Features and outcome of chronic myeloid leukemia at very young age: Data from the International Pediatric Chronic Myeloid Leukemia Registry

Abstract

Introduction: Chronic myeloid leukemia (CML) is rare in the first two decades of life comprising only 3% of newly diagnosed pediatric and adolescent leukemias. We studied the epidemiologic and clinical features of patients with CML diagnosed at younger than 3 years of age and evaluated treatment and long-term outcome. Method: Data from the International Pediatric I-BFM/CML Registry were retrospectively analyzed using the European LeukemiaNet criteria of the year 2006. Characteristics and treatment outcome of patients <3 years old at diagnosis were evaluated from standardized forms. Results: Twenty-two patients (n = 22/479; 4.6%, male/female:14/8) were enrolled with a median age of 22 months (range, 10-34 m). Major symptoms comprised asthenia (30%), fever (30%), abdominal pain (20%), extramedullary signs (14%), hemorrhage (5%), and weight loss (5%). The extramedullary signs were specified in eight children: blueberry muffin (n = 1), sudden swollen abdomen (n = 1), sustained vomiting (n = 1), and cervical and inguinal lymph nodes (n = 5). Two of five children with cervical and inguinal lymph nodes were categorized as accelerated phase. Overall, 19 of 22 (86%) children were diagnosed in chronic phase, while the remaining three patients were in advanced phase. Median follow-up was 78 months (range, 7-196 m). Twenty-one out of 22 patients initially received imatinib, while one child received IFN + ARA-C. Imatinib was changed to second-line tyrosine kinase inhibitors (TKIs) in 29% of cases. During follow-up, 41% patients underwent stem cell transplantation (SCT). While on TKI, major molecular response (MMR) was achieved in 48% of children. Among the remaining patients, 21% are alive on TKI without MMR and 22% achieved complete molecular response following SCT. Twenty-one of 22 (95%) children are alive, while one patient died of posttransplant complications.

Treatment and follow‐up of children with chronic myeloid leukaemia in chronic phase (CML‐CP) in the tyrosine kinase inhibitor (TKI) era—Two decades of experience from the Tata Memorial Hospital paediatric CML (pCML) cohort

“…The significant delay in achieving CHR in under‐5 children is similar to the cohort from the I‐BFM pCML registry, showing delayed attainments of milestones in under‐3 children. Nonetheless, the rate of attaining MMR was comparable to older children in both the cohorts 26 . Aggressive nature of the disease and difficulty in dosing imatinib in younger children may be one of the reasons for a delayed response during the initial phase of treatment.…”

“…Nonetheless, the rate of attaining MMR was comparable to older children in both the cohorts. 26 Aggressive nature of the disease and difficulty in dosing imatinib in younger children may be one of the reasons for a delayed response during the initial phase of treatment.…”

Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations

“…According to current recommendations, vaccinations with live vaccines are completed by the age of 4-6 years in most countries. As CML is rarely seen in children below that age, only very few children face the issue of live vaccine administration during TKI treatment [27][28][29]. A problem exists for older children who missed their booster vaccinations, as well as an increasing number of children whose parents generally have refused vaccination (e.g., the measles vaccine) [27,28,30].…”

Chronic myeloid leukemia (CML) in children and adolescents—Clinicopathological findings

“…In the first two decades of life, CML is extremely rare, with reported incidences of 0.7/million/year in infancy to 1.2/million/year in adolescents 4,5 . Epidemiological studies conducted in the previous millennium reported poor survival with conventional chemotherapy 6 .…”

“…1 In the first two decades of life, CML is extremely rare, with reported incidences of 0.7/million/year in infancy to 1.2/million/year in adolescents. 4,5 Epidemiological studies conducted in the previous millennium reported poor survival with conventional chemotherapy. 6 Hydroxyurea (HU) and interferon-alfa (IFN-α) reduced the proliferation of leukemia cells but did not improve long-term survival.…”