Acute lymphoblastic leukemia a comprehensive review with emphasis on biology and therapy

Abstract

Background. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. It is now curable in 60–70% of children. Most of the current understanding of the biology and treatment of ALL originates from studies of children. In adults, although much progress has been achieved, ALL is curable in only 20–35% of patients. Methods. A review of the biology and treatment of ALL from the English literature was performed. Results. Immunophenotypic and cytogenetic analyses of ALL have contributed to a more rational classification of ALL. These analyses have identified subgroups with poor prognosis or with different therapeutic requirements. Overall, 60–70% of adults with ALL have poor prognostic features, including older age, a high leukocyte count, non—T‐cell innmunophenotype, Ph‐positive genotype, and longer time to achieve a complete remission. These patients have a cure rate of 20–25% whereas those without these risk factors, have a 60–70% probability of survival. The use of more intensive induction regimens with growth factor support may improve survival rates. Also, intensive consolidation‐intensification may improve survival rates. Most patients benefit from maintenance therapy, but the dose schedule must be optimized. Central nervous system (CNS) prophylaxis is beneficial, particularly for patients with a high risk for CNS relapse and when introduced early during induction of remission. Patients with high risk characteristics may benefit from allogeneic bone marrow transplantation (BMT) during first remission, and all other patients may benefit from it during first or subsequent relapse. Autologous BMT may be a valuable option for poor compliant patients. Conclusions. Although the prognosis of patients with ALL has improved markedly during the past decades, newer strategies, including more dose‐intensive therapy, the search for new drugs, and more target‐specific therapy, are needed to improve the current cure rates.

The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia

“…[3][4][5] Because most adult patients will relapse after a relatively brief remission, more effective therapeutic approaches are needed. In a recent review by Welborn,6 consisting of a compilation of 44 studies involving 861 patients and using a variety of reinduction treatment regimens for relapsed and refractory ALL, CR rates varied from 5 to 89% but median duration of CR was 6 months or less in all.…”

“…3,4 Prognostic variables that predict patient outcome include age, performance status, degree of leukocytosis, and leukemia karyotype and immunophenotype. [3][4][5] Once a patient relapses or fails to achieve a complete remission, salvage chemotherapy regimens have been reported to have reinduction rates of 20-60%, but, nevertheless, median CR remission duration averages only 3.4 months.…”

“…3,4 Prognostic variables that predict patient outcome include age, performance status, degree of leukocytosis, and leukemia karyotype and immunophenotype. [3][4][5] Once a patient relapses or fails to achieve a complete remission, salvage chemotherapy regimens have been reported to have reinduction rates of 20-60%, but, nevertheless, median CR remission duration averages only 3.4 months. 6 Over a period of 44 months, 66 patients at our institution were given salvage chemotherapy with the 'hyper-CVAD' regimen, a dose-intensive regimen patterned after the childhood Burkitt ALL therapy designed by Murphy et al 7 We called the regimen 'hyper-CVAD' after the acronym for the initial induction combination.…”

Relapse of Acute Lymphoblastic Leukemia in Pregnancy: Survival Following Chemoirradiation and Autologous Transfer of Interleukin-2-Activated Stem Cells

“…The disease can originate in lymphoid cells of B-cell or T-cell origin. ALL was among the first malignancies to be cured in the majority of children (60 -70%) [7]. In adults and adolescents, however, ALL is curable in only 20 -40% of patients [1].…”

“…In adults and adolescents, however, ALL is curable in only 20 -40% of patients [1]. Poor prognostic factors include age Ͼ10 years, leukocyte count Ͼ10,000/mm 3 , a high percentage of circulating lymphoblasts, pseudodiploid cytogenetics, CD34 expression, and the presence of the multidrug resistance-associated protein P-170 [7].…”