Pioneers in Hodgkin Lymphoma: Henry S. Kaplan, MD (1918-1984)

Colin G. Evans, PhD

The therapeutic palette for Hodgkin Lymphoma is growing, along with improvements in survival and cure rates.

Henry S. Kaplan MD

The therapeutic palette for Hodgkin Lymphoma is growing, along with improvements in survival and cure rates.1However, the prognostic picture looked very different 60 to 70 years ago. In the introduction to his 1962 article inRadiology,entitled “The Radical Radiotherapy of Regionally Localized Hodgkin’s Disease,” Henry S. Kaplan, MD, summarized the prevailing attitude toward this cancer2:

“The concept of Hodgkin’s disease as an inexorably fatal condition has taken firm hold, so much so that it is actually defined in one recent textbook as a,progressive condition leading inevitably to death.” Kaplan wryly continued, “If one were to accept such a definition at its face value, the advent of a curative form of therapy would presumably require a change in diagnosis!”2

Kaplan was born in Chicago, where he attended the University of Chicago, and then received his MD degree at the age of 22 from Rush Medical College. At Michael Reese Hospital he was a general radiology intern, and from there he went to the University of Minnesota and finished his training with Leo Rigler. After this training, he conducted research at the National Cancer Institute (NCI) in Bethesda and was subsequently appointed instructor at Yale, progressing to assistant professor. Three years later, he spent 1 year conducting research at the NCI, and from there, at age 30 years, was appointed professor and chairman of the Department of Radiology at Stanford.3,4

There, Kaplan turned his attention to human lymphomas. When he arrived at Stanford, the department of radiology had three nonshock-proof machines for radiography and another for fluoroscopy, which had bare wires conducting voltages as high as 200,000 volts, which would dangle above the patient.3

In his third year at Stanford, he met Edward Ginzton, a physicist, who with another physicist William Webster Hanson developed the linear accelerator for experimental physics. Aware of the shortcomings of the prevailing radiological treatment of Hodgkin and other lymphomas, Kaplan realized the need for a new kind of radiotherapy.

This new technology had to be deeply penetrating, skin sparing, and capable of delivering a precise beam to pinpoint small tumors or have a wide field to irradiate an entire regional lymphatic system. Kaplan proposed the development of a medical linear accelerator to treat cancer patients, and this suggestion led to the production of the first medical linear accelerator in the Western Hemisphere, specifically for radiotherapy. Today, linear accelerators are standard hospital equipment, and their development was a major technical advance that empowered radiotherapy.3,4

Together with Saul Rosenberg, and others, Kaplan also devised more aggressive radiation protocols.5These protocols used high-dose regional lymph node radiation2therapy to fight the disease, and at the time of Kaplan’s death, the disease could be cured in more than 80% of cases through various combinations of chemotherapy and radiation.3,5,6In an obituary for Kaplan, Malcolm A. Bagshaw, MD, who was then the chairman of the department of radiology at Stanford, described extended-field radiation treatment of Hodgkin disease as representing one of the major treatment advances in cancer therapy of the 20thcentury.4

In 1959, Kaplan was one of the founding members of the American Society for Therapeutic Radiology and Oncology. His prominence led him to chair a national committee to discuss the problem of training for radiotherapists. Through this committee, he almost single handedly formulated research and clinical training programs for radiotherapists.3,4

In tandem with his work on Hodgkin lymphoma and treating patients, he continued his work on mouse lymphomas. His research in this field has been described as a milestone in the understanding of the biology of the malignant lymphomas.3He brought with him to Stanford, a strain of mice (C57BL) in which thymic lymphomas could be easily induced with a few exposures to nonlethal doses of radiation. Kaplan and colleagues discovered that the effect could be blocked by either shielding a small volume of the bone marrow during the radiation exposure or by injecting nonirradiated bone marrow cells after the mice had been irradiated.3

During the course of further investigations Kaplan and a colleague, Miriam Lieberman, came to the conclusion that a virus was responsible for the malignancy following the irradiation. Subsequently, they characterized the unique oncogenic virus (Rad Lv).7-9Kaplan was convinced that laboratory and clinical research needed to be integrated to improve patient care. His determination to initiate and maintain a vigorous research program focusing on radiation cancer viruses, resulted in the opening, in 1975, of his Cancer Biology Research Laboratory. Here, up until his death, he participated in all aspects of his very active research program.3,4

Kaplan developed one of the most outstanding radiology departments in the world. He authored 490 papers, as senior author on the majority, sharing authorship with 295 coauthors, and wrote three textbooks.3,4

When asked how he would like to be remembered, Kaplan said, “I’d like to be remembered for my accomplishments that stand the test of time, such as the work on Hodgkin's disease. I’d like to be remembered as the codeveloper of the medical linear accelerator for cancer treatment, and for developing not just the machine, but the standards for its use. I’d like to be remembered for my service on the National Cancer Advisory board in 1960. These are my accomplishments.”4

References:

1. TargetedOnc.com. New treatments for Hodgkin lymphoma coming to clinics. http://www.targetedonc.com/conference/hematologic-malignancies-2015/new-treatments-for-hodgkin-lymphoma-coming-to-clinics. Accessed August 20, 2015.

2. Kaplan, HS. The radical radiotherapy of regionally localized Hodgkin's disease.Radiology. 1962;78:553-561.

3. Bagshaw MA, Jones HE, Kallman RF, Kriss JP. Memorial resolution Henry S. Kaplan (118-1984). Stanford Historical Society. http://histsoc.stanford.edu/pdfmem/KaplanH.pdf. Accessed August 20, 2015.

4. Bagshaw MA. A tribute to Henry Seymour Kaplan, MD 1918-1984.Cancer. 1985;55:2035-2036.

5. Rosenberg SA, Kaplan HS. Hodgkin's disease and other malignant lymphomas.Calif Med. 1970;113:23-38.

6. CancerProgress.net. Oncology luminaries: Dr. Henry S. Kaplan (1918-1984). http://cancerprogress.net/node/2091. Accessed August 22, 2015.

7. Lieberman M, Kaplan, HS. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice.Science. 1959;130:387-388.

8. Lieberman M, Haran-Ghera N, Kaplan HS. Potentiation of virus leukenogenesis in C57BL Mice By X-irradiation or urethane.Nature.1964;203:420-422.

9. Haran-Ghera N, Lieberman M, Kaplan HS. Direct action of a leukemogenic virus on the thymus.Cancer Res. 1966;26:438-442.