What are the treatment options for leukemia?

Treatment Options for Leukemia

The treatment of leukemia depends on the specific type, with chronic lymphocytic leukemia (CLL) typically treated with targeted therapies like BTK inhibitors or BCL2 inhibitors, while acute leukemias require more intensive chemotherapy regimens, with allogeneic stem cell transplantation being the only potentially curative option for high-risk disease. 1, 2

Chronic Lymphocytic Leukemia (CLL)

Initial Management Approach

• "Watch and wait" strategy is recommended for early-stage asymptomatic CLL patients, with regular monitoring of blood counts and clinical examinations every 3 months 1
• Treatment should only be initiated when patients develop criteria for "active disease" according to international guidelines 1

Indications for Treatment

• B symptoms (fever, night sweats, weight loss) 1
• Cytopenias not caused by autoimmune phenomena 1
• Symptoms or complications from lymphadenopathy, splenomegaly, or hepatomegaly 1
• Progressive lymphocytosis with lymphocyte doubling time <6-12 months 1
• Autoimmune complications (anemia or thrombocytopenia) poorly responsive to corticosteroids 2

Risk Stratification Before Treatment

• FISH testing for chromosomal abnormalities, particularly del(17p) and TP53 mutations, is essential for treatment selection 1
• Immunoglobulin heavy chain variable region (IGHV) mutational status helps predict treatment response 1
• Patient fitness assessment, including age, comorbidities, and renal function, guides treatment choice 1

First-Line Treatment Options

For physically fit patients without del(17p)/TP53 mutations:

• Fludarabine and cyclophosphamide (FC) is recommended as initial treatment, as this combination induces higher complete remission rates and longer progression-free survival than chlorambucil or purine analog monotherapy 2
• The addition of rituximab (FCR) has shown improved survival outcomes 2, 3
• Time-limited therapy with venetoclax (BCL2 inhibitor) plus obinutuzumab for 12 cycles is preferred, especially for patients with mutated IGHV 1

For patients with del(17p) or TP53 mutations:

• Bruton tyrosine kinase inhibitors (BTKis) such as ibrutinib, acalabrutinib, or zanubrutinib are the preferred first-line options 1, 3
• Alemtuzumab monotherapy or combination therapy may be considered 2
• Allogeneic transplantation within clinical trials might be considered as first-line therapy in these patients 2

For patients with comorbidities:

• Chlorambucil or dose-reduced fludarabine monotherapy can be given as first-line therapy, as they appear to be less myelotoxic than the FC combination 2
• Bendamustine is an alternative option for these patients 2

Treatment for Relapsed/Refractory Disease

• If relapse occurs >12 months after initial therapy, the first-line treatment may be repeated 2
• For early relapse (<12 months) or refractory disease, switch to an alternative class of agents 1
• Options include:
  • Fludarabine, FC or cladribine after chlorambucil 2
  • Fludarabine combinations with cyclophosphamide and/or mitoxantrone plus monoclonal antibodies in fludarabine-refractory patients 2
  • Monoclonal antibody (alemtuzumab), especially in chemotherapy-refractory patients 2
  • Bendamustine plus monoclonal antibodies after chlorambucil or purine analog-based therapy 2
  • Noncovalent BTK inhibitor (pitobrutinib) has shown response rates >70% after failure of covalent BTK inhibitors and venetoclax 3

Acute Leukemia

Acute Myeloid Leukemia (AML)

• Induction chemotherapy for younger patients (<55 years) generally consists of cytarabine (ara-C) and an anthracycline or anthracycline derivative 4
• For elderly patients who cannot tolerate intensive IV chemotherapy, oral regimens combining idarubicin and etoposide may be considered 5
• Daunorubicin is effective against a wide spectrum of tumors and is used in AML treatment 6

Acute Lymphoblastic Leukemia (ALL)

• Treatment typically includes asparaginase in combination with other chemotherapeutic agents 7
• The addition of daunorubicin to vincristine-prednisone regimen in adult ALL significantly increases the rate of complete remission 6

Special Considerations

CLL Blast Crisis

• Intensive chemotherapy regimens such as R-CHOP or R-HyperCVAD are recommended for physically fit patients 8
• For patients with del(17p), consider incorporating targeted agents such as BTK inhibitors or venetoclax into the treatment regimen 8
• For younger, fit patients, intensive chemotherapy followed by allogeneic stem cell transplantation offers the only potentially curative approach 8

Monitoring During and After Treatment

• Regular physical examinations and blood counts to assess response 1
• Bone marrow biopsy only in patients with complete hematologic remission to confirm complete response 1
• Imaging (chest X-ray, abdominal ultrasound/CT) if abnormal before therapy 1
• Special attention should be paid to the appearance of autoimmune cytopenias (autoimmune hemolytic anemia, autoimmune thrombocytopenia) that occur in 10–15% of CLL patients 2

Important Caveats

• Allogeneic stem cell transplantation is the only curative therapy for high-risk CLL [del(17p), del(11q)] and/or refractory disease 2
• Patients with del(17p) frequently do not respond to conventional chemotherapy with fludarabine or FC 2
• Treatment decisions should be based on disease activity rather than absolute lymphocyte count 9
• Monitor for tumor lysis syndrome risk, which is high with intensive chemotherapy 8
• Patients receiving asparaginase should be monitored for pancreatitis, glucose intolerance, hemorrhage, and hepatotoxicity 7