Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study
| Autor: | Allen Eng Juh Yeoh, Jing J. Eng, Kean H. Chiew, Ah M. Tan, Germaine S.M. Liew, Shawn H. R. Lee, Koon Mian Foo, Cheryl C.C. Neoh, Joyce Ching Mei Lam, Yiong Huak Chan, Zelia Z.L. Seeto, Bernice L. Z. Oh, Zhi W. Chen, Thuan C. Quah |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Asparaginase Vincristine History 21st Century 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Medicine Humans Doxorubicin Child Singapore business.industry Malaysia Infant Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical trial 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Child Preschool Toxicity Cohort Cytarabine Lymphoblastic leukaemia Female business medicine.drug |
| Zdroj: | European journal of cancer (Oxford, England : 1990). 142 |
| ISSN: | 1879-0852 |
| Popis: | In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes.The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p 0.001), as than 2003-PIIIa. Similarly in 2010-PIIIb and PVb, where one block of cytarabine was replaced by two doses of vincristine, admissions for fever were also fewer (0.47 versus 0.74 A/blk, p 0.001) than in 2003-PIIIb. However, the addition of single doses of vincristine and asparaginase in 2010-PIIIa, even with a mandatory seven-day rest, led to more hospitalisations (0.45 A/blk, p 0.001), increased risk of bacteraemia (relative-risk (RR) = 7.66, p = 0.005) and critical-care admissions (RR = 4.31, p = 0.13). Despite this, overall treatment-related mortality decreased from 2.7% to 0.8%. Taken together, the reduced phase delays allowed earlier completion of the intensive phase of treatment (standard risk: 38.1 versus 49.4 weeks, p 0.001; intermediate risk: 50.9 versus 58.8 weeks, p 0.001), while maintaining excellent 10-year event-free survival of 95.4% and overall survival of 96.2%.In non-HR ALL, replacing doxorubicin/cytarabine with vincristine/asparaginase during some DI blocks is effective in reducing toxicity without compromising outcomes.NCT0289464. |
| Databáze: | OpenAIRE |
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