High-frequency vincristine-steroid pulses do not benefit outcomes in acute lymphoblastic leukaemia

June 2023 Clinical practice Robin van Amersfoort
Leukemia; myeloid, 250X at 35mm. This type of leukemia has its origin in the bone marrow (myeloid tissue). It involves a malignant proliferation of immature white blood cells. This action can crowd out production of RBC s and platelets leading to anem

Vincristine-steroid pulses are commonly used during maintenance therapy for paediatric B-cell acute lymphoblastic leukaemia (ALL), but the impact of this treatment on the outcomes has not been well established. This systematic review and meta-analysis aimed to evaluate the impact of vincristine-steroid pulses on the outcomes. The results showed that high-frequency vincristine-steroid pulses had no beneficial effect on the survival or relapse rates when compared to low-frequency pulses. However, high-frequency vincristine-steroid pulses were associated with a significantly higher risk of adverse effects.

INTRODUCTION

Acute lymphoblastic leukaemia (ALL) is a malignancy that is more common in children than adults. B-cell acute lymphoblastic leukaemia and T-cell acute lymphoblastic leukaemia are distinguished. The combination of cytostatic vincristine and steroid-like prednisone pulses (vincristine-steroid pulses) are commonly used as a maintenance treatment in paediatric B-cell ALL. However, the impact of using these pulses in higher or lower frequencies has not been well established.

METHODS

The current study aimed to evaluate the influence of various frequencies of vincristine-steroid pulses on event-free survival (EFS), overall survival (OS), relapse rate, and adverse effects in paediatric B-cell ALL patients during maintenance therapy.1 This systematic review and meta-analysis examined the impact of the frequency of vincristine-steroid pulses during maintenance therapy for paediatric patients with newly diagnosed B-cell ALL. The authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12,513 patients), and assessed the risk of bias.

Historical and contemporary subgroups were created. Meta-analysis of EFS data suggested that there were no outcome differences between more  or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = 0.04). Moreover, no significant impact of reduced pulse frequency on overall survival or relapse risk was found. There were, however, increased odds of grade ≥3 non-hepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52).

CONCLUSION

This systematic review suggests that the previous benefit assumed by frequent pulses of vincristine-steroids in maintenance therapy for paediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. The results of this study will help guide the development of the next phase of clinical trials in the field of paediatric ALL and question the continued use of pulses during maintenance therapy, particularly in those patients experiencing toxicity.

REFERENCES

  1. Guolla L, Breitbart S, Foroutan F, et al. Impact of vincristine-steroid pulses during maintenance for B-cell pediatric ALL: a systematic review and meta-analysis. Blood. 2023;141(24):2944-2954.