Fatal interstitial pulmonary disease in a patient with dyskeratosis congenita after allogeneic bone marrow transplantation

Abstract

Summary:infections early after BMT 3 and the late complication of vascular damage which may be caused by hypersensitivity to the conditioning agents 4 or interstitial lung disease. 5 Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneicObstructive lung disease (OLD) has been described as a serious complication after allogeneic BMT. The developbone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic ment of OLD was strongly associated with chronic GVHD. 6 Both clinical and histologic features of DC are very similar anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP misto that of chronic GVHD. 7 Additionally, some cases of DC have been reported to develop chronic pulmonary matched brother. He developed grade II acute graftversus-host disease (GVHD) and thereafter chronic disease. 8,9 We describe a case of DC with chronic restrictive lung disease 7 years after HLA-DP mismatched GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical allogeneic BMT, and report the results of immunological and histologic examination. improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effecCase report tive and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic A 1-year and 10 months-old boy was referred to our hospital because of epistaxis. He was the third child of healthy infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the parents, and there was no family history of skin or hematological disorders. He was noted to have reticular pigmenskin and the liver. These findings raise the possibility that this pulmonary complication was associated with tation and progressive nail dystrophy of both fingers and toes. He also had a congenital visual defect of the left eye. DC itself. Keywords: dyskeratosis congenita; allogeneic bone A brain CT scan showed bilateral parieto-occipital calcifications. Leukoplakia of the oral mucous membrane was not marrow transplantation; chronic GVHD; restrictive lung disease observed. Laboratory data revealed a hemoglobin of 5.4 g/dl, white blood cell count of 3.8 × 10 9 /l (absolute neutrophil count of 1.4 × 10 9 /l), and a platelet count of 19 × 10 9 /l. Bone marrow aspiration showed hypoplasia of Dyskeratosis congenita is a rare hereditary disorder characall cell lineages, and the number of hematopoietic progeniterized by reticular hyperpigmentation of the skin, dystor cells was reduced in colony assay. Cytogenetic studies trophy of the nails, and leukoplakia of mucosal memwere normal and there were no chromosomal breaks. branes. 1 It is frequently associated with severe aplastic Because treatment with anabolic steroids and prednisolone anemia and malignant...

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure

“…Previous reports (Table 3) have described progression of the clinical signs of DKC after transplantation, which was indistinguishable from the natural course of disease. [8][9][10][11][20][21][22][23] In our series, all patients except one received low intensity conditioning regimens. The conditioning protocol was different across different centers.…”

“…However, the tolerability of the conditioning regimen is always limited by the increased risk of developing significant tissue injury as a result of irradiation and chemotherapy due to inherited defects in genome maintenance. [18][19][20][21][22][23] This hypersensitivity to irradiation and chemotherapy translated into poor survival of patients after SCT, using conventional myeloabaltive conditioning. 20,21 Short-term transplant-related complications are not uncommonly observed in patients with DKC in the setting of allo-HSCT.…”

“…Longer follow-up is still needed to determine if long-term toxicity is also reduced when using such regimens. 10,12,18,[22][23][24]35 …”

Dyskeratosis congenita

“…Patients with BMF due to DC do not respond to immunosuppressive therapy [45]. They are also at high risk of HSCT-related complications due to underlying pulmonary and liver disease [46][47][48][49][50]. In addition, recent studies have shown individuals can be "silent" carriers of a pathogenic mutation in a DC gene [12].…”

“…HSCT is clearly a life-saving measure, but has substantial risks either from toxicity from radiochemotherapy or immune-related complications. Reported problems include graft failure, GVHD, sepsis, pulmonary fibrosis, cirrhosis, and veno-occlusive disease [49;66], due, in part, to underlying pulmonary and liver disease [46][47][48][49][50]. As a result, long-term survival of patients with DC following HSCT has been very poor [49;66].…”