Osteonecrosis of the Jaw in Multiple Myeloma Patients (the IFM Registry).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4809-4809
Author(s):  
Jean Gabriel Fuzibet ◽  
Marie Hélène Viellard ◽  
Benoit B.R. Rossignol ◽  
Chantal C.D. Doyen ◽  
Cyril Hulin ◽  
...  

Abstract PURPOSE: to describe the incidence, characteristics and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM). PATIENTS AND METHODS : retrospective review of 51 ONJ collected from the IFM centers. For MM, age at diagnosis, isotype, DS staging, nature of chemotherapy and number of Stem-Cell Transplantation were the same that expected. RESULTS: ONJ occurred predominantly in the mandible (70%). The median time of exposure to biphosphonates (BP) was 45 months (4 to 144 months). BP therapy included: zoledronate (85%), pamidronate (10%), clodronate (5%), all of the patients have received intravenous BP before, two patients have no BP at the time of diagnosis of ONJ. RISK FACTORS: dental extraction (59%) other dental care (5%), dental infection (24%), others (30%), no risk factor (10%). SYMPTOMS: pain (92%), purulent discharge (37%), presence of exposed bone (60%), fracture (2%). MANAGEMENT: BP discontinuation (84%), medical treatment (86%), removal of sequestra (51%), extensive surgery (20%). EVOLUTION: improvement (55%), chronical symptoms (70%). INCIDENCE: we have not the number of exposed patients but: 46 centers/73 reported no ONJ.The first report was march 2001. In the same period, 1695 patients where included in IFM trials and only 16 ONJ where observed. Year of diagnosis: before 2004: 5 cases; 2004: 11 cases; 2005:26 cases; 2006: 7 cases; 2007(6 months): 2cases. CONCLUSION: ONJ is an adverse side effect of amino BP therapy (zoledronate>pamidronate), is time dependant and often after dental extraction. Preventive recommandations applied in 2005 can explain the decreasing incidence of ONJ in our study.

2006 ◽  
Vol 24 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Ashraf Badros ◽  
Dianna Weikel ◽  
Andrew Salama ◽  
Olga Goloubeva ◽  
Abraham Schneider ◽  
...  

Purpose To describe the clinical, radiologic, and pathologic features and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients. Patients and Methods A retrospective review of 90 MM patients who had dental assessments, including 22 patients with ONJ. There were 62 men; the median age was 61 years in ONJ patients and 58 years among the rest. Prior MM therapy included thalidomide (n = 67) and stem-cell transplantation (n = 72). Bisphosphonate therapy included zoledronate (n = 34) or pamidronate (n = 17) and pamidronate followed by zoledronate (n = 33). Twenty-seven patients had recent dental extraction, including 12 patients in the ONJ group. Median time from MM diagnosis to ONJ was 8.4 years for the whole group. Results Patients usually presented with pain. ONJ occurred posterior to the cuspids (n = 20) mostly in the mandible. Debridement and sequestrectomy with primary closure were performed in 14 patients; of these, four patients had major infections and four patients had recurrent ONJ. Bone histology revealed necrosis and osteomyelitis. Microbiology showed actinomycetes (n = 7) and mixed bacteria (n = 9). More than a third of ONJ patients also suffered from long bone fractures (n = 4) and/or avascular necrosis of the hip (n = 4). The variables predictive of developing ONJ were dental extraction (P = .009), treatment with pamidronate/zoledronate (P = .009), longer follow-up time (P = .03), and older age at diagnosis of MM (P = .006). Conclusion ONJ appears to be time-dependent with higher risk after long-term use of bisphosphonates in older MM patients often after dental extractions. No satisfactory therapy is currently available. Trials addressing the benefits/risks of continuing bisphosphonate therapy are needed.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4956-4956 ◽  
Author(s):  
Hyo Jung Kim ◽  
Hyeok Shim ◽  
Eunkyung Park ◽  
Min Kyoung Kim ◽  
Seok Jin Kim ◽  
...  

Abstract Abstract 4956 Introduction Osteonecrosis of the Jaw (ONJ) is a potentially serious complication of bisphosphonate (BP) therapy in multiple myeloma (MM). Despite of current update about bisphosphonate related ONJ (BRONJ), only a few Asian BRONJ cases were reported and incidence of BRONJ in Asian MM patients has not yet been definitively estimated. The purpose of this study was to determine incidence and characteristics of BRONJ in Korean MM patients who were receiving BP therapy. Patients and Methods We invited 9 hospitals of Korean Multiple Myeloma Working Group (KMMWP) to participate in a retrospective multicenter study on BRONJ in MM patients. To defined BRONJ incidence, we reviewed the data from 130 MM patients treated with BP in one hospital. We also reviewed the medical records of MM patients with BRONJ treated in 9 hospitals to know the patterns of disease. We analyzed patient and disease characteristics, type and number of BP infusions, previous history of dental procedures, locations of osteonecrosis, clinical symptoms, treatment and outcome. ONJ was defined as clinical evidence of exposed bone in the jaw, which has been present for more than 8 weeks. Results Nine of 130 MM patients (6.9%) treated with BP developed BRONJ in the hospital. Twenty-two patients with MM developed BRONJ after a median number of 17 BP infusions (range 6 - 50) in all 9 hospitals. None of the patients had been irradiated to the jaw. There were 14 male and 8 female patients. The median age was 62 years (range 46 – 75). Median time from MM diagnosis to BRONJ was 2.8 years (range 0.6 – 15.6). The MM isotype was IgG in 9, IgA in 8, IgM in 1, light chain in 3 and non-secretory myeloma in 1 patient. BP therapy included zoledronate (n = 2) or pamidronate (n = 4) and both drugs as sequential treatment (n = 16). Fifteen patients had recent problems in oral cavity (72.7%) and 14 had prior dental procedures (63.6%). The mandible was involved in 14 patients (63.6%), the maxilla in 7 (31.8%), and both the maxilla and mandible in 1 (4.5%). Patients usually presented with pain and soft tissue swelling. ONJ staging (Khan et al. Canadian consensus practice guidelines of Bisphosphonate associated ONJ. J Rheumatol 2008;35:1391-7) was used to define the severity, there were 5 patients in stage I, 14 in stage II and 1 in stage III. Because of the limitation of retrospective study, the stage of 2 patients could not be confirmed. Management of these established cases were discontinuation of BP and medical treatment including antibiotics and pain killer. Surgical debridement of necrotic bone was performed in 12 patients. From onset of exposed bone in jaw, patients were followed for median 11 months (range 4.2 - 42). Wounds of 10 patients were healed at median 175 days (range 60 – 404) after bone exposure. In 8 patients, lesions had persisted over 154 days (range 66 – 425). Evaluation was impossible for 4 patients due to loss of follow up. Four patients were dead because of disease progression (n = 3) or concomitant infection. BRONJ was healed in 2 of them. Conclusions To the best of our knowledge, this is the largest retrospective study ever reported about BRONJ in Asian MM patients. The incidence of BRONJ in Korean MM patients was 6.9% and this is similar with data in western countries. Clinical manifestations and outcome of BRONJ in Korean patients were not different from previously reported data, but no risk factors could be definitively identified with our retrospective analysis. In the name of KMMWP, prospective trials are ongoing to define incidence and risk factors of BRONJ in Korean MM patients. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5370-5370 ◽  
Author(s):  
Shin Young Hyun ◽  
Ji Eun Jang ◽  
Yundeok Kim ◽  
Doh Yu Hwang ◽  
Soo Jeong Kim ◽  
...  

Abstract Background The aim of this study is to identify risk factors associated with the development of severe bacterial infection (SBI) in patient with multiple myeloma (MM) during treatment with bortezomib-containing regimens. Methods A total of 98 patients with MM who were treated with bortezomib-based treatment between 2006 and 2012 were analyzed. Fifty three patients received bortezomib-dexamethasone, 25 patients received bortezomib-melphalan-prednisolone, 15 patients received bortezomib-doxorubicin-dexamethasone and 5 patients received other regimens. They received a total of 427 courses of treatment. The SBI was defined as at least grade 3 neutropenic/non-neutropenic infection by NCI Common Terminology Criteria for Adverse Events version 4.0. Using the logistic regression method, we analyzed risk factors for the development of SBI during each course of treatment. Results Median age of the patients was 62 years and 40.6% (30/98) of patients treated with bortezomib-containing regimens as first-line therapy. The SBI was developed in 57% (56/98) of patients and 19% (81/427) of bortezomib courses. Among 81 episodes of SBI, 42 (53%) episodes were clinically documented infection, 30 (37%) were microbiologically documented infections, and 9 (11%) were fever of unknown origin. The most common type of infection was pneumonia (60%). Poor performance status (ECOG ≥2) (Hazard Ratio [HR] 5.365, 95% Confidence Interval [CI] 2.004-14.364, P =.001) was the only risk factor for the development of SBI in 98 patients. When we analyzed the risk factors for the development of SBI which occurred during each treatment course, poor performance status (ECOG ≥2) (P <.001), early course of treatment (≤2 courses) (P <.001) and pretreatment lymphopenia (absolute lymphocyte count <1.0 x 109/L) (P = .043) were associated with increased risk for developing SBI in each course. These 3 risk factors remained independently significant in multivariate analysis: poor performance status (ECOG ≥2) (HR 3.920, 95% CI 2.305-6.666, P <.001), early course of treatment (≤2 courses) (HR 2.782, 95% CI 1.633-4.740, P <.001) and pretreatment lymphopenia (HR 1.728, 95% CI 1.016-2.937, P = .043). The probability of developing SBI in each treatment course was 5.1% in courses with no risk factor, 14.9% in 1 risk factor, 23.9% in 2 risk factors and 59.5% in 3 risk factors (P <.001, Figure 1). After treatment with bortezomib-containing regimens, patients who experienced SBI showed a significantly shorter overall survival than patients who didn't experienced SBI (median 6.1 month vs. 30.1 months, P = .004) although progression free survival was not different (median 18.1 months vs. 21.9 months, P = .418). The multivariate cox analysis demonstrated that the development of SBI was associated with inferior overall survival (HR 2.440, 95% CI 1.305-4.561, P = .005) as well as male sex (HR 2.323, 95% CI 1.236-4.367, P = .009). Conclusions In conclusion, we identified that poor performance status, early courses of treatment, and lymphopenia at the beginning of each treatment course were the risk factors for the development of SBI in patients with MM during treatment with bortezomib-containing regimens. Close monitoring for the development of SBI and appropriate treatment should be considered in the patients with risk factors. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 134 (6) ◽  
pp. 620-623 ◽  
Author(s):  
Kostas Zervas ◽  
Evgenia Verrou ◽  
Zisis Teleioudis ◽  
Konstantinos Vahtsevanos ◽  
Anastasia Banti ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sakiko Soutome ◽  
Mitsunobu Otsuru ◽  
Saki Hayashida ◽  
Maho Murata ◽  
Souichi Yanamoto ◽  
...  

AbstractTooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 637-637 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Lia A. Moulopoulos ◽  
Ioannis Melakopoulos ◽  
Athanasios Anagnostopoulos ◽  
...  

Abstract Purpose: Biphosphonates have been approved for the treatment of bone lesions in patients with multiple myeloma. Although these agents are usually well tolerated, osteonecrosis of the jaw (ONJ) has been recently associated with the use of pamidronate and zoledronic acid. Nevertheless, the true incidence of this complication is not clearly defined. Therefore, we studied the incidence, characteristics and risk factors for the development of ONJ among patients with multiple myeloma treated with biphosphonates in our institution. Patients and Methods: One hundred and thirty-seven patients who received biphosphonates (zoledronic acid: 50 pts, pamidronate: 29 patients, bondronate: 2 pts, pamidronate and zoledronic acid: 50 pts, zoledronic acid and bondronate: 5 pts) since January 1995 and had a minimum exposure of 6 months to the drug were included in this analysis. Since the first reports, which associated ONJ with biphosphonate treatment, we prospectively evaluated this complication (first patient diagnosed in July 2003): all patients complaining of symptoms suggestive of ONJ were referred to a maxillofascial surgeon who confirmed the diagnosis and managed the patients for this complication. The medical records of all patients who were included in the analysis were reviewed in order to exclude symptoms and signs of ONJ, which might have not been formally diagnosed. From this retrospective review, no patient with a highly probable diagnosis of ONJ was identified. Results: Ten patients (6.7%) developed ONJ. The median number of treatment cycles and time of exposure to biphosphonates were 26 infusions and 42 months for patients with ONJ compared to19 infusions (p=0.2) and 27 months (p=0.05) for patients with no ONJ. The cumulative hazard of ONJ increased with time to exposure from 0% for exposure 6–12 months to 13% (95% CI: 3–23) for exposure of 5 years. The use of thalidomide was not associated with the development of ONJ. No case of ONJ was observed among patients treated with pamidronate or pamidronate and ibandronate. In patients who received sequential pamidronate and zoledronic acid, all cases of ONJ occurred during the use of zoledronic acid. The cumulative hazard was significantly higher with zoledronic acid compared to pamidronate alone or sequential administration of pamidronate and zoledronic acid (p=0.022). Among the 10 patients, who developed ONJ, 7 had had dental extraction prior to the development of the complication, 2 had dentures and only one had not had either. In spite of the discontinuation of biphosphonate treatment, only one patient experienced improvement of osteonecrosis, in 7 cases it remained stable and in 2 cases osteonecrosis progressed. Conclusions: The use of biphosphonates in patients with multiple myeloma seems to be associated with the development of ONJ. Our cohort study is the first one which provides a fairly accurate estimate of the incidence of documented ONJ after treatment with biphosphonates. Length of exposure and the type of biphosphonate used appear to be the most important risk factor for this complication. The risk of developing osteonecrosis appears to be higher with zoledronic acid than with pamidronate and may be precipitated by dental extraction.


2009 ◽  
Vol 9 ◽  
pp. S19-S20
Author(s):  
JG Fuzibet ◽  
B Rossignol ◽  
MH Vieillard ◽  
E Fontas ◽  
C Hulin ◽  
...  

Author(s):  
Dr. Dhan Singh Sinsinwar ◽  
Dr. Ravi Gupta

INTRODUCTION: Lower Segment Cesarean Section (LSCS) delivery is a major obstetrical surgical procedure to save the lives of mothers and foetus. Surgical site infections (SSI) are the most common reason about 20% to be unplanned admitted after discharging of the patient to their home. Various risk factors in SSI following LSCS has been identified which includes subcutaneous hematoma, subcutaneous hematoma, tobacco use in pregnancy, incision length > 16.6 cm , body mass index >30 or 35 kg/m2, prolonged second stage (compared with first stage) , no antibiotic prophylaxis, duration of labour >12 h , premature rupture of membranes , gestational diabetes, previous cesarean delivery and emergency delivery. MATERIAL AND METHODS: A total of 646 patients were included in the study of which 27 were diagnosed as SSI. Risk factor for SSI was divided into three categories: 1) host-related factors, 2) pregnancy and intrapartum-related factors, and 3) procedure-related factors. Purulent discharge was obtained from the surgical incision site 48 hours postoperatively with sterile disposable swabs. Blood sample for blood culture was collected when the possibility of septicemia or bacteremia as suggested by the presence of fever, shock, or other signs and symptoms of sepsis associated with the surgical wound. The bacterial isolates obtained were identified as per standard identification procedures in time microbiology laboratory. Antibiotic susceptibility of the organisms done as per protocol. RESULTS: A total of 646 patients were included in the study of which 94 (14.55%) were diagnosed as SSI. mean age of patients who underwent LSCS was 24± 4.57 years. Of the 646 patients in 18 - 20 years 125 (19.3%),21-25 years 304 (47.1%), 26-30 years 189 (29.3%) and in > 30 years age group 28 (4.3%) cases were observed, of the total 94 SSI cases 11 (8.8%) were in the age group if 18 - 20 years, 39 (12.8%) were in the age group of 21-25 years, 32 (16.9%) were in 26-30 years age group and 12 (42.9%) were in the > 30 years age group. Acinetobacter spies was the commonest isolate 29(30.9%) followed by staphylococcus aureus 22 (23.4%), Escherichia coli 21 (22.3%) and Klebsiellapneumoniae. premature rupture of membrane (PROM), antibiotics given earlier than 2 hours and increased duration of stay in the hospital were found to be statistically significant. It was interpreted that PROM > 24 hrs is likely to increase the chances of infection. As the duration of hospital stay increases by 1 day, the chances of infection increase. CONCLUSION: Identification, management and proper assessment of risk factors are necessary to in reduction of SSI rates. Premature rupture of membrane (PROM), antibiotics given earlier than 2 hours, BMI >25 and increased duration of stay in the hospital were associated with increased SSI rate.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3398-3398 ◽  
Author(s):  
Johannes Drach ◽  
Verena Sagaster ◽  
Victoria Odelga ◽  
Hannes Kaufmann ◽  
Jutta Ackermann ◽  
...  

Abstract Bortezomib is an active agent for treatment of multiple myeloma (MM) and may even be effective in patients (pts) with adverse prognostic factors including unfavorable cytogenetic abnormalities. However, it is unknown whether or not bortezomib may overcome the negative prognostic impact of a CKS1B gene amplification at chromosome 1q21 (amp1q21), which has recently been reported as a negative prognostic factor even in the setting of a total therapy approach. We therefore evaluated chromosome 1q21 among other abnormalities in 46 pts with relapsed/refractory MM who were treated with single-agent bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks). Median age of pts was 63 years (range, 40 – 82 ) and median time to bortezomib therapy was 40 months (median number of prior therapies: 3; 96% of pts had high-dose pulsed dexamethasone, 61% thalidomide, 85% alkylating agents, and 41% high-dose melphalan). A response to bortezomib was noted in 45% of pts, with 17% of pts achieving a CR/near CR. Amp1q21 as determined by interphase FISH was observed in 20 of the 46 pts (43.5%). Treatment outcome after bortezomib was negatively affected by presence of amp1q21: The overall response rate was 30% (versus 58% in pts with normal 1q21; P = .06) and the CR/near-CR rate was 10% (versus 23%). Moreover, amp1q21 was associated with shortened time to treatment failure (median, 2.4 versus 6.6 months; P = .043) and overall survival (OS) (median, 4.4 versus 19.8 months; P = .003) compared to pts with normal 1q21. Beta-2-microglobulin and 14q32 translocations were unrelated to treatment outcome with bortezomib. In contrast, median OS was short in the presence of low serum albumin (4.8 versus 17.8 months; P = .036) and deletion of 13q14 (6.7 months versus median not yet reached; P = .06). Using amp1q21, low serum albumin, and deletion of 13q14 as risk factors, patients with significantly different median OS after bortezomib treatment were discriminated: Pts with ≥ 2 risk factors had a median OS of only 4.9 months as opposed to pts with 1 risk factor (median OS 16.5 months) or without any risk factor (median OS not yet reached) (P = .004). In conclusion, FISH-defined amp1q21 is a strong adverse prognostic factor for pts with relapsed/refractory MM treated with single-agent bortezomib. We are currently investigating whether or not bortezomib combinations may be more effective in MM pts with amp1q21.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5121-5121 ◽  
Author(s):  
Mimi I. Hu ◽  
Ana O. Hoff ◽  
Bela Toth ◽  
K. Altundag ◽  
Marcella Johnson ◽  
...  

Abstract Osteonecrosis of the jaw or maxilla (ONJM) is a rare but clinically significant disorder recently reviewed in a large retrospective study by our group (Hoff et al, 27th ASBMR Meeting 2005, Presentation #1218). A subset of the ONJM patients with breast cancer or myeloma was followed at the University of Texas M.D. Anderson Cancer Center (UTMDACC) dental clinic. This analysis describes the natural history of ONJM in this subset. Thirteen of 29 ONJM patients treated with intravenous bisphosphonates (IVBP) at UTMDACC and 1 ONJM patient treated elsewhere were evaluated in the dental clinic for more than 6 months (myeloma, n=7; breast cancer, n=7). Measurement of the maximum length of exposed bone was documented at each visit. Each patient received a standard regimen of conservative dental care with debridement only when indicated. All patients received zoledronic acid (mean cumulative dose 80mg; range 24–152mg) and 10 patients also received pamidronate (mean cumulative dose 1665mg; range 90–2700mg). This subset was followed for a median duration of 18.2 months (range: 7.1–67.3 months). The mean length of exposed bone at initial evaluation was 11 mm (range: 2–29 mm). The lesion from baseline to the most recent clinic visit progressed in 7 patients (50%), remained stable in 2 (14%), regressed in 2 (14%), and resolved in 3 (21%). Persistent ONJ was seen if IVBP was stopped (n=8), decreased in frequency (n=1), or continued at the same dose/frequency (n=2) (Graphs 1, 2). Complete resolution occurred in 3 multiple myeloma patients; IVBP was decreased in one and discontinued in 2 of the resolved cases (heavy lines on Graph 1). Our experience shows that ONJM is a disorder with slow resolution in most patients, lasting as long as 5 years. In the oncologic setting where there is clear benefit of bisphosphonate therapy, studies to optimize the dosing regimen may be needed. Graph 1. Myeloma (n=7) Graph 1. Myeloma (n=7) Graph 2. Breast Cancer (n=7) Graph 2. Breast Cancer (n=7)


Sign in / Sign up

Export Citation Format

Share Document