General Health

Risks Linked to Hematopoietic Stem Cell Transplantation

History

In 1939, a woman with aplastic anaemia received the first human bone marrow transfusion. This woman received frequent blood transfusions and tried an intravenous bone marrow injection to increase her leukocyte and platelet counts without any negative outcomes.

From the 1950s until the 1970s, a team at the Fred Hutchinson Cancer Research Center under the direction of E. Donnall Thomas invented stem-cell transplantation utilising bone marrow-derived stem cells. Later, Thomas’ contributions were recognised with the Nobel Prize in Physiology or Medicine. According to Thomas’ research, bone marrow infusions given intravenously may replace bone marrow and promote the generation of new blood cells. A potentially lethal disorder called graft-versus-host disease was also made less likely owing to his work. In collaboration with University of Washington scientist Eloise Giblett, he created genetic markers that could verify donor matches.

The first doctor to successfully execute a human bone-marrow transplant for a condition other than cancer was Robert A. Good of the University of Minnesota in 1968. John Kersey, who was also connected to the University of Minnesota, performed the first effective bone marrow transplant to treat lymphoma in 1975.

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The 16-year-old youngster who underwent his treatment is currently the longest-living lymphoma transplant recipient.

Prognosis

The prognosis is greatly influenced by the disease type, stage, stem-cell source, HLA-matching status (for allogeneic HSCT), and conditioning programme. A transplant offers the possibility of a cure or long-term remission if the inherent issues of graft vs host disease, immunosuppressive drugs, and the variety of opportunistic infections can be overcome. The survival rates of almost all subpopulations and demographic groups receiving transplants have gradually increased in recent years.

To assess mortality for allogeneic stem cell transplantation, the prediction model created by Sorror et al. utilising the Hematopoietic Cell Transplantation-Specific Comorbidity Index can be employed (HCT-CI). The HCT-CI was created and validated by scientists at the American Fred Hutchinson Cancer Research Center. The HCT-CI modifies and improves the Charlson Comorbidity Indicator, a well-validated comorbidity index (CCI) The CCI was previously utilised by patients undergoing allogeneic HCT, although it appears to provide less accurate survival prediction and discrimination than the HCT-CI score technique.

Patients who successfully had HSCT and total body radiation as children had increased fat mass percentages, which significantly hindered their adult capacity for activity. This indicates an increased risk of cardiovascular disease in later life for people who underwent effective HSCT therapy.

Risks to donor

The likelihood of a problem depends on the patient’s circumstances, the healthcare professionals involved, the apheresis technique, and the colony-stimulating factor that was utilised (G-CSF). Filgrastim (Neupogen, Neulasta) and lenograstim are medications for G-CSF (Graslopin).

Drug risks

Filgrastim is typically given during the stem cell harvest for 4-5 days at a dose of 10 micrograms/kg. Known adverse effects of filgrastim include splenic rupture, acute respiratory distress syndrome, alveolar haemorrhage, and allergic reactions (usually experienced in the first 30 minutes). Additionally, levels of platelets and haemoglobin drop after the treatment and don’t recover to normal until one month afterwards.

To evaluate whether older patients (those over 65) respond similarly to those under 65, not enough research has been conducted. It is well established that G-CSF injection can cause atherosclerotic plaque inflammation and coagulation issues. It has also been demonstrated that G-CSF causes genetic changes in agranulocytes from healthy donors. There is no statistically significant evidence for or against the hypothesis that G-CSF can develop myelodysplasia (MDS) or acute myeloid leukaemia (AML) in susceptible individuals.

Access risks

The jugular, subclavian, or femoral veins can all be accessed with a central line in addition to the peripheral veins that are used for the majority of patients. During apheresis, 20% of women and 8% of males experienced unpleasant reactions, the majority of which were numbness/tingling, and nausea.

Clinical observations

According to a study including 2,408 donors, 80% of donors who get filgrastim treatment suffer bone soreness, mainly in the back and hips (aged 18 to 60). The donation is not advised for people who have a history of back issues. Additional symptoms that were reported by more than 40% of donors were discomfort in the muscles, headaches, fatigue, and problems sleeping. Most patients saw a return to normal of these symptoms one month after donation.

In a meta-study with information from 377 donors, 44% of patients said that peripheral blood HSCT had caused them harm. Prior to the collection surgery, pain from G-CSF injections also produced generalised skeletal pain, fatigue, and reduced energy.

Severe reactions

In a study of 2,408 donors, it was found that 15 donors (or 0.6 per cent) experienced serious adverse events that necessitated prolonged hospitalisation, but none of these events was fatal. Donors were not found to have higher than average cancer rates after up to 4–8 years of follow-up. One study based on a survey of medical teams conducted between 1993 and 2005 included over 24,000 peripheral blood HSCT patients and found a significant cardiovascular adverse reaction risk of about one in 1,500. In the first 30 days after HSCT, this study discovered a two-in-10,000 chance of cardiovascular mortality.

References

1.   https://www.worldcat.org/title/annals-of-internal-medicine-supplement/oclc/183357811

2.   https://pubmed.ncbi.nlm.nih.gov/19059940/

Author

 Yash Batra

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