The Main Timeline


This timeline contains the original history as researched by M. Barela:
1666 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. Thomas Hodgkin
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)
1887 Wilhelm Ebstein and PK Pel both publish papers noting a cyclic fever over a period of 1 to 2 weeks in a fair number of Hodgkin's cases. Now called Pel-Ebstein Fever although there is controversy about this being a real indication of Hodgkin's (see 1959).
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.
1959 Richard Asher questions whether Pel-Ebstein Fever in 5-10% of Hodgkin's patients is truly an indicator of Hodgkin's or just exists because it has a name.
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.  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
1994 First hints that Hodgkin's cancerous cells are derived from B lymphocytes.  Confirmed in 1999 (below). Source
1995 Stanford reports on use of Stanford V chemotherapy and adjuvant radiotherapy for bulky / advanced Hodgkin's Disease
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
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 The 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
July 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)
Oct. 2008 Lamprecht and Mathas discover Interleukin-21 (IL-21) is produced by Hodgkin's cancer cells (only thought until now to be in T Cells).  This explains a great deal of the behavior of Hodgkin's including alot of other immune cells clustered around HD cells in cultures.  Targeting IL-21 may be a potential treatment, possibly a test for the disease. Journal: Blood, Vol 112, No. 8, 2008, 3339-3347
 

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