Case report of spontaneous, nonspinal fractures in a multiple myeloma patient on long-term pamidronate and zoledronic acid.
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ABSTRACT:
SUBMITTER: Wernecke G
PROVIDER: S-EPMC2553167 | biostudies-other | 2008 Sep
REPOSITORIES: biostudies-other
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Project description:Zoledronic acid and pamidronate are the two bisphosphonates approved in the United States to reduce multiple myeloma skeletal complications. Little prior evidence exists comparing survival outcomes between the two. We evaluated the incidence of skeletal-related events and overall survival in patients with myeloma treated with zoledronic acid versus pamidronate using a cohort of 1018 United States veterans. At a median follow-up of 26.9 months, patients receiving zoledronic acid had a 22% reduction in risk of death compared to pamidronate (hazard ratio 0.78; 95% confidence interval, 0.67-0.92). The benefit persisted after controlling for potential confounders. Adjusted Cox modeling with inverse probability weighting and propensity score matching supported these findings. Zoledronic acid was also associated with a 25% decrease in skeletal-related events. Zoledronic acid is associated with increased overall survival and decreased skeletal-related events compared to pamidronate in patients with multiple myeloma and should become the preferred bisphosphonate.
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Project description:Multiple Myeloma is a cancer of plasma cells associated with significantly reduced survival. Long term survivorship from myeloma is very rare and despite advances in its treatment the disease is generally considered incurable. We report a patient diagnosed with myeloma carrying a germline mutation of a tumour suppressor gene who has effectively been cured.A 36-year-old woman was diagnosed with IgG lambda myeloma in 1985. She was treated with melphalan chemotherapy followed by high-dose melphalan and autologous stem cell rescue and since remained in complete remission despite not having received any additional therapy. After eliciting a prior history of multiple primary melanomas and breast cancer, she was tested for and shown to be a carrier for a germline mutation in CDKN2A.This is the second case report of germline mutation of CDKN2A being associated with myeloma. CDKN2A is a stabiliser of p53. Long term survivorship after high dose DNA damaging chemotherapy with melphalan in this patient is compatible with an increased chemo-sensitivity due to impairment of the DNA repair pathway.
| S-EPMC5674776 | biostudies-literature
Project description:As multiple myeloma (MM) treatments evolve, frequent updates are required to monitor the long-term effect of changes in approach. Traditionally, MM is considered an incurable disease, with most patients eventually relapsing. However, improvements in treatments has raised the possibility that MM might be functionally curable. To examine improvements in long-term survival, we followed 4329 patients with newly diagnosed MM treated with autologous stem cell transplantation (ASCT) at the University of Arkansas for Medical Sciences from 1989 through 2018. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis, Cox proportional hazards models, relative survival analysis, and cure modeling among different time periods, risk groups, and demographic traits. Steady improvements in OS were found, with patients treated in 2014 or later having superior OS (hazard ratio, 0.35; 95% confidence interval [CI], 0.27-0.45) and reduced excess risk for MM death (relative excess risk, 0.30; 95% CI, 0.22-0.41) compared with patients treated in 1997 or earlier. Patients treated during intervening time periods often had intermediate survival, but trends in OS, PFS, and landmarked analyses were inconsistent. Cure models support the potential for cure, ranging from 6.3% to 31.3%, depending on the year of treatment, with 10.0% to 18.6% of patients achieving their normal life expectancy across multiple periods. There was some evidence of reductions in early mortality within 3 years of diagnosis, longer complete response (CR) duration, and reductions in relapse after achieving CR. However, results differed depending on age, risk group, and cytogenetic characteristics.
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Project description:Chronic myeloid leukemia (CML), a clonal myeloproliferative disorder of pluripotent hematopoietic stem cells, results from the Philadelphia chromosome (Ph) chromosome. The Ph is from a translocation, t(9;22)(q34q11), that creates a BCR-ABL fusion gene, which is transcribed into proteins with abnormal tyrosine kinase activity, driving the abnormal proliferation of white blood cells. Multiple myeloma (MM) is a proliferation disorder of plasma cells derived from a single clone, which may lead to uncontrolled growth, kidney injury, destructive bone lesions, hypercalcemia and anemia. It is extremely rare that MM and CML should occur in the same patient either synchronously or metachronously. To date, MM accompanied with CML has only been reported in limited studies, and the the cause behind the occurrence of both malignancies together is not understood. With the advent of novel therapies, the survival time in patients with CML and MM has improved. Therefore, the further investigation of the pathophysiology and clinical characteristics of these cases is valuable. The present study reports the case of a 79-year-old male who had been diagnosed with CML and treated with tyrosine kinase inhibitor, and then developed immunoglobulin G-κ MM after 6 years. This report should provide valid raw data for clinical research.
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Project description:The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n?=?167) and multiple myeloma (MM; n?=?163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240?µg/kg plerixafor plus 10?µg/kg G-CSF, or placebo plus 10?µg/kg G-CSF to mobilize and collect CD34+ cells for autologous hematopoietic stem cell transplantation. Overall survival (OS) and progression-free survival (PFS) were evaluated over a 5-year period following the first dose of plerixafor or placebo. The probability of OS was not significantly different in patients with NHL or MM treated with plerixafor or placebo (NHL: 64%; 95% confidence interval [CI], 56% to 71% versus 56%; 95% CI, 44% to 67%, respectively; MM: 64%; 95% CI, 54% to 72% versus 64%; 95% CI, 53% to 73%, respectively). In addition, there was no statistically significant difference in the probability of PFS over 5 years between treatment groups in patients with NHL (50%; 95% CI, 44% to 67% for plerixafor versus 43%; 95% CI, 31% to 54% for placebo) or those with MM (17%; 95% CI, 10% to 24% for plerixafor versus 30%; 95% CI, 21% to 40% for placebo). In this long-term follow-up study, the addition of plerixafor to G-CSF for stem cell mobilization did not affect 5-year survival in patients with NHL or patients with MM.
| S-EPMC6091693 | biostudies-literature
Project description:Discontinuation of denosumab is associated with the increase of bone turnover markers to above-baseline levels (so-called rebound in bone turnover) and rapid bone loss. Several studies have reported vertebral fractures (VFs), particularly multiple spontaneous clinical VFs (MSCVFs), occurring after discontinuation of denosumab. There is currently no recommendation for the management of VFs including MSCVFs. Presently, romosozumab is the strongest anti-osteoporotic agent that inhibits sclerostin and rapidly increases bone mass, but it is uncertain that romosozumab is an effective treatment choice to treat VFs occurring after discontinuation of denosumab. Herein we reported a novel case of a 60-year-old woman who was treated with romosozumab after discontinuation of denosumab and subsequently suffered MSCVFs under romosozumab treatment. She had a history of two osteoporotic VFs (T6 and T8) and received five doses of 60 mg denosumab every 6 months following the osteoporosis diagnosis. As per the patient's convenience, the sixth denosumab injection was postponed. To improve the persistent low bone mass in the lumbar spine (T-score -3.8), 210 mg romosozumab was administered monthly after 9 months following the last denosumab injection. At the first romosozumab injection, she had no clinical symptoms such as low back pain, but her bone formation and resorption marker levels elevated compared with those treated with denosumab. After three doses of romosozumab, spontaneous severe low back pain occurred, and time-course radiographs revealed five new VFs (T12, L2, L3, L4, and L5). Romosozumab administration had no suppressive effect on bone resorption during the rebound in bone turnover after discontinuation of denosumab. This case suggests that romosozumab is not effective in preventing VFs or MSCVFs after denosumab discontinuation.
| S-EPMC7284126 | biostudies-literature
Project description:In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.
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Project description:Hypophosphatasia is a rare inherited disorder characterized by defective skeletal mineralization and low alkaline phosphatase activities in the serum. The genetic cause of hypophosphatasia is believed related to inactivating mutations in the TNSALP gene, encoding tissue-nonspecific alkaline phosphatase. Another rare inheritable disease, Saethre-Chotzen syndrome, leads to premature fusion of the cranial sutures caused by heterozygous mutations of the human TWIST1 gene. Because the two disorders apparently are not genetically related (only reported individually) yet both involve defective skeletal formation, we believe it is important to report our findings on a patient harboring mutations of TNSALP and TWIST1.
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Project description:Data Access Committee EGAC00001003078
| EGAC00001003078 | EGA
Project description:PurposeRib fixation for flail chest has been shown to improve in-hospital outcome, but little is known about treatment for multiple rib fractures and long-term outcome is scarce. The aim of this study was to describe the safety, long-term quality of life, and implant-related irritation after rib fixation for flail chest and multiple rib fractures.MethodsAll adult patients with blunt thoracic trauma who underwent rib fixation for flail chest or multiple rib fractures between January 2010 and December 2016 in our level 1 trauma facility were retrospectively included. In-hospital characteristics and implant removal were obtained via medical records and long-term quality of life was assessed over the telephone.ResultsOf the 864 patients admitted with ≥ 3 rib fractures, 166 (19%) underwent rib fixation; 66 flail chest patients and 99 multiple rib fracture patients with an ISS of 24 (IQR 18-34) and 21 (IQR 16-29), respectively. Overall, the most common complication was pneumonia (n = 58, 35%). Six (9%) patients with a flail chest and three (3%) with multiple rib fractures died, only one because of injuries related to the thorax. On average at 3.9 years, follow-up was obtained from 103 patients (62%); 40 with flail chest and 63 with multiple rib fractures reported an EQ-5D index of 0.85 (IQR 0.62-1) and 0.79 (0.62-0.91), respectively. Forty-eight (48%) patients had implant-related irritation and nine (9%) had implant removal.ConclusionsWe show that rib fixation is a safe procedure and that patients reported a relative good quality of life. Patients should be counseled that after rib fixation approximately half of the patients will experience implant-related irritation and about one in ten patients requires implant material removal.
| S-EPMC6689022 | biostudies-literature