Pilot studies of species-specific chemotherapy of childhood acute lymphoblastic leukemia using genotype and immunophenotype

Citation
R. Manera et al., Pilot studies of species-specific chemotherapy of childhood acute lymphoblastic leukemia using genotype and immunophenotype, LEUKEMIA, 14(8), 2000, pp. 1354-1361
Citations number
28
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA
ISSN journal
08876924 → ACNP
Volume
14
Issue
8
Year of publication
2000
Pages
1354 - 1361
Database
ISI
SICI code
0887-6924(200008)14:8<1354:PSOSCO>2.0.ZU;2-7
Abstract
Genotype and immunophenotype can be used to define biological species of ac ute lymphoblastic leukemia (ALL). The purpose of these two pilot studies, c onducted between 1986 and 1994, was to explore the feasibility and acceptab ility of classifying ALL in this manner for selection of treatment rather t han using conventional risk for failure factors such as age and initial whi te blood cell count. The possibility that conventional risk factors would b e overcome and survival improved by this approach was also considered. Flow cytometry and chromosome analysis were used to classify the ALL of 150 chi ldren into one of five biologic categories as defined by cell surface antig ens, DNA index and chromosome number and arrangement. Chemotherapy regimens depended on the assigned category. There was no provision for crania[ irra diation and use of alkylating agents, anthracyclines and epipodophyllotoxin s was restricted in order to reduce risk of late adverse sequelae. All pati ents are included in the analysis regardless of presenting condition or adh erence to protocol. The majority of patients were Mexican-American or Afric an-American. Eight-year event-free survival (EFS) is 60.7% (+/-4%) and 8-ye ar overall survival (OAS) 72.6% (+/-3.7%). EFS and OAS varied significantly among the biologic categories despite differences in chemotherapy regimens . When the patients with B-precursor ALL were retrospectively classified by current Pediatric Oncology Group (POG) criteria, 8-year EFS was 82% (+/-7. 3%) for the good risk group, 68.9% (+/-5.9%) for the standard risk and 48.8 % (+/-7.6%) for the poor risk, all significant differences. However, when r etrospectively classified according to the Rome/NCl prognostic criteria the 8-year EFS for standard risk patients was 69.1% (+/-5.1%) and for high ris k 58.8% (+/-6.9%), not a statistically significant difference. Numbers of T cell and B cell patients are too few for comparison. Gender and ethnicity influenced survival as in treatment based on prognostic factors. Initial ce ntral nervous system (CNS) relapse occurred in five patients (3%) and combi ned CNS and hematological relapse in six (3%). Factors significantly associ ated with CNS and combined relapse were leukemic pleocytosis in the initial CSF sample, pro-B immunophenotype and DNA index <1.16, but not initial whi te blood cell count. Only three survivors appear to have serious late adver se sequelae, the only neurologic the result of asparaginase-induced cortica l vein thrombosis, The results suggest that use of biologic species as defi ned by immunophenotype and genotype to select therapy of ALL is feasible an d acceptable but under the conditions of these studies offered no apparent therapeutic advantage over conventional risk grouping. However, the introdu ction of molecular genotyping and novel gene targeted therapeutic agents ju stify further exploration of this approach.