Response Definitions

Choice of the most effective treatment to achieve maximal response is important as, with chemo(immuno)therapy, higher response rates confer longer remissions, especially in the absence of minimal residual disease (MRD). Data supports the use of 6 cycles of initial treatment as long as toxicity is manageable. IWCLL response definitions are provided in Table 1 (Hallek et al., 2008; Oscier et al., 2012).

MRD status has more recently been introduced to facilitate response assessment, with complete and partial response (CR and PR, respectively) being defined in four categories: CR+MRD+, CR+MRD-, PR+MRD+, and PR+MRD-. However, MRD response assessment is currently only recommended in the context of clinical trials (Hallek, 2017).

Table 1. Response definitions after treatment for patients with CLL (Hallek et al., 2008; Oscier et al., 2012).
  Group Complete Response* Partial Response** Progressive Disease

Lymphadenopathy

A

None > 1.5 cm

Decrease ≥50%

Increase ≥50%

Hepatomegaly

A

None

Decrease ≥50%

Increase ≥50%

Splenomegaly

A

None

Decrease ≥50%

Increase ≥50%

Blood Lymphocytes

A

<4.0 x 109/L

Decrease ≥50% from baseline

Increase ≥50% over baseline

Marrow

A

Normocellular, <30% lymphocytes, no B-lymphoid nodules

 

 

Platelet count

B

>100 x 109/L

>100 x 109/L or increase ≥50% over baseline

Decrease of ≥50% from baseline secondary to CLL

Haemoglobin

B

>11 g/L

>11 g/dL or increase ≥ 50% over baseline

Decrease of >2 g/L from baseline secondary to CLL

Neutrophils

B

>1.5 x 109/L

>1500/µL or > 50% improvement over baseline

 

*Complete response (CR): all of the criteria have to be met, and patients have to lack disease-related constitutional symptoms; **Partial response (PR): at least two of the criteria of group A plus one of the criteria of group B have to be met; Stable disease (SD) is absence of progressive disease (PD) and failure to achieve a PR. The International Workshop on Chronic Lymphocytic Leukaemia has recently agreed that blood lymphocytosis alone should not be a criterion for disease progression or relapse, based on the lymphocytosis observed in patients treated with B cell receptor (BCR) signalling inhibitors in the absence of disease progression.

In addition, a number of other terms are used to describe disease response or failure to treatment:

  • Relapse is defined as disease progression at least 6 months after achieving a CR or PR.
  • Refractory disease is defined as treatment failure (no Cr or PR) or disease progression within 6 months of anti-leukemic therapy.
  • Ultra high-risk disease is defined as patients with a TP53 abnormality (previously untreated or relapsed); patients who relapse within 2 years of, or are refractory to purine analogue-based therapy regardless of biomarker results (Stilgenbauer et al., 2015).