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Dr. Rai and the B cells; Dr. Chiorazzi and the B-cell receptors

Dr. Rai and the B cells; Dr. Chiorazzi and the B-cell receptors

Kanti Rai, MD, still remembers the life and quick death of a 3-year-old girl from Port Washington, Long Island, diagnosed with acute lymphocytic leukemia. It was almost 50 years ago when he was chief resident in pediatrics at North Shore Hospital, Manhasset, New York. He was shaken to his core. His mentor, Arthur Sawitsky, MD, suggested that he might try research, which is easier on the heart.

And that is when he walked into the laboratory to try to figure out leukemia, and where he met a new breed of patients —mostly older people who were either dying or living out their lives with chronic lymphocytic leukemia (CLL).

By that time, he was working at the Brookhaven National Laboratory under the direction of Eugene Cronkite, MD. Dr. Rai remembers seeing three of Dr. Cronkite's patients: One who had CLL for 15 years and would show up for his annual exam in top form; another who was shuttled into the laboratory by wheelchair and only lived 1.5 years after his diagnosis; and the third who fell somewhere in the middle: He was sick but living for years with his symptoms.

Dr. Rai asked Dr. Cronkite, who was older and a full head taller, why there was such a difference in patients with the same disease. "That is for you to figure out, my boy," he said. And so it was that Dr. Rai asked for all the charts from every CLL patient seen at Brookhaven—around 80 patients—and tried to get a sense of the biology of the disease.

Staring at the wall

He made a table of each patient and pinned the tables up on the wall. And he stared. And stared. After a year or so of wall-watching with not much insight, he identified the 25 patients who were doing well and pinned their tables to one wall; those who were doing poorly or who had died were pinned on another; and on the final wall were the tables of the remaining patients.

"Suddenly," he said. "It hit me. The bone marrow of the people who died was completely compromised. They were all anemic, and their platelet counts were low. And these characteristics were there from the get-go, from the time of diagnosis." Indeed, those with normal levels were living longer. "The preservation of bone marrow became the key to predicting the amount of disease," he said.

Remember that this was before scientists knew much of anything about T cells or B cells. Soon after, CLL became known as a B-cell disease. In 1975, five years after the pin-up epiphany, Dr. Rai's findings were published in the journal Blood. By then, he was an oncologist at Long Island Jewish Medical Center in New Hyde Park (now part of the North Shore Health System in Manhasset), where he still practices in the Division of Hematology-Oncology, and things began falling into place for the disease and its patients.

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