Correspondence

Clonal Relapse in Hodgkin's Disease

N Engl J Med 1997; 337:499August 14, 1997

Article

To the Editor:

In classic Hodgkin's disease, the characteristic Reed–Sternberg cells represent a minority of less than 1 percent of cells in affected tissue. The pathogenic role of these cells and their clonal nature have been matters of debate for a long time. Recently, in studies using micromanipulation of Reed–Sternberg cells from single lymph-node sections and subsequent amplification of rearranged immunoglobulin genes by the polymerase chain reaction (PCR), evidence was obtained that Reed–Sternberg cells represent a clonal B-cell population.1,2 In these studies Reed–Sternberg cells were isolated from one lymph node for a given case.

We found that clonal Reed–Sternberg cells can disseminate and recur in patients with relapses of Hodgkin's disease. We analyzed biopsy material from a patient who received the diagnosis of Hodgkin's disease of the mixed-cellularity subtype, at clinical stage IA, in 1991 and who relapsed in 1993 with involvement of inguinal and abdominal lymph nodes and bone marrow. We amplified the rearranged immunoglobulin heavy- and light-chain genes in cultured Reed–Sternberg cells derived from the peripheral blood of this patient in 19943 and in single Reed–Sternberg cells from the patient's bone marrow.4 Identical sequences were in Reed–Sternberg cells from both sources. Primers covering the complementarity-determining region 3 were chosen from the Reed–Sternberg cell-specific sequence of the functional heavy-chain rearrangement.

PCR analysis was used to screen the biopsy specimen from the patient's cervical lymph node, obtained at the time of the initial diagnosis in 1991, for the presence of Reed–Sternberg cells of the same clone. The identical sequence, including eight somatic mutations, was detected by reading 61 base pairs. This finding indicates the evolution of a clonal population of Reed–Sternberg cells from the primary localized manifestation of Hodgkin's disease (stage IA), leading to the dissemination of the clone in stage IVB. This clone persisted despite complete remission after aggressive treatment, including high-dose chemotherapy and autologous bone marrow transplantation. These results demonstrate the clonal dissemination and recurrence in relapsing disease, two properties of malignant cells, of Reed–Sternberg cells in classical Hodgkin's disease.

Editor's note: Two articles on the topic of clonality in Hodgkin's disease, by Marafioti et al. and Ohno et al., along with an editorial on the subject by Schwartz, appear elsewhere in this issue of the Journal.

Andrea Jox, M.D.
Thomas Zander
Volker Diehl, M.D.
Jürgen Wolf, M.D.
University of Cologne, D-50924 Cologne, Germany

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Citing Articles (8)

Citing Articles

1. 1

   Roman K Thomas, Claudia Wickenhauser, Dieter Kube, Hans Tesch, Volker Diehl, Jürgen Wolf, Martina Vockerodt. (2004) Repeated Clonal Relapses in Classical Hodgkin's Lymphoma and the Occurrence of a Clonally Unrelated Diffuse Large B Cell Non-Hodgkin Lymphoma in the Same Patient. Leukemia & Lymphoma 45:5, 1065-1069
   CrossRef

2. 2

   Roman Kurt Thomas, Anne Kallenborn, Claudia Wickenhauser, Joachim Ludwig Schultze, Andreas Draube, Martina Vockerodt, Daniel Re, Volker Diehl, Jürgen Wolf. (2002) Constitutive Expression of c-FLIP in Hodgkin and Reed-Sternberg Cells. The American Journal of Pathology 160:4, 1521-1528
   CrossRef

3. 3

   Daniel Benharroch, Elena Dima, Amalia Levy, Ofra Ohana-Malka, Samuel Ariad, Isebrand Prinsloo, Eugenia Mejirovsky, Martin Sacks, Jacob Gopas. (2000) Differential Expression of Sialyl and Non-Sialyl-CD15 Antigens on Hodgkin-Reed-Sternberg Cells: Significance in Hodgkin's Disease. Leukemia & Lymphoma 39:1-2, 185-194
   CrossRef

4. 4

   Maurice P. H. M. Jansen, Anton H. N. Hopman, Fredrik J. Bot, Annick Haesevoets, Marian J. P. L. Stevens-Kroef, Jan Willem Arends, Andrea Jox, Jrgen Wolf, Frans C. S. Ramaekers, Harry C. Schouten. (1999) Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?. The Journal of Pathology 189:4, 527-532
   CrossRef

5. 5

   M. Kornacker, A. Jox, M. Vockerodt, H. Tesch, H. Bohlen, V. Diehl, J. Wolf. (1999) Detection of a Hodgkin/Reed-Sternberg cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease. British Journal of Haematology 106:2, 528-531
   CrossRef

6. 6

   Hans Tesch, Heribert Bohlen, Jürgen Wolf, Andreas Engert. (1998) Pathogenese und Therapie des Hodgkin-Lymphoms. Medizinische Klinik 93:2, 82-90
   CrossRef

7. 7

   Andrea Jox, Jürgen Wolf, Volker Diehl. (1997) Hodgkin's disease biology: recent advances. Hematological Oncology 15:4, 165-171
   CrossRef

8. 8

   Schwartz, Robert S., . (1997) Hodgkin's Disease — Time for a Change. New England Journal of Medicine 337:7, 495-496
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