scholarly journals Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report

Leukemia ◽  
2000 ◽  
Vol 14 (3) ◽  
pp. 369-373 ◽  
Author(s):  
JH Laver ◽  
JC Barredo ◽  
M Amylon ◽  
M Schwenn ◽  
J Kurtzberg ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Oncology Group ◽  
Cranial Radiation ◽  
Group Report ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1220-1224
Author(s):  
AJ Carroll ◽  
WM Crist ◽  
MP Link ◽  
MD Amylon ◽  
DJ Pullen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Chain Gene ◽  
Oncology Group ◽  
Chromosome 14 ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia

We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2110-2117 ◽  
Author(s):  
RO Bash ◽  
WM Crist ◽  
JJ Shuster ◽  
MP Link ◽  
M Amylon ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Clinical Features ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Genetic Defect ◽  
Gene Rearrangements ◽  
Oncology Group ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.

scholarly journals Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2110-2117 ◽  
Author(s):  
RO Bash ◽  
WM Crist ◽  
JJ Shuster ◽  
MP Link ◽  
M Amylon ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Clinical Features ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Genetic Defect ◽  
Gene Rearrangements ◽  
Oncology Group ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.

scholarly journals The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1220-1224 ◽  
Author(s):  
AJ Carroll ◽  
WM Crist ◽  
MP Link ◽  
MD Amylon ◽  
DJ Pullen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Chain Gene ◽  
Oncology Group ◽  
Chromosome 14 ◽  
Pediatric Oncology Group ◽  
Cell Acute Lymphoblastic Leukemia

Abstract We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.

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.

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.

Treatment of CNS relapse in children with acute lymphoblastic leukemia: A Pediatric Oncology Group study.

1993 ◽  
Vol 11 (2) ◽  
pp. 271-278 ◽  
Author(s):  
N J Winick ◽  
S D Smith ◽  
J Shuster ◽  
S Lauer ◽  
M D Wharam ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Treatment Protocol ◽  
Intrathecal Therapy ◽  
Oncology Group ◽  
Treatment Comparison ◽  
Cns Relapse ◽  
Cranial Radiation ◽  
Pediatric Oncology Group

PURPOSE To assess the efficacy and toxicity of chemotherapy and cranial radiation for the treatment of children with acute lymphoblastic leukemia (ALL) following first isolated CNS relapse. PATIENTS AND METHODS One hundred twenty children were treated on Pediatric Oncology Group (POG) protocol 8304. All children had received prophylactic CNS therapy during their initial treatment. The treatment protocol included a four-drug reinduction and six weekly doses of triple intrathecal therapy (TIT). Cranial radiation, 24 Gy, was followed by monthly TIT. Systemic consolidation and maintenance therapy included 6-week cycles of mercaptopurine/methotrexate (6MP/MTX) and vincristine/cyclophosphamide (VCR/CTX), with randomization to intervening pulses of prednisone/doxorubicin (PDN/DOX) or teniposide (VM26)/cytarabine (Ara-C) for a total of 88 weeks. RESULTS All 120 patients achieved a second complete remission. There have been 61 protocol failures. Thirty-five patients had a bone marrow relapse, four with simultaneous CNS involvement and one with concurrent testicular leukemia. Thirteen patients had a second isolated CNS relapse, 10 a testicular relapse, and two relapsed in other sites. One patient died in remission. Overall event-free survival (EFS) at 4 years was 46% +/- 7%. The toxicity associated with this protocol was minimal except for leukoencephalopathy, which occurred in 20 (17%) patients. The treatment comparison between VM26/Ara-C or PDN/DOX pulses showed a trend toward superior EFS (P = .12) in favor of VM-26/Ara-C. CONCLUSION To date, this represents the largest series of patients with ALL treated uniformly for an isolated CNS relapse. Since marrow relapse remains the primary site of failure, future protocols must intensify systemic therapy.

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