scholarly journals Children’s Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia

2020 ◽  
Vol 38 (28) ◽  
pp. 3282-3293 ◽  
Author(s):  
Kimberly P. Dunsmore ◽  
Stuart S. Winter ◽  
Meenakshi Devidas ◽  
Brent L. Wood ◽  
Natia Esiashvili ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Leucovorin Rescue ◽  
Cell Acute Lymphoblastic Leukemia ◽  
To Receive

PURPOSE Nelarabine is effective in inducing remission in patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with newly diagnosed disease. PATIENTS AND METHODS From 2007 to 2014, Children’s Oncology Group trial AALL0434 (ClinicalTrials.gov identifier: NCT00408005 ) enrolled 1,562 evaluable patients with T-ALL age 1-31 years who received the augmented Berlin-Frankfurt-Muenster (ABFM) regimen with a 2 × 2 pseudo-factorial randomization to receive escalating-dose methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX) or high-dose MTX (HDMTX) with leucovorin rescue. Intermediate- and high-risk patients were also randomly assigned after induction to receive or not receive six 5-day courses of nelarabine that was incorporated into ABFM. Patients who experienced induction failure were nonrandomly assigned to HDMTX plus nelarabine. Patients with overt CNS disease (CNS3; ≥ 5 WBCs/μL with blasts) received HDMTX and were randomly assigned to receive or not receive nelarabine. All patients, except those with low-risk disease, received cranial irradiation. RESULTS The 5-year event-free and overall survival rates were 83.7% ± 1.1% and 89.5% ± 0.9%, respectively. The 5-year disease-free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no nelarabine (n = 336) were 88.2% ± 2.4% and 82.1% ± 2.7%, respectively ( P = .029). Differences between DFS in a four-arm comparison were significant ( P = .01), with no interactions between the MTX and nelarabine randomizations ( P = .41). Patients treated with the best-performing arm, C-MTX plus nelarabine, had a 5-year DFS of 91% (n = 147). Patients who received nelarabine had significantly fewer isolated and combined CNS relapses compared with patients who did not receive nelarabine (1.3% ± 0.63% v 6.9% ± 1.4%, respectively; P = .0001). Toxicities, including neurotoxicity, were acceptable and similar between all four arms. CONCLUSION The addition of nelarabine to ABFM therapy improved DFS for children and young adults with newly diagnosed T-ALL without increased toxicity.

High-Dose Cyclophosphamide for the Treatment of Refractory T-Cell Acute Lymphoblastic Leukemia in Children

2014 ◽  
Vol 36 (5) ◽  
pp. e265-e270 ◽  
Author(s):  
Rachel Kobos ◽  
Neerav Shukla ◽  
Thomas Renaud ◽  
Susan E. Prockop ◽  
Farid Boulad ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Leukemia In Children

scholarly journals Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study

2010 ◽  
Vol 9 (1) ◽  
pp. 105 ◽  
Author(s):  
Amanda L Cleaver ◽  
Alex H Beesley ◽  
Martin J Firth ◽  
Nina C Sturges ◽  
Rebecca A O'Leary ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Outcome Prediction ◽  
Lymphoblastic Leukemia ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

2018 ◽  
Vol 10 ◽  
pp. 44-51 ◽  
Author(s):  
Wasil Jastaniah ◽  
Naglla Elimam ◽  
Khalid Abdalla ◽  
Aeshah A. AlAzmi ◽  
Mohammed Aseeri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Cell Acute Lymphoblastic Leukemia

Outcome of Children with T-Cell Acute Lymphoblastic Leukemia (T-ALL) and Standard Risk (SR) Features: Results of CCG-1952, CCG-1991 and POG 9404.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 680-680 ◽  
Author(s):  
Yousif Matloub ◽  
B.L. Asselin ◽  
Linda C. Stork ◽  
Meenakshi Devidas ◽  
Harland Sather ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Trials ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Intensified Chemotherapy ◽  
Standard Risk

Abstract Children with T-ALL have generally had a poorer prognosis than patients with precursor-B ALL. Patients with T-ALL are more likely than those with B-precursor ALL to be > 9 years and present with WBC > 50,000/ul, bulky lymphadenopathy and mediastinal mass. Since 1996, the former CCG has stratified protocol eligibility for patients with ALL based on NCI defined Standard Risk (SR = age between 1-9.99 years; WBC < 50,000/ul) or High Risk (HR) groups, regardless of immunophenotype. In contrast, the former POG has treated all T-cell patients on protocols separate from those for precursor-B ALL. This report compares the outcomes among children with T-cell ALL treated on recently completed or ongoing CCG and POG phase III trials for ALL. CCG-1952 enrolled 2176 eligible children with SR ALL between 1996 and 2000; 106 (5%) had T-cell immunophenotype. Treatment was a standard BFM regimen with prednisone and 2 phases of delayed intensification (DI) with a 2x2 randomization of IT methotrexate (MTX) v ITT and MP v TG. From June 2000 to March 2004, CCG-1991 has enrolled 1794 SR ALL patients: 80 (4%) had T-ALL. Treatment included a similar BFM backbone with substitution of dexamethasone and a 2x2 randomization between escalating IV v oral MTX and 1 v 2 DIs. POG-9404 (opened 1996; closed 2001) was developed exclusively for T-cell disease and enrolled 363 patients with T-ALL; 84 (23%) fit the NCI SR group criteria. On the latter protocol, patients received treatment similar to that developed by the Dana-Farber Leukemia Consortium for high risk B-precursor ALL, with randomization to ± 4 cycles of high dose MTX (5 Gm/m2) and leucovorin. All patients on 9404 received 1800 cGy prophylactic cranial radiation while CCG patients did not. Outcome for T-ALL on CCG-1952 is substantially worse than for B-precursor ALL, with 5 year event-free survival (EFS) of 73% compared to 82% (p = 0.007). Interim analysis of CCG-1991 also shows a significantly worse outcome for T-ALL compared to B-precursor ALL: 3y estimated EFS 78% v 90%, p = 0.0002. In contrast, estimated 5y EFS for patients with SR T-ALL on POG-9404 is 88% (90% on the superior high dose MTX regimen). Comparison of the SR v HR T-ALL patients treated on POG 9404 shows a significant advantage for the SR group (5y EFS of 90% v 75%, p < 0.004). This is in contrast to comparison of T-ALL patients on CCG-1952 (SR) v the concurrent CCG-1961 HR study where T-ALL patients have similar outcome (5y EFS 73% v 72%, p = 0.77). These data suggest that patients with T-ALL and SR features have better EFS when treated with more intensified chemotherapy regimens. Because early EFS for T-cell patients treated on CCG-1991 is worse than on POG 9404, the former study was closed to further accrual of patients with T-ALL. The COG ALL Committee is developing a study for exclusive enrollment of patients with T-ALL using intensive therapy based on the current COG HR ALL regimen, regardless of SR or HR features.

Low CNS Relapse Incidence without Radiotherapy and Improvement of Outcome: Results of Subsequent EORTC-CLG 58881 and 58951 Trials in Pediatric T-Cell Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 133-133 ◽  
Author(s):  
Barbara De Moerloose ◽  
Stefan Suciu ◽  
Alina Ferster ◽  
Françoise Mazingue ◽  
Nicolas Sirvent ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Intensive Treatment ◽  
Phase Iii ◽  
Average Risk ◽  
Long Term Outcome ◽  
Cns Relapse ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Abstract 133 Background: T-cell acute lymphoblastic leukemia (ALL) accounts for 15% of ALL cases in children and has been associated with a higher risk for central nervous system (CNS) relapse and a worse prognosis. In EORTC trials 58831 and 2, standard risk (SR) patients (pts) were not irradiated but received intermediate dose methotrexate (MTX) courses; for medium and high risk pts, high dose (HD) MTX was added to the treatment regimen and the administration of cranial radiotherapy (RT) was randomised. The omission of RT didn't result in an increase of CNS or systemic relapse and consequently, CNS-directed chemotherapy was substituted for RT in all following trials. The long-term outcome of T-ALL pts in the subsequent phase III trials (58881 and 58951) are presented here. Methods: The BFM backbone for ALL treatment was applied to all EORTC-CLG trials since 1983. As CNS treatment in study 58881, SR pts received 4 HD MTX courses (5 g/m2) in interval therapy and 10 IT MTX injections during the intensive treatment phases. Pts with CNS-3 status at diagnosis received 2 additional IT injections during induction, 2 during consolidation and 6 HD MTX courses + IT during maintenance. T-ALL pts with poor prephase response (PPR) at day 8 or who didn't achieve complete remission (CR) after induction were included in the very high risk (VHR) group. VHR CNS-directed chemotherapy included 10 IT MTX injections, 6 IT triple and 10 HD MTX courses during intensive treatment phases, followed by 4 IT MTX injections during maintenance (the latter for CNS-3 pts only). In the 58951 trial, all T-ALL pts had an intensified induction. The CNS-directed therapy of all average risk T-ALL pts was intensified to 11 HD MTX courses, 1 IT with MTX and 15 triple IT. MRD ≥ 1% at the end of induction was added as VHR criterium. All non-transplanted VHR pts received 1 IT MTX injection, 19 IT triple and 9 HD MTX courses. Several randomized questions were addressed in both trials of which most relevant for T-ALL pts: in study 58881 the comparison E.coli asparaginase (ASP) Medac versus (vs) “other ASP” (= Erwinia ASP or E.coli ASP Bayer); in trial 58951 1) the comparison dexamethasone (DEX 6 mg/m2/d) vs prednisolone (PRED 60 mg/m2/d) in induction and 2) conventional vs prolonged E.coli ASP for non-VHR pts. Results: 303 and 296 T-ALL pts were included in trials 58881 and 58951 resp, representing 14.5% and 15.2% of all pts. Outcome results and type of events for the entire 58881 and 58951 cohorts and according to several subgroups are presented in the table. The 8-year isolated and overall CNS relapse incidences were 6.8% and 10.9% in study 58881, 5.3% and 8.5% in study 58951. The 8-year EFS, DFS and OS improved remarkably in study 58951. In the latter trial, outcome improvement was particularly seen in pts with initial WBC<100x10E9/L and in the good prephase responders (GPR) which had a significant better outcome than those with PPR. 58881 pts assigned to the “other ASP” arm had an inferior outcome. Concerning the DEX/PRED comparison in the 58951 T-ALL cohort, no advantage was seen for EFS (hazard ratio (HR) (99%CI): 1.26 (0.70;2.27)) or OS. There even was a trend towards worse EFS for pts with initial WBC>100x10E9/L and for pts with PPR treated in the DEX arm (HR (99%CI): 1.52 (0.63;3.64) and 1.47 (0.64;3.35)). Prolonged ASP treatment did not improve outcome of the whole T-ALL 58951 cohort. Conclusion: Prophylactic and therapeutic RT can safely be omitted from frontline treatment of children with T-ALL. Adequate ASP therapy, intensified induction treatment and CNS directed therapy can result in a significant improvement of the outcome of at least 2/3rd of T-ALL pts, particularly those with initial WBC<100x10E9/L and GPR. Disclosures: No relevant conflicts of interest to declare.

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.

Sign in / Sign up

Export Citation Format

Share Document