ORLANDO, Florida It is not the wild west, but there are significant variations between treatment centers in supportive care for children who have undergone hematopoietic stem cell transplants, and some of the variations can negatively affect the results.That was the central theme of a session at the annual transplant and cell therapy meeting here that focused on divergent practices among US transplant centers. UU. In relation to diet, when it is safe to return to school and when to revaccinate children who have reconstituted immune systems.

Food for thoughtFor example, the neutropenic diet, which is still used in some centers, is a remnant from the first days of bone marrow transplants, when the risks were not well understood and where transplant recipients were protected in aseptic or sterile environments, said Cynthia Taggart, RD, of the Cincinnati Children's Hospital Medical Center in Ohio.

"The history of the neutropenic diet is based on logic, prudent practice and reasonable theoretical logic, but there is no evidence to support this idea," he said.

The decidedly Spartan neutropenic diet does not allow fresh fruits or vegetables, requires that meat and fish be cooked at a reasonable price and does not allow cold meats or shared foods."In the last 20 years there has been a lot of research showing that we don't have a common name for the neutropenic diet, we really don't know when to start the neutropenic diet, and then we often have our own opinions on what we should allow our patients to have or not have, "said Taggart.He noted studies comparing diet regimes that found no advantage or even possible detriments to a neutropenic diet compared to a more forgiving diet based on food safety principles, such as cooking meat at a minimum temperature of 165 F (73.9 C).

Cynthia Taggart

For example, a retrospective study of 726 patients at Northwestern Memorial Hospital in Chicago, Illinois, where the neutropenic diet was discontinued in 2006, showed a higher rate of infections, especially after grafting among HSCT recipients who ate a neutropenic diet in comparison with those who ate a general hospital diet. Patients with neutropenic diet had more frequent diarrhea and urinary infections and an increase in graft-versus-host disease grade 2-4 (GVHD), although there were no significant differences in survival rates. (Biol Blood Marrow Transplant. 2012; 18: 1385-1390).

In 2019, Taggart and his colleagues published the results of a controlled study before and after in pediatric patients and consecutive young adults who underwent HSCT at their center in 2014.From January to June of that year, all patients underwent a traditional neutropenic diet, and from July 1 until the end of the year they received a modified bone marrow transplant diet (BMT). The researchers evaluated both subjective measures (e.g., food cravings, limiting factors for eating and quality of life) and objective measures (e.g., rates of bloodstream infections, GVHF, mortality, days of total parenteral nutrition (TPN) and norovirus infections) (Blood marrow transplant Biol. 2019; 25: 1382-1386).The patients were happier with the less restrictive diet, and the researchers found that there were no significant differences in the first 100 days in any of the objective measures mentioned above, "so it made no difference in what diet they were and improved satisfaction of the patient when he received a diet based on food safety instead of a neutropenic diet, "said Taggart.At its center, patients and caregivers receive information on food safety principles, including cleaning hands, utensils and food preparation surfaces with hot soapy water before and after handling food; avoiding cross contamination of ready-to-eat foods by keeping them separated from raw meats; cook food at safe internal temperatures as recorded on a food thermometer; and quickly refrigerating food.

"It is time to get away from the neutropenic diet and work to improve the quality of life of our patients to improve their oral intake while undergoing a transplant," he said.

Back to school?There is no clear consensus on the ideal time to return to school for transplant recipients, said Neel S. Bhatt, MBBS, MPH, of the Fred Hutchinson Cancer Research Center in Seattle.

For example, the National Medical Marrow Donor Program states that "depending on the type of transplant and recovery, a child may return to school with several months of transplant. Other children may return to school a year or more after the transplant. ".

In contrast, the Pediatric Blood and Marrow Transplant Consortium states that "in general, once T cells grow back and function properly, all isolation precautions can be stopped (and) your child can return to work / school. ".

Dr. Neel Bhatt

Bhatt noted that a cross-sectional survey of the directors of transplant centers of the Center for International Research on Blood and Marrow Transplants (CIBMTR) asking if their centers had a standard operating procedure (SOP) for the back-to-school process showed that , of the 45 directors of pediatric centers that responded, 28 had a POE and the remaining 17 did not.

Of those surveyed with a SOP back to school, one center said there is a minimum of 9 months before an allogeneic transplant recipient can return to school, a second suggests waiting 6 to 12 months after an allogeneic or autologous transplant, and a third reported that he recommended a minimum of 3 months after an autologous transplant, 6 months after an allogeneic transplant of related donors and 12 months after a transplant of unrelated donors.

In addition, the centers varied according to the functional measures that were used to allow the return to school, such as suspending or decreasing medications against GVHD, CD4 cell count, absolute lymphocyte count and other factors such as psychological preparation and fatigue levels

Helping children reintegrate into academic settings can include workshops for school staff that include conferences, group discussions and presentations or hospital visits, and developmentally appropriate peer education programs, with the aim of improving support for The boy who returns.

"Returning to school is an important milestone for survivors after completing therapy. This process of returning to school is complex, and the support of all stakeholders is essential for a successful transition," Bhatt summarized.

Shot in the armWhen it comes to the decision to revaccinate children who have undergone HSCT and with what vaccines, "variability is the norm," said Donna J. Curtis, MD, MPH, of the University of Colorado School of Medicine and the Colorado Children's Hospital in Aurora.

He cited an investigation that showed that before the advent of vaccination guidelines, individual transplant centers created their own, and that even with the guidelines, providers choose to deviate in terms of when to vaccinate, what to give and the rationale for those decisions. .

"Why do we deviate from the guidelines? I want to point out, as everyone knows, that our patients are really complicated," Curtis said.

Dr. Donna Curtis

He said there are both real and perceived gaps in the guidelines that can lead to centers being diverted or ignored, he said, as the populations of more homogeneous patients included in older studies used as evidence; missing data on newer technologies, such as umbilical cord blood transplants, depleted T-cell grafts, chimeric antigen receptor (CAR) T-cell therapy and newer biological agents; and the reality that vaccine recommendations are updated regularly, with new vaccines frequently in practice.

In addition, doctors do not always rely on the guidelines because they change so often, Curtis said, noting that the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC / APIC) issues updated guidelines (a often with changing recommendations) annually.

Despite the small variations in the recommendations on time, however, the guidelines issued by major international organizations are very similar, Curtis emphasized. She specifically mentioned the guidelines of the European Conference on Infections in Leukemia (ECIL) of 2017, published in 2019; the 2013 clinical practice guide of the Infectious Diseases Society of America (IDSA) for immunocompromised host vaccination; and a 2011 report of the International Consensus Conference on clinical practice in chronic IBD on the vaccination of allogeneic HSCT receptors.

As an example, the ECIL guidelines recommend that children who have undergone an allogeneic or autologous HSCT receive the Haemophilus influenzae type b (Hib) vaccine that begins no earlier than 3 months after HSCT, and the Neisseria meningitidis and DTaP vaccine ( diphtheria, tetanus, and pertussis) (but not the Tdap vaccine) no later than 6 months after HSCT. For other vaccines, there are different recommendations regarding the type of transplant (autologous or allogeneic).

In an interview with Medscape Medical News, Curtis recommended that transplant centers comply with the guidelines of bone marrow transplant organizations whenever possible.

"I think those should be our authorities, the reliable guidelines that we should use as a basis, but because there are gaps in them, each center will have to give its answer on how to apply them," he said. said.

Quality of care at stakeSession assistant Christopher E. Dandoy, MD, MSc, of the Cincinnati Children's Medical Center, told Medscape Medical News that variations in practice can affect the quality of care.

"Unless there is evidence to support a & # 39; true North & # 39; regarding these different processes and practices, it leads us to interpret what we believe we should be doing, and the wide variation in attention leads absolutely to different results, "he said.

"My idea is that we can learn from each other, take advantage of the opportunity to learn what other centers are doing, share data without problems, especially about the important results for families, such as returning to school, that means everything to a child. Therefore, we should be more cognitive and make sure that if there is no evidence, we try to find what works, "he said.

Zachariah DeFilipp, MD, of the Cancer Center of the Massachusetts General Hospital in Boston, told Medscape Medical News that practice variations such as those described in the session are also common to the practice of HSCT in adults.

"It's also something we've been thinking about," he said. "Many of the traditional transplant recommendations for lifestyle problems have been very conservative, which means that usually when there is a question about & # 39; can I go back to work or go out in public? & # 39 ; the default has been to say & # 39; No & # 39; "

"There is probably little real published evidence to justify those recommendations," DeFillip explained, "and when they were made, we were in a different era of supportive care for our transplant patients. Maybe those were the right decisions at that time, but as transplant has evolved, we probably don't need to be so strict with patients, because some of these recommendations can really affect the patient's quality of life after transplant. "

Taggart did not report a source of funding. Bhatt reported the support of the Seattle Children's Research Fund of CBDC Research & # 39; s. Curtis did not reveal a source of funding. Taggart, Bhatt, Curtis, Dandoy and DeFillip have not disclosed relevant financial relationships.

ASTCT and CIBMTR 2020 cell therapy and transplant meetings: session presented on February 20, 2020.

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