Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study

PURPOSE Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.

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Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽

10.1182/blood.v81.3.602.602 ◽

1993 ◽

Vol 81 (3) ◽

pp. 602-609 ◽

Cited By ~ 54

Author(s):

PD Sadowitz ◽

SD Smith ◽

J Shuster ◽

MD Wharam ◽

GR Buchanan ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Pediatric Oncology ◽

Lymphoblastic Leukemia ◽

Randomized Study ◽

Intrathecal Chemotherapy ◽

Primary Therapy ◽

Oncology Group ◽

Continuation Therapy ◽

Pediatric Oncology Group

Abstract Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6- mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty- eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.

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New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases

Blood ◽

10.1182/blood.v96.7.2543 ◽

2000 ◽

Vol 96 (7) ◽

pp. 2543-2549 ◽

Cited By ~ 76

Author(s):

Nancy R. Schneider ◽

Andrew J. Carroll ◽

Jonathan J. Shuster ◽

D. Jeanette Pullen ◽

Michael P. Link ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Pediatric Oncology ◽

Lymphoblastic Leukemia ◽

Cell Lineage ◽

Blast Cell ◽

Derivative Chromosome ◽

Oncology Group ◽

Pediatric Oncology Group ◽

B Lineage

Abstract To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

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