The mission of the Division of Paediatric Haematology-Oncology is to provide quality clinical care for children with cancer and haematological disorders, and to develop effective therapies through clinical trials, improvements in haematological progenitor cell transplantation, translational research and international outreach.
We seek to improve the outcome of children with cancer in Southeast Asia through the integration of education, research and clinical care. The annual St Jude-Viva Forum in Paediatrics Oncology is the combined effort of the St Jude International Outreach Program and Viva Foundation for Children with Cancer, with the aim of providing paediatric oncologist in Asia the opportunity to learn and network with each other to foster collaborations. The Viva-Asia Acute Leukaemia and the Viva-Asia BMT Working Groups meet at the Forum each year to enhance regional collaboration and provide the opportunity to learn from each other's experience.
We have established a web conferencing system used for:
- Guiding MRD studies in childhood Acute Myelogenous Leukaemia (AML) for national protocols in Japan and Taiwan
- Training scientists from Japan, Taiwan, Hong Kong and South Korea
- Overseas paediatric cancer centres from Canada, India, Saudi Arabia and Brazil to have consultations with us
Malaysia-Singapore ALL 2010 Study
This is the successor trial of the recently reported Ma-Spore ALL 2003 study (Yeoh et al. J Clin Oncol 2012) for children and adolescents with Acute Lymphoblastic Leukaemia (ALL). It is a multi-centre study involving NUH and KK Women and Children's Hospital in Singapore, and the University Malaya and Sime Darby Medical Centre in Malaysia. The Malaysia Singapore (Ma-Spore) ALL 2010 study uses minimal residual disease (MRD) levels to determine early response to remission induction and tailor the intensity of chemotherapy
Malaysia-Singapore AML 2010 Study
This multi-centre study for children and adolescents with AML involves the same institutions participating to Ma-Spore ALL 2010. It uses a modification of the MRC AML 10 treatment back bone replacing the second anthracycline block with high dose cytarabine in efforts to avert cardiotoxicity. It relies on MRD quantitation by flow cytometry and newly identified markers to assess response and select treatment intensity.
Singapore Paediatric Oncology Group Protocol for Osteosarcoma
This study uses multi-agent chemotherapy, cisplatin, doxorubicin, high dose methotrexate, ifosfamide with etoposide for metastatic patients, and limb salvage surgery with biological materials (host bone) or prosthesis.
Intra-arterial Chemotherapy with Melphalan for Advanced Intraocular Retinoblastoma Study
This study uses super-selective intra-arterial (ophthalmic artery) chemotherapy in the treatment of advanced intra-ocular retinoblastoma, Reese Ellsworth (RE) IV & V or International Intra-ocular Retinoblastoma Classification (ICIR) C, D & E.
Blood / Marrow Transplantation
Novel Preparative / Conditioning Regimens
Development of successive novel preparative regimens with aims to:
- Minimise treatment-related toxicities
- Improve donor engraftment
- Control graft-versus-host disease (GVHD)
- Preserve 'graft-versus-leukaemia (GVL) / 'graft-versus-tumour' (GVT) and 'graft-versus-infections' (GVI) activities
- Sensitise cancer cells to effector cells in stem cell grafts
- Enhance post-transplant immune reconstitution
- Shorten length of stays as inpatient and costs containment
Development of laboratory approaches to study immune recovery of patients who received any of these:
- Engineered donor grafts, e.g. selective T-cell depletion
- Unmanipulated donor grafts, e.g. post-transplant cyclophosphamide
- Donor lymphocytes, e.g. NK cells, T-cells
MRD-based intervention in patients eligible for advanced cellular therapy and/or BMT, aimed to improve pre-BMT disease status and/or post-BMT disease control.
Survivorship / Late Effects
Philanthropic supported clinical research programmes in:
- Hormonal and fertility preservation (in collaboration with endocrinology)
- Neuro-cognitive development (in collaboration with neuro-development paediatrics)
- Physical rehabilitation programme led by allied health professional or nurse
We have been a research centre with the "National Marrow Donor Program" (NMDP), USA and the "Centre for International Blood and Marrow Transplant Research" (CIBMTR), USA since 2002.
Gene Expression Profiling in Acute Leukaemia
Mononuclear cells from bone marrow of patients on the Ma-Spore ALL 2010 and AML 2010 studies are interrogated using whole genome gene expression profiling and newly discovered algorithms to determine its value in disease subgrouping and prognosis.
New Markers for MRD Studies in ALL and AML
Relying on extensive expertise in MRD monitoring and advanced instrumentation, we are validating recently discovered markers for MRD studies by flow cytometry in ALL and AML in both paediatric and adult patients.
We are studying the impact of gene mutations and pharmacogenetics on treatment outcome in children with ALL. Our study incorporates prognostically important mutations in genes like Ikaros, BIM, ABCB1 and IL15 mutations. We are also determining the pharmacogenomics of busulfan in Asian patients. Finally, we are studying Thiopurine Methyltransferase (TPMT) and Catechol-O-methyltransferase (COMT) polymorphisms in children with solid tumors who received cisplatin correlating the findings with those of audiometric testing.
Cell Therapy of Cancer
We have developed unique methods to expand and activate NK cells, as well as to redirect NK cells and T lymphocytes through genetic engineering. These methods, which have been adapted to clinical-grade conditions, are being applied to treat children and adults with different malignancies. Research in the laboratory aims at discovering novel ways to redirect immune cells and at enhancing their anti-cancer potential.
Three cell therapy-based clinical protocols have been approved by NUH and Singapore General Hospital ethical boards and the Health Science Authority of Singapore. These protocols use expanded allogeneic NK cells to treat children and adults with various malignancies including AML, myelodysplastic syndrome, T-cell ALL, sarcoma and neuroblastoma.
We also organise a Pre-Forum Workshop specifically for our colleagues in the developing countries of the region. In the past years, we have discussed effective leukaemia and solid tumor protocols for countries with limited resources, palliative care, hospital registries, supportive care and effective fund raising.
In collaboration with St. Jude Children's Research Hospital, we have established a twinning partnership with the Southern Philippines Medical Centre (SPMC), a government referral centre for the whole island of Mindanao. We have also developed a Retinoblastoma Program for Mindanao Island in collaboration with Dana Farber Children's Hospital Cancer Centre and St. Jude Children's Research Hospital, supported by the Khoo Teck Puat Foundation and the Viva Foundation for Children with Cancer. The project aims at facilitating early diagnosis through education and developing SPMC as a referral centre.