MR appearances of bone marrow in children following bone marrow transplantation

Two cases are presented of children who demonstrated complete absence of bone marrow signal on MR imaging of the spine following bone marrow transplantation. The possible causes for these appearances are discussed.     

Haploidentical bone marrow transplantation in Mexico

Haploidentical hematopoietic cell transplantation using CD34⁺ cells depleted of T lymphocytes by the CliniMACS is a treatment for hematological malignancy. We report on four Mexican children, three with acute lymphocytic leukemia and one with chronic myelocytic leukemia, who was transplanted with 12 × 10⁶ CD34⁺ stem cells/kg body weight (98% of purity) with a follow‐up of years. The engraftment was successful in three of the four children. All showed cytomegalovirus reactivation, and one died because of graft rejection and infectious complication. The risk of infections was a major problem. Pediatr Blood Cancer 2012; 59: 950–952. © 2012 Wiley Periodicals, Inc.     

Enteral nutrition after bone marrow transplantation

Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only. Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.     

Recent advances in bone marrow transplantation

The major barriers to successful bone marrow transplantation (BMT) are graft-versus-host disease (GVHD), infection, rejection and relapse. The combination of methotrexate and cyclosporin is significantly better than either alone in controlling GVHD. Removal of T cells from donor marrow prior to BMT has also decreased GVHD significantly, but a 5-10% rejection rate occurs and an increased relapse risk is being reported by some centres. Cyclosporin is valuable in the treatment of both acute and chronic GVHD. Interstitial pneumonitis due to cytomegalovirus (CMV) is a major cause of mortality. Protection can be provided with CMV hyperimmune globulin and also by the avoidance of blood donors who are CMV antibody positive. Fractionated total body irradiation is associated with decreased toxicity compared to single dose. There is a 75% 4 year disease-free survival following BMT for acute non-lymphoblastic leukemia in first remission, a 50% survival for acute lymphoblastic leukemia in second remission and an 88% survival for chronic myeloid leukemia in chronic phase. BMT for beta-thalassaemia major in young patients without organ dysfunction cures 80% of patients and identical results are achieved for severe aplastic anaemia when BMT is undertaken prior to blood product transfusion.     

Haploidentical bone marrow transplantation for osteopetrosis

HLA-matched bone marrow transplantation is an effective form of treatment for some patients with malignant osteopetrosis, a defect of osteoclast function. Following transplant, normal osteoclasts differentiate from donor-derived marrow stem cells and can function normally in some of these patients. For patients without an HLA-matched marrow donor, pharmacologic treatments have not yet proved effective. This article demonstrates that normal osteoclast function can be obtained following the transplantation of HLA-nonidentical marrow that has been purged of T lymphocytes in vitro.     

Long-term effects of bone marrow transplantation

As increasing numbers of children are surviving beyond the 1st decade after marrow transplantation and increasing numbers of children are receiving marrow transplants each year, the delayed effects related to the transplant procedure itself, the original disease, and/or the transplant preparative regimen are becoming apparent. Late effects related to the transplant procedure include those of engraftment stability, the chronic immunosuppression of chronic graft-versus-host disease and delayed immunologic recovery. Recurrent disease is the major late effect related to the patient's original disease. The late effects which may be related to previous therapy administered and/or the transplant preparative regimen include abnormalities of neuroendocrine function, ocular problems, dental developmental abnormalities in young children, central nervous system dysfunction and the development of secondary malignancies. To improve the quality of life of marrow transplant recipients and to prevent some of the growth and development abnormalities which may occur, an awareness of the problems encountered to date is needed.     

Recent advances in bone marrow transplantation

The major barriers to successful bone marrow transplantation (BMT) are graft-versus-host disease (GVHD), infection, rejection and relapse. The combination of methotrexate and cyclosporin is significantly better than either alone in controlling GVHD. Removal of T cells from donor marrow prior to BMT has also decreased GVHD significantly, but a 5–10% rejection rate occurs and an increased relapse risk is being reported by some centres. Cyclosporin is valuable in the treatment of both acute and chronic GVHD. Interstitial pneumonitis due to cytomegalovirus (CMV) Is a major cause of mortality. Protection can be provided with CMV hyperimmune globulin and also by the avoidance of blood donors who are CMV antibody positive. Fractionated total body irradiation is associated with decreased toxicity compared to single dose. There is a 75% 4 year disease-free survival following BMT for acute non-lymphoblastic leukaemia in first remission, a 50% survival for acute lymphoblastic leukaemia in second remission and an 88% survival for chronic myeloid leukaemia in chronic phase. BMT for β-thalassaemia major in young patients without organ dysfunction cures 80% of patients and identical results are achieved for severe aplastic anaemia when BMT is undertaken prior to blood product transfusion.     

Pediatric feeding and swallowing disorders after bone marrow transplant

Reduced oral intake is a known complication of bone marrow transplant (BMT) and may result in short-term tube feedings. Although most children return to typical eating habits, a subgroup of children requires intervention. The focus of the current investigation was to retrospectively identify the incidence and characteristics of feeding and swallowing disorders in pediatric patients during the first 100 days after BMT and to determine what factors contribute to feeding/swallowing disorders past the BMT acute phase (100+ d). The charts of 292 sequential patients undergoing BMT were reviewed. Seventy-two children (25%) were referred for feeding and/or swallowing intervention with a mean age of 78.6 months (SD=±63.4). Sixteen patients underwent instrumental evaluation with swallowing dysfunction identified in 50% (n=8) of the patients. Oral-motor dysfunction was reported in 33% (n=24) and feeding disorders occurred in 61% (n=44) of the patients referred for treatment. This single-institution review describes the impact of this interruption in the first 100 days after transplant on feeding and swallowing and determined what factors place a child at an increased risk for requiring tube feeding for 100+ days after transplant. The type of BMT, the use of a tube during the first 100 days, and the age were all significant predictors of requiring a tube when considered together for the individual patient. Children who do not require a tube in the first 100 days are significantly less likely to require one in future, approximately 85% less likely to require one whereas children receiving an autologous transplant are approximately 70% less likely to require a tube than children receiving an allogenic transplant. Providers should consider an intervention for younger children undergoing BMT to help maintain or facilitate the development of their feeding and swallowing skills. This may lead to improved feeding outcome in the pediatric BMT population.     

Gastrointestinal and nutritional sequelae of bone marrow transplantation

The nature of the gastrointestinal injury following bone marrow transplantation and its clinical and nutritional sequelae are poorly defined. Prospective assessments of gastrointestinal function, nutritional status, and wellbeing were therefore carried out in 47 consecutive patients (28 males, 19 females; mean age 8.4 years) undergoing bone marrow transplant. 31 diarrhoeal episodes (median duration 9.5 days) occurred in 27 patients at a median of 10 days after transplantation. Ninety one per cent of episodes were associated with protein losing enteropathy. Protein losing enteropathy was more severe in graft-versus-host disease (GVHD) comparing with other causes. It led to a substantial fall in serum albumin and there was a negative correlation between faecal alpha 1-antitrypsin concentrations and serum albumin. Transient pancreatic insufficiency developed in 18 patients, and pancreatitis in one. Intestinal permeability was normal in 12 patients who had no diarrhoea during the conditioning treatments. Diarrhoeal patients had a significantly greater decrease in nutritional status and wellbeing than patients without diarrhoea. Gastrointestinal injury following bone marrow transplantation is thus complex. Severe protein losing enteropathy in this context suggests the presence of GVHD.     

Thyrotoxicosis after matched unrelated bone marrow transplantation

Acquired hyperthyroidism is most commonly autoimmune in etiology. In the setting of allogeneic bone marrow transplantation (BMT), the use of radiotherapy (total body irradiation) as part of the regimen prior to BMT is known to cause endocrine dysfunction, especially hypopituitarism and hypothyroidism, but hyperthyroidism is rare. The authors report this unusual and late complication in a young boy after BMT for relapsed childhood lymphoblastic leukemia and discuss the possible etiologies.     

Stages in pediatric bone marrow transplantation.

Bone marrow transplantation is a relatively new and aggressive procedure that is being used in the treatment of leukemia and aplastic anemia. We observed approximately 30 children and their families at the UCLA Medical Center throughout the procedure. Various psychological responses during the treatment are outlined. Eleven stages are identified, including the patient's and family's first awareness of this procedure, the preadmission evaluation and psychosocial assessment, the introduction into isolation, the donor's hospitalization, the transplantation itself, and the various reactions and interactions of the patient, family, and staff throughout these stages.     

Endocrine complications following pediatric bone marrow transplantation

Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly.     

Pulmonary fungal infections after bone marrow transplantation

Of 319 pediatric patients treated with bone marrow transplantation (BMT) during a 10-year period, 27 developed pulmonary fungal infections (PFI). Only 2 patients (7%) survived. Twenty-three patients (85%) had been treated with systemic antifungal therapy immediately before or at the time of diagnosis. Nineteen patients (70%) were neutropenic, and 4 of the 8 patients who were not neutropenic were being treated with systemic steroids for graft vs. host disease (GVHD). Seven patients (26%) died within 7 days of diagnosis. The diagnosis was made ante-mortem in 9 patients (33%). Radiographic abnormalities were variable. At the onset of chest X-ray (CXR) change, the pulmonary infiltrates were unilateral in 14 patients (52%) and, at diagnosis, bilateral in 18 (66%). At diagnosis the infiltrates were interstitial in 3 patients (11%), alveolar in 20 (74%) and mixed in 4 (15%). Six patients (22%) developed cavitary lesions. The infecting agents were Aspergillus in 21 patients (78%), Candida in 7 (26%), Mucormycosis in 3 (11%), and Fusarium in 1 (4%). Five patients (19%) had mixed fungal infections and 7 (26%) had concurrent cytomegalovirus (CMV) pulmonary infections. Although the radiographic changes are often nonspecific in PFI, alveolar or nodular infiltrates in neutropenic patients or in those being treated for GVHD should strongly suggest a fungal etiology.     

Treatment of adrenoleukodystrophy with bone marrow transplantation

Three children with adrenoleukodystrophy (ALD) underwent allogeneic bone marrow transplantation (BMT) between 1992 and 1993. The first boy had attention deficits, marked neuropsychological deficits and widespread demyelination in the frontal lobes on MRI before transplantation. Four years later he has mentally deteriorated and the demyelination on MRI has progressed. The second boy had no symptoms but had white matter lesions on MRI when diagnosed. He was regularly followed with MRI and neuropsychological investigations until BMT 18 months later. A progress of the lesions was noted on the initial MRI investigations, and 4 months before BMT a worsening of deficits in attention and kinaesthetic praxis could be observed. He rapidly deteriorated after the transplantation and died 18 months later. Both PCR and in situ hybridization confirmed the presence of donor cells in the brain. The third boy had no symptoms but white matter lesions on MRI when diagnosed. The neuropsychological tests remained normal but a slight progress was observed on MRI just before transplantation. This boy is still healthy 3.5 years after BMT. BMT as treatment for ALD has to be considered very early, even in a child without symptoms but signs of demyelination on MRI, if a suitable donor is available.