Rai Helped Launch an Age of Innovation in Leukemia

OncologyLive, Vol. 19/No. 15, Volume 19, Issue 15

Partner | Cancer Centers | <b>Northwell Health</b>

Kanti R. Rai, MD, has been a leader in the diagnosis and treatment of chronic lymphocytic leukemia for more than 40 years. He was honored in the Hematologic Malignancies category with a 2017 Giants of Cancer Care® award.

Kanti R. Rai, MD

Her name was Laurie, she was 3 years old, and her love of life touched his heart. ”She was a bright, sprightly girl, walking with a hop, skip, and a jump,” recalled Kanti R. Rai, MD. “I saw this young couple who had been told 3 hours earlier that their daughter might have leukemia, and they walked slumped over, steps behind her.”

The year was 1958, and at the time, acute childhood leukemia was a death sentence. Rai, then chief resident in pediatrics at North Shore University Hospital in Manhasset, New York, was about to meet his first patient with the illness. Along with his attending hematologist, Arthur Sawitsky, MD, he examined Laurie and later learned that she had the fatal disease.

“When I heard from my teacher that this child would be dead in 6 months, I thought this teacher of mine was a horrible, heartless bastard,” Rai said nearly 60 years later. “[In fact], he was none of that—he was very experienced and a kind human being, and he was telling me what the reality was.”

It was a terrible era for pediatric patients with cancer, and leukemia research was just beginning in Boston under the leadership of Sidney Farber, MD, Rai noted. At that time, 90% of children diagnosed with acute childhood leukemia died within 6 to 18 months.

The news devastated Rai, who bonded with Laurie during her subsequent readmissions until her death 7 months later. Noting his reaction, Sawitsky suggested Rai pursue a leukemia-themed fellowship after residency. “I thought that was very good,” Rai says, “because I wanted to do something and learn about leukemia.” And indeed he did.

He eventually developed the Rai staging system, which categorized the treatment and classification of chronic lymphocytic leukemia (CLL), helping to revolutionize how to best treat and help patients.

Today, Rai helps lead the CLL Research and Treatment Program at the Feinstein Institute for Medical Research, where he also is a professor at the Karches Center for Oncology Research, and he serves as a professor of medicine and molecular medicine at Hofstra Northwell School of Medicine, all part of Northwell Health in Great Neck, New York. He has spent more than 50 years treating patients, training young physicians, and conducting research, and he has published his findings in more than 200 original papers and book chapters.

Family Ties

Above all, Rai said, he can’t imagine doing anything other than what he has already done in medicine. “I have lived long enough, and I should be grateful for the opportunities I have had,” he said. “I am truly a blessed person. I love what I do—it gives me a sense of purpose: doing something which is socially helpful and good.For Rai, born and raised in Jodhpur, India, in the 1930s and ’40s, the desire to help young children was ingrained at an early age. One of 8 children living in an area “where the standard of living was low,” Rai said, he was raised by his father, an officer in the local government, and his mother, a homemaker devoted to her family. Love was plentiful even if money was not.

“Jodhpur was a backward community, but in terms of values and standards, it was good,” he said. “My siblings and I had all the give-and-take that is the usual universal experience, and my parents took care of everything. College, higher education—that was their mission and pride.” His younger sister and his older sister’s daughter also became doctors. “I was not the exception.”

At about age 8, Rai spent a month one summer with his uncle, Vridhi Rai, a charismatic local doctor based in a village about 60 miles from Rai’s hometown. One warm morning, Rai awoke and saw, on the street outside, “a line of camels with their drivers, who had been sent for my uncle, because somebody in those families had been sick and needed the doctor to come to their house.” His uncle would head out early to see patients before attending his regular daily clinics.

At his request, Rai accompanied his uncle on those house calls, waiting outside with the camels and drivers. “Word would go out in the house that the doctor’s son was outside with the camel, and they would come and invite me inside the house,” he recalls. “They treated me like royalty and would give me goodies. I was treated well.”

The snacks aside, Rai was most impressed with his uncle’s approach and focus. “I watched him deal with the people, not with artificial kindness or compassion, but genuine empathy,” he said. “He took care of them without any regard for how poor or how well-to-do they were. I saw children with malnutrition, infection—young children suffering—and he would care for them.”

Rai realized he wanted to help people in the same way. “I said [that] I would like to follow in my uncle’s footsteps and provide service,” he said. “And…if I [had] children, my children would be treated royally, too. It was a win-win for everyone!”

Today, family continues to be a strong focus, and Rai readily cites his immediate family’s support that helped sustain him throughout the decades. “I would not be anywhere if not for the trust and support and love of my dear wife Susan with whom I will celebrate 50 years of marriage in 2018,” he said.

The Path from India to New York

They have 2 children: Samantha, who works as a family medicine physician with her husband, Jay Zaslow, MD, at the Open Door Family Medical Center in Mount Kisco, New York; and Josh, a software engineer for the educational software company, Quizlet, who lives in San Francisco, California, with his wife, Cici, a preschool teacher. The elder Rais also enjoy the company of their grandchildren, Ella and Mira.Rai attended high school and Jaswant College, both in Jodhpur, and ultimately went to Jaipur, 150 miles away from his hometown, to attend SMS Medical College. He graduated in 1955, but yearned to see more of the world.

“I wanted to travel, but I knew my parents could not afford to pay for it,” he said. He learned about and was chosen for an overseas opportunity that offered internships and residencies in the United States for early-career physicians based in countries such as Pakistan, Sri Lanka, and India, because there weren’t enough US-based candidates to fill the open seats.

“Where would you like to go?” the selection committee asked him. Rai had no idea, other than his interest in pediatrics. From a list of US hospitals, he chose Lincoln Hospital, based in the Bronx. “It was eeny, meeny, miny, mo,” he said. “I knew I wanted to come to New York, because I’d seen pictures of neon lights in Times Square, and I knew the name Lincoln. I thought, ‘How could I go wrong?’”

After his residency training, Rai became chief resident in pediatrics at North Shore University Hospital. It was there that he met Sawitsky, who would become one of his most revered mentors. “He was an outstanding doctor and very research-oriented, and he guided me and taught me hematology, taking me by the hand when this little girl came into my life,” Rai said. “I want to absolutely recognize [that] if not for his guidance, mentorship, and teachings, I would be lost someplace— God knows where.”

After performing a fellowship in hematology and nuclear medicine at Long Island Jewish Hospital, Rai began working with Eugene P. Cronkite, MD, a scientist at Brookhaven National Laboratory in Upton, New York. Cronkite studied the proliferation rate of leukemia cells in people, comparing the activity with normal blood cell counts in bone marrow using newly developed tracer technology with tritiated thymidine to assess new cell birth.

“It was the 1950s, and it was pioneering,” Rai said. “It was hard work on my microscope, taking blood and bone marrow samples and spending hour after hour on each patient sample, working on them for months. At the time, it was heady work—we would work and talk and fight. It was an exciting period.”

A Breakthrough on Cubicle Walls

Rai noted that today, such work can be done reliably and quickly with the press of a button. “But do I have any sense of embarrassment or failure that today, it is child’s play? No, at the time, this was the epitome of technological advancement.”Brookhaven was where Rai would eventually determine how to better treat patients with leukemia. Throughout Rai’s life, his mentors advised him to grab opportunities as they arose, “to keep my eyes open and to take chances—see where it takes you,” he said, citing Yogi Berra: “If you see a fork in the road, take it.” Rai opened himself up to figuring things out.

That philosophy led to what has been called Rai’s breakthrough and major contribution to the oncology world: the development of the Rai staging system. “[That] brought me fame, but I think it was the training and the opportunities [Sawitsky and Cronkite] provided that made it possible to see the light,” Rai said.

At Brookhaven, Rai noticed that some patients with CLL, typically a disease of the elderly, would die within a few years of diagnosis, while others kept returning to the clinic for 15 to 20 years with the same diagnosis but no lingering health issues. “I asked Dr Cronkite, ‘What is going on? Are we making a diagnosis error, that some people are doing so very differently?’ He looked at me, put his hand on my shoulder, and said, ‘That is for you to figure out.’ That challenge sank into me.”

Rai began to scrutinize the medical records of all the people in the clinic who had CLL and started charting the summaries of 65 to 70 people, along with their medical histories, on the walls of his cubicle using a pad of yellow lined paper. “I stared at them, and nothing came through,” he said. “Then I had the idea to put all the good prognosis people on one wall, then those dying or dead on the opposite wall, and everybody else on the middle wall. This was in the 1960s, so there was no computer to use or any fancy [software] that we have today. I still remember that people passing through my cubicle started to whisper, ‘This Indian guy is crazy, always staring at the walls.’”

But over time, Rai worked it out. “All the people who died relatively quickly were different in that their hemoglobin red cells and/or platelets were low from the get-go,” he said. “Those who had normal counts but the same disease were on the opposite wall, their bone marrow functioning was seriously compromised, and their outlook was poor. This was my aha moment.”

His results took a few months to summarize and confirm, but when he shared his findings with his mentors, they were impressed: “Cronkite said, ‘I think you’ve got something there, my boy.’” The journal Blood published his paper, “Clinical Staging of Chronic Lymphocytic Leukemia,” coauthored by Sawitsky, Cronkite, and 3 other colleagues in 1975. More than 40 years later, his work is the basis for diagnosing and staging CLL in the United States.

“That made it possible for other people to become interested in how clinicians and researchers could get a handle on this disease,” he says. “Before, it was an amorphous, boring disease. The staging made it possible to attack it in a sane, logical manner that was not possible before.”

Rai is quick to share the recognition, even though it is his name that the staging system carries. “I am given a lot of credit today, but I saw [that] my idea was simple and got the ball rolling. The next generation of people, my active colleagues, deserve the credit for subsequent advances.”

These potential innovations, such as the role immunology will play in future cancer treatment, are what excite Rai. “We have by no means reached a cure, but these immunological approaches are opening doors where we can eventually say that ‘I would like to plan a strategy that might lead us to a cure,’” he said. “Before, we would say ‘That could lead us to a better remission.’ Now we are closer to eliminating residual disease. I would not have dreamed that was possible in my lifetime.”