Pediatric Acute Lymphoblastic Leukemia Regimens Research Articles

Minimal Residual Disease (MRD) after Frontline Therapy in Adolescent and Young Adult (AYA) Patients with Acute Lymphoblastic Leukemia (ALL) Treated on Two Separate Regimens.

Retrospective and prospective studies have demonstrated that AYA patients (pts) with ALL have superior outcomes when treated with pediatric rather than adult-type regimens. Pediatric ALL regimens are therefore being applied as frontline therapy for adults up to age 30. Given the relatively favorable outcome for this group and the length of therapy employed, it will be several years before the superiority of this approach can be confirmed. MRD by multiparameter flow cytometry (MFC) might be an early measurement of treatment efficacy, since detection of MRD after initial induction has been shown to predict for decreased disease-free survival (DFS). MRD monitoring may thus provide an early indication of later success for different ALL regimens in AYA patients. MRD was measured by four color MFC using lineage specific antibodies in conjunction with antibodies directed at aberrant antigens. The limit of detection was one cell in ten-thousand. MRD data for 43 pts </= 30 years of age treated with the adult regimen of hyper CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) with or without rituximab was compared with MRD data obtained from 13 pts treated with the pediatric ABFM regimen. The median age of the two groups was 22 years (range 15–30) and 20 years (range 14–28), respectively. MRD data on day 21 of therapy was available for 33 of 43 pts (77%) treated with hyer-CVAD; 22/33 (67%) were negative, 10/33 (30%) were positive, and one pt had insufficient cells for analysis. On day 90 of therapy, 21 of the 43 pts had data available, and all were MRD negative. All pts treated with the ABFM protocol had MRD assessments performed on day 29 of induction therapy; 8 (62%) were negative, 2 (15%) had suspicious cells in an insufficient sample, and 3 (23%) were positive. Of the 9 pts with MRD measurements on day 84 of therapy, all were negative except for 1 pt who relapsed before day 84. These preliminary data indicate that AYA pts with ALL receiving either hyper-CVAD or ABFM therapy have similar MRD status at the end of induction and after approximately 3 months of consolidation. Given the likely importance of MRD in predicting DFS, this comparison suggests that hyper-CVAD and ABFM may show similar outcomes in this population. Continued accrual and longer follow-up will be required to confirm this hypothesis.

Favorable Outcome for Adolescents With Acute Lymphoblastic Leukemia Treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols

Historically, adolescents with acute lymphoblastic leukemia (ALL) have had inferior outcomes when compared with younger children. We report the outcome of adolescents treated on Dana-Farber Cancer Institute (DFCI; Boston, MA) ALL Consortium Protocols conducted between 1991 and 2000. A total of 844 patients aged 1 to 18 years, with newly diagnosed ALL were enrolled onto two consecutive DFCI-ALL Consortium Protocols. We compared outcomes in three age groups: children aged 1 to 10 years (n = 685), young adolescents aged 10 to 15 years (n = 108), and older adolescents aged 15 to 18 years (n = 51). With a median follow-up of 6.5 years, the 5-year event-free survival (EFS) for those aged 1 to 10 years was 85% (SE, 1%), compared with 77% (SE, 4%) for those aged 10 to 15 years, and 78% (SE, 6%) for those aged 15 to 18 years (P = .09). Adolescents were more likely to present with T-cell phenotype (P < .001) and less likely to have the TEL-AML1 fusion (P = .05). The incidence of pancreatitis and thromboembolic complications, but not asparaginase allergy, was higher in patients 10 years of age compared with those younger than 10 years. However, there was no difference in the rate of treatment-related complications between the 10- to 15-year and 15- to 18-year age groups. Adolescents were more likely to present at diagnosis with biologically higher risk disease (T-cell phenotype and absence of the TEL-AML1 fusion) and more likely to experience treatment-related complications than younger children. However, the 5-year EFS for older adolescents was 78% +/- 6%, which is superior to published outcomes for similarly aged patients treated with other pediatric and adult ALL regimens. Based on this experience, we currently are piloting our regimen in patients aged 18 to 50 years.