Br J Haematol. 2015 Apr 20. doi: 10.1111/bjh.13453. [Epub ahead of print]
Giona F et al.

Abstract

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term 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/m2 /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 91·5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0·1% (major molecular response; MMR) and ≤0·01% (molecular response; MR) at 12 months were 66·6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78·6% 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.

Ann Hematol. 2015 Apr 19. [Epub ahead of print]

Gurrea Salas D et al

Abstract

In contrast to adult medicine, specific scoring systems predicting the treatment response for an individual pediatric patient (pt) with chronic myeloid leukemia (CML) have not yet been defined. We evaluated to what extend prognostic scores as described for adults (e.g., Sokal, Hasford, EUTOS score) resulted in comparable risk group categorizations in a pediatric cohort. Parameters for score calculation were extracted from a data set of 90 patients enrolled into trial CML-PAED-II and treated by a standard dose of imatinib. At month 3 and at month 6, treatment response was analyzed based on the transcript ratio BCR-ABL1/ABL1. By the EUTOS, Hasford, and Sokal scores 81, 59, and 62 % of the patients were categorized as low risk, respectively; 19, 14, and 16 % of the patients as high risk, respectively; and by Hasford and Sokal scores 27 and 22 % of the patients, respectively, as intermediate risk. Twenty-seven out of 72 patients analyzable (38 %) exhibited a transcript ratio >10 % at month 3. We show that only the EUTOS score, but not the Sokal and Hasford score, correlates with this early outcome (p = 0.008). Analyzing the EUTOS score separately, we can demonstrate that lowering the cutoff from 87 to 48 points for categorization in low- and high-risk individuals increases the odds ratio from 2.4 (95 % CI 0.6 to 10.4) to 3.6 (95 % CI 1.3 to 10.9). Data are provided on the distribution of risk categories and resulting discrepancies when adult scores are applied on children and adolescents with CML at diagnosis. A larger number of patients and longer follow-up are still needed to develop a prognostic score specifically adapted to the pediatric and adolescent age cohorts.

Eur J Cancer. 2014 Oct 24;50(18):3206-3211. doi: 10.1016/j.ejca.2014.10.007. [Epub ahead of print]

Millot F, Guilhot J, Baruchel A, Petit A, Leblanc T, Bertrand Y, Mazingue F, Lutz P, Vérité C, Berthou C, Galambrun C, Sirvent N, Yacouben K,Chastagner P, Gandemer V, Reguerre Y, Couillault G, Khalifeh T, Rialland F.

Abstract

Purpose:

The aim is to study statural growth in a large cohort of children with chronic myeloid leukaemia (CML) treated with front-line imatinib.

Methods:

Retrospective data from 81 children less than 18years of age with CML identified in the French pediatric registry were analysed. Height was expressed as standard deviation score (SDS).

Results:

A gradual decrease in height SDS was observed over time since starting imatinib. The height SDS was significantly lower 12months and 24months after the start of imatinib overall (p<10-4) irrespective of gender and pubertal age. The height SDS was significantly (p<10-4) lower 12months after the start of imatinib in boys and girls, and in the prepubertal age group as well as in the postpubertal age group, respectively. A similar finding was observed in the subgroups of boys and girls starting imatinib at a prepubertal or postpubertal age. Loss in height SDS 12months after the start of imatinib was of the same range in boys when compared to girls and in patients who started imatinib at a prepubertal age compared to those who started at a postpubertal age.

Conclusion:

Growth velocity was altered during the first years of imatinib treatment in boys as well as in girls and in prepubertal age patients as well as in adolescents.

Pediatr Clin North Am. 2015 Feb;62(1):107-19. doi: 10.1016/j.pcl.2014.09.008.

Hijiya N, Millot F, Suttorp M.

Abstract

Chronic myelogenous leukemia (CML) is a rare disease in children. There is little evidence of biological differences between CML in children and adults, although host factors are different. Children develop distinct morbidities related to the off-target effects of tyrosine kinase inhibitors. The goal of treatment in children should be cure rather than suppression of disease, which can be the treatment goal for many older adults. This article reviews data from the literature on the treatment of CML, discusses the issues that are unique to CML in children, and recommends management that takes these issues into consideration.

Ann Oncol. 2014 Oct 30. pii: mdu490. [Epub ahead of print]

Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M,Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G; on behalf of the GIMEMA CML Working Party.

Abstract

Background:

The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.

Patients and methods:

To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analysed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period.

Results:

Young adults (18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, p<0.001), and the greater spleen size (median value: 4.5 cm, 3.0 cm and 1.0 cm, p<0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among young adults, than among adult and elderly patients (18%, 9%, and 6%, p<0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in young adults, and the probability of transformation was higher (16%, 5% and 7%, p=0.011).

Conclusions:

The characteristics of CML or the host response to leukemia, differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.

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