Prognostic Value of Different Profiles of the Early Response to Therapy in Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 23, 2007

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Presenter: Semochkin, S.V.
Presenter's Affiliation: Federal scientific clinical center for pediatric hematology, oncology and immunology, Russia
Type of Session: Scientific

Background

The early response of patients during induction therapy is essential for patient risk-stratification in childhood acute lymphoblastic leukemia (ALL), and has long been recognized as an important prognosticator. However, there are few data available that specifically look at this feature in adolescents and young adults with ALL who are treated under clinical protocols. The purpose of this study was to assess the predictive value of the early response to therapy in adolescents and young adults with ALL.

Materials and Methods

  • Study was conducted from 1991-2003
  • 124 patients (pts) (m-77, f-47) with a de novo ALL were enrolled
  • Ages of patients ranged from 10 to 29 years old
  • 49/124 (39.5%) pts were treated under protocol ALL-MB-91 (original protocol--the Berlin-Moscow-91)
  • 75/124 (60.5%) pts were treated under the ALL-BFM-90m (Berlin-Frankfurt-Munster Group modified protocol from 1990)
  • Early response was estimated based on the number of circulating blasts on day 8 as well as the status of a bone marrow on days 15, 33, and 36 of treatment
  • The bone marrow status was measured on the standard scale: M1 (<5%) and M2 (5-25%) and M3 (>25% blasts)

Results

  • 6-year event-free survival (EFS) = 61.3%
  • 6-year overall survival (OS) = 65.3%
  • Survival rate of patients (pts) with poor response to steroids on day 8 (>1000 blasts/µl) was 2 times lower in comparison with pts with the good response: EFS = 33.3 vs. 69.4% (p=0.006)
  • M3 status on day 15 of treatment was an adverse prognostic factor:
    • EFS 33.3% (M3: 21/102, or 20.6% of pts)
    • EFS 73.7% (M2: 19/102, or 18.6% of pts)
    • EFS 71.0% (M1: 62/102, or 60.8% of pts) (p<0.001)
  • M2 status on day 15 had no clear prognostic value (p>0.05).
  • EFS of pts with poor response on day 8 but favorable M1/M2 status on day 15 was better compared to patients with a good response on day 8 but adverse M3 status on day 15:
    • EFS was 57.1 vs. 46.2% for above groups, respectively (p=0.375)
  • M2/M3 status on days 33 and 36 had the strongest adverse prognostic value:
    • EFS 16.7% (M3: 6/109/5.5% pts)
    • EFS 28.6% (M2: 7/109/6.4% pts)
    • EFS 72.9% (M1: 96/109/88.1%) (p<0.001)
  • Early response to therapy did not depend on age and/or gender of patients or on the specific therapeutic protocol used (p > 0.05)

Author's Conclusions

  • The early response to therapy is a very important prognostic factor in the treatment of adolescents and young adults with ALL.
  • M3 status on day 15 and the M2/M3 status on days 33 and 36 were all strong predictors of an adverse outcome.
  • Age, gender, and type of protocol treatment did not affect the early response to therapy.

Clinical/Scientific Implications

The authors provide us with very enlightening data on the various factors influencing the early response to anti-leukemic therapy among adolescent and young adult patients with ALL. They also provide us with additional confirmation as to the significant value of early response to therapy as a prognosticator. Although patients were treated on one of two main chemotherapy protocols, this did not significantly affect the early therapeutic response, nor did patient age or gender. In contrast, the M3 bone marrow status on day 15 and the M2/M3 statuses on days 33 and 36 were strongly predictive of a negative outcome, just as one would expect given that higher percentages of blasts in the marrow at later time points during treatment would not be expected to bode well. Clinicians can thus continue to use early therapeutic response as a guide for determining ultimate prognosis.