A review of the European LeukemiaNet recommendations for the management of CML

Abstract

Several guidelines and recommendations on the management of chronic myeloid leukemia (CML) have been prepared by several scientific societies. The European LeukemiaNet (ELN) appointed a panel of experts who submitted their recommendations to peer-reviewed scientific journals in 2006, 2009, and 2013. Here, we make a critical review of the last, 2013, ELN recommendations, concerning the use of the five available tyrosine kinase inhibitors (TKIs), the evaluation of cytogenetic and molecular response, and the strategy of treatment. Three TKIs (imatinib, nilotinib, dasatinib) are recommended first-line. Bosutinib and ponatinib are available second-line; ponatinib is particularly indicated in case of the T315I mutation. Achieving an optimal response, not only for survival but also for a deeper, stable, treatment-free remission, requires a BCR-ABL transcripts level ≤ 10 % at 3 months, ≤ 1 % at 6 months, ≤ 0.1 % at 1 year, and ≤ 0.01 % later on. Molecular monitoring must include mutational analysis in every case of failure. A successful treatment of accelerated and blastic phase requires TKIs, and in many cases also allogeneic stem cell transplantation.

Dasatinib in Firstand Second-Line Therapy of Chronic Myeloid Leukemia: Efficacy, Safety and Quality of Life

“…Однако у некоторой части пациентов не удается до-стичь ответа на терапию иматинибом или развивается непереносимость препарата [4][5][6][7]. В современных ре-комендациях по лечению больных ХМЛ в хронической фазе предлагается в качестве первой линии терапии, а также в качестве второй линии при неудаче лечения иматинибом применение ИТК 2-го поколения (ИТК2) [4,8,9]. Дазатиниб является одним из новых эффективных препаратов при ХМЛ.…”

Molecular screening and the clinical impacts of BCR‑ABL KD mutations in patients with imatinib‑resistant chronic myeloid leukemia

“…The T315I mutation was detected in 15% of 112 patients with CML who failed to respond to imatinib mesylate treatment (13). The T315I mutation is only sensitive to ponatinib (16).…”

Critical appraisal of European LeukemiaNet (ELN) 2013 recommendations for the management of chronic myeloid leukemia: is it early for a warning?

“…Whether switching to a second-line treatment would yield a better outcome than keeping on the initial drug is another unsolved issue to be investigated for patients with warning signs. One would expect to obtain superior results with second-generation TKIs (2GTKIs) in such a case; however, there are currently no solid data showing that the switch would be beneficial [6].…”

“…failure -switch to another treatment), and gray zones (i.e. warning signs) have not been overrated by the NCCN [6]. For example, a BCR-ABL1 (IS) transcript level above 10% at 3 months requires treatment change in accordance with the NCCN guidelines [5], whereas it is considered to be only a 'warning' sign according to the ELN recommendations which suggests careful and close monitoring of the patient [3].…”