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

Abstract

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...

Endocrine late effects after bone marrow transplant

“…All 34 patients showed normal glucose levels during an intravenous glucose tolerance test (GTT) and a normal haemoglobin A1C concentration. Hirayama et al (1998) reported a child who, following BMT including TBI and splenic irradiation, went on to develop type II non‐insulin‐dependent diabetes mellitus 8 years post transplant; a causal relationship, however, between TBI and the development of diabetes mellitus has never been established. Taskinen et al (2000) assessed glucose and lipid metabolism after BMT in 23 long‐term survivors (median age 20 years).…”

Diabetes mellitus after stem cell transplantation in a patient with acute lymphoblastic leukemia: Possible association with tacrolimus

“…The donors had type‐1 diabetes at the time of BMT. There are also reports of non‐insulin‐dependent diabetes mellitus (NIDDM) in patients treated with high‐dose chemotherapy and autologous and allogeneic BMT 6,7 . In a case of allogeneic BMT, although the 14‐year‐old donor had no symptoms of DM at the time of transplant, she transferred NIDDM to the recipient 6 .…”

“…There are also reports of non‐insulin‐dependent diabetes mellitus (NIDDM) in patients treated with high‐dose chemotherapy and autologous and allogeneic BMT 6,7 . In a case of allogeneic BMT, although the 14‐year‐old donor had no symptoms of DM at the time of transplant, she transferred NIDDM to the recipient 6 . In the present case, the first scenario is more likely because the donor was selected by the Japanese bone marrow bank and received clinical screening evaluations prior to donation.…”

Diabetes Mellitus after Allogeneic Hematopoietic Stem Cell Transplantation

“…The etiopathogenesis of DM after transplantation is unclear and most possibly multifactorial, involving side effects of chemotherapeutic agents, pancreatic irradiation, cytokine influence, endocrine replacement, corticosteroid therapy and genetic predisposition [5,7,8,12,13,14]. …”