100 Papers, 10 Years: Cancer Transplant Pioneers Model 'Team Science'

Helen Leask, PhD

January 24, 2022

Two close colleagues at New York's Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic's impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Giralt said: "We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences."

Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Giralt and Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

"People who are multilingual have different roles [as much as] different languages," said Perales. "When I'm in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins."

When it comes to clinical science, however, English is the language of choice.

Global Leaders in HSCT

Giralt and Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy 'conditioning,' then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Giralt and Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Giralt's publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Perales, Giralt and their coauthors concluded that the data provided "strong support" for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Giralt and Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

Impact of the Pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Giralt. He and Perales realized that they needed to be "thoughtful and careful" about which studies to continue. "For example, the CD-34 selection trials we did not close because these are our workhorse trials," Giralt said. "We have people we need to treat, and some of the patients that we need to treat can only be treated on trial."

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

"We were living through a critical time, but that doesn't mean we [aren't] obligated to continue our mission, our research mission," said Giralt. "It really is team science. The way we look at it ... there's a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we're both very much [working on] how can we improve what we call 'the Memorial way' of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn't do myeloma [like me]. So in those two areas, we're helping develop the junior faculty in a different way."

Something More in Common

Right from the start, Perales and Giralt also shared a commitment to mentoring. Since 2010, Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

"[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program," said Giralt.

He cited Perales' track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Perales seamlessly stepped into Giralt's shoes, while Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Perales said: "The key aspect [of these promotions] is the fantastic working relationship that we've had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it's this ability that we've had to work together and that relationship of trust, which has been key."

"Sergio is somebody who lifts people up," Perales added. "Many people will tell you that Sergio has helped them in their career. ... And I think that's a lesson I've learned from him: training the next generation. And [that's] not just in the U.S., but outside. I think that's a key role that we have. And our responsibility."

Asked to comment on their 100th-paper milestone, Perales firmly turned the spotlight from himself and Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: "This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK."

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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