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The frequency of bone mineral density by site and distribution according to the WHO definition of osteoporosis using an age-matched (Z-scores) reference range
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Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duratio...
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... [10][11][12] In young men/children treated for malignancy, the frequencies of hypogonadismassociated symptoms such as erectile dysfunction were found to be almost triple those of healthy, young males (12.3% vs 4.2%). 13,14 Although data are limited, some studies have found that a large percentage (>60%) of treated multiple myeloma (MM) patients have symptoms of hypogonadism, 15 indicating that provider awareness and early recognition are indicated to provide timely intervention. Worse symptom severity has been reported in patients with advanced cancer and more significant systemic inflammatory states. ...
Introduction
The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature.
Objective
In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM).
Methods
This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords “hematologic cancer,” “hematologic malignancy,” blood cancer,” “leukemia,” “lymphoma,” “hypogonadism,” “multiple myeloma,” and “testosterone.”
Results
The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.
Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.
The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density.
Conclusion
There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.
... The studied females and males were slightly older than females and males with MM studied by Wichert et al. [8], but younger than females and males described by other authors [9][10][11][12][13][14][15][16]. Age of the patients described in case reports was highly diverse [15,[17][18][19][20][21]. ...
Introduction
In the literature there is lack of information on the influence of gender and time since autologous hematopoietic stem cell transplantation (HSCT) on the immune reconstitution in multiple myeloma (MM) patients.
Objective
The aim of this study was to assess the diversity of the immune reconstitution according to gender in MM patients after autologous HSCT on the day of the clinic discharge and on the 29th day after discharge, as well as to investigate the changes in the immune system in females and males after staying at home for 28 days.
Method
The studied population comprised 13 females and 13 males after autologous HSCT. On the day of the clinic discharge and on the 29th day after discharge blood samples were taken to analyse 22 immunological parameters. Statistical analysis was performed using STATISTICA 10 StatSoft Poland. For multiple comparisons, the Bonferroni correction was used.
Results
No statistically significant differences were observed in the analysed immunological parameters between the studied females and males with MM on the day of the clinic discharge and on the 29th day after discharge. However, on the 29th day after the clinic discharge compared to the day of the clinic discharge, statistically significant differences were found in 8 immunological parameters among females and 6 immunological parameters among males.
Conclusion and recommendation
Our results indicate that the immune reconstitution is similar but not the same in patients of both genders. Statistically significant differences in the immune response in the studied females and males imply that gender may play a role in the immune reconstitution and that the results obtained in MM patients should be analysed separately in females and males. In order to explain the observed changes in the immune system according to gender, further research should be carried out on a larger population. This would most probably make it possible to find their clinical application.
... After a thorough screening process, a total of 18 studies were deemed suitable for incorporation in this systematic review and subsequent meta-analysis, as depicted in the PRISMA flow diagram ( Figure 1). Table 1 presents a summary of the primary features of the incorporated studies [26,33,[41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. The studies incorporated in the analysis were carried out across various continents, including North America (n = 6; USA), Europe (n = 7; United Kingdom, France, Switzerland, the Netherlands, Bulgaria, and Turkey), Australia (n = 2), Asia (n = 2; Philippines and South Korea), and Africa (n = 1; Egypt). ...
... Various methodologies have been employed to assess the levels of vitamin D, encompassing both single and combined chemiluminescent immunoassay [42,47,48], ELISA [43,56], tandem mass spectrometry [49], liquid chromatography-tandem mass spectrometry [50], liquid chromatography-tandem mass spectrometry or high-performance liquid chromatography [26], and liquid chromatography-tandem mass spectrometry or immunoassay [51]. The methodology for measuring vitamin D levels was not defined in nine studies [33,41,[44][45][46][52][53][54][55]. Different cut-off values (expressed in ng/mL) were utilized to ascertain adequate, inadequate, and deficient serum vitamin D concentrations in individuals diagnosed with MM. ...
Background:
Multiple myeloma (MM) is a hematological malignancy characterized by the exponential growth of malignant plasma cells. Individuals diagnosed with MM exhibit a deficiency in vitamin D and may suffer fatigue, a loss of muscular strength, persistent musculoskeletal aches, and pain. The objective of this systematic review and meta-analysis is to determine the prevalence of vitamin D insufficiency and deficiency in individuals diagnosed with MM.
Methods:
We searched five electronic databases using relevant keywords. The quality of the included studies was evaluated using the critical appraisal tool developed by the Joanna Briggs Institute. We employed a random-effects model and presented the findings in the form of percentages accompanied by 95% confidence intervals (CI). This protocol has been officially registered in PROSPERO under the registration number CRD42021248710.
Results:
The meta-analysis comprised a total of eighteen studies and found that, among patients with MM, the occurrence of serum vitamin D deficiency and insufficiency was 39.4% (95% CI: 25.8 to 52.9, n = 3746) and 34.1% (95% CI: 20.9 to 47.2, n = 3559), respectively. The findings indicate that a greater proportion of newly diagnosed patients exhibited vitamin D deficiency and insufficiency, with rates of 43.0% and 41.6%, respectively, compared to those receiving treatment (rates of 41.6% and 32.3%, respectively). The findings of the sensitivity analyses were consistent, and most of the studies (72.2%) were deemed to be of high quality. The results of Egger's test indicated the absence of publication bias.
Conclusions:
Patients diagnosed with MM have been found to exhibit significantly elevated levels of both vitamin D deficiency and insufficiency. Therefore, it is recommended to consider vitamin D testing as an additional parameter in the current criteria for the clinical evaluation of MM.
... Survivors often experience fatigue, bone pain, sleep problems, and functional decline -all of which can impact physical, emotional, and social health [4]. Many MM survivors also have unfavorable body composition, specifically a high prevalence of obesity and sarcopenia, the latter reflecting a marked loss of skeletal muscle mass and function [5][6][7]. These body composition phenotypes may contribute to the decreased quality of life (QOL) seen in the MM population. ...
PurposeMultiple myeloma (MM) is the second most common hematologic malignancy in the USA, with higher rates observed in older adults and African Americans (AA). Survivors experience fatigue, bone pain, reduced functioning, and obesity, highlighting the value of developing lifestyle interventions for this diverse group. This study explores lifestyle behaviors and supportive care needs to inform future programs tailored to the MM community.MethodsMM survivors, ≥ 100 days post autologous stem cell transplant (ASCT) with a BMI ≥ 20 kg/m2, were recruited from two university hospitals. Diet, physical activity, and quality of life (QOL) were measured using validated measures. Qualitative interviews gathered information on survivorship needs and interests related to supportive interventions. Quantitative data was analyzed using descriptive statistics; qualitative data were analyzed using deductive strategies.ResultsSeveny-two MM survivors participated (65% white, 35% black). Participants were 62.5 ± 15.8 years of age. Fifty percent were classified as obese and 65% were insufficiently active. Participants reported diets high in added sugars and saturated fats. QOL measures indicated clinically significant challenges in physical and sexual function. Most (87%) were interested in a lifestyle program. Predominant themes regarding survivors’ desires for a lifestyle program included social support, guided exercise, meal preparation support, and disease management information.Conclusion
This study demonstrates the need for and interest in lifestyle change support among a racially diverse sample of MM survivors. Interventions that are group-based, target knowledge gaps, social connections, accountability, and provide structured framework with professional instruction will best address the needs of this survivor population.
... Studies have highlighted the nutritional deficiencies frequently seen in MM patients. Greenfield et al. [64] found that 37.5% of participants were vitamin D deficient (<30 nmol/L) while an additional 21.8% had inadequate levels (30-50 nmol/L). Twentyfive percent were also found to be folate deficient and 6% had reduced levels of vitamin B12. ...
... Patterns of Leydig cell dysfunction post-HCT include patients with elevated luteinizing hormone (LH) and normal testosterone levels (compensated hypogonadism) or elevated LH and low testosterone levels (hypogonadism) [34]. Recovery of hypogonadism does occur, and can sometimes be as early as within the first year after transplant [34][35][36][37][38][39][40][41][42][43]. ...
Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.
... Pain in myeloma arises not only from infiltration of the bone marrow by malignant plasma cells, bone osteolysis and fracture, but also from side effects of treatments, particularly chemotherapyinduced peripheral neuropathy, and may continue to be significant in patients with stable disease who are off active treatment [4]. In animal models and clinical studies of patients with bone-related malignancy, experience of pain and other symptoms are the result of the interactions between a) host/tumour factors such as cytokines operating locally within the bone where the plasma cells are multiplying [5,6]; b) the acute and chronic effects of antimyeloma therapy [4,7]; c) long-term potentiation and sensitisation in the ascending pain pathways in the spinal cord and brain, balanced by descending modulatory controls [8]; d) pharmacokinetic and pharmacodynamic consequences of analgesic absorption and metabolism [9]; e) a range of other circulating pathophysiological factors, ranging from renal function, endocrine, dietary as well as cytokines and mediators of inflammation which can impact on physiological mechanisms of pain [4,10] Examples of genetic factors contributing to pain experience include the three main opioid receptors (mu, kappa and delta) whose genes contain inherited variants that occur relatively frequently in human populations [11][12][13][14]. Such genetic variation has been associated with gender differences in the response to experimentally induced pain [15][16][17], and higher requirements for mu agonist drugs such as morphine and higher quantities of potentially toxic metabolites of morphine [18,19]. ...
The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.
... Proteasome inhibitors and immune modulatory drugs, combined with chemotherapy, have changed the management of MM and substantially extended progression-free and overall survival [3]. However, high levels of steroids are usually prescribed, exacerbating muscle weakness and increasing the risk of bone fractures [4,5]. Fatigue and bone pain also frequently persist long after treatment completion, and during disease stability [6]. ...
PurposeTo explore the attitudes and practices of clinical haematologists towards promoting physical activity (PA) and exercise for patients with multiple myeloma (MM).Methods
Using a quantitative cross-sectional survey, clinical haematologists reported on the perceived benefits and acceptability of PA and exercise and frequency, confidence and barriers to providing exercise advice.ResultsClinical haematologists (n=34; 68% response rate), who cumulatively treated ~340 patients with MM each week, completed the survey. Almost all (97%) agreed that PA was important, with benefits for quality of life, activities of daily living, mental health and fatigue. Whilst 88% discussed PA at least occasionally with their patients, approximately two-thirds were not confident advising specific exercises (68%) or identifying PA resources (62%). Despite this, 44% never referred patients to exercise professionals, with 18% only doing so if the patient asked. Over half did not recommend exercise when patients had spine fractures or were physically unwell. No differences were observed in individual factors (age, gender, practice type and own PA participation) and promotion of PA.Conclusions
Clinical haematologists perceive PA as important, but lack confidence on what exercise/s to recommend and if exercise is appropriate for specific disease complications. They tend to not refer patients to exercise professionals.Implications for Cancer SurvivorsPatients with MM often suffer from symptoms and toxicities that may be alleviated through PA. However, PA participation rates are low. Support for clinical haematologists for when and how to discuss exercise, and clearer referral pathways to exercise professionals may improve PA uptake and hence ensure access to optimal care, thereby improving patient outcomes.
... Survivors often experience fatigue, bone pain, sleep problems, and functional decline -all of which can impact physical, emotional, and social health [3]. Many MM survivors also have unfavorable body composition, speci cally a high prevalence of obesity and sarcopenia; the latter re ecting a marked loss of skeletal muscle mass and function [4][5][6]. These body composition phenotypes may contribute to the decreased quality of life (QOL) seen in the MM population. ...
Purpose: Multiple Myeloma (MM) is the second most common hematologic malignancy in the U.S., with higher rates observed in older adults and African Americans (AA). Survivors experience fatigue, bone pain, and reduced functioning. The high incidence of obesity among MM survivors may be partly responsible. These factors highlight the value of developing lifestyle interventions to meet the needs of this diverse group. This study aims to inform the development of a lifestyle program tailored to the MM community.
Methods: MM survivors who were ≥100 days post autologous stem cell transplant (ASCT) with a BMI ≥20 kg/m² were recruited from two university hospitals, with the goal of obtaining sufficient representation of AA participants. They completed dietary, physical activity, and quality of life (QOL) questionnaires and a qualitative interview.
Results: 72 MM survivors participated (65% white, 35% black). Participants were 62.5±15.8 years of age. 50% were classified as obese and 65% were insufficiently active. Participants reported diets high in added sugars and saturated fats. QOL measures indicated clinically significant challenges in physical and sexual function. Most (87%) were interested in a lifestyle program. Predominant themes regarding survivors’ desires for a lifestyle program included social support, guided exercise, meal preparation support, and disease management information.
Conclusion: This study demonstrates the need for and interest in lifestyle change support among a racially diverse sample of MM survivors. Interventions that are group-based, target knowledge gaps, social connections, accountability, and provide structured framework with professional instruction will best address the needs of this survivor population.
... A number of individual mechanistic factors potentially contribute to the increased risk of CV disease following HCT including pre-existing risk factors, pre-transplant treatment, the transplant itself (including graft-versus-host disease, GvHD) and posttransplant treatment and the contribution of immune dysfunction and endocrinopathies [14][15][16][17][18][19][20][21][22][23][24][25]. ...
Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09–6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.
