Variability the Norm for Support of Pediatric HSCT Patients

Neil Osterweil

March 02, 2020

ORLANDO, Florida — It's not the wild West, but there are significant variations across treatment centers in supportive care for children who have undergone hematopoietic stem cell transplants, and some of the variations may adversely affect outcomes.

That was the central theme of a session at the Transplantation & Cellular Therapy annual meeting here focusing on divergent practices among US transplant centers concerning diet, when it's safe to return to school, and when to revaccinate children who have reconstituted immune systems.

Food for Thought

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

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

The decidedly Spartan neutropenic diet allows no fresh fruit or vegetables, requires meat and fish to be cooked to a fare-thee-well, and does not allow deli-counter meats or shared foods.

"In the last 20 years there has been a lot of research that shows that we don't have a common name for the neutropenic diet, don't really know when to start the neutropenic diet, and then we often have our own opinions about what we should allow our patients to have or not have," Taggart said.

She pointed to studies comparing diet regimens that found either no advantage or even potential detriments to a neutropenic diet compared with a more lenient diet based on principles of food safety, such as cooking meat to 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 engraftment among HSCT recipients who ate a neutropenic diet compared with those who ate a general hospital diet. Patients on the neutropenic diet had more frequent diarrhea and urinary tract infections, and an increase in grade 2-4 graft-vs-host disease (GVHD), although there were no significant differences in survival rates. (Biol Blood Marrow Transplant. 2012;18:1385-1390).

In 2019, Taggart and colleagues published results of a controlled before-and-after study in consecutive pediatric and young adult patients who underwent HSCT at their center in 2014.

From January through June of that year, all patients were placed on a traditional neutropenic diet, and starting on July 1 through the end of the year were given a modified bone marrow transplant (BMT) diet. The investigators evaluated both subjective measures (eg, food cravings, limiting factors to eating, and quality of life) and objective measures (eg, rates of bloodstream infections, GVHF, mortality, days of total parenteral nutrition (TPN) and norovirus infections) (Biol Blood Marrow Transplant. 2019;25:1382-1386).

Patients were happier with the less restrictive diet, and the investigators discovered that there were no significant differences in the first 100 days in any of the objective measures mentioned before, "so it didn't make a difference which diet they were on, and it improved patient satisfaction when they were receiving a food safety-based diet over a neutropenic diet," Taggart said.

At her center, patients and caregivers are educated about the principles of food safety, 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 separate from raw meats; cooking foods to safe internal temperatures as registered on a food thermometer; and promptly refrigerating foods.

"It is time to move away from the neutropenic diet and to work on improving our patients' quality of life to improve their oral intake as they undergo transplantation," she said.

Back to School?

There is no clear consensus on the ideal timing for returning to school for transplant recipients, said Neel S. Bhatt, MBBS, MPH, from the Fred Hutchinson Cancer Research Center in Seattle.

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

In contrast, the Pediatric Blood and Marrow Transplant Consortium states that "in general, once the T-cells grow back and are functioning properly, any isolation precautions may be stopped, [and] your child may return to work/school."

Dr Neel Bhatt

Bhatt noted that a cross-sectional survey of transplant center directors from the Center for International Blood and Marrow Transplant Research (CIBMTR) asking whether their centers had a standard operating procedure (SOP) for the return-to- school process showed that, of the 45 pediatric center directors who replied, 28 had such an SOP and the remaining 17 did not.

Of the respondents with a school-return SOP in place, one center said that there is a minimum of 9 months before an allogeneic transplant recipient would be allowed to return to school, a second suggests waiting 6 to 12 months after either an allogeneic or autologous transplant, and a third reported recommending a minimum of 3 months after an autologous transplant, 6 months after a related-donor allogeneic transplant, and 12 months after an unrelated-donor transplant.

In addition, centers varied according to which functional measures were used to allow a return to school, such as being off or tapering of anti-GVHD medications, CD4 cell counts, absolute lymphocyte counts, and other factors such as psychological readiness and fatigue levels.

Helping children reintegrate into academic settings may involve workshops for school personnel that include lectures, group discussions and presentations or hospital tours, and developmentally appropriate peer-education programs, with the goal of improving support for the returning child.

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

A Shot in the Arm

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

She cited research showing that before the advent of vaccination guidelines, individual transplant centers created their own, and that even with 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 you all know, that our patients are really complicated," Curtis said.

Dr Donna Curtis

There are both real and perceived gaps in the guidelines that may lead to centers deviating from or ignoring them, she said, such as the more homogeneous patient populations included in older studies used as evidence; missing data on newer technologies such as umbilical cord blood transplants, T cell-depleted grafts, chimeric antigen receptor (CAR) T-cell therapy and newer biologic agents; and the reality that vaccine recommendations are updated regularly, with new vaccines frequently coming into practice.

In addition, clinicians don't always trust guidelines because they change so frequently, Curtis said, noting that the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (CDC/APIC) issues updated guidelines (often with changing recommendations) annually.

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

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

In an interview with Medscape Medical News, Curtis recommended that transplant centers adhere to guidelines from bone marrow transplant organizations whenever possible.

"I think that those should be our authorities, the trusted guidelines that we should use as a foundation, but because there are gaps in them, each center is going to have to come up with their answer as to how to apply them," she said.

Quality of Care at Stake

Session comoderator Christopher E. Dandoy, MD, MSc, from Cincinnati Children's Medical Center, told Medscape Medical News that practice variations may affect the quality of care.

"Unless there's evidence to support a 'true North' as far as these different processes and practices, it leads to us interpreting what we think we should be doing, and the wide variation in care absolutely leads to different outcomes," he said.

"My thought is that we can learn from each other, take the opportunity to learn what other centers are doing, share data seamlessly, especially about important outcomes for families such as going back to school — that means everything to a kid. So we should be more cognitive and make sure that if there isn't evidence, then we try to find what's working," he said.

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

"It's something we've been thinking about as well," he said. "A lot of traditional transplant recommendations for lifestyle issues have been very conservative, meaning that typically when there's a question about 'Can I go back to work or out in public?' the default has been for us to say 'No.' "

"There is probably little true 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 as strict with the patients, because some of these recommendations can really impair a patient's quality of life after transplant."

Taggart did not report a funding source. Bhatt reported support from the Seattle Children's CBDC Research Pilot Funds Program. Curtis did not disclose a funding source. Taggart, Bhatt, Curtis, Dandoy, and DeFillip have disclosed no relevant financial relationships.

Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR 2020: Session presented February 20, 2020.

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