Translate page

English English
en Englishbg Bulgarianzh-CN Chinese (Simplified)hr Croatiancs Czechda Danishnl Dutchfi Finnishfr Frenchde Germanel Greekiw Hebrewhi Hindiid Indonesianit Italianja Japaneseko Koreanmk Macedonianpl Polishpt Portuguesero Romanianru Russiansr Serbiansk Slovaksl Slovenianes Spanishsv Swedishth Thaitr Turkishvi Vietnamese

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach (Hijiya N et al. Blood, October 2015)

Blood, 2015 Oct 28 (Epub ahead of print)
Hijiya N. et al.

 

Abstract

Chronic myelogenous leukemia (CML) in children is relatively rare. Due to lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate some genetic differences exist in pediatric and adult CML. As children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid life-long exposure to TKIs and their associated adverse effects. Blood and marrow transplantation (BMT) in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.

Copyright © 2015 American Society of Hematology.

Leukostasis in children and adolescents with chronic myeloid leukemia: Japanese pediatric leukemia/lymphoma study group (Kurosawa H et al. Pediatr Blood Cancer, October 2015)

Pediatr Blood Cancer. 2015 Oct 20. doi: 10.1002/pbc.25803. [Epub ahead of print]
Kurosawa H et al. 
 

Abstract:

 

Background:  

The details of leukostasis in children and adolescents with chronic myeloid leukemia (CML) are unknown. This study determined the characteristics of leukostasis in children and adolescents with CML.

PROCEDURE: 

A total of 256 cases from a retrospective study of patients with CML conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group from 1996 to 2011 were analyzed, and of these, 238 cases were evaluated in this study.

RESULTS: 

Leukostasis was diagnosed in 23 patients (9.7%). The median leukocyte count and spleen size below the left costal margin in cases with leukostasis were significantly higher and larger when compared to those in cases without leukostasis (458.5 × 109 /l vs. 151.8 × 109 /l (P < 0.01), and 13 vs. 5 cm (P < 0.01), respectively). Leukostasis occurred with ocular symptoms in 14 cases, priapism in four cases, and dyspnea, syncope, headache, knee pain, difficulty hearing, and aseptic necrosis of the femoral head in one case each. One case had two leukostasis symptoms simultaneously. Three cases were diagnosed before imatinib became available. Five cases received special treatment, and in the remaining 15 cases, all of these symptoms resolved after treatment with imatinib.

CONCLUSIONS: 

This retrospective study represents the largest series of children and adolescents in which leukostasis of CML has been reported. Our data provide useful insight into the characteristics of leukostasis in recent cases of children and adolescents with CML.

 

© 2015 Wiley Periodicals, Inc.

Long-term results of high-dose imatinib in children and adolescents with CML in chronic phase: The Italian experience (Giona F et al. Br J Haematol, Apr 2015)

 

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.

Atypical chronic myeloid leukemia in two pediatric patients (Freedman JL et al. Pediatr Blood Cancer, August 2015)

Pediatr Blood Cancer. 2015 Aug 14. doi: 10.1002/pbc.25694. [Epub ahead of print]

Freedman JL et al.

 

Abstract

Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

© 2015 Wiley Periodicals, Inc.

Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients? (Gurrea Salas D et al. Ann Hematol, Apr 2015)

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.

  1. Chronic myloid leukemia in children: clinical findings, management, and unanswered questions (Hijija N et al. Pediatr Clin North Am, February, 2015)
  2. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia (Millot F et al. Eur J Cancer, Oct. 2014)
  3. Differences among young adults, adults and elderly chronic myeloid leukemia patients (Castagnetti F et al. Ann. Oncol, Oct. 2014)
  4. Managing children with CML: Pediatric CML Guideline if IBFM (Fuente et al. Br J Haematology, July 2014)