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Milestones in Hodgkin Lymphoma

An article on the cure of Hodgkin lymphoma by Sandra J. Horning, MD, and these accompanying milestones were published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.

1832 Sir Thomas Hodgkin publishes "On Some Morbid Appearances of the Absorbent Glands and Spleen," about a series of six patients with clinical findings that were different from tuberculosis, syphilis, and inflammation.
1865 Samuel Wilks reports on similar cases with lymph node and splenic enlargement and names the disorder "Hodgkin's disease." This invariably fatal illness is treated with herbs, surgery, and arsenic.
1900s German pathologist Carl Sternberg (1898) and American pathologist Dorothy Reed (1902) independently provide detailed accounts of the giant "Reed-Sternberg" cells, which are the microscopic hallmarks of Hodgkin lymphoma.
W. Pusey and N. Senn note remarkable regressions of Hodgkin lymphoma upon exposure to X-rays.
1931 Rene Gilbert administers large fields of radiation therapy to patients with Hodgkin lymphoma.
1943 Temporary reduction in the size of lymph nodes is reported in six Hodgkin patients treated with nitrogen mustard by Rene Gilbert and colleagues.
1950 Vera Peters reports excellent survival rates in Hodgkin patients treated with radiotherapy to adjacent lymph nodes not known to contain disease.
1962 Henry Kaplan introduces the linear accelerator in the treatment of Hodgkin lymphoma at Stanford University. Cures are reported after wide-field radiotherapy treatment of localized Hodgkin lymphoma.
1964 Vincent DeVita Jr. and colleagues are the first to demonstrate the cure of advanced-stage Hodgkin lymphoma in approximately 50 percent of patients with combination chemotherapy using the MOPP (mustard, vincristine, procarbazine, prednisone) regimen.
1966 Robert J. Lukes and James J. Butler describe the natural history of Hodgkin lymphoma related to histopathologic classification. Saul Rosenberg and Henry Kaplan describe the orderly progression of Hodgkin lymphoma and Rosenberg reports on the staging of this disease.
1975 Gianni Bonadonna reports on a chemotherapy combination, ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), which is effective after failure of MOPP. ABVD later becomes the standard chemotherapy regimen for Hodgkin lymphoma, curing more than two-thirds of patients with advanced or bulky disease.
Adverse effects of MOPP, including secondary leukemia and sterility, are reported. Late effects of radiotherapy are observed in the form of secondary cancers (particularly lung and breast) and cardiovascular disease. Remissions are achieved with high-dose chemotherapy and autologous transplantation in Hodgkin lymphoma recurrent after chemotherapy and radiation therapy. This approach becomes the standard second-line therapy for advanced disease.
1994 Ralf Küppers plucks individual Reed-Sternberg cells from Hodgkin tissues and establishes that they represent malignant B cells by gene rearrangement analyses.
Randomized trials in North America and Europe combine limited field, lower-dose radiotherapy with a brief course of less toxic chemotherapy (e.g. ABVD), resulting in cure rates of 90 percent or greater in limited-stage disease. Brief chemotherapy (Stanford V) and radiotherapy are introduced for advanced disease. The German Hodgkin Study Group reports superior survival with an intensive chemotherapy regimen, escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), in advanced Hodgkin lymphoma.
2000s Positron-emission-tomography scans early in the treatment course predict the outcome of treatment with ABVD, suggesting that therapy could be more personalized, reserving radiotherapy and prolonged or more intensive treatments for a subset of patients. First successful treatments of lymphocyte-predominant Hodgkin lymphoma with a monoclonal antibody, rituximab, are reported by investigators in Germany and at Stanford University.