scholarly journals Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 926-935 ◽  
Author(s):  
Kirk R. Schultz ◽  
D. Jeanette Pullen ◽  
Harland N. Sather ◽  
Jonathan J. Shuster ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Pediatric Oncology ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Risk Groups ◽  
Oncology Group ◽  
Cancer Group ◽  
Pediatric Oncology Group ◽  
Very High

Abstract The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) joined to form the Children's Oncology Group (COG) in 2000. This merger allowed analysis of clinical, biologic, and early response data predictive of event-free survival (EFS) in acute lymphoblastic leukemia (ALL) to develop a new classification system and treatment algorithm. From 11 779 children (age, 1 to 21.99 years) with newly diagnosed B-precursor ALL consecutively enrolled by the CCG (December 1988 to August 1995, n = 4986) and POG (January 1986 to November 1999, n = 6793), we retrospectively analyzed 6238 patients (CCG, 1182; POG, 5056) with informative cytogenetic data. Four risk groups were defined as very high risk (VHR; 5-year EFS, 45% or below), lower risk (5-year EFS, at least 85%), and standard and high risk (those remaining in the respective National Cancer Institute [NCI] risk groups). VHR criteria included extreme hypodiploidy (fewer than 44 chromosomes), t(9;22) and/or BCR/ABL, and induction failure. Lower-risk patients were NCI standard risk with either t(12;21) (TEL/AML1) or simultaneous trisomies of chromosomes 4, 10, and 17. Even with treatment differences, there was high concordance between the CCG and POG analyses. The COG risk classification scheme is being used for division of B-precursor ALL into lower- (27%), standard- (32%), high- (37%), and very-high- (4%) risk groups based on age, white blood cell (WBC) count, cytogenetics, day-14 marrow response, and end induction minimal residual disease (MRD) by flow cytometry in COG trials.

Outcomes for B-Precursor Patients in Legacy Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG) Studies in Childhood Acute Lymphoblastic Leukemia (ALL): A Children’s Oncology Group (COG) Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 847-847
Author(s):  
Paul S. Gaynon ◽  
Bruce C. Camitta ◽  
Yousif Matloub ◽  
Paul L. Martin ◽  
Naomi Winick ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Oncology Group ◽  
Cancer Group ◽  
Early Responder ◽  
Pediatric Oncology Group ◽  
Double Trisomy ◽  
Standard Risk ◽  
Very High

Abstract Background: Improved post induction intensification (PII) has led to improved outcome for children with ALL over past decades. The merger of POG and CCG provided an opportunity to compare strategies, specifically, POG: intermediate dose methotrexate (Mtx, 1–2 g/m2) with leucovorin (lv) rescue; CCG: Berlin Frankfurt Münster (BFM) Protocol Ib and Protocol II (delayed intensification, DI), “augmented” with additional vincristine (Vcr), escalating-dose parenteral Mtx with no lv rescue, and l-asparaginase (Asp). Methods: Between 1996 and 2005, POG 9904/5/6 trials and CCG 1991/1961 trials accrued 6774 B-precursor patients, age > 1 year. NCI standard risk (SR) patients received induction with Vcr, Asp, dexamethasone; NCI higher risk (HR) patients received induction with Vcr, Asp, daunorubicin, and prednisone. POG allocated PII based on age, gender, presenting WBC and the presence or absence of double trisomy 4+10 or t(12;21). CCG allocated PII based on age, presenting WBC, and the Induction Day 7/14 marrow response. POG SR patients without trisomies 4+10 were randomized +/− DI. CCG SR patients received at least one DI. CCG SR slow early response (SER) patients received daunomycin in induction and augmented intensification. ALL CCG HR patients received at least one DI and many received “augmented” intensification; some POG HR patients received no DI. A subset of POG HR patients, defined by age, gender, and WBC, with very high risk of relapse were designated “Pragmatic Very High Risk” (VHR) and assigned to a modification of CCG Augmented BFM (Aug BFM, NEJM1998; 338:1663, see Table). Results: The 5-year EFS was 84±2% (n=1831) and 88±2% (n=2539) for POG and CCG SR patients (p<0.003). POG and CCG SR patients with double trisomies 4+10 had 5-year EFS of 91±3% (n=387) with no DI and 95±3% (n=317) with one or two DI’s, respectively. The 5-year EFS was 60±4% (n=992) and 71±2% (n=1412) for POG and CCG HR patients (p< 0.001). Results are similar when adjusted for ethnicity. Both SR and HR patients on CCG trials had a statistically significant 25% reduction in risk of an adverse event. Conclusions: This is a non-randomized cross-study comparison. Differences in patient population, treatment assignment, and clinical practice may affect results and interpretation. However, our data suggest the overall superiority of the CCG modified BFM strategy and support the COG decision to build current trials, e.g., AALL0331 and AALL0232, on this platform. Studies Included POG 9904 POG 9904 POG 9905 POG 9906 CCG 1991 CCG 1991 CCG 1961 CCG 1961 RER: rapid early responder; SER slow early responder; Aug BFM: augmented BFM (NEJM1998; 338:1663); Doxo: doxorubicin; Cpm: cyclophosphamide; Ida: idarubicin ; lv :leucovorin NCI SR NCI SR NCI SR + HR NCI HR NCI SR NCI SR NCI HR NCI HR Double Trisomy 4 + 10 t(12;21) Pragmatic VHR Day 14 RER Day 14 SER Day 7 RER Day 7 SER Mtx 1 g versus 2 g/m2 + lv Mtx 1 g versus 2 g/m2 + lv Mtx 1 g versus 2 g/m2 + lv POG Modified Augmented "BFM" ± Vcr + IV Mtx Daunomycin rescue ± stronger intensification Augmented "BFM’ ±DI ±DI Augmented "BFM" 10 vs 6 months intensification Doxo versus Ida/Cpm

Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.

1992 ◽  
Vol 10 (4) ◽  
pp. 606-613 ◽  
Author(s):  
R Trueworthy ◽  
J Shuster ◽  
T Look ◽  
W Crist ◽  
M Borowitz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Oncology ◽  
Progenitor Cell ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Oncology Group ◽  
Dna Index ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Diploid Cells

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.

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

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 602-609 ◽  
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.

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 ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2543-2549 ◽  
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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