Treatment‐free remission after imatinib discontinuation is possible in paediatric patients with chronic myeloid leukaemia

Giona, Fiorina; Saglio, Giuseppe; Moleti, Maria Luisa; Piciocchi, Alfonso; Rea, Massimiliano; Nanni, Mauro; Marzella, Deborah; Mariani, Simone; Laurino, Marica; Diverio, Daniela; Gottardi, Enrico; Foà, Robin

doi:10.1111/bjh.13103

Cited by 22 publications

(27 citation statements)

References 9 publications

(12 reference statements)

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“…We thus discontinued IM in two additional children with sustained long‐lasting MR. Regular molecular monitoring confirmed persistent MR 4.5 –MR 5 in all three patients more than 34 months from IM discontinuation (Giona et al , ).…”

Section: Discussionmentioning

confidence: 83%

Long‐term results of high‐dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

et al. 2015

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SummaryImatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its longterm efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m 2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91Á5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0Á1% (major molecular response; MMR) and ≤0Á01% (molecular response; MR) at 12 months were 66Á6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78Á6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.

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Section: Discussionmentioning

confidence: 83%

Long‐term results of high‐dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

et al. 2015

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“…35,36 The available information is concordant with the adult experience, and we would not preclude children from attempting TFR. However, this would be an area where clinical trials would be especially important and should always be considered the first priority when considering a TKI withdrawal attempt.…”

Section: Which Patients Should Not Be Considered For a Tfr Attempt?mentioning

confidence: 81%

Moving treatment-free remission into mainstream clinical practice in CML

Hughes

Ross

2016

Blood

284

260

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The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacologic control is the paradigm. Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing (treatment free remission [TFR]). Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy. Based on the accumulated data on TFR, we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity. For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting. We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.

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“…Treatment results of these guidelines have been previously reported [17,18]. Here, we analyze the adherence to treatment and monitoring in P and AP centers.…”

Section: Methodsmentioning

confidence: 92%

“…Since December 2007, with the aim of reducing bone alterations and deceleration of growth rates [15] and/or of improving treatment compliance, IM at the same dose for 3 weeks monthly (intermittent therapy) has been recommended for patients with a persistent BCR-ABL1 IS ≤0.01% (MR) and in patients with a major MR but poorly compliant to treatment [16,17]. Moreover, since 2009, IM discontinuation has been suggested for patients with BCR-ABL1 IS ≤0.0032% > 72 months and with ≤1-log transcript fluctuations after responses to IM [18].…”

Section: Methodsmentioning

confidence: 99%

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

et al. 2018

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Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.

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Treatment‐free remission after imatinib discontinuation is possible in paediatric patients with chronic myeloid leukaemia

Abstract: Survival and complications in patients with thalassaemia major treated with transfusion and deferoxamine. Haematologica, 89, 1187-1193.

Cited by 22 publications

References 9 publications

Long‐term results of high‐dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

Long‐term results of high‐dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

Moving treatment-free remission into mainstream clinical practice in CML

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

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