Management of Chronic Myeloid Leukemia in Childhood

Abstract

Childhood chronic myelogenous leukemia (CML) is a rare malignancy, and experience with optimal treatment is very limited. Traditionally, allogeneic hematopoietic stem cell transplantation was considered the only curative treatment. Imatinib, a small-molecule inhibitor of the BCR-ABL tyrosine kinase (TKI), has been proven highly successful in adults with CML, resulting in prolonged molecular response with limited drug toxicity. This drug is now included as front-line therapy for CML in pediatrics as well, though valid concerns about serious late sequelae remain unresolved. Specific pediatric treatment guidelines have not yet been formulated, and most algorithms are derived from experience in adult CML. This overview attempts to summarize pediatric studies on issues such as dose, duration, adverse effects, and steering criteria for TKI treatment, adapting guidelines developed in adult medicine to pediatrics. Most importantly, pediatric patients with CML receiving TKI treatment should be enrolled into formal trials.

Elevated p53 Protein Expression; A Predictor of Relapse in Rare Chronic Myeloid Malignancies in Children?

“…Molecular, cytogenetic, morphological, and clinical features define the risk profile for CML where 95% of the patients are presented with the Philadelphia chromosome, created by t(9;22)(q34;q11), leading to the BCR-ABL fusion gene. Progression from chronic phase through accelerated phase to blast crisis is often associated with the appearance of chromosomal abnormalities in addition to the BCR-ABL fusion gene [23].…”

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients

“…It has also had a significant impact on the decreased frequency of DLI in the treatment of CML relapse. 22,23 The use of DLI as monotherapy to induce or strengthen the graft vs disease effect in the case of RIC HSCT in our patients did not show an explicit result of DLI in this condition. Indication for DLI combined with TT was the detection of increasing MRD levels (in one patient), and for DLI combined with TT or CT was the relapse of disease.…”

Wskazania do transplantacji komórek krwiotwórczych u dzieci i młodzieży – rekomendacje Polskiej Pediatrycznej Grupy ds. Transplantacji Komórek Krwiotwórczych – 2014

“…Niezależnie od fazy CML, w której doszło do rozpoznania białaczki, leczenie zawsze rozpoczyna się od zastosowania imatynibu w dawce zależ-nej od fazy choroby [18][19][20]. Wyjątek stanowią chorzy z mutacją T315I w obrębie domeny BCR-ABL, u których stwierdza się pierwotną oporność na działanie imatynibu, a także na inhibitory kinazy tyrozynowej nowej generacji, takie jak dazatynib i nilotynib.…”