Good Prognosis for High-Risk Ph-Negative ALL With Chemotherapy After Early Cytologic Response and Low Minimal Residual Disease Level on Flow Cytometry


Key Points

  • Delayed consolidation and maintenance chemotherapy in patients with good early cytologic response and flow cytometry–determined minimal residual disease < 5×10-4 after early consolidation was associated with 5-year disease-free survival and overall survival probabilities of 55% and 59%.
  • On multivariate analysis, high flow–minimal residual disease was the only significant prognostic factor for disease-free survival and overall survival.

In a Spanish trial (PETHEMA ALL-AR-03) reported in the Journal of Clinical Oncology, Ribera et al found high disease-free and overall survival rates with delayed consolidation and maintenance chemotherapy in high-risk Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL) patients with early cytologic response and low levels of minimal residual disease as assessed by flow cytometry after early consolidation.

Study Details

The study included 326 patients with high-risk Philadelphia chromosome–negative ALL aged 15 to 60 years treated between 2003 and 2012. Among those completing early consolidation therapy, patients with good early cytologic response, defined as <10% blasts in bone marrow at day 14 of induction therapy, and flow cytometry–measured minimal residual disease (flow–minimal residual disease) level < 5×10-4 at the end of early consolidation were assigned to delayed consolidation and maintenance therapy and those with poorer early cytologic response and flow–minimal residual disease level ≥ 5×10-4 after early consolidation were scheduled for allogeneic hematopoietic stem cell transplantation.

Overall, complete remission was achieved in 282 patients (87%; 66% of these with standard induction and 34% with intensified induction), and early consolidation was completed in 236 (84%) of the patients with complete remission. Of these 236, 179 (76%) were available for assignment by intention-to-treat to receive chemotherapy (n = 108) or allogeneic hematopoietic stem cell transplantation (n = 71).

Prognosis by Treatment

After median follow-up of 45 months, median disease-free survival was 19 months and 5-year disease-free survival probability was 37% among the 282 patients with complete remission, and median overall survival was 22 months with a 5-year overall survival probability of 35% in the entire cohort of 326 patients. The 5-year disease-free survival and overall survival probabilities were 32% and 37% among patients assigned to allogeneic hematopoietic stem cell transplantation and 55% and 59% among those assigned to chemotherapy.

Multivariable analysis in the entire cohort showed that poor minimal residual disease clearance (≥ 1×10-3 after induction and ≥ 5×10-4 after early consolidation) was the only prognostic factor for disease-free survival (odds ratio [OR] = 3.79, P < .001) and overall survival (OR = 3.56, P = .001).

The investigators concluded, “Prognosis for [Philadelphia chromosome–negative, high-risk] ALL in adolescents and adults with good early response to induction and low [flow–minimal residual disease] levels after consolidation is quite favorable when [allogeneic hematopoietic stem cell transplantation] is avoided. In this study, the pattern of [minimal residual disease] clearance was the only prognostic factor for [disease-free and overall survival].”

Josep-Maria Ribera, MD, PhD, of Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Badalona, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from Fondo de Investigaciones Sanitarias and Red Temática de Investigación Cooperativa en Cáncer, Instituto Carlos III. The study authors reported no potential conflicts of interest.

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