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Title: Thyroid dysfunction among long-term survivors of bone marrow transplantation

Abstract

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versusmore » two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.« less

Authors:
; ;
Publication Date:
Research Org.:
Department of Pediatrics, University of Minnesota Health Sciences Center, Minneapolis, Minnesota
OSTI Identifier:
6794546
Alternate Identifier(s):
OSTI ID: 6794546
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Med.; (United States); Journal Volume: 73:5
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; CHEMOTHERAPY; SIDE EFFECTS; RADIOTHERAPY; THYROID; BIOLOGICAL RADIATION EFFECTS; ANEMIAS; BONE MARROW; DYNAMIC FUNCTION STUDIES; LEUKEMIA; PATIENTS; TRANSPLANTS; ANIMAL TISSUES; BIOLOGICAL EFFECTS; BODY; DISEASES; ENDOCRINE GLANDS; GLANDS; HEMATOPOIETIC SYSTEM; HEMIC DISEASES; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; ORGANS; RADIATION EFFECTS; RADIOLOGY; SYMPTOMS; THERAPY; TISSUES 550603* -- Medicine-- External Radiation in Therapy-- (1980-); 551000 -- Physiological Systems; 550900 -- Pathology

Citation Formats

Sklar, C.A., Kim, T.H., and Ramsay, N.K.. Thyroid dysfunction among long-term survivors of bone marrow transplantation. United States: N. p., 1982. Web. doi:10.1016/0002-9343(82)90411-9.
Sklar, C.A., Kim, T.H., & Ramsay, N.K.. Thyroid dysfunction among long-term survivors of bone marrow transplantation. United States. doi:10.1016/0002-9343(82)90411-9.
Sklar, C.A., Kim, T.H., and Ramsay, N.K.. Mon . "Thyroid dysfunction among long-term survivors of bone marrow transplantation". United States. doi:10.1016/0002-9343(82)90411-9.
@article{osti_6794546,
title = {Thyroid dysfunction among long-term survivors of bone marrow transplantation},
author = {Sklar, C.A. and Kim, T.H. and Ramsay, N.K.},
abstractNote = {Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.},
doi = {10.1016/0002-9343(82)90411-9},
journal = {Am. J. Med.; (United States)},
number = ,
volume = 73:5,
place = {United States},
year = {Mon Nov 01 00:00:00 EST 1982},
month = {Mon Nov 01 00:00:00 EST 1982}
}
  • Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtrationmore » rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.« less
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  • Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination ofmore » plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.« less
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