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Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy.
Br J Haematol. 2008 Nov; 143(4):503-10.BJ

Abstract

The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect.

Authors+Show Affiliations

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@mte.biglobe.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18986386

Citation

Yanada, Masamitsu, et al. "Prospective Monitoring of BCR-ABL1 Transcript Levels in Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukaemia Undergoing Imatinib-combined Chemotherapy." British Journal of Haematology, vol. 143, no. 4, 2008, pp. 503-10.
Yanada M, Sugiura I, Takeuchi J, et al. Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. Br J Haematol. 2008;143(4):503-10.
Yanada, M., Sugiura, I., Takeuchi, J., Akiyama, H., Maruta, A., Ueda, Y., Usui, N., Yagasaki, F., Yujiri, T., Takeuchi, M., Nishii, K., Kimura, Y., Miyawaki, S., Narimatsu, H., Miyazaki, Y., Ohtake, S., Jinnai, I., Matsuo, K., Naoe, T., & Ohno, R. (2008). Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. British Journal of Haematology, 143(4), 503-10. https://doi.org/10.1111/j.1365-2141.2008.07377.x
Yanada M, et al. Prospective Monitoring of BCR-ABL1 Transcript Levels in Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukaemia Undergoing Imatinib-combined Chemotherapy. Br J Haematol. 2008;143(4):503-10. PubMed PMID: 18986386.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. AU - Yanada,Masamitsu, AU - Sugiura,Isamu, AU - Takeuchi,Jin, AU - Akiyama,Hideki, AU - Maruta,Atsuo, AU - Ueda,Yasunori, AU - Usui,Noriko, AU - Yagasaki,Fumiharu, AU - Yujiri,Toshiaki, AU - Takeuchi,Makoto, AU - Nishii,Kazuhiro, AU - Kimura,Yukihiko, AU - Miyawaki,Shuichi, AU - Narimatsu,Hiroto, AU - Miyazaki,Yasushi, AU - Ohtake,Shigeki, AU - Jinnai,Itsuro, AU - Matsuo,Keitaro, AU - Naoe,Tomoki, AU - Ohno,Ryuzo, AU - ,, PY - 2008/11/7/pubmed PY - 2009/1/8/medline PY - 2008/11/7/entrez SP - 503 EP - 10 JF - British journal of haematology JO - Br J Haematol VL - 143 IS - 4 N2 - The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/18986386/Prospective_monitoring_of_BCR_ABL1_transcript_levels_in_patients_with_Philadelphia_chromosome_positive_acute_lymphoblastic_leukaemia_undergoing_imatinib_combined_chemotherapy_ L2 - https://doi.org/10.1111/j.1365-2141.2008.07377.x DB - PRIME DP - Unbound Medicine ER -