Living-Donor Lung Transplantation After Bone Marrow Transplantation for Chediak-Higashi Syndrome.

An 8-year-old girl with Chediak-Higashi syndrome (CHS) had pulmonary complications after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) and eventually underwent single living-donor lobar lung transplantation (LDLLT). Electron micrographic findings showed vagus nerve tissue in extracted lung having granular inclusions, which are pathognomonic for CHS. Because her mother was the donor for both hematopoietic stem cell and lung transplantations, she was weaned from immunosuppression and is doing well 3 years after lung transplantation. Furthermore, an induced pluripotent stem (iPS) cell line was established from her skin fibroblasts for investigation and potential future treatment for CHS.

Oral rehabilitation of patients with Chediak-Higashi syndrome using zygoma and root form implant-supported fixed prostheses: A report of two patients.

Chediak-Higashi syndrome (CH-S) is a rare genetic immunodeficiency disorder. Fewer than 500 individuals with CH-S have been reported worldwide in the past 20 years. The dental management of patients in whom CH-S has been diagnosed has been rarely reported and only in the form of a case report. All reports addressed the severe periodontal disease found in those patients, and most studies concluded that periodontal treatment had an unfavorable prognosis. As a result, complete edentulism at an early age because of severe periodontal disease is expected. The purpose of this report was to present 2 patients with CH-S seeking oral rehabilitation after early tooth loss and severe bone resorption as a manifestation of severe periodontal disease. The treatment used bilateral zygoma implants and an all-on-4 concept. The complications encountered and management with a 5-year post-surgery follow-up are also presented.

A severe systemic presentation of pigmented villonodular synovitis in a child with underlying Chediak-Higashi syndrome.

Pigmented villonodular synovitis (PVNS), a condition of synovial hyperproliferation that mostly affects large joints, is rare in children and conventionally lacks systemic symptoms. This report describes a complex paediatric patient who underwent bone marrow transplantation to control the accelerated phase of the Chediak-Higashi syndrome. Diffuse PVNS developed in one knee 2.75 years later. Progression of PVNS was accompanied by the development of severe systemic symptoms, which resolved rapidly following subtotal surgical debridement. The patient remains well with minimal elevation of inflammatory marker levels 10.5 years later. As PVNS and Chediak-Higashi syndrome are both very rare diseases we propose a potential unifying hypothesis for this combination.

Unrelated cord blood transplantation can restore hematologic and immunologic functions in patients with Chediak-Higashi syndrome.

CHS is a rare hereditary fatal disease, if not treated. APs occur in 85% of patients and are usually the main cause of mortality, and HSCT from HLA-matched related and unrelated donors is the only effective treatment for CHS and prevents recurrences of APs. We reviewed the records of three patients with CHS who underwent UCBT at KHCC. Records were examined for clinical features at the time of UCBT, conditioning regimens, morbidities, and outcomes. Conditioning comprised BU, cyclophosphamide, horse ATG, and etoposide. All patients tolerated the conditioning well. Two patients are alive, one with mixed and the other with full donor chimerism; hematologic and immunologic defects of CHS have been corrected in both patients. They show no evidence of recurrences of APs and have normal growth and development. In patients with CHS who lack HLA-matched related and unrelated donors, UCBT is a suitable alternative source of stem cells to restore immunologic and hematologic functions and prevent AP relapses, even in mixed chimeric states. Long follow-up and close monitoring are essential to evaluate the long-term benefits of using UCBT in patients with CHS.

Síndrome de Chediak-Higashi / Chediak-Higashi syndrome

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Chediak-Higashi syndrome.

PURPOSE OF REVIEW: Chediak-Higashi syndrome, a rare autosomal recessive disorder, was described over 50 years ago. Patients show hypopigmentation, recurrent infections, mild coagulation defects and varying neurologic problems. Treatment is bone marrow transplant, which is effective in treating the hematologic and immune defects, however the neurologic problems persist. The CHS1/LYST gene was identified over 10 years ago and homologous CHS1/LYST genes are present in all eukaryotes. This review will discuss the advances made in understanding the clinical aspects of the syndrome and the function of CHS1/LYST/Beige. RECENT FINDINGS: Clinical reports of Chediak-Higashi syndrome have identified mutations throughout the CHS1/LYST gene. The nature of the mutation can be a predictor of the severity of the disease. Over the past decade the CHS1/LYST family of proteins has been analyzed using model organisms, two-hybrid analysis, overexpression phenotypes and dominant negatives. These studies suggest that the CHS1/LYST protein is involved in either vesicle fusion or fission. SUMMARY: Although CHS is a rare disease, the Chediak-like family of proteins is providing insight into the regulation of vesicle trafficking. Understanding the basic mechanisms that govern vesicle trafficking will provide essential information regarding how loss of CHS1/LYST affects hematologic, immunologic and neurologic processes.

Chediak-Higashi syndrome: a case report.

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.

Chediak-Higashi syndrome: four cases from Northern Finland.

UNLABELLED: Chediak-Higashi syndrome (CHS) is a rare multiorgan disease entity with autosomal recessive inheritance characterized by oculocutaneous albinism, bleeding tendency, recurrent bacterial infections and various neurological symptoms. Intracellular vesicle formation is deficient, resulting in giant granules in many cells, e.g. giant melanosomes in the melanocytes. Diagnosis has been based on morphological examination of peripheral blood and bone marrow, with giant granules seen in cells of the myeloid lineage and in lymphocytes. The ultimate diagnostic test is to look for a mutated LYST gene. Most patients develop an accelerated phase of the disease with deposition of lymphohistiocytes in the liver, spleen, lymph nodes and bone marrow, resulting in hepatosplenomegaly, bone marrow infiltration and haemophagocytosis. Peripheral blood neutropenia becomes more profound as anaemia and thrombocytopenia develop. Most patients succumb before the age of 10 years. Four patients with CHS are described, one of whom is a long-term survivor after successful allogeneic bone marrow transplantation, two succumbed during the accelerated phase and one is living with a chronic form of the disease. CONCLUSION: Allogeneic bone marrow transplantation from an HLA-matched sibling is the therapy of choice and should be performed early. If there is no matched family donor, an unrelated donor or a placental blood graft is a good alternative. The clinical picture of CHS is heterogeneous and therapeutic decisions need to be made on an individual basis.

Fludarabine and once-daily intravenous busulfan for allogeneic bone marrow transplantation for Chediak-Higashi syndrome.

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.

Chediak-Higashi syndrome: clinical, hematologic, and immunologic improvement after splenectomy.

A 10-year-old boy with Chediak-Higashi syndrome in accelerated phase failed to respond to treatment with ascorbic acid, vincristine, and prednisone. Splenectomy resulted in clinical, hematologic, and immunologic improvement: his leukocyte chemotactic and phagocytic functions returned to normal. We suggest that splenectomy be considered in treatment of the accelerated phase of Chediak-Higashi syndrome unresponsive to other forms of therapy.

Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies.

Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott-Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno-suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD.

Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) was successfully performed in four Chediak-Higashi (CHS) syndrome affected cats. Preparatory regimens included selective intestinal flora decontamination, fractionated total body irradiation for myeloablation, and prophylactic treatment for graft-versus-host disease with cyclosporin A. Neutrophil chemotaxis under-agarose and whole-blood platelet aggregation/secretion were characterized prior to BMT and after engraftment of donor-origin marrow cells. Liver and kidney biopsies were obtained and evaluated by light and electron microscopy before, and at 6 months post-BMT to determine what effect BMT might have on abnormal lysosome fusion in hepatocytes and renal tubule cells. The platelet storage pool defect was resolved by day 40 post-BMT. In vitro neutrophil migration in all cats appeared to improve with time after BMT and complete restoration was evident by day 175 post-BMT. No apparent differences were evident in either the liver or the kidney at 6 months post-BMT. One cat developed seizures and one developed posterior paresis 5 months post-BMT; neurologic impairment ultimately resulted in death of two cats at 6 and 8 months post-BMT, respectively. Neurologic lesions in both cats were characterized by non-suppurative encephalitis. Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats.

[Role of splenectomy in Chediak-Higashi syndrome in its accelerated phase]. / Ruolo della splenectomia nella sindrome di Chediak-Higashi (SCH) in fase accelerata.

Chediak-Higashi (C.H.S.) syndrome is a rare immunodeficiency, due to defective granulocyte activity. The syndrome is characterized by large inclusion bodies in the leukocytes, albinism, photophobia, nystagmus, and recurrent infections. Some patients develop hepatosplenomegaly, lymphadenopathy, pancytopenia and widespread organ infiltrates with mononucleated cells. This phase is called "accelerated (or lymphoma-like syndrome) phase". A 5 years old girl with C.H.S. in accelerated phase received initially medical treatment without improvement. A splenectomy was performed to remove the hypersplenism and the mechanical compression of the spleen on the gut. Few days after the splenectomy the fever and the pancytopenia disappeared. The pathological examination of the spleen showed multiple intraparenchymal abscesses. Unfortunately, six months after the operation, she died after an acute episode of pneumonia, with normal hematological pattern. The splenectomy may play a role in the "accelerated phase" of C.H.S., but new treatments (bone marrow transplantation) are necessary to remove the basic disease.