Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults

Summary:Patients with hematological malignancies are well nourished prior to allogeneic hematopoietic stem cell transplantation (HSCT). HSCT and associated complications can affect body composition. The study evaluated crosssectionally the prevalence and longitudinally the changes in lean body mass index (LBMI) in HSCT patients. Patients (n ¼ 82) were classified as normal or low LBMI. Logistic regression analyses were used to estimate odds ratios (OR) for low vs normal LBMI, between healthy volunteers and patients; for limited or extensive vs no chronic graft-versus-host-disease (GVHD); and for decreased (Karnofsky o80) vs normal functional status (480). Patients were significantly more likely to have low LBMI at 6, 12 months, 2-3, 4-6 and 46 years than volunteers. In all, 38% of patients were below pre-HSCT LBMI at 4-6 years post-HSCT. Low LBMI was significantly associated with steroid treatment (OR 2.6, confidence intervals (CI) 1.3-5.2, P ¼ 0.008); limited (OR 5.5, CI 1.7-18.5, P ¼ 0.005) or extensive chronic GVHD (OR 20.3,, Po0.001); and decreased performance status (Karnofsky scores of p80) (OR 2.7, CI 1.3-5.9, P ¼ 0.01). Patients were more likely to have low LBMI than volunteers. Chronic GVHD and low performance status were associated with low LBMI; thus, complications and/or treatment increase the likelihood of low LBMI. Patients with hematological malignancies are usually well nourished at the time of allogeneic hematopoietic stem cell transplantation (HSCT). 1,2 However, nutritional consequences after HSCT have not been well studied. Underweight patients are at increased risk of death in the early post-HSCT period, and nonrelapse mortality is greater for extremely underweight or overweight patients. 3,4 High body mass index (BMI), weight normalized for height, may also affect treatment-related toxicity and mortality. 5 Furthermore, low lean body mass (LBM) has been associated with poor outcome and increased length of hospital stay. 6 Allogeneic HSCT and associated complications, including infections and graft-versus-host-disease (GVHD), can affect body weight and body composition. Immunosuppressive therapy after transplantation has been shown to alter skeletal muscle metabolism. 7 Corticosteroids promote muscle atrophy by increasing the rate of protein catabolism, amino-acid efflux, while simultaneously decreasing the rate of protein synthesis. 8 Thus, treatment and complications following HSCT exert profound negative effects on LBM.As low LBM is associated with poor outcome, the evaluation of LBM and body fat changes in pre-and post-HSCT patients can aid in adapting nutrition policy, for example, nutrition support in malnutrition and food restriction in obesity. 9 Just as BMI is useful in evaluating the excess or deficit in body weight in individuals of different heights, the lean body mass index (LBMI, kg/m 2 ) and body fat mass index (BFMI, kg/m 2 ) are potentially useful in evaluating body composition parameters by effectively eliminating differences in LBM and body fat with height. 10 Height-indepe...

Section: Effects Of Treatmentmentioning

confidence: 89%

Section: Situation Before and After Hsctmentioning

confidence: 99%

Longitudinal follow-up of body composition in hematopoietic stem cell transplant patients

Kyle

Chalandon

Miralbell

et al. 2005

“…BMI and leptin concentrations correlated positively with each other and negatively with GH peaks, but not with growth rates or plasma IGF I concentrations. Kauppila et al 18 evaluated the GH response to GH-releasing hormone in adults given BMT and also found an inverse relationship between BMI and GH peak. The persistent low BMI after TBI and the poor growth response to standard doses of GH after TBIinduced GH deficiency suggest that nutritional support may be considered to optimize the growth rate of these patients.…”

Section: Discussionmentioning

confidence: 99%

Changes in height, weight and plasma leptin after bone marrow transplantation

Couto-Silva

Trivin

Esperou

et al. 2000

Summary:Short stature can be a severe side-effect of bone marrow transplantation (BMT). Because of the effect of weight changes on growth rate and on plasma insulin-like growth factor (IGF I), we analyzed changes in height and body mass index (BMI) in 53 patients given BMT. Group 1 (n = 22) was given 12 Gy total body irradiation (TBI) as six fractions, group 2 (n = 14) 10 Gy TBI (one dose), group 3 (n = 8) 6 Gy total lymphoid irradiation (one dose), and group 4 (n = 9) chemotherapy alone. At the first evaluation, 13/36 patients in groups 1 and 2 had low growth hormone (GH) peaks after stimulation. The mean plasma IGF I concentrations (z score) were similar in groups 1 (−2.9 ± 0.3) and 2 (−2.5 ± 0.3), and in groups 3 (−1.4 ± 0.3) and 4 (−1.4 ± 0.7), but those of group 1 were lower than those of groups 3 (P Ͻ 0.01) and 4 (P Ͻ 0.05), and those of group 2 than those of group 3 (P Ͻ 0.05). BMI during the 5 years after BMT did not change in groups 1 and 2, decreased in group 3, and increased in group 4. However, these changes were not significant. Most of the patients given TBI had BMI below the mean at 2 (66%) and 5 (57%) years later. Their BMI and leptin concentrations correlated positively with each other (P = 0.005), and negatively with GH peak (P = 0.02 for BMI and 0.007 for leptin). In conclusion, this study suggests that TBI actually decreases GH secretion and is followed by a persistent low BMI. The negative relationship between GH peak and leptin may indicate that both are markers of a TBIinduced hypothalamic-pituitary lesion. Bone Marrow Transplantation (2000) 26, 1205-1210. Keywords: bone marrow transplantation; body irradiation; body mass index; growth; growth hormone; leptin Short stature can be a severe side-effect of bone marrow transplantation (BMT). It may be caused by the initial disease and its treatment before BMT, by the conditioning protocol used for BMT, particularly the irradiation, by the complications of the BMT, and/or by the long-term corticosteroid therapy required to treat these complications. The irradiation may cause short stature in two ways: in patients given total body irradiation (TBI), hypothalamic-pituitary irradiation may decrease the secretion of growth hormone (GH); patients given TBI or total lymphoid irradiation (TLI) may suffer from bone lesions. 1 These lesions may be responsible for resistance to insulin-like growth factor I (IGF I), the secretion of which depends on GH and nutritional state, and a poor growth response to GH therapy. 2 The fall in weight following TBI in some patients, the effect of weight changes on growth rate and plasma IGF I, 3 and the very short adult height in many patients given TBI have prompted us to analyze the factors influencing changes in height and body mass index (BMI). We have done this by comparing patients given different conditioning protocols for BMT. Our aims were to determine if TBI actually decreases GH secretion, and if there is any relationship between the conditioning protocol and changes in BMI and plasma leptin concentrations. M...

“…In spite of hormone replacement therapy, most of them (13/14; 93%) had high serum LH and FSH levels indicating that the hypothalamus-pituitary axis was not suppressed. 26 Most often the estrogen dose used is titrated in consideration of clinical symptoms and usually this dose is thought to be high enough to prevent osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density after allogeneic bone marrow transplantation

Kauppila

Irjala²,

Koskinen³

et al. 1999

Self Cite

Summary:Bone turnover markers and bone mineral density (BMD) were studied in 25 adult patients (14 females, 11 males) who had undergone allogeneic bone marrow transplantation (BMT). The interval from BMT to the first examination was at least 1 year (mean 3, range 1-10). Mean age of the patients at the time of first evaluation was 42 (range 19-54) years. Blood samples and urine collections for evaluation of biochemical factors reflecting skeletal turnover were performed together with the first BMD measurement. BMD was measured from the lumbar vertebrae (L2 to L4) with computed tomography and results were expressed as Z-scores. At the time of the first measurement five patients (20%) had Z-scores Ͻ−2.5 s.d. and 12 patients (48%) between −1 and −2.5 s.d. In 12 patients BMD assessments were repeated and it seemed that reduction in BMD had mostly occurred during and shortly after BMT and remained the same during follow-up. The cross-linked carboxyterminal telopeptide of type I collagen (ICTP) correlated negatively with BMD (r = −0.45, P = 0.045) as did bone-specific alkaline phosphatase (BAP; r = −0.64, P = 0.002). No correlation between BMD and time interval from diagnosis to BMT, conditioning regimen, corticosteroid use or hospital stay during transplantation was found. In conclusion, bone disease is common after BMT. Our findings demonstrate an increased collagen and bone turnover and a high risk of osteoporosis. BMD measurements must be repeated regularly and collagen markers such as ICTP and BAP can be beneficial in estimating the activity of bone disease. Keywords: allogeneic bone marrow transplantation; ICTP; bone-specific alkaline phosphatase; bone mineral density; osteoporosis Transplant recipients are at risk of osteoporosis. Muchmore et al 1 reported low mean density of vertebral bone in heart transplant patients. Bone loss takes place mostly during the initial year after transplantation. 2 Rapid loss of vertebral mineral density has also been reported after renal transplantation, with most of the loss occurring within the first 6 months. after. Bone loss was related to number of hospital days but not to any other factor.Patients after allogeneic BMT are also exposed to numerous factors that can affect bone mineral metabolism: induction and consolidation therapies, bed rest, 5,6 conditioning regimen for BMT, steroids, 7 CsA therapy 8,9 and GVHD. 10 In female patients disturbance of gonadal function causes chronic estrogen deficiency 11 with an increased risk for osteoporosis. Carlson et al 12 studied the effect of myeloablative therapy on bone metabolism during the first 3 months after transplantation and found significant changes in serum markers of bone metabolism, which implied a net loss of bone over the study period. In 1997 Keilholz et al 13 reported normal BMDs after ABMT with a median interval of 5 years from autografting.The purpose of the present study was to evaluate the occurrence of bone disease after BMT by measuring BMD and biochemical markers of bone metabolism. Patients and methodsWe exami...