scholarly journals Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study

2019 ◽  
Vol 37 (25) ◽  
pp. 2246-2256 ◽  
Author(s):  
Rob Pieters ◽  
Paola De Lorenzo ◽  
Philip Ancliffe ◽  
Luis Alberto Aversa ◽  
Benoit Brethon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Study Groups ◽  
Phase Iii ◽  
Free Survival ◽  
Wbc Count

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A ( MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.

scholarly journals Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1112-1115 ◽  
Author(s):  
James B. Nachman ◽  
Nyla A. Heerema ◽  
Harland Sather ◽  
Bruce Camitta ◽  
Erik Forestier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Study Groups ◽  
Event Free Survival ◽  
Prognostic Implication ◽  
Monosomy 7 ◽  
Free Survival ◽  
Modal Chromosome Number

Abstract One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.

Is It Better to Treat Adolescents with Acute Lymphoblastic Leukemia as Old Children or as Young Adults?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3968-3968 ◽  
Author(s):  
Marta Alves ◽  
Liane Daudt ◽  
Karina L. M. Mazzucco ◽  
Adriano Taniguchi ◽  
Tiago Nava ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Poor Risk ◽  
Wbc Count

Abstract PURPOSE: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. PATIENTS AND METHODS: From January 1997 to December 2007, 34 and 11 adolescents (10 to 20 years of age) were treated according to German pediatric BFM 90 and 95 and adult BFM 84 protocols, respectively. Age, B/T lineage, WBC count, complete remission, cytogenetics, and response to steroids were analyzed. Age, B/T lineage and WBC count were similar. Poor risk-cytogenetics (t (9;22),t(4;11) and hypodiploidy less than 45 chromosomes were present only in BFM 90 and 95 group. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving overall survival (OS) and event-free survival (EFS). RESULTS: OS in 10 years and EFS was, respectively, 68.6% and 68.7% for the pediatric protocol and 31.4% and 21.6% for the adult protocol. CONCLUSION: This study’s findings were similar to others in USA, UK, France, Italy and Holland that clearly demonstrate that current pediatric regimens are more effective for adolescents and may contribute to indicate that adolescents should be included in intensive pediatric protocols. Keywords: leukemia, survival, adolescent.

scholarly journals Improved results of treatment of adult acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1242-1248 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
CA Ries ◽  
MP Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Induction Phase ◽  
Free Survival ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Disease Free

Abstract We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

scholarly journals Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children’s Oncology Group AALL0434 Methotrexate Randomization

2018 ◽  
Vol 36 (29) ◽  
pp. 2926-2934 ◽  
Author(s):  
Stuart S. Winter ◽  
Kimberly P. Dunsmore ◽  
Meenakshi Devidas ◽  
Brent L. Wood ◽  
Natia Esiashvili ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Disease Free Survival ◽  
High Dose ◽  
Oncology Group ◽  
Cns Involvement ◽  
Free Survival ◽  
Leucovorin Rescue

Purpose Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children’s Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen. Patients and Methods COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase. Results AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival ( P = .005) and overall survival ( P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%–89.5%) and 89.4% (95% CI, 85.7%–93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement. Conclusion AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.

scholarly journals Improved results of treatment of adult acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1242-1248
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
CA Ries ◽  
MP Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Induction Phase ◽  
Free Survival ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Disease Free

We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial.

1993 ◽  
Vol 11 (3) ◽  
pp. 527-537 ◽  
Author(s):  
D G Tubergen ◽  
G S Gilchrist ◽  
R T O'Brien ◽  
P F Coccia ◽  
H N Sather ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Disease Free Survival ◽  
Cranial Irradiation ◽  
Phase Iii ◽  
Intrathecal Methotrexate ◽  
Free Survival ◽  
Cancer Group ◽  
Drug Induction

PURPOSE The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. PATIENTS AND METHODS Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. RESULTS The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. CONCLUSION Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.

Effect of Protracted High-Dose l-Asparaginase Given as a Second Exposure in a Berlin-Frankfurt-Münster–Based Treatment: Results of the Randomized 9102 Intermediate-Risk Childhood Acute Lymphoblastic Leukemia Study—A Report From the Associazione Italiana Ematologia Oncologia Pediatrica

2001 ◽  
Vol 19 (5) ◽  
pp. 1297-1303 ◽  
Author(s):  
C. Rizzari ◽  
M.G. Valsecchi ◽  
M. Aricò ◽  
V. Conter ◽  
A. Testi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Experimental Treatment ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
High Dose ◽  
Intermediate Risk ◽  
Free Survival ◽  
Significant Difference

PURPOSE: To assess in a randomized study the therapeutic effect of the addition of high-dose l-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)–based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m2 repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi l-asparaginase product. RESULTS: Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P = .64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.

scholarly journals Outcome of Adolescents with Acute Lymphoblastic Leukemia Treated by Pediatrics versus Adults Protocols

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Abeer Ibrahim ◽  
Amany Ali ◽  
Mahmoud M. Mohammed
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Aged Patients ◽  
Treatment Protocols ◽  
Free Survival ◽  
Therapeutic Protocols ◽  
Disease Free

Objective.Several studies showed better outcome in adolescents and young adults with acute lymphoblastic leukemia (ALL) treated with pediatrics protocols than similarly aged patients treated with adults protocols, while other studies showed similar outcome of both protocols. We conducted this study to compare the outcome of our pediatrics and adults therapeutic protocols in treatment of adolescents ALL.Patients and Methods.We retrospectively reviewed files of 86 consecutive adolescent ALL patients aged 15–18 years who attended to outpatients clinic from January 2003 to January 2010. 32 out of 86 were treated with pediatrics adopted BFM 90 high risk protocol while 54 were treated with adults adopted BFM protocol. We analyzed the effect of different treatment protocols on achieving complete remission (CR), disease-free survival (DFS), and overall survival (OS).Results.The 2 patients groups have almost similar characteristics. The CR was significantly higher in pediatrics protocol 96% versus 89%(P=0.001). Despite the fact that the toxicity profiles were higher in pediatrics protocol, they were tolerable. Moreover, the pediatrics protocol resulted in superior outcome in EFS 67% versus 39% (P=0.001), DFS 65% versus 41%(P=0.000), and OS 67% versus 45%(P=0.000).Conclusion.Our study’s findings recommend using intensified pediatrics inspired protocol to treat adolescents with acute lymphoblastic leukemia.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

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