Volume 7 Supplement 1

24th Annual Meeting of the National Cancer Institute of Mexico

Open Access

Clonal evolution in a patient with CML detected by FISH precedes imatinib treatment failure

  • Virginia Enriquez1,
  • Judith Cruz1,
  • Olga Gutierrez1,
  • Maria Teresa Salles1,
  • Pablo Vargas2,
  • Arturo Martínez2,
  • Myrna Candelaria1,
  • Rafael Hurtado2 and
  • Eduardo Cervera1Email author
BMC Cancer20077(Suppl 1):A41

DOI: 10.1186/1471-2407-7-S1-A41

Published: 5 February 2007

Background

Imatinib (IM) inhibits the TK protein from chromosome Philadelphia (Ph). However, less than 10% of IM-treated patients become resistant. Second generation TK inhibitors are on active clinical research aimed to overcome most, but not all, important mutations.

Case report

A 61 year-old male was diagnosed on Sep/98 with CML chronic phase, he was treated with hydroxiurea, interferon and Ara-C. On July/01 the patient was on complete hematological response (CHR), but Ph positive in karyotyping (Ky) and fluorescence in-situ hybridization (FISH), there were not additional abnormalities. Patient began IM treatment, 400 mg/day. After 4 months of treatment, +der(22) was detected, but the patient was still on CHR. On subsequent visits, the patient had an increased frequency of chromosomal abnormalities, and after 2 years he lost CHR, regardless of the increase IM dose and the concomitant use of Ara-C. The patient was included on a dasatinib phase II protocol. 2 weeks after he had a profound cytopenia and 2 months after had CHR. Table 1 shows clinical and hematological and Ky and FISH follow-up.
Table 1

Clinical and hematological and Ky and FISH follow-up

Sample

Date

Ky

FISH

Treatment & clinical condition

1

Jul/01

Only Ph

Only Ph 35%

Began IM 400 mg/d CHR

2

Nov/01

Ph plus double Ph

Not enough material

IM 400 mg/d CHR

3

Jan/02

No growth

Only Ph 26%

IM 400 mg/d CHR

4

Sep/02

Hipodiploid plus Ph

Only Ph 22%

Clone BCR amplified without Ph 3%

Clone ABL amplified and Ph 5%

IM 400 mg/d Leucocytosis

5

Jun/03

Only Ph

Only Ph = 28%

Clone BCR amplified without Ph = 1%

Clone ABL and/or BCR amplified with Ph = 28%

Clone ABL and/or BCR amplified and double Ph = 51%

Clone ABL and BCR amplified with triple Ph = 11%

Clone ABL lost with Ph = 5%

IM 600 mg/d

6

Nov/03

Ph plus lost Y, marker chromosome, trisomy chr 19, double Ph and trisomy chr 8.

Only Ph = 4%

Clone ABL amplified without Ph = 1%

Clone ABL and/or BCR amplified with Ph = 18%

Clone ABL and/or BCR amplified with double Ph = 74%

Clone ABL and BCR amplified with triple PH = 1%

Trisomy chr 8 = 72%

IM 600 mg + Ara-C

7

Jul/04

No growth

Only Ph = 44%

Clone ABL amplified with Ph = 6%

Clone ABL and/or BCR amplified with double Ph = 17%

IM 800 mg/d

sample

Jan/ 05

  

Began with dasatinib

8

Dec/05

No growth

Only Ph = 18%

Dasatinib

Conclusion

Additional abnormalities found on Ky and FISH could preceed treatment failure. Molecular monitoring is required to guide treatment decisions. The role of second generation TK inhibitors needs to be defined.

Authors’ Affiliations

(1)
Instituto Nacional de Cancerología
(2)
Hospital Angeles del Pedregal

Copyright

© Enriquez et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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