ALCL ALK-Positive (Anaplastic Large Cell Lymphoma - ALK-Positive)

Anaplastic Large Cell Lymphoma – ALK-Positive (ALCL ALK+) – Treatment Options

Introduction
Anaplastic large cell lymphoma (ALCL) is a subtype of peripheral T-cell lymphoma. The ALK-positive form is characterized by chromosomal translocations involving the ALK gene, most commonly t(2;5), leading to the expression of ALK fusion proteins. ALK+ ALCL is more common in children, adolescents, and young adults, and is associated with a favorable prognosis compared with ALK-negative disease. Patients typically present with lymphadenopathy, B symptoms (fever, night sweats, weight loss), and extranodal involvement (skin, bone, lung, liver, soft tissues). Treatment is directed at achieving long-term remission and potential cure.

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1. First-Line Therapy

• Chemotherapy Backbone:

  • Historically, CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) was standard.

  • Current preferred regimen: CHP (cyclophosphamide, doxorubicin, prednisone) + brentuximab vedotin (anti-CD30 antibody–drug conjugate).

    • Replaces vincristine with brentuximab vedotin.

    • Demonstrated superior progression-free survival (PFS) and overall survival (OS) compared to CHOP in CD30+ ALCL.

• Pediatric and Adolescent Patients:

  • Treated with pediatric intensive multi-agent regimens (e.g., ALCL99 protocol), tailored for age and risk category.

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2. Consolidation Therapy

• Autologous stem cell transplantation (ASCT):

  • Considered in selected high-risk adults or patients with inadequate response to induction.

  • Not routinely required in patients achieving durable remission with first-line therapy.

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3. Relapsed or Refractory ALCL ALK+

• Brentuximab vedotin (single-agent):

  • Highly effective, induces durable responses, FDA-approved for relapsed/refractory systemic ALCL.

• ALK inhibitors (targeted therapy):

  • Crizotinib, ceritinib, alectinib, lorlatinib – effective in relapsed ALK+ ALCL by targeting ALK fusion proteins.

  • Particularly useful in pediatric/young adult relapsed disease.

• Chemotherapy options:

  • ICE regimen (ifosfamide, carboplatin, etoposide) or gemcitabine-based salvage regimens.

• Stem cell transplantation:

  • Allogeneic SCT considered for refractory or multiply relapsed disease, especially in younger patients.

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4. Supportive Care

• Growth factor support (G-CSF) to reduce chemotherapy-related neutropenia.

• Infection prophylaxis and monitoring in immunosuppressed patients.

• Psychosocial and survivorship support, especially for adolescents and young adults undergoing long-term therapy.

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5. Prognosis

• ALK-positive ALCL has a more favorable prognosis compared to ALK-negative ALCL.

• 5-year overall survival: Often exceeds 70–80% with modern therapy.

• Prognostic factors include age, disease stage, extranodal involvement, performance status, and IPI (International Prognostic Index) score.