Valerie Neff Newitt
October 2019—Histocompatibility laboratories that provide services for cellular therapy transplant patients have one more inspection option to consider, thanks to a new edition of the CAP’s histocompatibility checklist released in September.
The revised histocompatibility checklist is what led the Foundation for the Accreditation of Cellular Therapy in April to approve the CAP as an accrediting organization.
“It’s a win for the CAP, a win for labs, and a win for FACT,” says Patricia Kopko, MD, an advisor to the CAP Histocompatibility/Identity Testing Committee and professor of pathology at the University of California San Diego.
Until now, only the American Society for Histocompatibility and Immunogenetics (ASHI) had deemed status from FACT for accrediting histocompatibility laboratories that support centers that perform human stem cell transplantation, says Manish Gandhi, MD, vice chair of the Histocompatibility/Identity Testing Committee, a member of the CAP Checklists Committee, and associate professor of laboratory medicine and pathology at Mayo Clinic in Rochester, Minn.
“Our CAP team worked closely with the FACT committee and made changes to the checklist so that it meets FACT standards. Most of the checklist requirements were modified to provide more clarity to the requirements of laboratories supporting human stem cell transplantation,” Dr. Gandhi says. Some of the requirements were separated to address laboratories that support only one type of transplantation—solid organ or stem cell—and not the other. Others were modified to support histocompatibility laboratories that perform primarily registry typing.
“All of these led to FACT providing the CAP with deemed status,” Dr. Gandhi says. “The major advantage is that institutions that are CAP accredited and needed additional accreditation from alternative agencies for their histocompatibility laboratories can now opt for CAP accreditation.”
Mark Fung, MD, PhD, chair of the Histocompatibility/Identity Testing Committee and professor and vice chair of population health, Department of Pathology, University of Vermont Medical Center, says the most important thing for labs to understand is that CAP accreditation of HLA labs is now recognized by both the solid organ and the stem cell transplant accrediting organizations, which are the United Network for Organ Sharing and FACT. And that, says Dr. Kopko, means fewer inspections that tie up resources. “Inspections cost money and employee time, not to mention the stress involved,” she says.
Arthur Bradley Eisenbrey, MD, PhD, the CAP’s liaison to FACT and clinical associate professor of pathology, Wayne State University School of Medicine and the University of Toledo College of Medicine and Health Science, agrees. “When you’ve got your laboratory supervisor and director preparing for inspections and then addressing inspection findings for more than one agency, time and money is being spent on redundant activities. And they’re not doing clinical service when they’re doing that.”
Dr. Eisenbrey, a past committee chair who has been involved in the push for FACT status for a decade, says, “Now when CAP accredits a hospital laboratory system with an HLA lab, that lab is going to be inspected and accredited by CAP too. If a laboratory is supporting cellular therapy or hematopoietic cell transplant, they will no longer require separate inspections.”
[dropcap]T[/dropcap]he checklist changes themselves are largely ones of verbiage and clarification of the histocompatibility checklist requirements. “They include references to hematopoietic stem cell transplants where, before, we in CAP basically had assumed that was understood,” Dr. Eisenbrey says.
“We did have to tweak some language to align ourselves,” Dr. Kopko says. “But if you are running a good HLA laboratory and you see the changes we made, you’re not going to look at it and say, ‘Oh no, since when does this apply?’ Instead, you’re going to say, ‘I’m already doing this.’ Certainly labs need to be aware of the changes, but good labs are already doing all of this and more.”
Some requirements were merged and others were modified. “There are 27 requirements with a modifier added in,” Dr. Gandhi says, “and I don’t think it should impact anyone. It’s just very specific. It tells labs supporting solid organ transplant, ‘These are things you need to do,’ and it tells labs supporting stem cell transplantation, ‘These are the things you need to do.’ The only addition covers a registry; it is something FACT wanted and we agreed.”
A sampling of the revised requirements:
- HSC.21275 Final Report. “There are new things that have to be in a final report,” Dr. Eisenbrey says. “CLIA requirements had been what the CAP had required for our reports in the past. This requirement now enumerates very specifically histocompatibility-related things that had not been required previously.” They consist of a summary of the methods used, the loci tested, objective findings, limitations of the methods when applicable, interpretation, and a list of ambiguous allele combinations and unresolved alleles for high-resolution typing, if applicable. A new note for donor registries specifies that aggregate reports can be provided for a group of donors. “There are laboratories that have hundreds, even thousands, of potential stem cell donors at a time, and they are typing huge batches of potential donors. So this allows for aggregate results,” Dr. Eisenbrey says, adding that it’s new and has never before been a consideration for the CAP. “It’s very specific and intended for donor registries only.”
- HSC.21287 Result Review. The previous requirement was for results to be reviewed by the director (technical supervisor) or her or his designee, most frequently the lab supervisor, prior to release. The revision formally adds another level of review before final release of typing results. “I have seen many varied implementations of the previous reporting requirement,” Dr. Eisenbrey says, “including three-level reviews and post-release reviews by the laboratory director. This is a formalization of a more stringent practice.”
- HSC.21350 Clinical Transplant Registries and Transplant Data Retention. The requirement’s note says the source of the donor organ or donor hematopoietic stem cells should be recorded. “It is an example of a requirement that has been changed to be very specific to say ‘hematopoietic stem cells.’ There are a number of requirements that add just that phrase,” Dr. Eisenbrey says, noting that for most labs this change in wording will make no difference.
- HSC.29869 Final Crossmatch Results Availability. This requirement’s note begins as follows: “Laboratories supporting solid organ transplants must be capable of performing prospective crossmatches and must have a written policy describing in what situations pre- or post-transplant crossmatching is performed for all types of solid organ transplants. Results of the final crossmatch must be available before a kidney transplant is performed.”“In the note we specifically added ‘supporting solid organ transplants,’” Dr. Eisenbrey says, “because most stem cell transplants do not have a final cross. So we’ve clarified for the stem-cell-only labs that this didn’t apply to them.”
- HSC.38097 Sequence Based Typing. “A great deal of histocompatibility typing for stem cell donors as well as solid organ donors is done by sequence-based molecular testing. So this item added additional language to clarify what needs to be done for sequence-based testing,” Dr. Eisenbrey says. It will require laboratories to have records of templates with sufficient specificity for a locus or allele, appropriate monitoring of all steps, adequate electrophoretogram quality, and other things. “This will also affect laboratories that are not supporting stem cell as well. So any laboratory with a clinical study in next-generation sequencing for whole organ transplants needs to consider the points in this requirement.”
- HSC.38845 HLA Identity Confirmation for Hematopoietic Progenitor Cell Transplantation. Here, too, the language has been made more specific for hematopoietic stem cell transplantation. And the note cites the National Marrow Donor Program. “That is because FACT is the accrediting body for laboratories that do transplants under the National Marrow Donor Program,” Dr. Eisenbrey explains. “This is bringing this requirement up to the National Marrow Donor Program standards.”
- HSC.40000 Section Director/Technical Supervisor Qualifications. “This requirement vets the laboratory directors to make sure they have met training and experience requirements to be a director of a lab doing stem cell transplants,” Dr. Eisenbrey says. “CAP was already doing it, but it was not there specifically in the checklist requirements.”
Says Dr. Kopko: “This is a specialty area and not part of laboratory medicine typically known in a pathology residency program. In fact, a boarded pathologist cannot direct a histocompatibility lab without an additional two years of training in histocompatibility. Now inspectors must ensure that the director of the laboratory has appropriate training.”
Dr. Fung says that CAP members who want to perform inspections of HLA labs that support stem cell transplant programs now must have already participated in a past CAP HLA lab inspection. “Or, if this is their first time, they are now required to shadow or observe one of those inspections before they are allowed to do one on their own.”
[dropcap]M[/dropcap]ost of the other changes in the new edition of the histocompatibility checklist are subtle, Dr. Eisenbrey says, in large part because of the CAP’s inspection history. “We have a lot of experience and expertise in histocompatibility,” he says. “CAP’s been there since the beginning of it.”
ASHI and the CAP have been working together for years to bring their checklists into agreement. “We didn’t want to be going in opposite directions on anything. We wanted to be consistent,” Dr. Eisenbrey says. “Still, FACT did not recognize the CAP. It was particularly problematic for large centers because they usually had to be accredited in their laboratory by the Joint Commission, CAP, and ASHI. We made the point that not only is this not fiscally sound, but it could be confusing.”
It took much communication (with “invaluable support,” says Dr. Fung, from CAP staff Lyn Wielgos and Loretta Liubinskas) and copious effort to educate FACT about CAP checklists to eventually see progress. “Part of the issue,” Dr. Kopko explains, “was that previously FACT did not realize we had more than one checklist that applies to a lab. They were just looking at our histocompatibility checklist and not at the laboratory general checklist. A lot of the fundamental things required for good laboratory medicine are not in the histocompatibility checklist but are in the general checklist. FACT thought all that was being left out.”
While FACT’s deemed status has arrived on Dr. Fung’s watch, he says it has taken an uninterrupted succession of committee chairs and strong, consistent support from the CAP staff to get the job done.
“I would argue that all the heavy lifting occurred way before I became chair,” he says, pointing to Dr. Eisenbrey as the chair who “got the ball rolling.” Dr. Eisenbrey was supported by his vice chair, Dr. Kopko. She served next as chair and was later succeeded by her vice chair, Dr. Fung. In turn, Dr. Fung will be succeeded by his vice chair, Dr. Gandhi. “So you’re looking at four generations of committee chairs for this effort,” Dr. Fung says, “and then some. I don’t think we could have accomplished this without that continuity.”
Dr. Eisenbrey says he is proud that the CAP was open to FACT’s “sometimes blunt criticism and recommendations.” Dr. Fung says the CAP checklist is better for it: “One of the great benefits of our collaboration with FACT is that our own checklist has been strengthened with more details and distinctions between stem cell and solid organ transplants. So now the CAP checklist for HLA is, I would say, complete. It covers all forms of transplantation.”
In the end, all groups’ standards are “as close to being equivalent as possible,” Dr. Eisenbrey says. “And that is a big win for the histocompatibility community and all of the laboratories involved.”
Valerie Neff Newitt is a writer in Audubon, Pa.