Autoimmune polyendocrine failure — Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism — after allogenic bone marrow transplantation in a patient with lymphoblastic leukaemia

Summary:Autoimmune thyroid disease (AITD) may occur in patients after hematopoietic stem cell transplantation (HSCT). In all, 10 cases of AITD (seven allogeneic and three autologous HSCT) were diagnosed among 721 HSCT recipients, including two patients with sequential hyper-and hypothyroidism. The 5-year actuarial rates for AITD after allogeneic and autologous HSCT were 2.9 and 4%, respectively. Significant risk factors included HSCT for chronic myeloid leukemia, the HLA B46 and DR9 loci and the A2B46DR9 haplotype, while female donors showed trend to significance. On multivariate analysis, only female donors and HLA DR9 remained significant. For autologous HSCT, the associations with HLA B46 and DR9 were also significant. Only three donors had a family history of AITD. A review of other reported cases confirmed the predominance of female donors, although the other associations including graftversus-host disease, familial AITD and other autoimmune phenomena might be related to reporting bias. Since the actuarial incidence of AITD from female donors with predisposing HLA alleles may be over 30%, susceptible recipients should be carefully monitored. Owing to the small number of reported cases and different HLA associations with AITD in different populations, our observations await confirmatory data from other registries.

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation

Lie

Kung

et al. 2005

“…In humans, it has been reported that autoimmune diseases such as autoimmune thyroiditis, [38][39][40] Graves' disease, 41 insulin-dependent diabetes mellitus 42,43 and myasthenia gravis 44,45 are transferred to recipients after BMT. It has also been reported that autoimmune diseases such as psoriasis vulgaris, 46,47 ulcerative colitis 46 and palmoplantar pustular psoriasis 40 are resolved after BMT in patients suffering from both leukemia and autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Prevention of autoimmune hearing loss in MRL/lpr mice by bone marrow transplantation

Lee

Iwai

Sugiura

et al. 2000

Summary:We examined the effects of bone marrow transplantation (BMT) on immune-mediated inner ear diseases in MRL/Mp-lpr/lpr (MRL/lpr) mice, which manifest not only lupus nephritis but also sensorineural hearing loss (SNHL) at the age of 20 weeks. These mice were treated with cyclophosphamide (CY) and irradiation (5 Gy × 2), followed by the transplantation of bones plus bone marrow cells from allogeneic normal C57BL/6 mice at the age of 12 weeks. Hematolymphoid cells were reconstituted with donor-derived cells 3 months after BMT. Thus-treated MRL/lpr mice showed neither lupus nephritis nor SNHL even 24 weeks after BMT. No pathological findings were observed in either glomeruli or cochleae. These findings suggest that BMT can be used to prevent the development of autoimmune SNHL in MRL/lpr mice. Bone Marrow Transplantation (2000) 26, 887-892. Keywords: MRL/lpr mouse; autoimmune hearing loss; bone marrow transplantation It has become widely recognized that autoimmune mechanisms are involved in inner ear diseases 1-3 such as steroidresponsive sensorineural hearing loss (SNHL) 4 and Méni-ère's disease, 5 as first proposed by McCabe in 1979. 1 Inner ear dysfunction causes various audiovestibular symptoms such as SNHL, tinnitus and vertigo. The presence of SNHL as a part of or in combination with systemic autimmune diseases such as systemic lupus erythematosus (SLE), 6-8 rheumatoid arthritis (RA), 9-12 Behçet's disease, 13,14 Cogan's syndrome, 15,16 and ulcerative colitis 17,18 has been reported.MRL/lpr mice were found to spontaneously develop SNHL as well as SLE by autoimmune mechanisms. The mice carrying the lymphoproliferation (lpr) mutation have defects in the Fas gene, and a defect in negative selection of self-reactive T cells in the thymus. In cooperation with abnormal T cells, auto-reactive B cells produce autoantibodies or immune complexes which are deposited in the lesions of both the stria vascularis of the cochlea and the basement membranes of the glomeruli. [19][20][21][22] It has recently been reported that SNHL in MRL/lpr mice can be improved by steroid therapy and the levels of serum immune complexes were found to be reduced after steroid therapy. 23 We have also reported that the SNHL and cochlear pathology can be transferred to normal mice by the injection of lymphocytes from MRL/lpr mice. 24 In addition, we have demonstrated that autoimmune diseases are induced by abnormal hemopoietic stem cells (HSCs). When normal mice are reconstituted with bone marrow cells or HSCs from animals with autoimmune diseases such as SLE, 25 diabetes mellitus 26 and focal and segmental glomerular sclerosis, 27 the autoimmune diseases are transferred to the normal mice. In addition, we have found that BMT can be used to treat these autoimmune diseases. 28,29 In the present study, we show that autoimmune SNHL in MRL/lpr mice can be prevented by allogeneic BMT. Materials and methods AnimalsMRL/lpr mice (H-2K k ) were purchased from SLC Japan (Shizuoka, Japan). C57BL/6 (B6) (H-2K b ) mice were purchased from CLEA Japan (Osa...

“…5 IDDM are recognized as organ specific autoimmune diseases occurring in genetically predisposed subjects after exposure to one or more environmental factors. Vialettes et al 7 and Lampeter et al 8 described transfer of IDDM by allogeneic bone marrow transplantation. However, it is generally considered that NIDDM is an etiological multi-factorial disease and not related to immunological mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 It is generally considered that insulin-dependent diabetes mellitus (IDDM) is related to immunological mechanisms, and there is a report of adoptive transfer of IDDM. 7,8 However, it is supposed that non-insulin-dependent diabetes mellitus (NIDDM) has nothing to do with immunological mechanism in humans although immunological mechanisms have been reported to be implicated in an animal model. 9 This is the first report of a patient who developed unilateral renal dysfunction and NIDDM after allogeneic BMT for which total body irradiation (TBI) and/or splenic irradiation were used in the preparative regimen.…”

mentioning

confidence: 99%

Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child

Hirayama

Azuma

Kumamoto

et al. 1998

Summary:We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m 2 ؋ 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1. years post transplant. He presented with microhematuria and proteinuria 4. years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulindependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation. Keywords: BMT nephropathy; diabetes mellitus; bronchial asthma Late-onset complications after bone marrow transplantation often become life-threatening or decrease quality of life in patients. Significant complications include second malignancy, growth retardation, thyroid dysfunction, gonadal dysfunction and cataract formation. Recently nephropathy and diabetes mellitus (DM) have been noted. [1][2][3][4] We describe a patient with the successive complications of asthma, nephropathy and DM after BMT which are gradually reducing quality of life. In this case nephropathy was a unilateral renal dysfunction related to splenic top-up irradiation. Whether additional splenic irradiation has a beneficial effect for hematological malignancy is contro- versial. 5,6 It is generally considered that insulin-dependent diabetes mellitus (IDDM) is related to immunological mechanisms, and there is a report of adoptive transfer of IDDM. 7,8 However, it is supposed that non-insulin-dependent diabetes mellitus (NIDDM) has nothing to do with immunological mechanism in humans although immunological mechanisms have been reported to be implicated in an animal model. 9 This is the first report of a patient who developed unilateral renal dysfunction and NIDDM after allogeneic BMT for which total body irradiation (TBI) and/or splenic irradiation were used in the preparative regimen. Case reportA 7-year-old boy was diagnosed with acute lymphoblastic leukemia in September 1987. Blasts were phenotypically T cell antigen positive with chromosomal hypodiploidy. He had hyperleukocytosis (WBC 730 ϫ 10 9 /l) and massive hepatosplenomegaly at the time of diagnosis. He was treated with vincristine, l-asparaginase, doxorubicin and prednisolone with response. Second-line chemotherapy with methotrexate (MTX) and l-asparaginase were given. He achieved a complete hematological response after 5 weeks, although splenomegaly persisted. He was referred for BMT following maintenance chemotherapy for 2 months. Before grafting, he was prepared with high-dose cytosine arabinoside 3 g/m 2 twice daily i.v. for 5 consecutive days (total 10 doses), total body irradiation (TBI) of 12 Gy in fou...