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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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Conditional probability of relapse for patients remaining in continuous complete remission for the given years after completion of treatment by Total Therapy study. Note the progressive decrease in the probability of off-therapy relapse for each successive treatment group, and the absence of relapse in patients remaining in remission at 4 years off therapy in study 15.
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Figure 3: Conditional probability of relapse for patients remaining in continuous complete remission for the given years after completion of treatment by Total Therapy study. Note the progressive decrease in the probability of off-therapy relapse for each successive treatment group, and the absence of relapse in patients remaining in remission at 4 years off therapy in study 15.

Mentions: Analysis of the conditional probability of post-therapy relapse for each treatment group (Figure 3) showed that there was still an estimated risk of relapse of 0.65% (95% CI, 0.04% to 1.17%) beyond 10 years after completion of therapy in studies 11 and 12, whereas no relapse was observed beyond 10 years in studies 13A, 13B and 14. In study 15, there were 13 relapses in the first year after completion of treatment, 7 between 1 and 2 years, 4 between 2 and 3 years, 2 between 3 and 4 years, and 1 at 6 years. Of the 418 patients in study 15 who completed all treatment and remained alive and event-free at the time of analysis, 313 (75%) had been followed for 4 years or more after completion of therapy. With 827.6 person-years of follow-up (after completion of therapy for 4 years) of the 313 patients, the 95% and 99% upper confidence bound of the expected number of relapse per 100 person-years of follow-up beyond 4 years after completion of treatment are 0.57 and 0.8, respectively. To provide a conservative estimate of the future risk of relapse among the 4-year post-treatment event-free survivors, we performed a sensitivity analysis covering a range of likely to unlikely scenarios, in which 1 to 4 hypothetical additional relapses will occur during 2 additional years of follow up. The analyses showed the 99% upper confidence bound of the actuarial risk of 0.42 to 0.74 relapse per 100 person-years of follow-up (Supplementary Table 4), indicating an extremely low risk of further relapse.


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)

Conditional probability of relapse for patients remaining in continuous complete remission for the given years after completion of treatment by Total Therapy study. Note the progressive decrease in the probability of off-therapy relapse for each successive treatment group, and the absence of relapse in patients remaining in remission at 4 years off therapy in study 15.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Conditional probability of relapse for patients remaining in continuous complete remission for the given years after completion of treatment by Total Therapy study. Note the progressive decrease in the probability of off-therapy relapse for each successive treatment group, and the absence of relapse in patients remaining in remission at 4 years off therapy in study 15.
Mentions: Analysis of the conditional probability of post-therapy relapse for each treatment group (Figure 3) showed that there was still an estimated risk of relapse of 0.65% (95% CI, 0.04% to 1.17%) beyond 10 years after completion of therapy in studies 11 and 12, whereas no relapse was observed beyond 10 years in studies 13A, 13B and 14. In study 15, there were 13 relapses in the first year after completion of treatment, 7 between 1 and 2 years, 4 between 2 and 3 years, 2 between 3 and 4 years, and 1 at 6 years. Of the 418 patients in study 15 who completed all treatment and remained alive and event-free at the time of analysis, 313 (75%) had been followed for 4 years or more after completion of therapy. With 827.6 person-years of follow-up (after completion of therapy for 4 years) of the 313 patients, the 95% and 99% upper confidence bound of the expected number of relapse per 100 person-years of follow-up beyond 4 years after completion of treatment are 0.57 and 0.8, respectively. To provide a conservative estimate of the future risk of relapse among the 4-year post-treatment event-free survivors, we performed a sensitivity analysis covering a range of likely to unlikely scenarios, in which 1 to 4 hypothetical additional relapses will occur during 2 additional years of follow up. The analyses showed the 99% upper confidence bound of the actuarial risk of 0.42 to 0.74 relapse per 100 person-years of follow-up (Supplementary Table 4), indicating an extremely low risk of further relapse.

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