Anaplastic large cell lymphoma

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Classification according to ICD-10
C84.6 Anaplastic large cell lymphoma, ALK positive
C84.7 Anaplastic large cell lymphoma, ALK negative
ICD-10 online (WHO version 2019)
Histological preparation of an ALCL in HE staining .

The anaplastic large-cell lymphoma (ALCL) is a malignant T-cell - lymphoma that after, WHO -Classification to the non-Hodgkin's lymphoma is counted. The name is derived from the terms ' anaplasia ' and 'large cell lymphoma'. It was first described in 1985 as a separate tumor entity.

Epidemiology

Anaplastic large cell lymphoma occurs mainly in children and adolescents, but older adults can also be affected. It makes up about 15% of non-Hogkin's lymphomas in children. In pediatric patients, the median age of onset is about ten years. With a ratio of 1.8: 1, boys are more often affected.

clinic

In 60 to 70% of patients, the diagnosis is only made at an advanced stage (III or IV). Often there is extranodal (outside of the lymph nodes) involvement of the skin, bones and connective tissue. Occasionally, leukocytosis occurs, mainly in the form of neutrophilia .

Pathophysiology

In the ALK-positive form, there is a chromosomal translocation with the formation of a fusion protein. The most common translocation is the t (2; 5) q (p23; q35). This leads to the formation of a fusion protein from nucleophosmin (NMP) and anaplastic lymphoma kinase (ALK). This translocation activates various intracellular signaling pathways that contribute to tumor development.

Diagnosis

The diagnosis is made using a biopsy . The WHO requires the detection of typical cells and the expression of the cytokine receptor CD30 as diagnostic criteria . The detection of anaplastic lymphoma kinase (ALK) is prognostically significant . Almost all cases of ALCL in childhood are ALK-positive.

therapy

Treatment mainly takes place in specialized centers as part of therapy studies. Various chemotherapeutic agents are used , such as methotrexate , vinblastine , ifosfamide , cyclophosphamide and doxorubicin . Accompanying is dexamethasone administered.

Since the end of 2012, an antibody-drug conjugate (ADC) for the treatment of systemic anaplastic large-cell lymphoma (sALCL) has been available in the European Union with the substance brentuximab vedotin . Brentuximab Vedotin links an anti- CD30 antibody to the cytostatic drug monomethyl auristatin E (MMAE) via an amino acid linker . The medicinal product is approved for the treatment of adults in the event of a relapse or recurrence of sALCL, or in the case of therapy-resistant (not responding to conventional therapies) sALCL.

forecast

In children, the 5-year event-free survival rate of around 70–75% is somewhat lower than in other NHLs. However, in the event of a relapse, 50–60% of patients can still be treated successfully, so that the overall survival rate is around 90%. Adult patients with an ALK-positive ALCL have a better event-free survival rate of 60% than ALK-negative patients with 36%.

literature

  • MC Kinney, RA Higgins et al: Anaplastic large cell lymphoma: twenty-five years of discovery. In: Arch Pathol Lab Med . (2011); 135 (1), pp. 19-43.
  • HD Foss, T. Marafioti and others: The many faces of anaplastic large cell lymphoma. In: The Pathologist. 2000; 21 (2), pp. 124-136.

Individual evidence

  1. ↑ H. Stein , DY Mason, et al .: The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. In: Blood . Volume 66, Number 4, 1985, pp. 848-858.
  2. ↑ D. Wright, P. McKeever, R. Carter: Childhood non-Hodgkin lymphomas in the United Kingdom: Findings from the UK Children's Cancer Study Group. In: Journal of Clinical Pathology . Volume 50, Number 2, February 1997, pp. 128-134, ISSN  0021-9746 . PMID 9155693 . PMC 499737 (free full text).
  3. ↑ a b B. Burkhardt, M. Zimmermann et al .: The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. In: British Journal of Hematology . Volume 131, Number 1, October 2005, pp. 39-49, ISSN  0007-1048 . doi: 10.1111 / j.1365-2141.2005.05735.x . PMID 16173961 .
  4. ↑ RD Gascoyne, P. Aoun et al .: Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. In: Blood. Volume 93, Number 11, June 1999, pp. 3913-3921, ISSN  0006-4971 . PMID 10339500 .
  5. ↑ R. Chiarle, C. Voena, et al .: The anaplastic lymphoma kinase in the pathogenesis of cancer. In: Nature Reviews Cancer . Volume 8, Number 11, January 2008, pp. 11-23, doi: 10.1038 / nrc2291 . PMID 18097461
  6. ↑ ALCL 99 study ( Memento from December 17, 2010 in the Internet Archive )
  7. ↑ NM Okeley, JB Miyamoto, Zhang X et al .: Intracellular activation of SGN-35, a potent anti-CD30 anti-body-drug conjugate. In: Clin Cancer Res. 2010; 16, pp. 888-897. PMID 20086002
  8. ↑ Summary of the European public assessment report (EPAR) for Adcetris
  9. ↑ W. Woessmann, M. Zimmermann include: relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM) -type first-line therapy: a BFM-group study. In: Journal of Clinical Oncology. Volume 29, Number 22, August 2011, pp. 3065-3071.
  10. ↑ KJ Savage, NL Harris et al: ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK + ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. In: Blood. Volume 111, Number 12, June 2008, pp. 5496-5504, ISSN  1528-0020 . doi: 10.1182 / blood-2008-01-134270 . PMID 18385450 .