11/104. Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation. We investigated whether a T cell-reduced allogeneic stem cell transplant (SCT) with minimal conditioning and subsequent donor lymphocyte infusions (DLI) could reduce the incidence and severity of GVHD while retaining stable engraftment. Five patients with hematological malignancies (three MM, one CLL, one chediak-higashi syndrome) were conditioned with TBI (200 cGy). One patient additionally received fludarabine (120 mg/m(2)). CsA and mofetyl-mycophenolate (MMF) were administered to prevent GVHD. All patients were grafted with >3 x 10(6)/kg highly purified CD34( ) cells together with 2 x 10(6)/kg CD3( ) cells (three patients) or 1 x 10(5)/kg CD3( ) cells (two patients). Quick hematopoietic recovery and initial mixed donor chimerism was observed. Treatment-related toxicity was minimal in all but one patient who died of treatment-refractory GVHD on day 112. The four other patients only achieved partial donor T cell chimerism. BM and PBMC donor chimerism was lost between day 40 and 209 despite DLI. Three patients are alive with disease and one is in CR. We conclude that T cell-reduced SCT using 200 cGy as the conditioning regimen does not result in stable hematopoietic engraftment. Predominant donor T cell chimerism is not a prerequisite for initial allogeneic hematopoietic proliferation. However for sustained long-term engraftment it is of major importance. ( info) |
| chediak-higashi syndrome is a rare autosomal recessive disorder, primarily affecting neutrophils, and is often lethal by the third decade of life. bone marrow transplantation is the only curative therapy currently available. This case describes a child undergoing a bone marrow transplant from a matched sibling donor, resulting in hematopoietic chimerism with only a small percentage of donor neutrophils found long term. The presence of a small percentage of donor neutrophils has resulted in normal development and no increased incidence of infections. Hematopoietic chimerism offers a cure with a potential reduction in the side-effects that result from marrow transplantation and the associated preparative therapies. ( info) |
13/104. Clinicopathological aspects of chediak-higashi syndrome in the accelerated phase. This report describes clinical and laboratory features of a case of chediak-higashi syndrome that presented in the accelerated phase of the disorder. This female infant presented with a fever, marked neutropenia, large cytoplasmic granules in leukocytes and a constellation of features that suggested a virus-associated hemophagocytic syndrome. The clinical course was marked by limited response to the therapeutic agents that included ascorbate, cytotoxic agents and granulocyte colony-stimulating factor. ( info) |
| A 14-week-old boy with undiagnosed chediak-higashi syndrome developed fever with a high temperature and acute cardiac failure after having received a scheduled vaccination. We hypothesize that decreased concentrations and receptor binding of serum and tissue diadenosine polyphosphates, such as AP4A, AP5A, or AP6A, which are stored in various tissues and serve as extra-cellular signaling molecules or are secreted by cells in response to physiologically stressful stimuli, lead to the observed severe tachyarrhythmia. Diadenosine polyphosphates normally have a negative chronotropic and inotropic effect. This is the first report of severe cardiac failure in a child with chediak-higashi syndrome and we suggest that cardiac arrhythmias should be considered in such children in the event of high fever. Our hypothesis requires further investigation in other patients. ( info) |
| chediak-higashi syndrome (CHS) is a hereditary multiorgan disease associated with a lymphoproliferative disorder termed 'accelerated phase' (AP). As AP is often life-threatening, hematopoietic stem cell transplantation has been proposed as the only curative treatment for CHS. Here, we report a 1-year-old Japanese boy with CHS who received an HLA-matched unrelated BMT at the AP stage, which resulted in split chimerism. We evaluated the chimerism status of isolated leukocytes and found that only a limited population of T and NK cells was of donor origin and the majority of these and other hematopoietic cells was of host origin. Clinical outcome was successful, and the patient is currently alive and well, free of AP and serious infections more than 18 months after BMT. ( info) |
16/104. chediak-higashi syndrome in a black infant. A light and electron microscopic study with special emphasis on erythrophagocytosis. Clinicopathologic observations in the case of a black infant with chediak-higashi syndrome are reported. light and electron microscopic examination of spleen, liver and lymph nodes revealed abnormal large lysosomes as well as marked erythrophagocytosis without hemosiderosis in infiltrating histiocytes and kupffer cells. In addition, there were abnormal ocular findings. It is suggested that the erythrophagocytosis without hemosiderosis might also be a specific anatomic expression of this disease due to defective lysosomal digestion of phagocytosed erythrocytes. ( info) |
| Platelet function studies were performed on two patients with the chediak-higashi syndrome, one of whom had a history of easy bruising unrelated to thrombocytopenia. Both patients had prolonged bleeding times, abnormal platelet aggregation, and a defect of platelet storage granules, manifested by reduced platelet ADP, an increased ATP/ADP ratio, increased adenine nucleotide specific radioactivity after 3H-adenine labeling, and decreased platelet uptake of radioactive 5-hydroxytryptamine. These findings confirm preliminary data in animals with the chediak-higashi syndrome, provide and explanation for impaired primary hemostasis in these patients, and illustrate another disorder in which platelet storage-pool deficiency occurs. ( info) |
| BACKGROUND: The change of visual function in chediak-higashi syndrome has not been well described.CASES: The visual function of a 12-year-old Japanese girl with ocular albinism due to chediak-higashi syndrome was followed by periodic ophthalmological examinations.OBSERVATIONS: A lack of pigmentation in the iris and ocular fundus, and pigmentary degeneration of the peripheral retina were observed. The visual loss and the constriction of visual field progressed with increasing age. The electroretinogram was extinguished at 12 years of age.CONCLUSIONS: The constriction of the visual field may be due to the pigmentary degeneration of the ocular fundus. Ophthalmologists should be aware that progressive visual loss and the constriction of visual field can occur in patients with chediak-higashi syndrome as they grow older. ( info) |
19/104. Accelerated phase at initial presentation: an uncommon occurrence in chediak-higashi syndrome. The authors describe an Indian child, who presented in the accelerated phase of the chediak-higashi syndrome. The disease usually presents in early childhood with recurrent skin and mucosal infections. This patient had subtle pigmentary abnormalities and no family history of the disease, which made the clinical diagnosis difficult. The cytopenias, hepatosplenomegaly, lymphohistiocytic infiltrate in the bone marrow, and the characteristic granules in the leucocytes clinched the diagnosis. This case underscores the importance of a bone marrow examination in patients with unusual presentations of rare disorders. ( info) |
| An HLA-identical sibling bone marrow transplant was done for a patient with chediak-higashi syndrome. The preparative regimen included intravenous fludarabine (40 mg/m2/dx4) and busulfan (130 mg/m2/dx4). busulfan was given once daily. Pharmacokinetic studies showed the area under the concentration-time curve of the once-daily intravenous busulfan was similar to that seen with the total daily dose administered with an every-6-hourly regimen. Toxicity was minimal. Myeloid engraftment occurred on day 17 and donor chimerism was complete. Fludarabine and once-daily intravenous busulfan is well tolerated and is adequate for engraftment of sibling transplant in chediak-higashi syndrome. ( info) |