Hematopoietic stem cell transplantation (HSCT) is the only possible cure for many malignant hematologic diseases and is the riskiest treatment in hematology. It includes a series of systemic treatments, each step of which is critical to the long-term survival of the patient.
“Exit” is generally defined as a transfer out of the laminar flow unit after the patient’s white blood cells have returned to normal and the risk of infection has been significantly reduced, but this is only the first step in a long journey to successful transplantation, and is followed by a series of monitoring and treatment, including the following three areas.
Monitoring of graft-versus-host disease and adjustment of immunosuppression
Graft versus host disease (GVHD), commonly known as “rejection”, is an immune attack by donor cells on the recipient’s organs due to differences in HLA (human leukocyte antigens) after implantation in the patient. The higher the HLA match, the lower the incidence of severe rejection; conversely, the lower the HLA match, the higher the incidence of severe rejection.
Homozygous full compatibility is the best match, and kinship hemimelia is the worst match. During the transplantation process, physicians choose different intensities of graft-versus-host disease prophylaxis, i.e., apply different immunosuppressive agents, depending on the mating situation. However, even with the application of immunosuppressive prophylaxis, a certain percentage of patients still experience rejection.
Acute rejection
Acute rejection
Any rejection that occurs within three months is called an acute rejection. Acute rejection is characterized by rash, diarrhea, and liver function impairment, which can be very dangerous or even fatal in severe cases. The liver function is usually obtained through blood biochemistry, and as a patient self-observation is mainly to note the rash and diarrhea, which is very helpful for doctors to determine the condition.
- Rash
Patients should note the presence of a rash when cleaning their bodies daily, the shape of the rash, whether it is scratchy or painful, and whether it is increasing or decreasing in distribution.
- Diarrhea
Diarrhea can be caused by improper diet, intestinal bacterial or viral infections, in addition to rejection, and the treatment of diarrhea is completely different for different causes, so a very careful differential diagnosis is needed once diarrhea occurs after transplantation.
Patients should still be careful to maintain a clean diet after discharge and gradually transition to a regular diet as appropriate to avoid diarrhea due to improper diet. The patient should be aware of the color and shape of the stool, whether it is accompanied by bleeding or mucous membranes, whether the diarrhea is accompanied by abdominal pain, the location of the abdominal pain, its duration, the pattern of aggravation and relief, and so on.
The most important way to cooperate with your doctor is to record accurately the time of diarrhea, the nature of diarrhea, and the amount of diarrhea, to relieve the stool in the potty instead of the flush toilet, to separate the stool from the urine as much as possible, to measure the stool volume with a measuring cup, and to take pictures.
If the stool is watery and scatty, record the total amount, not just the amount of scat. A decrease in abdominal pain, a decrease in the watery component of the stool, and a decrease in the number of stools suggest improvement of the disease, and vice versa. Severe acute detrusor reactions require hospital admission.
Chronic rejection
After 3 months of transplantation, rejection may still occur, which is called chronic rejection. Chronic rejection has a variety of manifestations and is not as aggressive as acute rejection, but occurs slowly and continues to progress, which may affect the patient’s quality of life and long-term survival. Common manifestations include manifestations of dryness signs (dry mouth, dry eyes), skin rash, liver function impairment, poor digestive function, and chronic lung function impairment.
At this time, patients are generally followed up in the outpatient setting, and treatment is mainly through adjustment of immunosuppressive dosage. Therefore, patients are advised to familiarize themselves with the dosage of autoimmunosuppressants and to record in detail the changes in dosage and the reasons for the increase or decrease, and to follow up regularly at the clinic.
Monitoring of malignant disease relapse
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most intense treatment for malignant hematologic diseases, a proportion of patients still experience disease relapse after transplantation, especially those who did not achieve complete remission before transplantation. Once relapse occurs after transplantation, follow-up treatment is limited and is the most important cause of survival in post-transplant patients, and therefore close monitoring is required.
Monitoring includes the detection of minimal residual disease (MRD) and the detection of bone marrow chimerism.
- The former is mainly to detect the presence of residual tumor cells in patients by bone marrow smear, flow cytometry, and molecular biology methods;
- The latter mainly identifies the source of hematopoietic cells in the patient after transplantation, which should be at least >95% donor-derived cells after transplantation, otherwise it suggests the possibility of disease recurrence.
Early detection and early intervention is the key to reduce the mortality of relapse after transplantation. Therefore, it is recommended that patients with malignant hematologic disease undergo monthly bone aspiration testing in the first year after transplantation, extending to every 2 months in the second year, 3 to 6 months in the third year, and annually thereafter until 5 years after transplantation.
In addition, patients with solid tumors such as lymphoma should not be monitored for bone marrow alone, but should also have regular enhanced CT (electron computed tomography) or PET/CT (positron emission computed tomography) examinations of the lesion site.
Monitoring for various infectious diseases
Hematopoietic stem cell transplant patients are immunocompromised due to prior high-dose radiotherapy, chemotherapy, and post-transplant immunosuppression, etc. They are susceptible to various opportunistic infections, i.e., pathogens that are not pathogenic or less pathogenic to immunocompetent people may cause serious infections in post-transplant patients.
The most common of these is lung infection, and the pathogens can be bacteria, fungi (including Aspergillus, Yersinia pneumoniae, etc.), viruses (cytomegalovirus, etc.), and severe lung infection is the most common cause of nonrecurrent death in post-transplant patients. Therefore, patients with fever, cough, sputum, and shortness of breath after activity should be seen promptly, have a lung CT performed, and be admitted to the hospital if necessary.
Hemorrhagic cystitis is one of the common complications in the early post-transplant period, mainly manifesting as frequent, urgent, and painful urination, which may include visual hematuria and, in severe cases, urinary tract obstruction. Post-transplant cystitis is mainly caused by viral infections (polyomavirus is the most common) and is generally a self-limiting disease with symptoms lasting from 2 weeks to 1 month, with no specific medications. Drinking plenty of water, alkalizing the urine, and maintaining a daily urine volume of 3000-5000 mL can help relieve painful symptoms.
In addition, enterocolitis and herpes zoster are relatively common infectious diseases after transplantation. Patients who are well enough should be routinely on antiviral, fungal, and pneumocystis prophylaxis until 1 year after transplantation, or at least until immunosuppressive drugs are discontinued.