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Randomized Controlled Trial
. 2015 Feb;168(4):533-46.
doi: 10.1111/bjh.13160. Epub 2014 Oct 13.

Increased post-induction intensification improves outcome in children and adolescents with a markedly elevated white blood cell count (≥200 × 10(9) /l) with T cell acute lymphoblastic leukaemia but not B cell disease: a report from the Children's Oncology Group

Caroline Hastings  1 , Paul S Gaynon, James B Nachman, Harland N Sather, Xiaomin Lu, Meenakshi Devidas, Nita L Seibel
Affiliations
Randomized Controlled Trial

Increased post-induction intensification improves outcome in children and adolescents with a markedly elevated white blood cell count (≥200 × 10(9) /l) with T cell acute lymphoblastic leukaemia but not B cell disease: a report from the Children's Oncology Group

Caroline Hastings et al. Br J Haematol. 2015 Feb.

Abstract

Children and adolescents presenting with a markedly elevated white blood cell (ME WBC) count (WBC ≥200 × 10(9) /l) comprise a unique subset of high-risk patients with acute lymphoblastic leukaemia (ALL). We evaluated the outcomes of the 251 patients (12% of the study population) with ME WBC treated on the Children's Cancer Group-1961 protocol. Patients were evaluated for early response to treatment by bone marrow morphology; those with a rapid early response were randomized to treatment regimens testing longer and stronger post-induction therapy. We found that ME WBC patients have a poorer outcome compared to those patients presenting with a WBC <200 × 10(9) /l (5-year event-free survival 62% vs. 73%, P = 0·0005). Longer duration of therapy worsened outcome for T cell ME WBC with a trend to poorer outcome in B-ALL ME WBC patients. Augmented therapy benefits T cell ME WBC patients, similar to the entire study cohort, however, there appeared to be no impact on survival for B-ALL ME WBC patients. ME WBC was not a prognostic factor for T cell patients. In patients with high risk features, B lineage disease in association with ME WBC has a negative impact on survival.

Keywords: acute lymphoblastic leukaemia; elevated white blood cell count; intensification; paediatric.

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Figures

Figure 1
Figure 1
1a EFS, ME vs non-ME 62.1% vs 73.1%, p = 0.0005 1b OS, ME vs non-ME 72.7% vs 81.8%, p = 0.0015 1c EFS, B-ALL, ME vs non-ME, 47.9% vs 73%, p =< 0.0001 1d EFS, T-ALL, ME vs non-ME, 72% vs 73.7%, p = 0.81 ALL, acute lymphoblastic leukaemia; ME, markedly elevated white blood cell count; EFS, event-free survival; OS, overall survival.
Figure 1
Figure 1
1a EFS, ME vs non-ME 62.1% vs 73.1%, p = 0.0005 1b OS, ME vs non-ME 72.7% vs 81.8%, p = 0.0015 1c EFS, B-ALL, ME vs non-ME, 47.9% vs 73%, p =< 0.0001 1d EFS, T-ALL, ME vs non-ME, 72% vs 73.7%, p = 0.81 ALL, acute lymphoblastic leukaemia; ME, markedly elevated white blood cell count; EFS, event-free survival; OS, overall survival.
Figure 1
Figure 1
1a EFS, ME vs non-ME 62.1% vs 73.1%, p = 0.0005 1b OS, ME vs non-ME 72.7% vs 81.8%, p = 0.0015 1c EFS, B-ALL, ME vs non-ME, 47.9% vs 73%, p =< 0.0001 1d EFS, T-ALL, ME vs non-ME, 72% vs 73.7%, p = 0.81 ALL, acute lymphoblastic leukaemia; ME, markedly elevated white blood cell count; EFS, event-free survival; OS, overall survival.
Figure 1
Figure 1
1a EFS, ME vs non-ME 62.1% vs 73.1%, p = 0.0005 1b OS, ME vs non-ME 72.7% vs 81.8%, p = 0.0015 1c EFS, B-ALL, ME vs non-ME, 47.9% vs 73%, p =< 0.0001 1d EFS, T-ALL, ME vs non-ME, 72% vs 73.7%, p = 0.81 ALL, acute lymphoblastic leukaemia; ME, markedly elevated white blood cell count; EFS, event-free survival; OS, overall survival.
Figure 2
Figure 2
2a DFS, randomized RER, ME, Standard vs Augmented Intensity 2b DFS, randomized RER, ME, Standard vs Increased Duration, 75% vs 59.7% DFS, disease-free survival; RER, rapid early responder; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 2
Figure 2
2a DFS, randomized RER, ME, Standard vs Augmented Intensity 2b DFS, randomized RER, ME, Standard vs Increased Duration, 75% vs 59.7% DFS, disease-free survival; RER, rapid early responder; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 2
Figure 2
2a DFS, randomized RER, ME, Standard vs Augmented Intensity 2b DFS, randomized RER, ME, Standard vs Increased Duration, 75% vs 59.7% DFS, disease-free survival; RER, rapid early responder; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 2
Figure 2
2a DFS, randomized RER, ME, Standard vs Augmented Intensity 2b DFS, randomized RER, ME, Standard vs Increased Duration, 75% vs 59.7% DFS, disease-free survival; RER, rapid early responder; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 2
Figure 2
2a DFS, randomized RER, ME, Standard vs Augmented Intensity 2b DFS, randomized RER, ME, Standard vs Increased Duration, 75% vs 59.7% DFS, disease-free survival; RER, rapid early responder; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 3
Figure 3
3a DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Intensity 3b DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Duration DFS, disease-free survival; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 3
Figure 3
3a DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Intensity 3b DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Duration DFS, disease-free survival; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 3
Figure 3
3a DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Intensity 3b DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Duration DFS, disease-free survival; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 3
Figure 3
3a DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Intensity 3b DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Duration DFS, disease-free survival; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
Figure 3
Figure 3
3a DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Intensity 3b DFS, randomized, by lineage and ME/non-ME, Standard vs Increased Duration DFS, disease-free survival; ME, markedly elevated; WBC, white blood cell count; Std, standard; Aug, augmented; Inc, increased; Dur, duration; BFM, Berlin-Frankfurt-Munster.
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