UNDER THE MICROSCOPE
The Philippine Society for Blood and Bone Marrow Transplantation is holding its eighth post-graduate course this weekend with the theme: Transplant 360°: Stakeholders’ Perspectives on HSCT at the Henry Sy Auditorium, St. Luke’s Medical Center BGC on Sept. 27-28, 2024. As a guest lecturer, I will be giving a talk on Chimerism, which is a post-stem cell transplant monitoring test, available only at St. Luke’s Medical Center.
Leukemia is the fifth leading cause of cancer-related death in the Philippines and the ninth most common cancer type with more than 5,700 new cases in 2020. In children, leukemia is more treatable than in adults with the usual chemotherapy regimens, yet we have very low survival rates (32.9 percent) compared to the United States (80 percent). The traditional treatments for leukemias involve intensive chemotherapy which is very toxic and carries high risks of side effects. Now there is hope for our leukemia patients with Hematopoietic Stem Cell Transplantation (HSCT).
HSCT is a relatively new technique which is indicated for many diseases, including leukemias, lymphomas, aplastic anemia, autoimmune diseases, some types of solid tumors, and even HIV/AIDS. Patients with these disorders are facing life-threatening conditions and HSCT offers an alternative to the usual chemotherapies and other treatments.
To qualify for HSCT, a patient must be under 65 years of age and have normal kidney, liver, lung and heart functions. That’s because these patients will undergo intensive chemotherapy to wipe out the tumor cells, and in the process, wipe out the normal bone marrow elements that produce blood cells. This procedure is called myeloablative therapy.
Non-myeloablative therapy can be offered, since many patients have co-morbidities that disqualifies them from the more aggressive protocol. With this treatment protocol, the goal is to allow donor and host cells to co-exist and hope for a graft-versus-tumor effect.
HCST can be autologous, where the patient’s own stem cells are collected and stored before intensive chemotherapy wipes out the malignant cells along with the immune system. The stored stem cells are re-infused back into the patient to reconstitute the immune system.
It can be allogeneic, where a donor’s stem cells are infused into the patient after a similar chemotherapeutic regimen. More allogeneic HSCT is now being done.
After the stem cell infusion, the patient is still in an immune-deficient state and is prone to life-threatening infections and bleeding until the infused donor stem cells home in to the bone marrow spaces (engraft) and start producing blood cells, white blood cells and platelets. At this time, support with blood products is essential to tide the patient over in this critical period.
Once the patient’s blood counts rise, it is time to monitor if the stem cells have engrafted via engraftment analysis where DNA from the blood elements are analyzed. If they come from the donor alone(complete donor chimerism), or there is a mixture of recipient and donor DNA (mixed chimerism), or from the patient, which means failure of engraftment. A repeat HSCT can be done for the last scenario.
Who can be donors in HSCT? Ideally, it is someone who matches the patient’s HLA (Human Leucocyte antigen) type completely to avoid rejection and possible graft-versus-host disease (GVHD). In other countries, they have bone marrow donor registries wherein they HLA-type random volunteer donors and try to find a match of patients from this pool.
Absent this donor registry, and barring an identical twin, the closest relatives, the patient’s own siblings have a one in four chance of being a complete match. Since Filipino families are large, most of the time, there is a 50 percent chance of a complete match with one or more siblings. In case of haploidentical matches, they are still considered good donors due to a phenomenon known as graft-versus-tumor effect in which the immune cells of the donor recognize and eliminate residual tumor cells in the patient.
Monitoring of the engraftment process is imperative throughout the patients’ lives, since there is always a chance of leukemia relapse, a major cause of treatment failure.
Three-year survival rates are 79 to 92 percent depending on the original disease, compared with 24 percent without HSCT in acute myeloid leukemia. This outcome is certainly better than other therapies and HSCT patients have better quality of life.
A complication of HSCT is graft-versus-host-disease (GVHD) wherein the donor stem cells, having successfully engrafted, recognize the patient’s own cells as foreign and tries to reject them. There are treatment protocols for GVHD.
HSCT, being an expensive treatment, is not covered by Philhealth. Very few Filipinos can avail of it. It is time Philhealth consider reimbursing the costs of HSCT for our less affluent countrymen and women. That should take care of the “excess” funds the Philhealth is so eager to give back to the national government.