My name is Alex Shepard and I am a Cellular Therapies Laboratory Specialist. I currently work in the Cellular Therapies Laboratory at Children’s Healthcare of Atlanta, Egleston Campus in Atlanta, Georgia, United States. The laboratory supports the bone marrow transplant (BMT) program at Children’s by processing and infusing products obtaining hematopoietic progression cells, or stem cells. The BMT program at Children’s, who performed approximately 100 transplants last year, is one of the largest pediatric transplant programs in the country. In addition to performing autologous and allogenic pediatric transplants for hematologic disorders, Children’s also offers transplantation for immune dysregulation and immunodeficiencies such as severe combined immunodeficiency and hemophagocytic lymphohistiocytosis, transplants to cure sickle cell disease by allogeneic transplant or autologous transplant with gene therapy, and CAR-T cell therapy.¹

I have worked in a clinical laboratory since graduating from North Dakota State University in Fargo North Dakota, United States in 2009. In order to become a Medical Laboratory Scientist (MLS) in the United States, many laboratories require certification, and some states require licensure. I am certified through the American Society of Clinical Pathology (ASCP). There are multiple ways to become certified as an MLS though ASCP in the United States. For my path to certification, I took the required college courses, applied, and was accepted to an approved hospital internship program, which I completed. After graduating from college, I was able to sit for the certification exam. Because I was applying to be certified as a generalist, the exam included questions concerning all major areas of the laboratory: blood bank, urinalysis and body fluids, chemistry, hematology, immunology, microbiology, and laboratory operations.² However, an MLS can become certified in just one section of the laboratory or can choose to specialize in one section of the lab after several years of working in that section. I am certified as a Medical Laboratory Scientist, and maintain my credentials every three years; therefore, my credentials are MLS(ASCP)^CM. To maintain my credentials, I have to complete 36 hours of approved continuing education credits every three years, submit my application to ASCP, and pay the application fee.³ In addition to certification, 11 states and Puerto Rico require Medical Laboratory Scientists to have a state license to perform their jobs.⁴

It is possible for someone with the international MLS certification (MLS(ASCPⁱ)) to obtain the U.S. version (MLS(ASCP^CM)). There are several requirements. First, the MLS must have the MLS(ASCPⁱ) certification and be in good standing with the organization. Next, the applicant must submit an application including a university transcript that shows the individual has completed coursework that is equivalent to a U.S. baccalaureate degree from a university, and the individual must have five years of clinical work experience in all testing areas in the last ten years. However, a Medical Laboratory Scientist does not have to take the certification exam again! An important note is that once a professional changes their credentials from MLS(ASCPⁱ) to MLS(ASCP), it is not possible to revert back to the international version.⁵

There is no ‘special’ training for someone to start working in a cellular therapy laboratory. For me, I first started out working in the cellular therapy laboratory at Yale New Haven Hospital after a position opened up and my manager suggested I apply. There is extensive on-the-job training, due to the irreplaceable nature of each product that enters the laboratory. This training can take up to six months before feeling fully comfortable performing all tasks independently. A newer education program available through the American Association of Blood Bankers is called the “AABB Cellular Therapies Certificate Program”. This program offers individuals the opportunity to learn about important elements in the cellular therapy field, including scientific, operational, and regulatory issues.⁶ Completion of this program does not give an individual any additional credentials, but does providing additional continuing education credits, and could help someone stand out in the field in other ways.

The Cellular Therapies Laboratory (CTL) where I work is a two-room laboratory, with three biosafety cabinets. The main processing room is where all clinical products are sampled and processed. This room also houses patient files, labels, supplies, and all the other equipment needed to process cellular therapy products. Our secondary room also has a biosafety cabinet that is only used for genetically modified products, and this is where we house our control-rate freezers, liquid nitrogen tanks, and a small office where we have computer workstations.

The CTL supports the Children’s Bone Marrow Transplant Unit, which has ten in-patient beds, and a 4-bed outpatient clinic. There are additional overflow beds on the adjacent Hematology/Oncology unit that are able to be used as needed. We can perform transplants in any of these locations. In any given week, we can have two to three transplants, either in the inpatient or (less frequently) outpatient setting. The most common transplant product for allogeneic donors is bone marrow, due to the higher number of CD34+ cells (stem cells) compared to the lower number of CD3+ T lymphocytes. We have the ability to modify the product to either remove the plasma by washing the product in COBE 2991 or remove red blood cells with density separation by Ficoll-Paque. After modifying the product, we then take it to the floor for the transplant.

The second most common type of product the laboratory handles are stem cells collected in apheresis, in which the patients are given medication to ‘mobilize’ the stem cells. This pushes CD34+ stem cells to the peripheral blood stream. Patients have their blood filtered through a machine, which is set to capture these stem cells which can be processed in the laboratory. We then cryopreserve their cells using the control rate freezers and store them in liquid nitrogen vapor. When it is time for the patient’s transplant, we take the small bag of frozen cells to the floor, thaw it at their bedside, and then hand it to the provider, who infuses the cells. The third most common type of product we manipulate is cord blood. These cells are frozen by various cord blood banks across the world and are sent to us frozen. We store these frozen samples of cord blood in liquid nitrogen vapor and on the day of transplant, thaw them the laboratory and then take them to the floor for infusion.

Every day presents something different in a cellular therapy laboratory. Our major processes involve the collection, processing, infusion, and/or cryopreservation of stem cells. We may have to go to the operating room to assist with harvesting bone marrow for a matched sibling donor who is getting a stem cell transplant. Or, if the apheresis department is collecting a patient for Kymriah, we freeze stem cells collected by apheresis to ship to Novartis, where the T-lymphocytes are genetically modified and sent back to us to infuse into a patient. When we are not handling patient products, there are many operational lab tasks to perform as well. We have to log the lot and expiration date of all supplies that enter the lab, and all supplies we use for a specific process. We also have to document that we clean all surfaces once a week, and also when we use equipment. We are always planning ahead as well. We will start getting paperwork and reagents ready several days before the patient’s transplant date in order to be prepared and efficient when performing our job.

Cellular therapy is an exciting field to be in right now. There are multiple research trials that are using gene therapy to modify patients’ cells and either cure them of previously uncurable diseases or use their own cells to fight cancer. And, in the future, these research treatments could become the standard of care instead of research trials. Also, it is so rewarding to know that, as an MLS, we play an integral role in patient care. There have been patients for whom I have participated in the full cycle of going to the operating room, assisting with the bone marrow harvest, taking the product back to the laboratory to sample and process, and then taking the product to the floor and assisting with starting the infusion. Being able to do all of that and meet the patient and their family is very worthwhile.

References:

1. Blood and Marrow Transplant Program [Internet]. Atlanta: Children’s Healthcare of Atlanta; c2021 [cited 2021 Mar 3]. Available from: https://www.choa.org/medical-services/cancer-and-blood-disorders/blood-and-marrow-transplant-program
2. Medical Laboratory Scientist, MLS(ASCP) International Medical Laboratory Scientist, MLS(ASCPⁱ) Examination Content Guide [Internet]. Chicago: American Society for Clinical Pathology; 2020 [cited 2021 Mar 3]. Available from: https://www.ascp.org/content/docs/default-source/boc-pdfs/boc-us-guidelines/mls_imls_content_guideline.pdf?sfvrsn=18
3. U.S. Credential Maintenance Program [Internet]. Chicago: American Society for Clinical Pathology; 2020 [cited 2021 Mar 3]. Available from: https://www.ascp.org/content/docs/default-source/boc-pdfs/boc-stay-credentialed-general-cmp-pdfs/ascp-cmp-us-booklet-final-web.pdf?sfvrsn=8
4. Personnel Licensure [Internet]. McClean: American Society for Clinical Laboratory Science; c2021 [cited 2021 Mar 3]. Available from: https://ascls.org/advocacy-issues/licensur
5. U.S. Procedures for Examination & Certification [Internet]. Chicago: American Society for Clinical Pathology; 2020 [cited 3 Mar 2021]. Available from: https://www.ascp.org/content/docs/default-source/boc-pdfs/exam-content-outlines/ascp-boc-us-procedures-book-web.pdf?sfvrsn=35
6. Cellular Therapies Certificate Program [Internet]. Bethesda: American Association of Blood Banks; c2021 [cited 3 Mar 2021]. Available from: https://www.aabb.org/news-resources/resources/cellular-therapies/aabb-cellular-therapies-certificate-program