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A revised definition for cure of childhood acute lymphoblastic leukemia.

Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC, Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E, Downing JR, Leung WH, Relling MV, Evans WE - Leukemia (2014)

Bottom Line: Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years.The most important predictor of outcome after completion of therapy was the type of treatment.None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.

ABSTRACT
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).

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CONSORT diagram. Of the 562 patients treated in studies 11 and 12, 467 in study 13A, 13B and 14, and 498 in study 15, 438, 398, and 455 patients, respectively, remained in continuous complete remission upon the completion of treatment.
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Figure 1: CONSORT diagram. Of the 562 patients treated in studies 11 and 12, 467 in study 13A, 13B and 14, and 498 in study 15, 438, 398, and 455 patients, respectively, remained in continuous complete remission upon the completion of treatment.

Mentions: Of the 1527 patients enrolled in Total Therapy studies 11 to 15, 1291 (84.5%) were in continuous complete remission at the end of treatment including patients who underwent hematopoietic stem cell transplantation in first complete remission (Figure 1). As shown in Table 1, treatment outcome (event-free survival, survival and cumulative risk of any relapse) did not differ significantly between patients treated in studies 11 and 12, or among those treated in studies 13A, 13B, and 14, leading us to combine these cohorts into two groups for subsequent analyses. Patients treated in study 15 had a superior treatment outcome compared to those in studies 13A, 13B and 14, and therefore constituted a third comparison group. The 10-year event-free survival rate increased progressively over the three treatment periods (P<0.001): 65.2% (95% CI, 61.3% - 69.1%) vs. 74.8% (95% CI, 70.9% - 78.7%) vs. 85.1% (95% CI, 79.0% - 91.2%). The improved result in study 15 extended to NCI standard-risk B-ALL (p=0.006), NCI high-risk B-ALL (p<0.0001), and T-ALL (p<0.001) (data not shown). This improvement was also apparent in the analysis of overall survival (P<0.001): 76.5% (95% CI, 73.0% - 80.0%) vs. 81.1% (95% CI, 77.6% - 84.6%) vs. 91.7% (95% CI, 87.0% - 96.4%).


A revised definition for cure of childhood acute lymphoblastic leukemia.

Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC, Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E, Downing JR, Leung WH, Relling MV, Evans WE - Leukemia (2014)

CONSORT diagram. Of the 562 patients treated in studies 11 and 12, 467 in study 13A, 13B and 14, and 498 in study 15, 438, 398, and 455 patients, respectively, remained in continuous complete remission upon the completion of treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214904&req=5

Figure 1: CONSORT diagram. Of the 562 patients treated in studies 11 and 12, 467 in study 13A, 13B and 14, and 498 in study 15, 438, 398, and 455 patients, respectively, remained in continuous complete remission upon the completion of treatment.
Mentions: Of the 1527 patients enrolled in Total Therapy studies 11 to 15, 1291 (84.5%) were in continuous complete remission at the end of treatment including patients who underwent hematopoietic stem cell transplantation in first complete remission (Figure 1). As shown in Table 1, treatment outcome (event-free survival, survival and cumulative risk of any relapse) did not differ significantly between patients treated in studies 11 and 12, or among those treated in studies 13A, 13B, and 14, leading us to combine these cohorts into two groups for subsequent analyses. Patients treated in study 15 had a superior treatment outcome compared to those in studies 13A, 13B and 14, and therefore constituted a third comparison group. The 10-year event-free survival rate increased progressively over the three treatment periods (P<0.001): 65.2% (95% CI, 61.3% - 69.1%) vs. 74.8% (95% CI, 70.9% - 78.7%) vs. 85.1% (95% CI, 79.0% - 91.2%). The improved result in study 15 extended to NCI standard-risk B-ALL (p=0.006), NCI high-risk B-ALL (p<0.0001), and T-ALL (p<0.001) (data not shown). This improvement was also apparent in the analysis of overall survival (P<0.001): 76.5% (95% CI, 73.0% - 80.0%) vs. 81.1% (95% CI, 77.6% - 84.6%) vs. 91.7% (95% CI, 87.0% - 96.4%).

Bottom Line: Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years.The most important predictor of outcome after completion of therapy was the type of treatment.None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.

ABSTRACT
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).

Show MeSH
Related in: MedlinePlus