Hodgkins Lymphoma

The History of the Hodgkin's Lymphoma Timeline: What Were The Key Events of This Disease

Hodgkin's Lymphoma (Disease) has a colorful history: It was not the first cancer discovered but it was one of the first in which treatments were investigated and ultimately successful.

Here is the Hodgkin's Lymphoma timeline which details the events important in the history of Hodgkin's Lymphoma. The curiosity of which events occurred in early history may be of interest but ultimately the importance may lie in a long-term survivor matching their treatment timeframe with the ones presented to determine which treatments and methodologies were used and available during the same time. Below is a table showing the year and the corresponding event that took place in that time period.

1666	When was Hodgkin's Lymphoma discovered? Malpighi publishes the first recorded description of Hodgkin's disease in his paper De viscerum structuru exercitatio anatomica
1798	Thomas Hodgkin born in England
1823	Thomas Hodgkin publishes his doctoral thesis Dissertatio Physiologica Inauguralis De ABSORBENDI FUNCTIONE (Latin) in Edinburgh
1825	Hodgkin joins the staff of Guy's Hospital, London
1832	Hodgkin publishes his paper on lymphatic disease "On Some Morbid Appearances of the Absorbent Glands and Spleen" Published in Medico-Chirurgical Transactions, the journal of the Medical and Chirurgical Society in London.
1838	Richard Bright publishes his paper on lymphatic disease "Observations on abdominal tumors and Intumescence, Illustrated by Cases of Disease of the Spleen"
1856	Samual Wilks publishes his paper "Cases of Lardaceous Disease and Some Allied Affections with Remarks". Wilks quotes Bright but he thinks his observations original.
1865	Wilks describes disease further and attributes Hodgkin with discovering the disease.
1872	Langhans publishes the first histopathologic features of Hodgkin's Disease (German)
1878	Greenfield publishes the pathology of lymphomas with histopathologic features of Hodgkin's (English)
1894	Osler's textbook of Medicine is the first publication to mention chemotherapy for lymphoma (Fowler's solution - an arsenic containing medicinal).
1898	Carl Sternberg first detailed description of giant cells now called Reed-Sternberg cells (Germany)
1902	Dorothy Reed independently describes Reed-Sternberg cells (Johns Hopkins Hosp Rep, US)
1932	Chevalier and Bernard reaffirm radiotherapy for Hodgkin's mostly palliative
1939	Epstein reports better survival prognosis for women (Epstein E, Sex as factor in the prognosis of Hodgkins disease. Am. J. Cancer 35:230-233.)
World War 2	Explosion in Bari, Italy exposes servicemen to toxic effects of mustard gases. Follow-up of exposed shows marrow and lymphatic system suppression.
1943	Nitrogen Mustard (a mustard gas derivative) submitted to Goodman and Gilman at Yale for treatment of Hodgkin's disease and lymphosarcoma (could be first phase I/II trial on record)
Mid-40's	Gilbert and Craft advocate irradiation of nodes and surrounding areas - 5 year survival reported to be 25-35% 1947 Alpert and Petersen publish results of Nitrogen Mustard showing striking dissolution of tumor masses in patients with Hodgkin's Disease and lymphosarcoma
1949	Dameshek et al. publish paper on the use of Nitrogen Mustard for treatment of 50 consecutive cases of Hodgkin's
1950	Peters reports on unrandomized results of patients treated with high doses of radiotherapy to both involved and adjacent sites having improved survival over those receiving lower doses to involved sites and/or no irradiation to adjacent sites.
1962	Kaplan reports on radiotherapy in localized Hodgkin's. Studies initiated at Stanford 1962-67
1963	Scott publishes paper on using chlorambucil as maintenance chemotherapy following Nitrogen Mustard treatment for Hodgkin's
1963	Development of MOMP - first combination chemotherapy for Hodgkin's (consists of cyclophosphamide, vincristine, methotrexate, and prednisone)
1963	Easson and Russell publish "The Cure of Hodgkin's Disease" which reverses long standing belief that Hodgkin's was incurable
1964	Johnson et al. publish paper on vinca alkaloid drugs (vincristine & vinblastine)
1964	Systematic trials on the use of vinca alkaloids for remission induction after Nitrogen Mustard vs. use of chlorambucil
1964	MOPP combination chemotherapy derived by replacing methotrexate with procarbazine in MOMP
1964	EORTC launches the H1 trial on Hodgkin's Disease
Feb. 1965	The Paris international workshop on radiotherapy effectiveness, histologic classification, and staging systems. 4 stages were defined with differentiation between B symptoms
Sept.1965	Conference "On Obstacles to the Control of Hodgkin's Disease" held in Rye, NY, sponsored by ACS and NCI. 45 leaders in the field attend. The Rye staging system developed based on work done in Paris
1965	MacMahon distinguishes between 3 age groups (0-14, 15-34, 50+) for Hodgkin's, each with distinctive features
1966	Lukes and Butler describe the Reed-Sternberg variant cells called L&H cells in nodular lymphocyte-predominant Hodgkin's (Cancer Res)
1967	Results of MOPP on first 43 patients: 81% complete remission rate (a four-fold increase over single agent drugs)
1967-1973	NCI randomized trials on extended vs. involved field radiotherapy. Extended provides improved progression free survival but eventual survival differences minimal due to salvage therapies available
1968	Adriamycin becomes available as a new anticancer drug
1969	Stanford clinical trials on the use of exploratory laparotomy / splenectomy in staging
1970	Publication of survival curves for MOPP treated patients shows advanced Hodgkin's is curable by combination chemotherapy
April 1971	Ann Arbor meeting sponsored by ACS and NCI. Staging broken down into Clinical Stage (CS) based on x-ray, lymphangiogram, & physical exam and Pathologic Stage (PS) based on staging laparotomy, splenectomy, liver biopsy, open marrow biopsy and additional node biopsy. Generalized pruitis (itching) dropped from list of B symptoms
1972	Arseneau et al. report on secondary cancers following therapy for Hodgkin's disease
1972	Frei et al. report remission success of 56% in untreated patients with Hodgkin's treated using dacarbazine
1973	Sherins et al. report on male reproductive function in those in remission following treatment for Hodgkin's
1973	Bonadonna et al. from Italy report on trials of adriamycin, bleomycin, vinblastine and imidazole carboxamide verses MOPP combination chemotherapy
1974-1982	Randomized studies on effectiveness of ABVD or MOPP before and after irradiation in stage IIB and stage III A&B at Milan Cancer Institute Randomized studies comparing 12 cycles of MOPP verses monthly alternating with ABVD in stage IV disease
1974	Rosdahl, Larsen, and Clemmesen study Hodgkin's disease in patients with previous infectious mononucleosis. The mononucleosis timeline is not presented here. Note: mononucleosis is caused by the Epstein-Barr virus (EBV) investigated by MA Epstein in the 1960s. Brit. Med. J. 1:253-355 1975 Therapeutic antibodies are developed by Cesar Milstein and Georges Kohler. This work will lay the foundation for modern immunotherapy and monoclonal antibody therapy. They will win the Nobel Prize in 1984 for their work
1976-1982	EORTC H5 trials
1978	NCI study on the use of MOPP alone verses subtotal nodal irradiation shows MOPP superior in both relapse-free and overall survival
1979	BNLI compares MOPP with LOPP (leukeran/chlorambucil replaces mechlorethamine
1982	First paper on long term (LT) follow-up of ovarian function in women treated with MOPP by Shilsky et al.
1983	Microsoft cofounder Paul Allen leaves the company after a diagnosis of Hodgkin's Disease. He achieves remission and goes to found a number of successful companies. 1986 MOPP/ABV hybrid chemotherapy developed and published by Canadian researchers.
1987	Weiss, et al. using Southern Blot, detect Epstein-Barr virus (EBV) viral DNA in tissues of Hodgkin's disease Am J Pathol 1987;129:86. Herbst et al. and Weiss et al. confirm via PCR in 1990 and 1991 respectively
1987	EBVP (epirubicin, bleomycin, vinblastine, prednisone) introduced by Zittoun and tested in EORTC H7 trial
1991	The Lymphoma Research Foundation of America (LRFA), was founded by Ellen Glesby Cohen in Los Angeles, California USA
1992	Bulky disease (node or nodal mass > 10 centimeters in size) regarded as important in Hodgkin's staging
1992	The German Hodgkin's Study Group designed the BEACOPP regimen that used similar drugs as in the COPP/ABVD regimen, excluding velban and dacarbazine and adding etoposide, trying to increase efficacy
1994	Amanda Gee, a Hodgkin's patient in the UK, starts the first web site devoted to Hodgkin's Disease
Nov. 1994	Cure for Lymphoma Foundation founded in New York, New York USA
Dec 1994	Mike Barela, a recent Hodgkin's survivor in the US, launches the first combined Hodgkin's / Non-Hodgkin's Lymphoma web resource list site Lymphoma Resource Pages, later to become the Lymphoma Information Network
1995	Stanford reports on use of Stanford V chemotherapy and adjuvant radiotherapy for bulky / advanced Hodgkin's Disease
1997	Rituxan approved for b-cell Non-Hodgkin's lymphoma. With the discovery in 1999 that Reed-Sternberg cells are derived from B lymphocytes, research can proceed on the effectiveness of monoclonal antibodies in Hodgkin's
1999	Kapp et al. report on role of Intereukin-13 on the growth and stimulation of Hodgkin and Reed-Sternberg cells
1999	Cossman et al. report definitive proof that Reed-Sternberg cells in Hodgkin's Lymphoma are derived from germinal-center B lymphocytes
2001	WHO Classification for Lymphomas published - the term Hodgkin's Lymphoma is the preferred designation over Hodgkin's Disease
2002	LRFA and CFL merge to form the Lymphoma Research Foundation in the US
2002	Horning et. al. present results from phase II trial on rituxan for lymphocyte predominant Hodgkin's
Jul. 2003	Younes et al. publish a pilot study of rituxan in patients with recurrent, classic Hodgkin's disease
Nov. 2005	Klimm et al. in Germany further study Hodgkin's prognosis of Men vs. Women (see E. Epstein 1939 above) Journal of Clinical Oncology, Vol 23, No 31 (November 1), 2005: pp. 8003-8011
Dec. 2005	Mathas et al. determine the mechanism that causes normal B lymphocytes to mutate into the cancerous cells in Hodgkin's lymphoma
Dec 2005	Robertson, Knight, and Sharma determine the link between Epstein-Barr Virus (EBV) and several cancers including Hodgkin's lymphoma via molecular elimination of the retinoblastoma protein (Rb)

Source: Pexels

The History of the Hodgkin's Lymphoma Timeline: What Were The Key Events of This Disease

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