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Chronic lymphocytic leukemia

What's new

Clinical practice recommendations have been published on behalf of the American Society for Transplantation and Cellular Therapy (ASTCT) on the use of allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor (CAR) T-cell therapy in patients with chronic lymphocytic leukemia (CLL). CAR T-cell therapy is recommended for patients with CLL whose disease has relapsed and/or is refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor, regardless of response to a non-covalent BTK inhibitor. Allo-HCT is recommended for patients with relapsed or refractory CLL following CAR T-cell therapy, provided the patient is fit for the procedure and has achieved an objective response before transplantation. CAR T-cell therapy is also recommended for patients with CLL who relapse after allo-HCT. .

Background

Overview

Definition
CLL is a lymphoproliferative malignancy characterized by peripheral lymphocytosis due to the proliferation of clonal B cells.
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Pathophysiology
CLL is caused by somatic gene mutations involving multipotent and self-renewing hematopoietic stem cells, which leads to clonal proliferation and accumulation of mature B cells.
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Epidemiology
The incidence of CLL in the US is estimated at 4.83 per 100,000 person-years.
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Disease course
Accumulation of B cells in the bone marrow, blood, lymph nodes, and spleen can result in cytopenias, lymphadenopathy, splenomegaly, hepatomegaly, susceptibility to infection, bone marrow failure, and death.
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Prognosis and risk of recurrence
The overall survival at 5-years for patients with low-risk, intermediate-risk, high-risk, and very-high risk CLL is 93.2%, 79.4%, 63.6%, and 23.3%, respectively.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of chronic lymphocytic leukemia are prepared by our editorial team based on guidelines from the American Society for Transplantation and Cellular Therapy & Cell Therapy (ASTCT 2025,2024), the European Society of Medical Oncology (ESMO 2024,2021), the Canadian Expert Group on Chronic Lymphocytic Leukemia (CLL-CEG 2023), the British Society for Haematology (BSH ...
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Screening and diagnosis

Indications for screening: as per ESMO 2021 guidelines, do not obtain routine screening for CLL in the general population nor in relatives of patients with CLL.
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  • Diagnostic criteria

  • Patients with Richter's transformation (biopsy)

  • Differential diagnosis

Diagnostic investigations

History and physical examination: as per ESMO 2021 guidelines, elicit history and perform physical examinations, including careful palpation of all lymph node areas, spleen, and liver, in asymptomatic patients with early-stage disease,
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as well as before initiating treatment in patients with advanced or symptomatic stage disease.
B
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  • Laboratory testing

  • Screening for viral infections

  • Diagnostic imaging

Diagnostic procedures

Biopsy
As per ESMO 2021 guidelines:
Consider performing lymph node biopsy and/or bone marrow biopsy if immunophenotyping is not conclusive for the diagnosis of CLL.
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Consider performing bone marrow examination for the diagnostic evaluation of unclear cytopenia or in the presence of a non-conclusive phenotype before initiating treatment in patients with advanced or symptomatic stage disease. Consider performing a bone marrow biopsy as a baseline parameter to assess treatment response.
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  • Cytogenetic analysis

Medical management

Watchful waiting: as per ESMO 2021 guidelines, offer a watch-and-wait approach in patients with early disease.
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do not obtain routine imaging during a watch-and-wait period unless there are clinical symptoms
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  • Indications for treatment

  • Initial treatment

  • CAR therapy

  • Management of cytopenias

  • Management of hypogammaglobulinemia

  • Management of tumor lysis syndrome

  • Management of infection

Therapeutic procedures

Stem cell transplantation, indications: as per ASTCT 2025 guidelines, do not offer allogeneic hematopoietic cell transplantation in patients with CLL achieving an objective response, either complete or partial, to a covalent Bruton TKI or a BCL-2 inhibitor, whether used alone or in combination.
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  • Stem cell transplantation (management of donor-specific anti-HLA antibodies, prevention)

  • Stem cell transplantation (management of donor-specific anti-HLA antibodies, testing)

  • Stem cell transplantation (management of donor-specific anti-HLA antibodies, desensitization therapy)

  • Stem cell transplantation (management of donor-specific anti-HLA antibodies, follow-up)

  • Stem cell transplantation (management of non-donor-specific anti-HLA antibodies)

Specific circumstances

Patients with chronic hepatitis B or C
As per iwCLL 2018 guidelines:
Administer prophylactic antiviral agents to patients found to be chronic carriers of HBV, while undergoing therapy for chronic lymphocutic leukemia with immunosuppressive drugs.
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Initiate antiviral therapy before antileukemic treatment in patients with high titers of HBV or HCV DNA.
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  • Patients with CMV infection

  • Patients with autoimmune hemolytic anemia or immune thrombocytopenia

  • Patients with COVID-19 infection

  • Patients with Richter's transformation (biopsy)

  • Patients with Richter's transformation (mutational analysis)

  • Patients with Richter's transformation (screening for viral infections)

  • Patients with Richter's transformation (enrollment in clinical trials)

  • Patients with Richter's transformation (systemic therapy)

  • Patients with Richter's transformation (stem cell transplantation)

  • Patients with Richter's transformation (CAR therapy)

  • Patients with Richter's transformation (palliative care)

Preventative measures

Routine immunizations: as per BSH 2022 guidelines, offer routine immunizations at diagnosis in all patients, keep a vaccine logbook, and avoid administering live vaccines.
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  • Antimicrobial prophylaxis

Follow-up and surveillance

Assessment of treatment response
As per ESMO 2021 guidelines:
Obtain response assessment with a careful physical examination and blood cell count. Perform a bone marrow biopsy and obtain minimal residual disease assessment to define complete remission and minimal residual disease status within clinical trials,
B
as well as obtain CT.
B
Do not obtain routine minimal residual disease measurement, except after allo-SCT.
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  • Management of relapsed/refractory disease

  • Surveillance for malignancy