General Health

Post Transplantation Complications of Haematopoietic Stem Cells

Complications

Haematopoietic Stem Cell Transplantation (HSCT) is linked with substantial treatment-related mortality in the recipient, limiting its application to life-threatening illnesses. (The one-year survival rate is reported to be around 60%, although this statistic includes fatalities from both the underlying illness and the transplant process). Veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease, and the development of new malignancies are all serious complications.

Infection

Bone marrow transplantation frequently necessitates the destruction of the recipient’s bone marrow (myeloablation). Patients may go for several weeks without significant numbers of white blood cells to help fight infection before receiving new cells (engraftment). Despite preventive medications, this puts a patient at increased risk of infections, sepsis, and septic shock.

Antiviral drugs, such as acyclovir and valacyclovir, are, nevertheless, quite successful in preventing HSCT-related outbreaks of herpetic infection in seropositive patients. Immunosuppressive drugs used in allogeneic transplants to prevent or cure graft-versus-host disease raise the risk of opportunistic infection even more. Immunosuppressive medicines are administered for at least six months following transplantation, and for much longer if graft-versus-host disease is present.

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Transplant recipients lose acquired immunity, such as immunity to childhood illnesses like measles or polio. As a result, once-off immunosuppressive medicines, transplant patients must retreat with childhood immunizations.

Veno-occlusive disease

Hepatic veno-occlusive disease (VOD), now known as sinusoidal obstruction syndrome, can cause severe liver damage (SOS). Clinical signs of this illness include hepatomegaly, fluid retention, and elevated bilirubin levels. The broad cellular damage and blockage in the hepatic vein sinuses are now properly understood. A significant death rate is linked to severe SOS cases. Although defibrotide or anticoagulants may be useful in lessening the severity of VOD, they may also make bleeding problems more likely. It has been demonstrated that ursodiol can reduce the risk of VOD, perhaps by promoting bile flow.

Mucositis

Following ablative HSCT regimens, damage to the mucosal lining of the mouth and throat is a frequent regimen-related adverse effect. Though usually not life-threatening, it is extremely uncomfortable and keeps people either eating or drinking. In addition to intravenous infusions to avoid dehydration and malnutrition, painkillers are used to treat mucositis.

Hemorrhagic cystitis

In roughly 5% of children receiving HSCT, the mucosal lining of the bladder is impacted. This results in thrombocytopenia, frequent urination, stomach pain, and hematuria (blood in the urine).

Graft-versus-host disease

The inflammatory condition known as graft-versus-host disease (GvHD) is exclusive to allogeneic transplantation. The immune cells of the “new” bone marrow are attacking the tissues of the recipient. Because the immune system can still distinguish other variations between their tissues, this can happen even if the donor and recipient are HLA-identical. Because bone marrow transplantation is the only transplant surgery in which the donated cells must accept the body rather than the body accepting the new cells, the disease is appropriately named graft-versus-host disease.

Acute GvHD, which can affect the skin, gut, or liver, often develops three months following transplantation. Prednisone is a common example of a high-dose corticosteroid, although this immunosuppressive medication frequently results in fatal infections. Following an allogeneic transplant, chronic GvHD may also develop. Although it doesn’t always lead to death, it is the main cause of late treatment-related problems. Chronic GvHD may produce fibrosis, or the formation of scar tissue, comparable to scleroderma. This condition may result in functional disability and necessitate protracted immunosuppressive medication. T cells, which respond to foreign peptides on the host’s major histocompatibility complex, typically mediate GvHD.

If mesenchymal stromal cells can be employed in the prevention and treatment of GvHD, more research is required.

Graft-versus-tumor effect

The advantageous feature of the GvHD phenomenon is the graft-versus-tumour effect (GVT), also known as the “graft versus leukaemia” effect. Acute or particularly persistent GvHD after an allogeneic transplant, for instance, tends to lower the likelihood of cancer relapse in HSCT patients. This is brought on by a therapeutic immunological response of the transplanted donor T cells against the recipient’s damaged bone marrow. Compared to transplants from identical twins, allogeneic transplants have a higher success rate, and this reduced relapse rate proves that allogeneic HSCT is an immunotherapeutic procedure. The main advantage of transplants that don’t use the strongest immunosuppressive regimens is GVT.

Graft versus tumour therapy is more effective in chronic leukaemia, low-grade lymphoma, and occasionally multiple myeloma than it is in fast progressing acute leukaemias.

The patient can undergo a second transplant with more donor white blood cells if the malignancy returns following HSCT (donor lymphocyte infusion).

Malignancies

Oral cancer is more likely to develop in patients after HSCT. When compared to oral cancer in non-HSCT patients, post-HSCT oral cancer may respond more aggressively and have a worse prognosis.

References

https://pubmed.ncbi.nlm.nih.gov/32108275/

Author

 Yash Batra

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