Topics in Pediatric Leukemia -- Acute Lymphoblastic Leukemia

Samuel D. Esparza, MD; Kathleen M. Sakamoto, MD, PhD

In This Article


Over the past decade, advances in the treatment of childhood ALL have led to the current long-term, event-free survival rates of about 80%. Despite the overall good prognosis, some of the less common subtypes are at high risk of relapse. There is no universally accepted method of stratifying patients into risk groups, but there are clinical features of ALL that are generally acknowledged as prognostic factors. Age, sex, and initial leukocyte count are consistently cited as important prognostic factors.[27]

Patients between the ages of 2 and 10 years tend to have a more favorable prognosis. Infant ALL carries a high risk of early relapse despite intensive chemotherapy. These patients tend to have high initial WBC counts, CNS involvement at presentation, thrombocytopenia, massive organomegaly, and unfavorable karyotypic features, suggesting that this disease may be biologically different from typical ALL.[28] In most studies, girls have more favorable prognoses than boys. The reason is not completely understood. Initial WBC count is accepted as a prognostic indicator at diagnosis. Those with high initial WBC counts (greater than 50,000 per mm3) have poorer prognoses. T-cell ALL commonly presents with a high leukocyte count and has a high rate of lymphoblast proliferation.[29,30]

Race also appears to be a prognostic factor. Despite the lower incidence of childhood ALL in African Americans, prognosis is poorer than for white children. This is thought to be, in part, due to the fact that African American children tend to develop subtypes of ALL considered to be higher risk, such as T-cell ALL. Hispanic children also have an increased incidence of high-risk disease when compared with whites, but less so than African Americans.[31] Patients with a DNA index > 1.16 (eg, hyperdiploid) have better prognoses than those with a DNA index < 1.16.[32]

Future Challenges and Novel Therapies

One of the major problems in pediatric oncology is the need to design better therapy for children with ALL who relapse. This population of children represents the largest group of patients with cancer refractory to current therapies. Although recent improvement in survival is encouraging, there continues to be a subset of patients with childhood ALL who relapse, and about 20% of patients die of the disease.[33] Intensive regimens, including nucleoside analogs (such as gemcitabine and clofarabine), have shown promise in the treatment of heavily pretreated children with relapsed or refractory leukemia. Multicenter, phase 2 trials with a reinduction regimen of topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine are ongoing.[34,35,36] In addition, current modalities of therapy are nonspecific, causing significant risk to normal tissues.

Exciting work is being done to identify target-specific therapies to minimize toxicity and improve event-free survival. Imatinib mesylate is an example of an inhibitor of a tyrosine kinase involved in the pathogenesis of chronic myelogenous leukemia that has shown some efficacy, albeit limited, in the treatment of Philadelphia chromosome-positive ALL.[37] As encouraging as these novel approaches may be, they are far from being accepted as the standard of care for a disease that still imparts substantial morbidity and mortality.


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