American Society of Hematology

Case Study: Cervical Adenopathy, Weight Loss, and Night Sweats

The following case study focuses on a woman in her early 30s who presents with cervical adenopathy, weight loss, and night sweats. Test your knowledge by reading the background information below and making the proper selection.

A 32-year-old woman presents with cervical adenopathy, weight loss, and night sweats. Lymph node biopsy shows a CD30+, CD2+, CD3-, CD4+, anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. Staging evaluations reveal adenopathy in the mediastinum and retroperitoneum and no evidence of disease in the bone marrow. LDH is twice the upper limit of normal and ECOG performance status is 1.

What is the most appropriate initial therapy for this patient?

  1. R-CHOP x 6-8 cycles
  2. Brentuximab vedotin
  3. CHOP x 6-8 cycles
  4. CHOP x 4-6 cycles then proceed to autologous stem cell transplant
  5. ABVD
  6. Crizotinib

Answer

c. CHOP x 6-8 cycles

Explanation

Anaplastic large-cell lymphoma (ALCL) is an aggressive peripheral T-cell lymphoma that is characteristically strongly CD30+, and 60 to 85 percent of cases demonstrate expression of anaplastic lymphoma kinase (ALK) (usually a result of a fusion gene between NPM and ALK that leads to constitutive activation). Younger patients have a higher frequency of ALK positivity, and ALK+ ALCL is associated with a better prognosis, compared with ALK-negative disease and in comparison to other aggressive peripheral T-cell lymphomas.1 Therapy with 6 to 8 cycles of CHOP leads to a three-year event-free survival rate of 75 percent according to recent studies, and therefore is the best initial treatment for ALK+ ALCL.2 As ALCL is CD-20 negative (being of T-cell origin), rituximab is not included in the regimen. ABVD is the regimen recommended for Hodgkin lymphoma, another tumor that is frequently CD30+.

In relapsed or refractory ALK+ ALCL, both autologous and allogeneic stem cell transplantation have been investigated, though they are not recommended in first remission because of the prognosis associated with chemotherapy alone.3 In 2010, brentuximab vedotin was demonstrated to have activity in relapsed/refractory ALCL, though only two patients with ALCL were included in this original trial.4 Currently, additional data are available to support its use in relapsed/refractory disease, though none as a first-line agent.5 Finally, clinical response to crizotinib has been reported in a few patients with ALK+ ALCL; however, studies are currently underway to quantify this potential benefit.6  

  1. Gascoyne RD, Aoun P, Wu D, et al. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood. 1999;93:3913-3921.
  2. Schmitz N, Trümper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010.116:3418-3425.
  3. Casulo C and Horwitz S. Should eligible patients with T-cell lymphoma receive high-dose therapy and autologous stem cell transplant in the upfront setting? Curr Oncol Rep. 2010.12:374-382.
  4. Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812-1821.
  5. Foyil KV, Kennedy DA, Grove LE, et al. Extended retreatment with brentuximab vedotin (SGN-35) maintains complete remission in patient with recurrent systemic anaplastic large-cell lymphoma. Leuk Lymphoma. 2011. Epub ahead of print.
  6. Gambacorti-Passerini C, Messa C, and Pogliani EM. Crizotinib in anaplastic large-cell lymphoma. N Engl J Med. 2011;364:775-776.
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