J Korean Med Sci.  2017 Apr;32(4):642-649. 10.3346/jkms.2017.32.4.642.

Outcome of Reinduction Chemotherapy with a Modified Dose of Idarubicin for Children with Marrow-Relapsed Acute Lymphoblastic Leukemia: Results of the Childhood Acute Lymphoblastic Leukemia (CALL)-0603 Study

• Koh KN
• Im HJ
• Kim H
• Kang HJ
• Park KD
• Shin HY
• Ahn HS
• Lee JW
• Yoo KH
• Sung KW
• Koo HH
• Lim YT
• Park JE
• Park BK
• Park HJ
• Seo JJ

• KMID: 2371450
• DOI: http://doi.org/10.3346/jkms.2017.32.4.642

Abstract

This multicenter, prospective trial was conducted to develop an effective and safe reinduction regimen for marrow-relapsed pediatric acute lymphoblastic leukemia (ALL) by modifying the dose of idarubicin. Between 2006 and 2009, the trial accrued 44 patients, 1 to 21 years old with first marrow-relapsed ALL. The reinduction regimen comprised prednisolone, vincristine, L-asparaginase, and idarubicin (10 mg/m²/week). The idarubicin dose was adjusted according to the degree of myelosuppression. The second complete remission (CR2) rate was 72.7%, obtained by 54.2% of patients with early relapse < 24 months after initial diagnosis and 95.0% of those with late relapse (P = 0.002). Five patients entered remission with extended treatment, resulting in a final CR2 rate of 84.1%. The CR2 rate was not significantly different according to the idarubicin dose. The induction death rate was 2.3% (1/44). The 5-year event-free and overall survival rates were 22.2% ± 6.4% and 27.3% ± 6.7% for all patients, 4.2% ± 4.1% and 8.3% ± 5.6% for early relapsers, and 43.8% ± 11.4% and 50.0% ± 11.2% for late relapsers, respectively. Early relapse and slow response to reinduction chemotherapy were predictors of poor outcomes. In conclusion, a modified dose of idarubicin was effectively incorporated into the reinduction regimen for late marrow-relapsed ALL with a low toxic death rate. However, the CR2 rate for early relapsers was suboptimal, and the second remission was not durable in most patients.

Keyword

Childhood; Acute Lymphoblastic Leukemia; Relapse; Induction; Idarubicin

Figure

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  Fig. 1 Overview of treatment and outcome regarding 44 patients with relapsed ALL. ALL = acute lymphoblastic leukemia, CR = complete remission, CR2 = second complete remission, DOD = died of disease, TRM = treatment-related mortality, HSCT = hematopoietic stem cell transplantation.

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  Fig. 2 Survival of children with ALL. (A) OS and EFS in children with first BM relapse. Thick solid line = OS; dashed line = EFS. (B) EFS according to timing of relapse. Thick solid line = early relapse (< 24 months from initial diagnosis); thin solid line = late relapse (≥ 24 months from initial diagnosis). ALL = acute lymphoblastic leukemia, OS = overall survival, EFS = event-free survival, BM = bone marrow.

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  Fig. 3 EFS based on timing of relapse and post-remission treatment. (A) EFS of all patients who achieved CR2 according to post-remission treatment. EFS of patients with (B) early relapse and (C) late relapse who achieved CR2 according to post-remission treatment. Thick solid line = chemotherapy; thin solid line = allogeneic HSCT. EFS = event-free survival, CR2 = second complete remission, HSCT = hematopoietic stem cell transplantation.

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  Fig. 4 EFS based on timing of relapse and early response to reinduction chemotherapy. (A) EFS of all patients with available data according to early response to reinduction chemotherapy. EFS of patients with (B) early relapse and (C) late relapse with available data according to early response to reinduction chemotherapy. Thick solid line = RER; thin solid line =SER; dashed line = induction failure. EFS = event-free survival, RER = rapid early response, SER = slow early response.

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