is directly related
to the level of BCR-ABL transcripts, the higher is its level the higher
is the risk to become resistant. The improved quality of life in our
patients, after reduction of IM dosage, suggests that the subset of intolerant
patients who have a sustained molecular remission might be candidates
for lower doses of IM. Our observation can promote a clinical
trial to determine when, how and where it is possible to reduce IM standard
dose in imatinib-intolerant CML patients.
0664
TREATMENT AND RESISTANCE TO IMATINIB IN CML PATIENTS: EXPERIENCE OF A
PORTUGUESE CENTER
I. Castro, 1 A. Espirito Santo, 1 A. Carneiro, 1 M.J. Silva, 1 A. Fernandes, 2
J. Cancela, 1 F. Principe, 1 F. Ferreira, 1 R. Lemos, 2 J. Andrade, 1 A. Costa, 1 F.
Trigo, 1 I. Moreira, 1 T. Costa, 1 F. Silva, 1 J.E. Guimarães1 1 Hospital S João, PORTO; 2 Centro Genética Clinica, PORTO, Portugal
Background. Chronic myeloid leukaemia (CML) is a myeloproliferative
disorder characterized by identification of the Philadelphia chromosome
(Ph) or the product of the fusion gene resulting from t(9;22), the hybrid
BCR/ABL mRNA which encodes a oncoprotein with a constitutively
active tyrosine kinase. Before Imatinib (IM), Interferon ± Cytarabine
was considered standard therapy for the disease. Nowadays Imatinib,
a potent and specific inhibitor of the Bcr-Abl tyrosine kinase, is the first
choice treatment in CML. We decided to carry out a retrospective analysis
of our patients treated with this tyrosine kinase inhibitor (TKi)
emphasising disease monitoring. Material and Methods. Seventy two
patients (29 female; 43 male; median age 47 years) were evaluated for
haematological, cytogenetic and molecular response, and progression
248 | haematologica/the hematology journal | 2007; 92(s1)
to accelerated phase or blast crisis. Patients were treated with IM standard
doses; 30 of these 72 patients were treated with Interferon ±
Cytarabine before IM. Twelve patients who failed IM were analysed for
resistance, namely mutation analysis. Results. Patients were divided in
two treatment groups: Imatinib as first line (Group A; 42 patients; follow
up 5'50 months, median 42) and IM as second line (Group B; 30
patients; follow up 20-68 months, median 45). Complete haematological
response was achieved in all patients in Group A and in 76% in
Group B after 3 months of treatment. Major cytogenetic response was
94,1% (Group A) and 73% (Group B). Complete cytogenetic response
was 79,4% (Group A) and 53,8% (Group B) at 12 months. Complete
cytogenetic responders were monitorized by real time quantitative PCR.
Major molecular response (Q-PCR