Bone marrow transplantation in children

The most frequent indications for bone marrow transplantation and complications of this method of treatment are reviewed. The results are compared with results of conventional therapy. Attention is focused on increasing possibilities of autologous transplantations in children having no HLA-compatible siblings.     

Bone marrow transplantation in Fanconi anaemia

Five patients with Fanconi anaemia have been treated by bone marrow transplantation from HLA identical donors. Only one patient survived for more than 3 years. She is now perfectly healthy with complete haematological reconstitution with chimaerism and disparition of chromosomal abnormalities. In contrast, four patients died of acute severe GVHD soon after grafting. In addition, all had signs of severe cyclophosphamide toxicity. This evolution could be explained by a special sensitivity of FA cells to alkylating agents and may indicate the need to modify the conditioning regimen in FA patients.     

Bone marrow imaging in children

By virtue of its ability to separate hematopoietic from fatty marrow, MR imaging is ideal for detecting marrow lesions. This article reviews the techniques of bone marrow imaging, interpretive pitfalls, anatomic variations with patient age, and the alterations in bone marrow signal occurring in a variety of pathologic conditions.     

Pulmonary complications and respiratory function changes after bone marrow transplantation in children

We prospectively assessed the frequency of pulmonary complications and the natural course of lung function after bone marrow transplantation (BMT), as well as the effect of several risk factors in a homogeneous group of 39 children who underwent allogeneic or autologous BMT for haematological malignancies between 1992 and 1995. Four patients developed pneumonia within the first 3 months and three 3-6 months after BMT. A considerable percentage of acute bronchitis was recorded throughout the follow-up. Three patients died after the 6 month visit because of pneumonia (two patients) and pulmonary aspergillosis (one patient). No patients had obstructive lung disease syndrome. At 3 months after BMT, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and transfer factor of the lung for carbon monoxide (TL,CO) significantly decreased, but FEV1/FVC ratio and maximal expiratory flow at 25% of FVC remained unchanged, suggesting a restrictive defect with diffusion impairment. At 18 months, there was a progressive recovery in lung function, although only 11 patients had normalized. Seropositivity for cytomegalovirus had a significant effect on lung function whereas graft-versus-host disease also had an effect, although it was not statistically significant. Baseline respiratory function, type of transplant, type of conditioning regimen and respiratory infections did not significantly affect the outcome of BMT. The high frequency of severe lung function abnormalities found in this study, suggests a careful functional monitoring in all subjects undergoing bone marrow transplantation, even in the absence of respiratory symptoms.     

Bone marrow transplantation in adult thalassemic patients

One hundred seven adult patients with thalassemia aged from 17 through 35 years and transplanted from HLA-identical siblings between November 1988 and September 1996 were evaluated on December 31, 1997. The outcome experience of 20 consecutive patients transplanted between November 13, 1988 and January 10, 1991 and reported in September 1992 is updated after 5 additional years. The experience on 87 patients transplanted between May 1991 and September 1996 is described and evaluated as of the end of December 1997. Of 107 patients, 69 survive between 1.5 and 9 years after transplantation. Sixty-six of these patients do not have thalassemia and are identified as ex-thalassemic after bone marrow transplantation. The youngest survivor is 20 years old, 6 are older than 30 years, and the oldest is 37 years of age. Patients with chronic active hepatitis at the time of transplant were significantly more likely to die than patients without (P =.05; relative risk, 2.05). Marrow transplantation is a valid treatment option for older patients with thalassemia who have suitable donors and show deterioration with conventional therapy.     

Bone marrow transplantation in chronic granulomatous disease

We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft. CONCLUSION: Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.     

Bone marrow transplantation in the treatment of thalassemia

OBJECTIVE: To investigate the long-term results of the corridor operation in the treatment of symptomatic atrial fibrillation refractory to drug treatment. BACKGROUND: The corridor operation is designed to isolate from the left and right atrium a conduit of atrial tissue connecting the sinus node area with the atrioventricular node region in order to preserve physiological ventricular drive. The excluded atria can fibrillate without affecting the ventricular rhythm. This surgical method offers an alternative treatment when atrial fibrillation becomes refractory to drug treatment. PATIENTS: From 1987 to 1993, 36 patients with drug refractory symptomatic paroxysmal atrial fibrillation underwent surgery. The in hospital rhythm was followed thereafter by continuous rhythm monitoring and with epicardial electrograms. After discharge Holter recording and stress testing were regularly carried out to evaluate the sinus node function and to detect arrhythmias; whereas Doppler echocardiography was used to measure atrial contraction and size. MAIN OUTCOME MEASURES: Maintained absence of atrial fibrillation without drug treatment after operation; preservation of normal chronotropic response in the sinus node. RESULTS: The corridor procedure was successful in 31 (86%) of the 36 patients. After a mean (SD) follow up of 41 (16) months 25 (69%) of the 36 patients were free of arrhythmias without taking drugs (mean (SE) actuarial freedom at four years 72 (9)%)). Paroxysmal atrial fibrillation recurred in three patients; paroxysmal atrial flutter (two patients) and atrial tachycardia (one patient) developed in the corridor in three others. Among the 31 patients in whom the operation was successful sinus node function at rest and during exercise remained undisturbed in 26 and 25 patients respectively (mean (SE) actuarial freedom of sinus node dysfunction at four years (81(7)%)). Pacemakers were needed in five (16%) of the 31 patients for insufficient sinus node rhythm at rest only. Doppler echocardiography showed maintenance of right atrial contribution to right ventricle filling in 26 of the 31 patients after operation in contrast to the left atrium, which never showed such contribution. His bundle ablation was performed and a pacemaker implanted in the five patients in whom the corridor operation was unsuccessful. CONCLUSION: These results substantiate the idea of this surgical procedure. Modification of the technique is, however, needed to achieve a reliable isolation between left atrium and corridor, which would make this experimental surgery widely applicable in the treatment of drug refractory atrial fibrillation.     

Bone marrow allogenic transplantation in malignant osteopetrosis]

In recent studies, the economic criteria has begun to be integrated to the appraisal in cancerology. The question asked by the economist can be framed as follows: what incremental cost should the collectivity or the health insurance system consent, in order to improve the care of cancer patients? This involves first that the cost of the strategies, foreseen or already implemented, can be appraised, then, that indicators can be defined to capture health improvement, and finally, that this health improvement can be quantified. In this article, we present the process of integrated appraisal (cost/result approach). We specifically analyze costs in cancerology, their source and their evolution. We demonstrate the meaning of the integration of economic costs and medical results. We emphasize on the fact that part of the costs, especially those supported by the patient and his close relations, are most of the time excluded from the analysis. Two main points should be carefully analyzed, when proceeding to an appraisal in cancerology: the measurement of the patient's QoL, which represents an expression of the results of the strategy of care; the financing modalities, for the same type of care, if we consider the specificity of the structures involved and the organization of the care. We conclude by mentioning how difficult this task is and under which conditions it should be developed.     

Bone marrow transplantation for the treatment of alpha-mannosidosis

BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.     

Colour-coded duplex sonography in the diagnostic assessment of vascular complications after kidney transplantation in children

A 68-year-old man with a 28-year history of non-insulin dependent diabetes mellitus (NIDDM) was admitted to our hospital because of foot gangrene. He had previously suffered from cerebral infarction resulting in right hemiplegia and his right foot was amputated because of right femoral lesion presenting diabetic foot gangrene 5 years previously. The diabetic foot gangrene gradually became worse, although he had received various medications. Then, we attempted to treat the patient with low density lipoprotein (LDL)-apheresis ten times a month. The foot gangrene itself and the local circulation around the gangrene lesion were remarkably improved after treatment with LDL-apheresis. We present here the first case of diabetic foot gangrene improved by LDL-apheresis. LDL-apheresis therapy is anticipated to be a new therapeutic approach for treatment of fatal foot gangrene associated with diabetes mellitus.     

Bone marrow necrosis in bone marrow transplantation: the role of MR imaging

We describe an ALL patient who developed extensive bone marrow necrosis at the time of relapse 2 months after allogeneic bone marrow transplantation from an HLA-identical sibling. The excruciating and diffuse bone pain, fever and precipitous drop in peripheral blood counts were characteristic. This case illustrates the importance of repeat bone marrow biopsies for the diagnosis of disease relapse and the potential application of MR imaging in the assessment of patients with bone marrow necrosis.     

Bone marrow transplantation in primary immunodeficiency syndrome and in osteopetrosis

The designation primary immunodeficiency embraces a multiplicity of diseases of which only the more severe constitute indications for BMT (bone marrow transplantation)--e.g. severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, familial haemophagocytic lymphohistiocytosis and malignant osteopetrosis. In cases of immunodeficiency, the outcome of BMT is strongly dependent on the patient's age, clinical status at transplantation and the type of immunodeficiency. In children with SCID who undergo BMT during the first few months of life, lasting cures can be obtained in almost 100 percent of the cases, whereas there is only a 15 percent probability of success if the child is older, infected, cannot undergo cytostatic preconditioning or cannot be given T-cell depleted bone marrow.     

Bone marrow transplantation for non-Hodgkin's lymphoma: a review

High dose chemotherapy and stem-cell rescue (bone marrow transplantation) is used increasingly in the treatment of malignant disorder. Numerous trials have demonstrated the effectiveness of bone marrow transplantation in the treatment of non-Hodgkin's lymphoma. However, there are many unanswered questions as to the role of high-dose therapy in certain subtypes of lymphoma, the timing of transplant, and even the type of transplant to perform. An attempt will be made to clarify many of these unanswered questions. The utilization of high-dose therapy for non-Hodgkin's lymphoma is recommended for most patients who have relapsed after initial therapy. Transplantation in first remission is not recommended routinely. Allogeneic bone marrow transplantation should by reserved for individuals with poorly responding disease or in individuals with bone marrow involvement. The precise roles of purging and transplantation of individuals with low grade lymphoma are being investigated.     

Varicella vaccination in children after bone marrow transplantation

Herpes zoster (HZ) is one of the most common complications after bone marrow transplantation (BMT) in children. Apart from treatment with antiviral drugs, effective prevention by active immunization with varicella-zoster virus (VZV) appears to be possible. In this study 15 patients were vaccinated with a live attenuated VZV vaccine (Varilrix) 12-23 months after BMT. The vaccine was well tolerated without adverse reactions. Chickenpox or HZ were not observed for up to 2 years after immunization. Eight out of nine seronegative patients seroconverted and in six virus-specific IgG could still be demonstrated 2 years later. The incidence of VZV diseases in 133 non-immunized children after BMT was 26.3%. Infections usually occurred within 18 months after BMT.     

Nutritional considerations in children undergoing bone marrow transplantation

Bone marrow transplantation is often associated with multiple organ failure which is usually reversible. Oral mucositis and dysphagia, vomiting, diarrhoea, protein losing enteropathy, transient exocrine pancreatic impairment, hypoalbuminaemia, biochemical trace element and mineral deficiencies are all common following transplantation and have profound nutritional consequences. Malnutrition affects negatively the clinical outcome. Nutritional support is provided to malnourished patients and those who suffer deterioration in nutritional status despite the provision of dietetic counselling. Only a few randomised studies comparing enteral with parenteral nutrition after transplant exist. Both enteral tube feeding (in the absence of mucositis) and parenteral nutrition are effective in maintaining nutritional status. However, enteral nutrition is associated with a better nutritional response and fewer complications than parenteral. With existing enteral and parenteral nutrition regimens close monitoring of trace element and mineral status is required.