How Henry Kaplan Changed the Fate of Hodgkin Lymphoma
The list of cancers for which we have developed successful therapies, where cure rates far exceed failures and we can unequivocally say, “We done good,” is unfortunately small. Childhood acute lymphoblastic leukemia is one. Testicular cancer is another. And Hodgkin lymphoma was probably the first cancer that was cured with some regularity, even when it was not localized.
For those of us who completed our oncology training within the past decade or two, it is difficult to appreciate the universal mortality associated with a diagnosis of Hodgkin lymphoma in the first half of the 20th century. In her book, Henry Kaplan and the Story of Hodgkin's Disease, Charlotte DeCroes Jacobs, MD, Professor of Medicine in the Division of Oncology at Stanford University School of Medicine, takes us there, starting with the almost forgotten characterization of the disease by Thomas Hodgkin in 1832, moving us quickly to Dorothy Reed's description of the cell that has become the sine qua non of the diagnosis, and her challenge to the theory that it represented a form of tuberculosis, in 1902, and the publication in the same year of William Allen Pusey's application of Roentgen's cathode rays to the neck lymph nodes of a four-year-old boy with Hodgkin lymphoma, with subsequent regression of the nodes.
Yes, it's true—the first successful therapies, and ultimately cures—for lymphoma were at the hands of radiation oncologists, albeit with crude technology, limited dosing (50-75 kilovolts), and universal skin burns. This improved in the 1930s, with the Coolidge tube and fractionated radiotherapy, but it wasn't until the linear accelerator was applied that Hodgkin's lymphoma had met its match. And much of the use of this technology can be credited to Henry Kaplan.
Henry Seymour Kaplan was born in Chicago in 1918, the first son to Jewish immigrants from Kiev. Although raised by his ambitious mother to be a “great man of the world”—to compensate intellectually for what she perceived to be a grossly disfigured hand—his was not an easy childhood. He had few friends and limited social skills. When Henry was 16, his father died of lung cancer, and the family almost became destitute with the loss of income.
As a result, Henry worked constantly when he wasn't attending the University of Chicago or Rush Medical Center, and vowed to dedicate his life to curing the cancer that had killed his father. Interestingly, some of the other “great men and women” who would play major roles in curing Hodgkin lymphoma—Vera Peters, Saul Rosenberg, and Vince DeVita, among others—were described as being similarly brilliant, driven, and the first to attend college in their families. Perhaps to these scientists and clinicians, they saw in the attempt to cure cancer the same struggle they had already faced to overcome socioeconomic adversity, and it was thus familiar ground. Kaplan went on to the University of Minnesota for advanced radiology training, and then to Yale University, where he conducted research on radiation-induced leukemias and lymphomas in mice, finally landing at the National Cancer Institute to continue his work in carcinogenesis. In 1948, he was recruited by Stanford University to become head of radiology, which included radiation oncology.
At Stanford, Kaplan built what would become the premier radiation oncology program in the country. He recruited faculty, some of whom would go on to become Nobel Prize winners, and used his formidable personality to secure funding, laboratory, and office space.
In her acknowledgments, Jacobs thanks Kaplan's widow, Leah, who instructed the author to “portray the man as he was, not a saint.” Kaplan was not universally beloved, and many of the book's pages are devoted to his political battles at Stanford; his failure to recognize Peters for her contributions to establishing the curability of Hodgkin lymphoma and to accurately staging the disease; and to his disrespect of Rosenberg, probably his greatest faculty recruit.
Kaplan also convinced Stanford physics professor Edward Ginzton to use his six-million-volt linear accelerator, a technology developed by the British as radar to detect approaching enemy aircraft, for medical therapeutic purposes. Kaplan's genius was in bringing the accelerator to the clinic and demanding that it be maneuverable, to maximize flexibility in designing therapeutic fields. The first patient, an infant boy with a retinoblastoma, was successfully treated in January 1956.
The book takes us through the Stanford L, S, and C protocols, and deftly weaves patient stories into the text, even starting the book with a moving account of a patient reunion at Stanford to celebrate 20 years of progress in Hodgkin's Disease.
While Kaplan's colleagues often took issue with his authoritarian approach to science and leadership, his patients adored him, and he was a gifted clinician. It was Rosenberg who insisted on studying different therapeutic approaches methodically, via clinical trials, whereas Kaplan wanted to treat based on instinct.
This was an exciting time, and for those of us who were not yet practicing medicine at the times of the Rye and Ann Arbor meetings, or when DeVita first presented his findings on combination chemotherapy for Hodgkin lymphoma at the American Association for Cancer Research in 1965, we can feel the tension, and disbelief, in the meeting rooms—Hodgkin lymphoma was becoming curable, even most of the time.
Also Sensitive to Collateral Damage, Both on Doctors & Patients
The book is also sensitive to the collateral damage of this successful therapy, both on doctors and patients. It took Kaplan five years to have a child, likely because of radiation-induced infertility, and ultimately he died of lung cancer—a non-smoker, he attributed it to his exposure to radon paste as a resident in Chicago.
Other radiation therapists who died of occupational exposures in a non-OSHA era are also discussed, as was the impact Kaplan's scientific focus had on his family: Leah called Henry's laboratory his “mistress,” and his relationship with his son and brother were distant at best.
Patients suffered side effects to the new therapies, the most serious of which were secondary malignancies, considered uniformly deadly. We empathize with both patients and doctors when these cancers come to light, as they were equally devastated.
While the book at times lapses into the minutiae of university politics and can be somewhat redundant, it is a good read—a great read for those of us who trained in an era of evidence-based medicine, and want to learn what it was like to actually create the evidence, and for the first time make a difference in our patient's lives.