International Workshop Group on CLL (iwCLL) response criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma^[1]

Complete remission (CR)

Requires all of the following criteria:

Absolute lymphocyte count <4000/microL (4 × 10⁹/L).
No lymph nodes ≥1.5 cm in diameter.
No hepatomegaly or splenomegaly.
No constitutional symptoms attributable to CLL.*
Bone marrow recovery as demonstrated by ANC ≥1500/microL (1.5 × 10⁹/L), platelet count ≥100,000/microL (100 × 10⁹/L), and hemoglobin concentration ≥11 g/dL (110 g/L) in the absence of transfusion or growth factor support.
Bone marrow at least normocellular for age, without evidence for typical CLL lymphocytes by morphologic criteria and immunohistochemistry and without nodular lymphoid aggregates.^¶

CR with incomplete bone marrow recovery (CRi)

Fulfills all requirements for CR except has persistent neutropenia, anemia, or thrombocytopenia thought to be unrelated to the disease and likely related to drug toxicity. These patients must have a normal bone marrow aspirate and biopsy with no evidence of clonal infiltrates.

Partial remission (PR)

At least two of these criteria must be documented:

A decrease in the peripheral absolute lymphocyte count by at least 50% from the level prior to therapy.
A reduction in previously enlarged nodes by at least 50% with no increase in the size of any single lymph node and no new enlarged lymph nodes. An increase of <25% in a lymph node <1.5 cm is not considered significant.
A decrease in the size of the liver and/or spleen by at least 50%.

One of the following hematologic parameters must be met in addition to two of the above criteria in order to qualify for a PR:

Platelet count ≥100,000/microL (100 × 10⁹/L) or at least 50% improvement over baseline (if this value was abnormally low at baseline).
Hemoglobin concentration ≥11 g/dL (110 g/L) or 50% improvement over baseline (if this value was abnormally low at baseline) without red blood cell transfusions or erythropoietin support.

If only one parameter was abnormal before therapy, only one needs to improve to achieve PR.

Nodular PR

Persistent bone marrow nodules on bone marrow biopsy in patients achieving a CR or PR. Lymphoid aggregates should be evaluated with immunohistochemistry to determine whether they are comprised of CLL cells, lymphocytes other than CLL cells, or T cells. If nodules are not composed of CLL cells, a CR can be documented provided all other criteria are met.

Progressive disease (PD)^Δ

At least one of these criteria must be documented:

The appearance of a newly enlarged lymph node (≥1.5 cm), splenomegaly, hepatomegaly, or other organ infiltration.
An increase of 50% or more in size of a previously involved site (eg, lymph nodes, spleen, or liver) measuring ≥1.5 cm.
An increase of 50% or more in the total circulating lymphocyte count with absolute lymphocyte count of 5000/microL (5 × 10⁹/L) or greater.^◊
Richter's transformation documented by lymph node or other tissue biopsy.
Development of neutropenia, anemia, or thrombocytopenia attributable to CLL.^§

Stable disease

Patients who do not meet the criteria for a complete remission, partial remission, or progressive disease, have stable disease. Stable disease is therapeutically equivalent to a nonresponse (ie, refractory disease).

For patients treated with a therapy for a defined treatment duration, response assessment should be performed at least two months after the completion of therapy. For those receiving continued therapies or treatment strategies that include a maintenance phase, response assessment should be performed at least two months after achieving "maximum response" defined as a treatment phase where no additional improvement is seen during at least two months of therapy.

CLL: chronic lymphocytic leukemia; SLL: small lymphocytic lymphoma; ANC: absolute neutrophil count.

* These include ≥10% unintentional weight loss within the previous six months, fatigue that interferes with work or usual activities, fevers greater than 100.5°F (>38°C) for ≥2 weeks, or night sweats for >1 month.

¶ Assessment of residual CLL cells in the bone marrow for this purpose is not based on flow cytometry. Assessment for measurable residual disease (MRD, also called 'minimal residual disease') is reserved for clinical trials. Although bone marrow biopsy is required to confirm a CR, it is not always recommended in general practice as it may not impact management. If the above clinical and hematologic parameters are compatible with a CR and the clinician chooses not to perform a bone marrow biopsy, the documented response can be "partial remission."

Δ Transient increases in lymph node size may occur during treatment with novel inhibitors and should not be considered PD.

◊ For patients treated with therapies that may cause lymphocytosis (eg, kinase inhibitors), an increase in blood lymphocyte count, by itself, does not uniformly indicate an increased tumor burden, but may reflect redistribution of leukemia cells from lymphoid tissues. In such cases, increased lymphocytosis alone is not a sign of treatment failure or progressive disease.

§ Cytopenias cannot be used to determine disease progression during active therapy since they may be due to administered cytotoxic agents. Cytopenias that occur at least three months after the completion of therapy and are accompanied by an infiltrate of clonal CLL cells on bone marrow biopsy can be used to define disease progression. Specific values that define progression include a decrease in hemoglobin level by more than 2 g/dL (20 g/L) or to less than 10 g/dL (100 g/L) or a decrease in platelet count by more than 50% or to less than 100,000/microL (100 × 10⁹/L).

Reference:

Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018; 131:2745.

Graphic 99325 Version 4.0

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International Workshop Group on CLL (iwCLL) response criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma[1]

International Workshop Group on CLL (iwCLL) response criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma^[1]