Pretransplant assessment in Haemotopoietic Stem Cell Transplantation

Dr Tan Sen Mui
Hospital Ampang

Haemotopoietic Stem Cell Transplantation (HSCT) is widely applied with curative intent in a variety of haematological malignancies and non-malignant diseases. HSCT has evolved rapidly over recent decades whereby the list of transplant indications has been expanded. Now, it also offers as rescue modality for intensive treatment in other non haematological tumours which are chemo/radiosensitive or immunosensitive.

HSCT is associated with substantial morbidity and mortality. The patients are subjected to early risks of transplant related mortality (TRM) for the late benefit of long-term disease control. However, the overall transplant outcome has improved in parallel with the advancement of diagnostic techniques, better supportive care, emerging of reduced intensity conditioning and post-transplant immunotherapy.

On the other hand, the role of HSCT has been constantly changed following the development of targeted therapies in the management of some diseases such as Chronic Myeloid Leukaemia (CML) and lymphoproliferative disease. Therefore, it is important and mandatory for a proper pretransplant assessment to ensure the best possible use of this high-risk and expensive treatment commodity.
 
Many pretransplant factors influence the outcome of HSCT namely from the disease itself, person including both donor or recipient and environment. Each patient should have a comprehensive treatment plan in order to reduce the risks of refractory, relapse, life-threatening infection, severe organ toxicity prior to a HSCT when needed. Risk assessment has a long history in HSCT. It started with the recognition that disease stage was the main factor influencing outcome in HSCT not only in term of disease free survival but also impact to the TRM and overall outcome.

The next important pretransplant factor that determines a good outcome is the organs status of the recipient. A proper cardiac assessment is a must in view of the associated cardiovascular stress during HSCT such as handling volume expansion as well as direct cardiotoxicity in conditioning therapy apart from overcoming anaemia, vasoparalysis and myocardial suppression associated with sepsis. Moreover, some of the recipients already have reductions in cardiac function from previous cardiotoxic chemo drugs exposure. In addition, the expanding indication for HSCT has recruit some of the higher cardiac risk conditions for HSCT like older population or diverse diseases namely amyloidosis, systemic sclerosis, Thalassaemia, sickle cell disease, inherited storage disorders and so on.

The liver is also a determine factor because liver dysfunction has increase the risk of early and late complications after HSCT. The hepatic complications in HSCT encompass venous occlusion disease (VOD / SOS) of the liver which is a highly fatal condition, hepatitis either in acute or chronic form of which sometimes can be fulminant as well as liver fibrosis or cirrhosis resulting from VOD, viral infections and haemosiderosis. Furthermore, the worrisome problem in liver dysfunction recipients is abnormal liver metabolism of drugs causing severe systemic toxicity or trigger graft versus host disease (GvHD). Reactivation or acquisitions of viral infections such Hepatitis B that is endemic in our region or Hepatitis C can also jeopardize the overall outcome of HSCT.

Even though the potential post-transplant implications of abnormal pretransplant Pulmonary Function Tests (PFTs) remains elusive and controversial, a compromised lung function prior to transplant has definitely lead to the increased risk for pulmonary complications and mortality after myeloablative HSCT. Two most relevant parameters in assessing lungs function pretransplant consist of FEV1 and DLCO.

Kidneys are the other vital organs warrant assessment in HSCT. There are a few causes of renal dysfunction in HSCT either due to pre-existing renal disease such as in amylodosis or due to drugs toxicity from immunosuppressant agents, antimicrobial drugs, chemotherapy, tumour lysis syndrome, VOD /SOS, sepsis and later on TTP /HUS and bone marrow transplant (BMT) nephropathy as late renal complication post HSCT. In general, mortality rate of the recipients increases with worsening renal failure and can go beyond 80% for those who requiring dialysis. Those survived from acute renal failure have increased risk chronic kidney disease later on.

Pretransplant assessment becomes more complicated and challenging at this moment because of the lack of specific comorbidity scoring system that can cover critical information for HSCT such as disease status, tumor and histologic type/stage, extent of prior treatment, donor stem cell source and cell type and preparative regimen. Therefore, there is an urgent need to have an appropriate scoring system. With detailed information on risks and chances, prediction of outcome can become a reality. Finally, this high-cost, high-risk, low-volume procedure treatment option can be carried out in an effective way.