ALCL ALK (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 non-Hodgkin lymphoma that arises from mature T-cells. The ALK-positive (ALK+) variant is defined by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene, most commonly t(2;5), leading to expression of the ALK fusion protein. ALK+ ALCL typically affects children and young adults and has a better prognosis compared to ALK-negative disease. Clinical features include lymphadenopathy, B symptoms (fever, weight loss, night sweats), extranodal involvement, and sometimes leukemic presentation. Management strategies aim for cure in most patients, with chemotherapy as the backbone of treatment.

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1. First-Line Therapy

• Multi-agent chemotherapy:

  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone): Historically used.

  • CHP + brentuximab vedotin (anti-CD30 antibody-drug conjugate) has now become a preferred regimen for CD30-positive ALCL.

    • Superior to CHOP in randomized trials, leading to improved progression-free and overall survival.

• Children and adolescents: Often treated with intensive, multi-agent pediatric protocols (e.g., ALCL99 regimen).

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2. Consolidation and Stem Cell Transplant

• Autologous stem cell transplant (ASCT):

  • Considered in adults with high-risk disease or inadequate response to first-line therapy.

• Allogeneic stem cell transplant (allo-SCT):

  • Reserved for relapsed/refractory cases where durable remission is not achieved with chemotherapy or targeted therapy.

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3. Relapsed or Refractory ALK+ ALCL

• Brentuximab vedotin:

  • Highly effective in relapsed/refractory ALCL, inducing durable remissions in many patients.

• ALK inhibitors:

  • Crizotinib, ceritinib, alectinib, lorlatinib have demonstrated activity in relapsed/refractory ALK+ ALCL due to their ability to target the ALK fusion protein.

  • Particularly useful in pediatric or young adult patients.

• Other options:

  • Gemcitabine-based chemotherapy, ICE (ifosfamide, carboplatin, etoposide), or platinum-containing regimens as salvage.

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4. Supportive and Symptom Management

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

• Infection prophylaxis depending on treatment intensity.

• Psychosocial support for younger patients given the impact of diagnosis and treatment.

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5. Prognosis

• ALK+ ALCL generally has a favorable prognosis, with 5-year overall survival rates exceeding 70–80% in most series.

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