The Colony Stimulating Factors (CSFs) are a family of haemopoietic hormones that likely share a common ancestral origin and stimulate white blood cell development. They display unique but overlapping biological functions and stimulate the survival, proliferation, differentiation and functional activation of granulocytes and monocytes/macrophages and their precursor cells in vitro and in vivo. Each hormone has been purified and produced in active recombinant form. Recombinant G-CSF and GM-CSF are now being used around the world in a variety of clinical situations (e.g., in conjunction with chemotherapy and bone marrow transplantation) to promote the formation and function of these leukocytes. These molecules are among the first of a new generation of biological agents that will impact enormously on clinical medicine.
The sole BMT centre in Malaysia caters only for children. Since 1987, 89 transplants have been performed using reverse barrier nursing techniques. The overall survival rate is 73% with the majority of survivors leading normal lives. The early and late infection rates of 46% and 13%, respectively, are comparable to those of other centres. Although the early septicaemia rate is 36% the immediate mortality rate is < 10%. GVHD is less frequent and severe and the interstitial pneumonitis rate lower than that in the West. The average cost of US $8000 per transplant is much lower than the cost of a transplant performed overseas. Thus we believe that our paediatric BMT programme is simple and cost-effective.
Between January 1985 and June 1992, the Paediatric Department of Hospital Universiti Sains Malaysia has diagnosed congenital dyserythropoietic anaemia in three children, two of whom were siblings. The age of onset ranged from 1 to 3 years. All of them became transfusion-dependent before the age of 4 months. One of them was successfully treated with bone marrow transplantation.
Second malignant neoplasms (SMN) are an increasingly recognized late complication seen in childhood cancer survivors. A total of 3 cases of SMN have been found in the Department of Paediatrics, University Hospital Kuala Lumpur after a 15-year experience of treating childhood malignancies. Two cases are described here. The first developed abdominal non-Hodgkin's lymphoma 3 years after undergoing an allogeneic bone marrow transplant for second relapse of acute lymphoblastic leukaemia, while the second child developed myeloid leukaemia two years after completing treatment for acute lymphoblastic leukaemia. Progress in the management of childhood cancer in Malaysia and the availability of bone marrow transplantation facilities have increased the number of childhood cancer survivors; leading to increased incidence of SMN.
The thalassaemias are the commonest single gene disorders amongst the inherited diseases. In Malaysia, there are an estimated 2200 transfusion dependent thalassaemia patients. With a carrier rate of 3-5%, 120-340 new cases of thalassaemia are expected to be born each year. The reference treatments for these patients are regular blood transfusions and iron chelation therapy. With optimal management, these patients are able to survive into the third or fourth decade of life and most importantly avoid the complications related to transfusions and iron overload. The use of desferal locally is still limited to only those who can afford i.e. about 30% of the cases. Treatment for some of the complications such as hepatitis C, diabetes mellitus, growth impairment and pubertal delay, are now available. Curative treatment approaches like bone marrow transplantation have now become standard treatment for eligible cases whilst cord blood transplantation may yet offer hope for those who are without compatible sibling donors. Research on globin gene therapy looks very promising but will probably take some time to deliver. Hb F switching is a very novel idea but so far the results are mainly anecdotal. Finally, the strive for optimal management of thalassaemia must come hand in hand with a prevention programme to achieve a reduction of new cases.
The first cooperative study of the Asian Pacific bone marrow transplantation group included 75 patients with early leukemia who received human leukocyte antigen-matched sibling bone marrow transplants and were randomized into granulocyte colony-stimulating factor and control groups. The selected patients were registered from 10 centers in six countries and areas within Asia (Beijing, Taipei, Hong Kong, Japan, Korea, and Malaysia). The incidence of grades II-IV acute graft-vs.-host disease was 22.2%, and the 2-year survival rate was 62.7%. The period of protective isolation (27.1-66.7 days), period of hospitalization (38.6-130.5 days), and medical costs for 4 months (US $10,300-US $80,803) varied considerably. Good cooperation, i.e., low rate of protocol violation or rapid and precise presentation of case reports, was obtained.
In the setting of transplantation and chronic hepatitis B viral infection there is a unique histological feature termed cholestatic fibrosing hepatitis. The use of nucleoside analogues in the treatment of this condition has been successful. We describe a case of cholestatic fibrosing hepatitis, which occurred after intense immunosuppression for graft versus host disease in a patient with bone marrow transplantations. She was commenced on lamivudine therapy and showed good clinical, biochemical and virological response. However she succumbed due to sepsis.
Matched MeSH terms: Bone Marrow Transplantation/adverse effects*
Nocardia infection is rare in bone marrow transplant (BMT) recipients with less than 30 cases reported in the literature [1-4]. The majority of the cases occurred late in the post-transplant period. Common clinical presentations included formation of widespread and multiple abscesses. Bone marrow hypoplasia is an uncommon finding. We describe the first case of nocardiosis, diagnosed at day 100 after non-myeloablative allogeneic peripheral blood stem cell transplantation, presenting as pancytopenia and hypocellular marrow. Eradication of the infection with antibiotics resulted in complete hematological recovery.
Bone marrow stem cells (BMSC), known for its multipotency to differentiate into various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have been actively applied in tissue engineering. BMSC have been successfully isolated from bone marrow aspirate and bone marrow scraping from patients of various ages (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our laboratory showed the presence of a heterogenous population that showed varying prevalence of surface antigens and the presence of telomerase activity albeit weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization activity were observed.
A 5-month-old Chinese male infant was referred to the University Hospital, Kuala Lumpur for persistent fever, generalised rash and abdominal distension. Clinically he was suspected to have haemophagocytic lymphohistiocytosis. Haematological findings including the presence of several abnormal giant granules in neutrophils and single large azurophilic granules in many lymphocytes and monocytes in the peripheral blood established the diagnosis of Chediak-Higashi syndrome. The patient responded to allogeneic bone marrow transplant. This paper discusses the characteristic features, clinical course and management of this rare disorder. We suggest that peripheral blood film examination for the abnormal giant granules in granulocytes is an essential investigation in all young children with frequent recurrent infections or who are suspected to have virus-associated haemophagocytic syndrome or familial haemophagocytic lymphohistiocytosis.
Conventional therapies for severe ischemic heart disease are limited in applicability. While several angiogenesis researches have shown novel efficacy, safety and feasibility for clinical use, recently we have started the clinical trial of a sole cell therapy using autologous bone marrow mononuclear cells transplantation targeted into ischemic hibernating myocardium. Here, we review the background of bone marrow cell research and introduce therapeutic angiogenesis for severe ischemic heart disease by autologous bone marrow cells transplantation.
Matched MeSH terms: Bone Marrow Transplantation/methods*
To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
The treatment of haematological malignancy is multimodal and involves chemotherapy, radiotherapy and/or bone marrow transplants. With the advancement in cancer therapy, there is an increase in the survival of many children with childhood haematological malignancy. In addition, the late effect of the oncology treatment to the orofacial and dental development becomes significant in terms of the potential clinical impact that may affect the quality of life of the survivor. The severity of the long-term effects is dependent on the age of the child at initiation of treatment and whether chemotherapy is combined with radiation or not. The dental treatment may become more complex if the patient requires advanced restorative dental care and the roots malformation may complicate orthodontic treatment. Therefore these patients may require a scheduled careful preventive programme, long-term follow up, with prophylactic treatment and intervention at appropriate time to minimize the consequences of the disease and the given therapy.
We aimed to establish a method for quantitative analysis of mixed haematopoietic chimerism based on microchip electrophoresis of selected molecular markers following PCR amplification for accurate monitoring of graft status post-transplantation. A 12-year-old girl with relapsed acute lymphoblastic leukaemia who underwent allogeneic bone marrow transplantation had qualitative chimerism analysis using short tandem repeat markers at three time points following the procedure. Her archived DNA samples were then used to test the ability to correlate her clinical course with changes in the quantity of donor chimerism at the different time points. Quantitative chimerism analysis was performed on the Agilent 2100 bioanalyser and donor-recipient ratios were calculated from generated electropherograms. Complete donor chimerism (98%) was demonstrated three weeks post- transplantation. Decreasing amount of donor chimerism to 24% was shown after three months and this concurred with clinical relapse. Following a second transplant, full donor chimerism was reestablished where donor chimerism rose to 100%. High resolution microchip electrophoresis could be useful in predicting the occurrence of increasing recipient chimerism which may herald impending relapse in patients while the disease burden is still low. This investigational approach may provide useful information for clinicians to select appropriate intervention strategies to ensure successful transplantation.
Gingival overgrowth is a well-recognized unwanted effect associated with three major drugs / drug groups - phenytoin, cyclosporine and the calcium channel blockers. Cyclosporine is the first-choice immunosuppressant for preventing allograft rejection in patients who have received organ or bone marrow transplants. This report aims to highlight a case in which the patient on cyclosporine therapy had also contracted Hepatitis C virus infection.
Bone marrow derived Mesenchymal stem cells (MSCs) were evaluated as an alternative source for tissue engineering of peripheral nerves. Human MSCs were subjected to a series of treatment with a reducing agent, retinoic acid and a combination of trophic factors. This treated MSCs differentiated into Schwann cells were characterized in vitro via flow cytometry analysis and immunocytochemically. In contrast to untreated MSCs, differentiated MSCs expressed Schwann cell markers in vitro, as we confirmed by flow cytometry analysis and immunocytochemically. These results suggest that human MSCs can be induced to be a substitute for Schwann cells that may be applied for nerve regeneration since it is difficult to grow Schwann cells in vitro.
PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.
Matched MeSH terms: Bone Marrow Transplantation/methods*