First Kidney Cum Bone Marrow Transplant In Asia

The Cancer Institute, National Healthcare Group (NHG) and the National University Hospital under NHG have successfully performed the first Kidney cum Bone Marrow Transplant in Asia.

Patient's story

Mr Koh Hock Heng, 43 years old, had been suffering from biopsy proven IgA nephropathy since 1990, which led to end stage renal failure in 2001.

In 2003, Mr Koh suffered from progressive anaemia unresponsive to standard therapy. He underwent a bone marrow biopsy to screen for other possible causes and was diagnosed with Myelodysplstic Syndrome (MDS, a pre-leukaemic disease). The only curative treatment option for MDS is allogeneic (stem cells from sibling or matched donor) stem cell/bone marrow transplantation. But, as the patient also had kidney failure, he would not be able to tolerate the toxic aspects of standard bone marrow transplantation.

Ideally, for the patient to enjoy a good quality of life, he also required a kidney transplantation for his end stage renal disease. But, with a concurrent pre-leukemic disease, he could not be accepted for kidney transplantation without curative treatment for his MDS. Hence, NUH embarked on a new treatment process for both his pre-leukemic disease and kidney failure by performing both stem cell and kidney transplantations.

The treatment process

In consultation with the patient and his family together with the transplant team, Mr Koh Hock Heng decided to proceed with this new treatment process. His 39 years old brother, Mr Koh Chuan Hin volunteered to donate his bone marrow and kidney.

The donor, Mr Koh Chuan Hin was first admitted for recovery of his stem cells. He was discharged within 6 days without any problems or side-effects. Mr Koh Hock Heng then underwent Nonmyeloablative Stem Cell Transplantation (NMT) in July 2004 as the first part of his treatment process. Mr Koh Hock Heng was warded for 3 weeks and kept under close observation for potential side effects of his bone marrow transplantation and recovery of his blood counts. During these three weeks, he had some side-effects that is not unusual with bone marrow transplantation. There were managed accordingly without any major problems.

NMT essentially comprises of using much lower chemotherapy and radiation doses compared to standard bone marrow transplantation therapy. Following NMT, a state of mixed chimerism would be established with time. This basically involves the blending of donor and recipient immune systems (thus chimera). Once the mixed chimerism was established, it would result in a state of immune tolerance to other tissues or organs from his brother. Thus he would not reject his brother's kidney, for example. However, this chimeric immune system was normal in all other aspects, that is, it could fight against infections like any other individual.

For the next ten months following his discharge from NUH, he came back for regular follow-up consultations at the Specialist Outpatient Clinic (SOC). This continued till his blood cells fully converted to donor cells and the medications used to allow this to happen were then tapered and finally completely stopped. During this period, Mr Koh Hock Heng was able to work like his brother.

The NMT cured Mr Koh Hock Heng of the cancer (MDS). He then proceeded on with the second phase of his treatment, that is, kidney transplantation in June 2005.

The acceptance of the new kidney by his body was made possible as both his bone marrow and kidney came from his brother. Thus he would not need any lifelong immunosuppression.

After the kidney donation procedure, Mr Koh Chuan Hin was discharged from NUH after 8 days. Mr Koh Hock Heng was discharged from NUH 9 days after his kidney transplantation. Both were able to return to normal life within 1 to 2 months. Both the donor and recipient are currently well.

Benefits of the treatment process

The benefits Mr Koh Hock Heng enjoys are -

1. Achieving transplantation immune tolerance

The greatest significance of this novel treatment is achieving transplantation immune tolerance. Most patients who undergo organ transplantations (kidney, heart, lung, liver, etc) would need life-long immunosuppressant medications to suppress their immune system.

Patients on life-long immunosuppressant medications may face the risk of suffering from infections, etc. With transplantation immune tolerance, patients no longer need to take any medications to prevent the organ from being "rejected by the body". This has a tremendous impact on the patient's quality of life, life span, etc.

2. Leading a better quality of life

Without the novel treatment plan, Mr Koh Hock Heng would have had progressive MDS that would result in worsening of his anemia with time.

In addition, the MDS would eventually transform into leukemia (cancer). He would not have been suitable for a kidney transplant (the best treatment for kidney failure) and would have continued on dialysis.

The eventual outcome without treatment for his MDS and kidney failure is anticipated to be dismal. His quality of life would deteriorate day by day and he would have succumbed from his illness within 1-3 years.

3. Leading a normal Life

The best benefit for Mr Koh Hock Heng is that he is able to resume a normal productive life and contribute to society after his transplantation. This not only benefits himself but also his family and society.

Significance of this new treatment protocol for other patients

With the ability to achieve transplantation immune tolerance using this treatment protocol, it is possible to explore and adapt such treatment strategies for future living kidney transplantation.

Myelodysplstic Syndrome (MDS)

The incidence rate of new MDS cases is extrapolated to be about 230 per year. The rate is increasing as the ageing population increases.

MDS is a blood stem cell disorder, which leads to marrow failure with low cell counts for white and red cells as well as platelets. The low red cells and platelets counts require transfusion support but the low white cells count cannot be supported by any long term medical means in this population.

Majority of patients tend to pass away due to bleeding or infection related complications. In others, the MDS progresses to leukaemia (cancer) that is resistant to chemotherapy and they would succumb from this complication.

End stage renal failure

Renal disorders accounted for 1.6 percent of all deaths in Singapore in 2002 and is the seventh most common cause of death in Singapore. In Singapore, one in 5,000 Singaporeans is at risk of developing renal failure.

The main causes of renal failure include diabetes mellitus, glomerulonephritis and hypertension. For the glomerulonephritis, the most common cause is IgA nephropathy.

IgA nephropathy is due to a problem in one's body's immune system resulting in production of a particular type of antibody know as IgA that deposits in the kidney and cause kidney damage. It is not clear what causes activation of the antibody but it could be related to infections of the respiratory tract or intestines. n

Source : Singapore NHG

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