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    Establishment of an innovative staging system for extramedullary plasmacytoma. Zhu Qian,Zou Xiong,You Rui,Jiang Rou,Zhang Meng-Xia,Liu You-Ping,Qian Chao-Nan,Mai Hai-Qiang,Hong Ming-Huang,Guo Ling,Chen Ming-Yuan BMC cancer BACKGROUND:Extramedullary plasmacytoma (EMP) is a rare malignant disease that lacks a unique clinical staging system to predict the survival of EMP patients and to design individualized treatment. Instead, clinicians have chosen to use the multiple myeloma (MM) staging system. METHODS:Forty-eight EMP patients treated between 1996 and 2014 were included in this study. The new clinical stages were established according to independent survival factors using Cox regression model. RESULTS:Lymph node metastasis and a larger primary tumor (≥5 cm) were the only two independent poor prognostic factors for overall survival (OS) and disease-free survival (P < 0.05). Stage I was defined as the disease without those two poor prognostic factors. Stage II was defined as the presence of either factor, and Stage III was defined as the presence of both factors. OS was significantly different in each stage of the new staging system (P < 0.001), with a median follow-up time for Stage I, Stage II and Stage III of 68, 23 and 14 months. The new staging system had enhanced prognostic value compared to the MM staging system (the area under ROC 0.763 versus 0.520, P = 0.044). Although no difference was observed between treatments in Stage I, the combination treatment was associated with a significantly beneficial OS in the late stages (5-year OS: 15.3 % versus 79.5 %; P = 0.032). CONCLUSIONS:The new staging system exhibited a promising prognostic value for survival and could aid clinicians in choosing the most suitable treatment for EMP patients. 10.1186/s12885-016-2824-x
    [Clinical and cytogenetic characteristics of myeloma patients with overall survival less than 24 months]. Zhuang Junling,Tang Wenjiao,Li Hui,Chen Miao,Han Bing,Zhu Tienan,Duan Minghui,Li Jian,Zhang Wei,Xu Ying,Wang Shujie,Zhao Yongqiang,Zhou Daobin Zhonghua yi xue za zhi OBJECTIVE:To explore the clinical characteristics of multiple myeloma (MM) patients with overall survival (OS) less than 24 months so as to stratify high-risk population. METHODS:A total of 177 newly diagnosed MM inpatients were recruited from July 2008 to July 2012. Clinical parameters at diagnosis of international staging system (ISS), lactic dehydrogenase (LDH), serum calcium, extramedullary involvement and amyloidosis were collected and cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH). Response and death were recorded as endpoints. Otherwise the follow-up period was over 24 months. RESULTS:And 73 patients dying within 24 months were classified into high-risk group while another 104 survivors for over 24 months into control group. Age and gender at baseline were comparable. However, OS of high-risk group was only 8 months while it was not attained during a median follow up of 38 months in control group (P < 0.001). The most common cause of death was progressive disease in both groups. The pre-treatment percentages of the following parameters were significantly higher in high-risk group, including ISS stage III (76.71% (56/73) vs 50.00% (52/104), P = 0.002), renal dysfunction (47.95% (35/73) vs 31.73% (33/104), P = 0.029), elevated LDH (20.55% (15/73) vs 7.69% (8/104), P = 0.015) and plasma cell leukemia (PCL, 5.48% (4/73) vs 0 (0/104), P = 0.016). Conversely, extramedullary involvement, plasmacytoma, amyloidosis and hypercalcemia were similar. Despite comparable chemotherapeutic regimens, the rate of deep response, including complete response (CR) and very good partial response (VGPR), was significant lower in high-risk group than that in control group (12.33% (9/73) vs 53.85% (56/104), P < 0.001). Overall response rates (ORR, i.e. CR+VGPR+ partial response (PR)) were markedly different (38.36% (28/73) vs 86.54% (90/104), P < 0.001). Univariate analysis of cytogenetic abnormalities indicated a higher proportion of 1q21 amplification in high-risk group (35.62% (26/73) vs 25.15% (22/104), P = 0.033). Multivariate Logistic regression revealed that ISS, LDH and primary response worse than PR independently affected early death (P = 0.046, 0.005, < 0.001). CONCLUSIONS:MM patients with OS less than 24 months have distinct clinical characteristics. And aggressive regimens are needed to improve the outcomes of high-risk population.
    Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients. Wen Ge,Wang Weihu,Zhang Yujing,Niu Shaoqing,Li Qiwen,Li Yexiong Chinese journal of cancer research = Chung-kuo yen cheng yen chiu Objective:To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy (RT) in the management of extramedullary plasmacytoma (EMP). Methods:Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51 (range, 22-77) years. The median tumor size was 3.5 (range, 1.0-15.0) cm. The median applied dose was 50.0 (range, 30.0-70.0) Gy. Thirty-nine patients (70.9%) presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery (S) alone, 3 received chemotherapy (CT) alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients. Results:The median follow-up duration was 56 months. The 5-year local recurrence-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) rates were 79.8%, 78.6%, 65.2% and 76.0%, respectively. Univariate analysis revealed that RT was a favourable factor for all examined endpoints. Furthermore, head and neck EMPs were associated with superior LRFS, MMFS and PFS. Tumor size <4 cm was associated with superior MMFS, PFS and OS; serum M protein negativity was associated with superior MMFS and PFS; age ≥50 years and local recurrence were associated with poor MMFS. The dose ≥45 Gy group exhibited superior 5-year LRFS, MMFS and PFS rates (94.7%, 94.4%, 90.0%, respectively), while the corresponding values for the dose <45 Gy group were 62.5% (P=0.008), 53.3% (P=0.036) and 41.7% (P<0.001). Conclusions:Involved-site RT of at least 45 Gy should be considered for EMP. Furthermore, patients with head and neck EMP, tumor size <4 cm, age <50 years and serum M protein negativity had better outcomes. 10.21147/j.issn.1000-9604.2017.05.08
    Clinicopathological Profile of Myelomatous Pleural Effusion: Single-center Real-world Experience and Review of Literature. Yanamandra Uday,Deo Prateek,Sahu Kamal Kant,Nampoothiri Ram Vasudevan,Gupta Nalini,Prabhakaran Anusree,Dhibhar Deb Prasad,Khadwal Alka,Prakash Gaurav,Sachdeva Man Upadesh Singh,Lad Deepesh,Varma Neelam,Varma Subhash,Malhotra Pankaj Clinical lymphoma, myeloma & leukemia BACKGROUND:Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting. PATIENTS AND METHODS:In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes. RESULTS:Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months. CONCLUSION:MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis. 10.1016/j.clml.2018.12.003
    How We Manage Patients with Plasmacytomas. Fotiou Despina,Dimopoulos Meletios A,Kastritis Efstathios Current hematologic malignancy reports PURPOSE OF REVIEW:To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). RECENT FINDINGS:Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci. The role of flow cytometry and clonal plasma cell detection is currently under study together with other prognostic factors for the identification of patients with SP at high risk of progression to overt MM. Solitary plasmacytomas are treated effectively with local radiotherapy whereas systemic therapy is required at relapse. Clonal plasma cells that accumulate at extramedullary sites have distinct biological characteristics. Patients with MM and soft tissue involvement have poor outcomes and should be treated as ultra-high risk. A revised definition of SP that distinguishes between true solitary clonal PC accumulations and SP with minimal bone marrow involvement should be considered to guide an appropriate therapeutic and follow-up approach. Future studies should be conducted to determine optimum treatment approaches for patients with MM and paraskeletal or extramedullary disease. 10.1007/s11899-018-0452-z
    The impact of extramedullary disease at presentation on the outcome of myeloma. Wu Ping,Davies Faith E,Boyd Kevin,Thomas Karen,Dines Sharon,Saso Radovan M,Potter Mike N,Ethell Mark E,Shaw Bronwen E,Morgan Gareth J Leukemia & lymphoma This study was conducted to compare the presenting features and outcome of newly-diagnosed myeloma with and without extramedullary (EM) manifestations and to determine the optimum treatment. Seventy-five (16.3%) patients with EM involvement at diagnosis were compared with 384 cases without EM disease. EM patients had a more favourable International Staging System and a different distribution of myeloma isotypes. When adjusted according to the independent risk factors, patients in the EM group treated with chemotherapy alone had significantly shorter overall survival (OS) compared to those without EM disease receiving similar treatment. High-dose treatment (HDT) was associated with significantly improved OS in both groups; however, it had more impact on OS among EM group, overcoming the negative prognostic impact of presenting EM disease. Patients in the EM group treated with HDT have a similar outcome to those without EM manifestations treated with HDT. HDT should form an integral component of first-line treatment for patients with EM disease whenever possible. 10.1080/10428190802657751
    Management of central nervous system involvement in multiple myeloma after autologous hematopoietic stem cell transplantation. Mousavi-Fatemi Khatereh,Maleki Nasrollah Leukemia research reports Multiple myeloma (MM) is characterized by uncontrolled clonal proliferation of plasma cells, mainly in bone marrow, and its extramedullary involvement is rare. Central nervous system involvement in MM is a highly aggressive disease with a survival of less than 6 months. The best treatment regimen for MM with CNS involvement is still unknown and in most patients, the prognosis is unfavorable. To date, there is no report of CNS involvement without evidence of systemic involvement in a known case with MM. Here, we report a 58-year-old male with MM who recurred CNS involvement without evidence of systemic involvement following autologous stem cell transplant. 10.1016/j.lrr.2020.100210
    Comparison of outcomes after autologous stem cell transplantation between myeloma patients with skeletal and soft tissue plasmacytoma. Shin Ho-Jin,Kim Kihyun,Lee Ji Won,Song Moo-Kon,Lee Je-Jung,Lee Ho-Sup,Lee Won Sik,Kim Seok Jin,Chung Joo Seop European journal of haematology We aimed to compare the characteristics of skeletal and soft tissue plasmacytomas and to analyze clinical outcomes and prognostic factors of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with plasmacytoma. We retrospectively reviewed data from 93 myeloma patients with detectable extramedullary (EM) plasmacytoma at diagnosis or during the course of the disease, who underwent ASCT. Soft tissue plasmacytoma occurred more frequently in male patients and had higher levels of serum β2-microglobulin and lactate dehydrogenase and high frequency of advanced disease according to International Staging System compared to the skeletal plasmacytoma group. Both soft tissue and skeletal plasmacytoma groups showed similar plasmacytoma relapse patterns after ASCT and relapsed with EM plasmacytoma slightly more frequently in the bone compared to soft tissue sites. Compared to patients with skeletal plasmacytoma, patients with soft tissue plasmacytoma had worse median progression-free survival (PFS) (12 vs. 28 months) (P = 0.001) and overall survival (OS) (37 vs. 67 months) (P = 0.037) after ASCT. In a multivariate analysis, soft tissue plasmacytoma was an only independent poor prognostic factor for both PFS (HR, 2.398; 95% CI, 1.304-4.410) and OS (HR, 2.811; 95% CI, 1.107-7.135) after ASCT. These results demonstrate that, even though ASCT achieved a strong response in myeloma patients with soft tissue plasmacytoma, the presence of EM disease still contributed to a poor prognosis after ASCT compared to skeletal plasmacytoma, and these poor outcomes were not overcome by ASCT. 10.1111/ejh.12377
    Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome. Zeiser R,Deschler B,Bertz H,Finke J,Engelhardt M Bone marrow transplantation Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto- (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, beta2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto- and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT. 10.1038/sj.bmt.1704713
    Roundtable: How I treat a newly diagnosed patient with high-risk myeloma. Kaufman Jonathan L Hematology. American Society of Hematology. Education Program Initial management of high-risk myeloma remains a treatment challenge. Risk is defined by a combination of clinical and biological features, with fluorescence in situ hybridization detection of specific cytogenetic abnormalities driving categorization. High-risk abnormalities include t(4;14), t(14;16), t(14;20), del(17p), and +1q. Clinical features such as plasma cell leukemia, presence of 5% to 20% circulating plasma cells, and extramedullary disease all are factors in high-risk presentations. The driving principle of treatment of the high-risk patient is the use of a regimen with the greatest likelihood of a deep and prolonged remission, as defined by minimal residual disease negativity. I will describe prior and current treatment approaches, including induction, the role of autologous transplantation, and posttransplantation consolidation and maintenance therapy selection using the best available data to provide a rationale for these decisions. This case-based roundtable walks through treatment of a patient with newly diagnosed high-risk myeloma. 10.1182/hematology.2019000015
    [Clinical features of multiple myeloma patients with extramedullary disease: a report of 40 cases from a single center]. Chen Hai-fei,Fu Wei-Jun,Wang Dong-Xing,Yuan Zhen-Gang,Chen Yu-Bao,Hou Jian Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi OBJECTIVE:To analyze the clinical and laboratory features and risk factors of multiple myeloma (MM) with extramedullary disease (EM) and its extraosseous localizations at diagnosis and during the course of MM. METHODS:The clinical features, survival rate and prognostic factors were retrospectively analyzed in 40 patients having EM from a total of 418 MM patients hospitalized in Changzheng Hospital from 1993 to 2006. RESULTS:Among the 40 patients, the first three localizations of EM involved soft tissue, pleura or peritoneum and central nervous system (CNS). Median duration of follow-up was 30 months. The median overall survival (OS) was 28 months. Twenty-five patients (6%) were found to have EM at diagnosis (group A), and their median OS was 16 months and 15 patients (3.6%) developed EM during the course of the disease (group B), and their expected median OS was 72 months. There was a significant difference between group A and B (P = 0.0045) for OS. Compared with those in group A, patients in group B had a higher percentage of plasmacytes (P = 0.022) and plasmablasts (P = 0.029) in bone marrow, and less advanced stage for international staging system (ISS) (P = 0.027). Log-rank univariate analysis showed that higher CRP level, higher serum LDH, Stage II and III for ISS, Hb < 110 g/L at diagnosis were poor prognostic factors. However, multivariate analysis with COX model showed none of them were statistically significant. CONCLUSION:EM tumors are not a rare manifestation of MM. Soft tissue in the commonest area involved. Higher serum CRP and LDH level, more advanced stage for ISS, anemia and having EM are poor prognostic factors of MM.
    Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases. Rasche Leo,Bernard Corinna,Topp Max S,Kapp Markus,Duell Johannes,Wesemeier Carmen,Haralambieva Eugenia,Maeder Uwe,Einsele Hermann,Knop Stefan Annals of hematology Extramedullary (e) relapse in multiple myeloma(MM) has an adverse prognosis, but knowledge concerning biological features and preferred treatment is scarce. We screened the myeloma registry of our institution for eMM relapses and identified 24 cases among 357 patients (pts).Only 8% of eMM relapses occurred after initial therapy, but 54% occurred after third-line or subsequent therapy. Baseline molecular cytogenetics revealed high-risk features in 10 of 19 evaluable patients. Most frequently, eMM presented as soft tissue (67%) and organ involvement (25%) or malignant effusion (12.5%). Incidence of leptomeningeal/CNS involvement was 21%. At eMM relapse, bone marrow infiltration was absent in 46% and low in 21%. Ten eMM biopsies were available showing increased proliferation, i.e., Ki-67 of 67%(range, 30–90%) of all cancer cells. Pts received radiation therapy, dose-intense chemotherapy, novel agents, and allogeneic SCT resulting in an overall response rate of 54%. Median progression-free survival was 2 (95% CI 0.08–3.92) and median overall survival 7 months (95% CI 3.56–10.43), respectively,with only three patients being alive at 12 months from diagnosis. EMM relapse may present at any anatomical site with frequent CNS involvement. Biological features include increased proliferation and low rate of marrow involvement.Prognosis remains poor despite intensive treatment. 10.1007/s00277-012-1414-5
    Multiple Myeloma Presenting in Patients Younger than 50 Years of Age: A Single Institution Experience. Duek Adrian,Trakhtenbrot Luba,Avigdor Abraham,Nagler Arnon,Leiba Merav Acta haematologica INTRODUCTION:Multiple myeloma (MM) is uncommon in persons younger than 50 years of age. The presenting features in this age group are unclear. METHODS:We analyzed a cohort of patients <50 years of age with MM treated in our center. RESULTS:Twenty-three patients at a median age of 41.5 years (range 27-49) were analyzed. Patients presented at International Staging System (ISS) I-II (79%), had high frequency of bone lytic lesions (89%), extramedullary disease (26%), light-chain myeloma (45%), and translocation t(11;14) (68%). The subpopulation of patients carrying t(11;14) were younger (p = 0.025). This subgroup had higher bone marrow infiltration of plasma cells (75 vs. 47.5%), higher incidence of proteinuria (2.9 vs. 0.19 g/day), and poorer response to therapy: 85.7% of patients achieving complete/very good partial remission after induction therapy did not have t(11;14). A trend toward inferior progression-free survival (PFS) was observed in patients with t(11; 14) compared to patients without this translocation (median PFS 18 and 36 months, respectively). DISCUSSION/CONCLUSION:Translocation t(11; 14) seems to be more prevalent in young myeloma patients. Young myeloma patients and especially those who harbor translocation t(11; 14) may represent a distinct clinical entity that confers a poor outcome. 10.1159/000507414
    A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: analysis of parameters that improve outcome. Beksac Meral,Seval Guldane Cengiz,Kanellias Nicholas,Coriu Daniel,Rosiñol Laura,Ozet Gulsum,Goranova-Marinova Vesselina,Unal Ali,Bila Jelena,Ozsan Hayri,Ivanaj Arben,Balić Lejla Ibricevic,Kastritis Efstathios,Bladé Joan,Dimopoulos Meletios Athanasios Haematologica Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement extramedullary plasmacytoma at diagnosis (34.2% 19.3%; =NS.) and relapse (54.5% 9%; =0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached 46.5 months). Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need. 10.3324/haematol.2019.219295
    Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience. Katodritou Eirini,Terpos Evangelos,Kastritis Efstathios,Delimpasis Sossana,Symeonidis Argiris S,Repousis Panagiotis,Kyrtsonis Marie-Christine,Vadikolia Chrysa,Michalis Eurydiki,Polychronidou Genovefa,Michael Michael,Papadaki Sofia,Papathanasiou Maria,Kokoviadou Kyriaki,Kioumi Anna,Vlachaki Eythimia,Hadjiaggelidou Christina,Kouraklis Alexandra,Patsias Ioannis,Gavriatopoulou Maria,Kotsopoulou Maria,Verrou Evgenia,Gastari Vasiliki,Christoulas Dimitrios,Giannopoulou Evlambia,Pouli Anastasia,Konstantinidou Pavlina,Anagnostopoulos Achilles,Dimopoulos Meletios-Athanasios Annals of hematology Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly. 10.1007/s00277-015-2484-y
    Autologous stem cell transplant can overcome poor prognosis in patients with multiple myeloma with extramedullary plasmacytoma. Li Jian,Shen Kai-Ni,Huang Wen-Rong,Li Li-Hong,Chen Huan,Chen Wen-Ming,Liu Kai-Yan,Yu Li,Zhou Dao-Bin Leukemia & lymphoma 10.3109/10428194.2013.853296
    Extramedullary manifestation in multiple myeloma bears high incidence of poor cytogenetic aberration and novel agents resistance. Qu Xiaoyan,Chen Lijuan,Qiu Hairong,Lu Hua,Wu Hanxin,Qiu Hongxia,Liu Peng,Guo Rui,Li Jianyong BioMed research international Extramedullary disease (EMD) in multiple myeloma (MM) patients is an uncommon event and more attention was directed toward the feature of these patients. Cytogenetic aberration is an important characteristic of MM and is associated with patients' outcome. In this study, we aimed to compare the cytogenetic abnormality of patients with and without extramedullary manifestation, and to analyze the clinical outcomes of novel agents in EMD patients. We retrospectively investigated data from 41 MM patients. Our analyses showed del(17p13) in 31% of EMD versus 13% of medullary disease (P = 0.03) and amp(1q21) in 55% versus 32% (P = 0.019). No differences were shown in del(13q14) and t(4;14). 24/27 patients with EMD at diagnosis responded to the novel agents-containing regimens. However, when relapsed, 70% of patients did not benefit from the sequential use of novel agents as salvage therapy. In 14 patients who developed EMD at relapse phase, only 2 patients responded to novel agents therapy. Median overall survival of patients with extramedullary manifestations was 30 months, in comparison to 104 months for patients without EMD (P = 0.002). Patients with extramedullary manifestation bore high incidence of poor cytogenetic aberration and novel agents resistance. 10.1155/2015/787809
    Clinical analysis of 40 multiple myeloma patients with extramedullary plasmacytoma of the head. Sun Wan-Jun,Zhang Jia-Jia,An Na,Shen Men,Huang Zhong-Xia,Li Xin The Journal of international medical research Objectives To investigate the clinical characteristics, survival and prognosis of patients with multiple myeloma (MM) and head extramedullary plasmacytoma (EMP). Methods Forty MM patients were enrolled in the study (18 men, 22 women; median age, 55 years). Results Median overall survival (OS) and progression-free survival (PFS) were 24 (5-78) months and 17 (2-36) months, respectively. The 2-, 3- and 5-year OS rates were 51%, 20% and 7%, respectively. The 2-year PFS was 15%. Median OS and PFS in patients administered velcade were 26 (18-50) and 22.5 (5-78) months, compared with 20 (10-30) and 13.5 (2-36) months in patients without velcade, respectively. Median OS was 23.5 (5-50) months in patients with EMP at MM diagnosis ( n = 25) and 36 (22-78) months in patients with head EMP diagnosed during the disease course ( n = 15). Sixteen MM patients had EMP invasion of the head only and 24 had invasion at multiple sites. Median OS was 25 (22-78) months in patients with EMP of the head only and 22 (5-78) months in patients with EMP invasion at multiple sites. Conclusion MM patients with head EMP show a more aggressive disease course and shorter OS and PFS. The prognosis of these patients is poor, especially in patients with head EMP at MM diagnosis, though combined chemotherapy and radiotherapy may prolong survival. 10.1177/0300060516664820
    Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation. Weinstock Mathew,Aljawai Yosra,Morgan Elizabeth A,Laubach Jacob,Gannon Muriel,Roccaro Aldo M,Varga Cindy,Mitsiades Constantine S,Paba-Prada Claudia,Schlossman Robert,Munshi Nikhil,Anderson Kenneth C,Richardson Paul P,Weller Edie,Ghobrial Irene M British journal of haematology Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8·3% of the total study population. EMD was present at the time of diagnosis in 14·5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4·1 years (95% CI: 3·1, 5·1) and the median overall survival from time of EMD diagnosis was 1·3 years (95% CI: 0·8, 2·3). This report demonstrates that the incidence of EMD has not increased with the introduction of novel agents and stem cell transplantation. The most common EMD presentations in the relapsed setting were liver and pleural fluid. The presence of CD44 and CXCR4 expression may represent new markers of EMD that warrant further investigation. 10.1111/bjh.13383
    Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a study from the Chronic Malignancies Working Party of the EBMT. Gagelmann Nico,Eikema Diderik-Jan,Iacobelli Simona,Koster Linda,Nahi Hareth,Stoppa Anne-Marie,Masszi Tamás,Caillot Denis,Lenhoff Stig,Udvardy Miklos,Crawley Charles,Arcese William,Mariette Clara,Hunter Ann,Leleu Xavier,Schipperus Martin,Delforge Michel,Pioltelli Pietro,Snowden John A,Itälä-Remes Maija,Musso Maurizio,van Biezen Anja,Garderet Laurent,Kröger Nicolaus Haematologica We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; <0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: =0.86, and extramedullary organ: =0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival (=0.07) while single organ involvement was significantly worse (=0.001). Multiple organ sites were associated with worse outcome (<0.001 and =0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (=0.13 for both). 10.3324/haematol.2017.178434
    Solitary extramedullary and bone plasmacytomas versus multiple myeloma with extramedullary manifestation. Nair Bijay Oncology (Williston Park, N.Y.)
    [Clinical analysis of multiple myeloma patients with bone-related extramedullary disease: a longitudinal study on 834 consecutive patients in a single center of China]. Deng Shuhui,Xu Yan,An Gang,Sui Weiwei,Li Zengjun,Zou Dehui,Zhao Yaozhong,Qi Junyuan,Qiu Lugui Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi OBJECTIVE:To analyse the incidence, clinical features, prognosis of bone-related extramedullary disease (bEMD) and its relationship with strict EMD (sEMD) in MM patients. METHODS:The records of 834 consecutive newly diagnosed patients with MM in our hospital between 1993 and 2013 were retrospectively reviewed. RESULTS:①Among 834 patients at diagnosis, 32 cases (3.8%) showed bEMD, and 40 cases (4.8%) showed sEMD. Patients with bEMD at presentation showed significant lower level of lactate dehydrogenase (180.9 U/L vs 299.2 U/L, P=0.034) and higher overall response rate (ORR) (95.7% vs 66.7%, P=0.009) compared with sEMD patients. While the above two parameters were comparable between patients with bEMD and without EMD. ②As to the prognosis of patients without autologous hematopoietic stem cell transplantation (auto-HSCT), the overall survival (OS) of patients with sEMD, bEMD and without EMD was 14.0, 37.5, and 38.0 months, respectively. The time to progression (TTP) of the three groups was 11.5, 27.0, and 22.0 months, respectively. Compared to the patients with sEMD, the outcomes (both OS and TTP) of the other two groups was significantly better (P<0.05). Patients with bEMD at presentation was comparable to the patients without EMD, but the two groups were better than the patients with sEMD. ③The incidence of bEMD during follow-up was 0.5%. The OS of patients with sEMD, bEMD and without EMD during follow-up was 26.0, 17.0, and 40.0 months, respectively. The TTP of the three groups was 13.0, 11.0, and 25.0 months, respectively. The outcomes (both OS and TTP) of patients with bEMD at relapse/progression showed no significant difference as compared with the other two groups (P>0.05). CONCLUSION:The clinical features of MM patients with bEMD are different from the patients with sEMD. Outcomes of this population is significantly better than the latter, and is comparable to the patients without EMD. It suggests that bEMD alone has no negative prognostic significance in MM patients. 10.3760/cma.j.issn.0253-2727.2015.06.012
    The t(11;14)(q13;q32) translocation as a poor prognostic parameter for autologous stem cell transplantation in myeloma patients with extramedullary plasmacytoma. Shin Ho-Jin,Kim Kihyun,Lee Je-Jung,Song Moo-Kon,Lee Eun Yup,Park Sang Hyuk,Kim Sun-Hee,Jang Mi-Ae,Kim Seok Jin,Chung Joo Seop Clinical lymphoma, myeloma & leukemia INTRODUCTION:Fluorescence in-situ hybridization (FISH)-detected abnormalities, including del(17p), del(13q), and t(4;14), have been associated with inferior prognosis. However, there are few data about the prognostic significance of cytogenetic abnormalities for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with extramedullary plasmacytoma (EMP). PATIENTS AND METHODS:Between April 2004 and December 2012, 290 MM patients underwent ASCT at 3 centers. FISH data for bone marrow samples obtained at diagnosis were available for 58 patients who had EMP at diagnosis or during treatment. RESULTS:The t(11;14), t(4;14), del(13q), and 1q gain abnormalities were seen in 14.9%, 6.3%, 25.6%, and 42.9%, respectively. No t(14;16) or del(17p) cytogenetic abnormality was detected in the examined patients. Patients with t(11;14) had a lower response rate compared to patients with other cytogenetic abnormalities. EMP-specific relapse was higher in patients with t(11;14) than in patients with other cytogenetic abnormalities (42.9% vs. 10%-33.3%). Each of the 4 cytogenetic abnormalities predicted shorter median progression-free survival (6-12 months vs. 27-37 months) and shorter overall survival (16-22 months vs. 68 months or not reached) compared to no cytogenetic abnormality. The t(11;14) translocation was an important prognostic factor for both progression-free survival (hazard ratio, 25.154; P < .001) and overall survival (hazard ratio, 7.484; P = .024) in the multivariate analysis. CONCLUSION:In the current study, t(11;14), t(4;14), del(13q), and 1q gain were associated with worse survival in MM patients with EMP. The role of t(11;14) as a prognostic parameter for ASCT in MM patients with EMP should be confirmed with a large, well-designed study. 10.1016/j.clml.2014.12.007
    [Clinical Application of R-ISS Staging System in 412 Newly Diagnosed Patients with Multiple Myeloma]. Chen Hai-Min,Wei Wei,Peng Rong,Shi Hao-Tian,Chen Xiao-Ling,Wu Li-Xia,Zhou Nian,Zhou Fan Zhongguo shi yan xue ye xue za zhi OBJECTIVE:To evaluate the prognostic value of R-ISS staging system in patients with newly diagnosed multiple myeloma (NDMM). METHODS:The Chinical data of 412 patients with NDMM in our hospital from May 2010 to May 2016 were retrospectively analyzed. All the patients received conventional chemotherapy or thalidomide or bortezomib-based chemotherapy. All the patients with NDMM were divided into R-ISS-Ⅰ, R-ISS-Ⅱ and R-ISS-Ⅲ groups according to R-ISS staging system on the basis of ISS staging system, cytogenetics and LDH level. The progression-free survival (PFS) time and overall survival(OS) of different groups were compared. RESULTS:Among all 412 patients, 76 were rated as R-ISS-Ⅰ, 259 as R-ISS-Ⅱ and 77 as R-ISS-Ⅲ. The median PFS time in 3 groups were 44, 25 and 14 months respectively (P<0.01). The median OS time of the 3 groups were not reached 54 and 25 months respectively (P<0.01). Further analysis also found that statistically different survival associated with different R-ISS groups in the conventional chemotherapy group (P<0.05), bortezomib-based chemotherapy group (P<0.01), thalidomide-based chemotherapy group (P<0.01), transplantation group (P<0.05), different-age stratified group (≤65y P<0.01, 66-75y P<0.01,≥76y P<0.01), damaged renal function group (P<0.01) and extramedullary infiltration group (P<0.01). CONCLUSION:PFS and OS in the patients with multiple myeloma were different among three distrinct R-ISS stages. The R-ISS staging system has important clinical significance for the prognosis evaluation of multiple myeloma. 10.7534/j.issn.1009-2137.2019.01.018
    Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Lu J,Lu J,Chen W,Huo Y,Huang X,Hou J, Blood cancer journal The aim of this study was to understand the clinical features and treatment outcome of Chinese patients with multiple myeloma (MM). This retrospective study enrolled 940 newly diagnosed inpatients (median age, 59 years; immunoglobulin (Ig)D isotype, 6.5%) with complete follow-up data at three centers. In all, 85.8% of patients were of Durie-Salmon stage III and 48.3% were of International Staging System (ISS) stage III at diagnosis. Also, 9.6% of patients had extramedullary plasmacytoma. Compared with IgG, IgD-type patients were diagnosed at a younger age, and more patients were of ISS stage III, with hypercalcemia, elevated levels of lactate dehydrogenase, hyperuricemia, renal dysfunction and 1q21 amplification (P=0.03). The overall survival (OS) benefit was more prominent in IgG than in IgD when patients received bortezomib; however, they showed no significant difference when they received older therapies such as melphalan combined with prednisone or vincristine combined with adriamycin and dexamethasone. Fluorescence in situ hybridization (FISH) results showed that 17.6% had 17p13 deletion. Conventional cytogenetics revealed that 13.3% were hypodiploid and those cases had the worst survival, but hyperdiploid cases (9.3%) did not show any survival benefit compared with those with a normal karyotype (77.4%). Median OS and progression-free survival for all patients were 54 and 26 months, respectively. Significant factors for survival by multivariate analysis were gender, ISS stage, number of FISH abnormalities and extramedullary disease. MM in mainland China presents with different features, with patients being of younger age and having higher risk and more survival benefit in IgG patients receiving bortezomib. 10.1038/bcj.2014.55
    Progression with clinical features is associated with worse subsequent survival in multiple myeloma. Chakraborty Rajshekhar,Liu Hien D,Rybicki Lisa,Tomer Jacqulyn,Khouri Jack,Dean Robert M,Faiman Beth M,Kalaycio Matt,Samaras Christy J,Majhail Navneet S,Valent Jason American journal of hematology Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end-organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM- (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T was significantly shorter in CP/EM+ compared to CP/EM- and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM- and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow-up of 26 months from T , median overall survival was 50, 19 and 10 months for BP, CP/EM- and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM- vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM-: 2.42; P < 0.001 for all comparisons), along with age at T . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end-organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms. 10.1002/ajh.25415
    Analysis of clinical features, treatment response, and prognosis among 61 elderly newly diagnosed multiple myeloma patients: a single-center report. An Na,Li Xin,Shen Man,Chen Shilun,Huang Zhongxia World journal of surgical oncology BACKGROUND:We identified the clinical features of 61 cases of multiple myeloma (MM) patients over 65 years and analyzed the treatment and prognosis of the era of new drugs in elderly patients. METHODS:We identified 61 newly diagnosed symptomatic multiple myeloma (NDMM) among elderly Chinese patients more than 65 years old diagnosed from 2006 to 2012. RESULTS:Of the 205 consecutive MM patients whom we reviewed, 61 (29.76%) cases were NDMM patients aged more than 65 years and the others were younger than 65 years old. Among them, 40 (65.6%) cases were in end-stage (ISS stage III); meanwhile, 19 (31.2%) cases of them had MM with extramedullary plasmacytoma (EMP), observed in 42.1% patients at diagnosis, and the top three incidence of position were spinal canal, pleural, and soft tissue. In the whole column, the median follow-up was 38 months and median age was 72.5 years. Patients received bortezomib- or thalidomide-containing regimens as initial therapy. Comparing the two treatment groups, the complete remission (CR)/near-complete remission (nCR) rate was significantly higher in the bortezomib-containing regimens (61.5 vs.18.18%, P=0.001), no difference in progression-free survival (PFS) and overall survival (OS). Patients of age over 75 years had shorter OS than those of age over 65 years (49 vs. 24 months, P=0.001). The patients with EMP had shorter OS than those without EMP in two age groups (32 vs. 42 and 15 vs. 24 months, P=0.017 and 0.024, respectively). CONCLUSIONS:The results highlight that patients over 75 years and MM with EMP have a poorer outcome. While the CR rate is higher in bortezomib-containing regimens, no significant improvement is noted in respect to the survival outcomes; also, it cannot overcome the negative influence on survival of age and MM with EMP in elderly patients. 10.1186/s12957-015-0649-8
    The possible role of burden of therapy on the risk of myeloma extramedullary spread. Mangiacavalli Silvia,Pompa A,Ferretti V,Klersy C,Cocito F,Varettoni M,Cartia C S,Cazzola M,Corso A Annals of hematology Extramedullary relapse (EMR) represents a poor prognostic marker in the course of multiple myeloma (MM). We reviewed data from 329 patients, diagnosed between 2000 and 2010, without extramedullary disease at onset to explore possible risk factors for EMR. The median overall survival of our study cohort was 6.4 years. The risk of EMR was 28 % with a median time from diagnosis to first EMR of 2.2 years (0.2-9.1 years). Patients with soft tissue masses located in extra-osseous organs (EMR-S) showed the worst outcome, compared to those with tumor masses arising from adjacent bone (EMR-B) (median OS 1.6 vs 2.4 years, p = 0.006). In addition, patients with EMR-S showed a significant trend for further development of extramedullary masses in a very short time (3.7 vs 5.7 months for EMR-B, p = 0.043). Multivariate analysis failed to identify any clinically presenting features predictive for EMR. The occurrence of EMR was higher in patients with more complex treatment history, defined on the basis of longer treatment duration (≥6 vs <6 months) and on elevated number of treatment lines administered (>2 vs ≤2 lines) (HR = 4.5, p < 0.001 and HR = 9.0, p < 0.001, respectively, when one or both factors are present).In conclusion, increasing burden of treatment might be a possible risk factor for EMR. MM patients with multiple relapses should be comprehensively investigated including, when possible, a whole-body-targeted radiologic technique to accurately detect EMR. Treatment choice should take into account the very poor outcome for patients with soft tissue involvement. 10.1007/s00277-016-2847-z
    High-dose chemotherapy followed by autologous stem cell transplant for multiple myeloma: Predictors of long-term outcome. Kumar Lalit,Ramavath Dev,Kataria Babita,Tiwari Akash,Raj Abhishek,Chellapuram Santosh Kumar,Mookerjee Anjali,Sahoo Ranjit Kumar,Malik Prabhat S,Sharma Atul,Gupta Ritu,Sharma Om Dutt,Biswas Ahitagni,Kumar Rakesh,Thulkar Sanjay, The Indian journal of medical research Background & objectives:Survival of patients with multiple myeloma (MM) has improved in the past two decades following use of novel agents and autologous stem cell transplantation. To determine predictors of long-term outcome, data of MM patients who underwent autologous stem cell transplantation (ASCT) at a tertiary care centre in north India were retrospectively analyzed. Methods:Between 1995 and 2016, 349 MM patients underwent ASCT. Patients' median age was 52 yr, ranging from 29 to 68 yr, 68.2 per cent were males. Thirty three per cent patients had international staging system (ISS) Stage III and 68.5 per cent had received novel agents-based induction. High-dose melphalan (200 mg/m) was used for conditioning; patients with renal insufficiency (estimated glomerular filtration rate <40 ml/min) received melphalan 140-150 mg/m. Results:Post-transplant, 317 of 349 (90.8%) patients responded; complete [complete response (CR)] -213 (61%)], very good partial response (VGPR) -62 (17.8%) and PR in 42 (12%)]. Induction with novel agents, pre-transplant chemosensitive disease, transplant in first remission and serum albumin (≥3.5 g/dl) were predictors of significant response. At a median follow up of 73 months, median overall survival (OS) was 90 months [95% confidence interval (CI) 70.8-109.2], and progression-free survival (PFS) was 41 months (95% CI 33.0-49.0). On multivariate analysis, achievement of CR post-transplant, transplant in first remission, ISS Stages I and II (vs. III), absence of extramedullary disease and serum albumin ≥3.5 g/dl were predictors of prolonged OS. For PFS, achievement of post-transplant CR and transplant in first remission were predictors of superior outcome. Interpretation & conclusions:Treatment with novel agents, achievement of complete remission post-transplant, ISS Stages I and II, absence of extramedullary disease and transplant in first remission were predictors of long-term survival for patients with MM. 10.4103/ijmr.IJMR_1593_18
    Overexpression of c-myc is associated with adverse clinical features and worse overall survival in multiple myeloma. Szabo Agoston Gyula,Gang Anne Ortved,Pedersen Mette Ølgod,Poulsen Tim Svenstrup,Klausen Tobias Wirenfeldt,Nørgaard Peter Leukemia & lymphoma The role of c-myc in multiple myeloma (MM) is controversial. We conducted a retrospective study of 117 patients with MM diagnosed between 2004 and 2010 at Herlev Hospital. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) made from diagnostic bone marrow aspirates. Clinical data were obtained from the Danish Multiple Myeloma Database (DMMD). Overexpression of c-myc was found in 40% of patients. MYC translocation was found in 10% of patients. Overexpression of c-myc was not associated with MYC translocation. Overexpression of c-myc was associated with hypercalcemia (p = 0.02) and extramedullary myeloma (p < 0.01). Overexpression of c-myc was associated with shorter overall survival (OS) by multivariable analysis of the entire patient cohort [HR 1.92 (1.06-3.45), p = 0.03] and univariable analysis of high-dose-therapy (HDT)-ineligible patients [HR 2.01 (1.05-3.86), p = 0.04]. Further studies of c-myc overexpression in larger cohorts of patients with MM are warranted. 10.1080/10428194.2016.1187275
    Clinical characteristics and prognosis of multiple myeloma with bone-related extramedullary disease at diagnosis. Tian Chen,Wang Lu,Wu Ling,Zhu Lei,Xu Wengui,Ye Zhaoxiang,Zhao Zhigang,Wang Yafei,Zhang Yizhuo Bioscience reports Multiple myeloma (MM) is a hematological neoplasm which results in diffuse or focal bone infiltration and extramedullary lesions. It's reported that infiltration of organs by plasma cells indicated worse prognosis, but the prognosis of patients with bone-related extramedullary disease (bEMD) is still unknown. One hundred and fourteen newly diagnosed MM patients were retrospectively reviewed. Results showed that the clinical features, overall survival (OS), and progression-free survival (PFS) of patients with and without bEMD had no statistical significance. Rib (46.1%) and vertebrae (17.9%) are common sites bEMD involved. Patients with diffuse bEMD had worse prognosis compared with patients with focal bEMD. Bisphosphonates played an important role in prolonging the survival of patients with bEMD. Positron emission tomography (PET)/computed tomography (CT) is sensitive in discovering bEMD than whole body low dose CT suggesting PET/CT to be a promising technique for initial staging. High β2-microglobulin and low albumin indicated shorter survival in patients with bEMD. 10.1042/BSR20171697
    Defining and treating high-risk multiple myeloma. Usmani S Z,Rodriguez-Otero P,Bhutani M,Mateos M-V,Miguel J S Leukemia Multiple myeloma (MM) is more recently being recognized as a heterogeneous group of disease with variability in outcomes based on specific clinical and biologic predictors. MM patients can be broadly categorized into standard, intermediate and high risk for disease relapse, morbidity and mortality. The high-risk features include patient-specific factors such as old age, poor performance status and comorbidities; clinical features such as primary plasma cell leukemia and extramedullary disease; disease-specific biologic features such as deletion 17p, t(4;14) and high-risk gene expression profiling signatures. The current paper reviews the available data on best therapeutic approaches for high-risk MM. 10.1038/leu.2015.209
    Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data. Sevcikova Sabina,Paszekova Helena,Besse Lenka,Sedlarikova Lenka,Kubaczkova Veronika,Almasi Martina,Pour Ludek,Hajek Roman Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia BACKGROUND:Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells (PC) which accumulate in the bone marrow (BM). The advent of new drugs has changed the course of the disease from incurable to treatable, but most patients eventually relapse. One group of MM patients (10-15%) is considered high-risk because they relapse within 24 months. Recently, extramedullary relapse of MM (EM) has been observed more frequently. Due to its aggressivity and shorter survival, EM is also considered high-risk. AIMS:The goal of this study was to determine if the so-called high-risk genes published by the University of Arkansas group (UAMS) are even more deregulated in EM patients than in high-risk MM patients and if these patients may be considered high-risk. METHODS:Nine samples of bone marrow plasma cells from MM patients as well as 9 tumors and 9 bone marrow plasma cells from EM patients were used. Quantitative real-time PCR was used for evaluation of expression of 15 genes connected to the high-risk signature of MM patients. RESULTS:Comparison of high-risk plasma cells vs extramedullary plasma cells revealed 4 significantly deregulated genes (CKS1B, CTBS, NADK, YWHAZ); moreover, comparison of extramedullary plasma cells vs extramedullary tumors revealed significant differences in 9 out of 15 genes. Of these, 6 showed significant changes as described by the UAMS group (ASPM, SLC19A1, NADK, TBRG4, TMPO and LARS2). CONCLUSIONS:Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse. 10.5507/bp.2015.014
    Extramedullary Manifestation of Multiple Myeloma in the Oral Cavity. de Assis Pereira Hansen Cristiano,Filho Jayr Schmidt,de Mattos Nascimento Marina,Alves Fábio Abreu,Neotti Tatiane,D Almeida Costa Felipe Archives of Iranian medicine BACKGROUND:Extramedullary plasmacytomas occurs in about 20% of multiple myeloma (MM) recurrences. Extramedullary disease seems to respond poorly to thalidomide and has adverse prognostic implication. When disease recurs in the oral cavity with soft tissue infiltration, some authors defend upfront surgical excision prior to radiotherapy with the aim of achieving better local control. We describe herein such an atypical case of recurrence from MM, with complete local response after 2 cycles of chemotherapy. Unfortunately, disease progressed later on, and the patient died after 9 months post-recurrence. This emphasizes the prognostic impact of extramedullary disease manifestation in MM.
    Serum Lactate Dehydrogenase Can Be Used as a Factor for Re-Evaluating First-Relapsed Multiple Myeloma. Liu Yang,Wen Lei,Chen Huan,Chen Yao,Duan Wenbing,Kang Ying,Ma Ling,Huang Xiaojun,Lu Jin Acta haematologica BACKGROUND:Serum lactate dehydrogenase (LDH) is an adverse prognostic factor for newly diagnosed multiple myeloma (MM). However, the role of LDH in the prognosis of MM patients with relapse has not yet been thoroughly explored. OBJECTIVES:To explore the prognostic value of LDH in patients with first-relapsed MM. METHODS:Data for 112 MM patients who had a first relapse between January 2012 and December 2017 were retrospectively reviewed. Patients were classified into two groups based on the level of serum LDH at relapse (≥240 and <240 U/L). Characteristics and outcomes of the two groups were compared. RESULTS:During the first relapse, patients with high LDH levels had higher serum β2-microglobulin (p = 0.001), lower serum albumin (p = 0.006), lower platelet counts (p < 0.001), and a higher percentage of extramedullary relapse (p < 0.001) compared with patients with normal LDH levels. According to multivariate analysis, elevated serum levels of LDH (p = 0.001) and re-ISS stage 2/3 (p = 0.001) in relapsed MM patients were two key prognostic factors for overall survival. CONCLUSIONS:A high level of serum LDH at the time of first relapse may be a predictor of poor survival in relapsed MM patients. 10.1159/000505737
    The presence of large focal lesions is a strong independent prognostic factor in multiple myeloma. Rasche Leo,Angtuaco Edgardo J,Alpe Terri L,Gershner Grant H,McDonald James E,Samant Rohan S,Kumar Manoj,Van Hemert Rudy,Epstein Joshua,Deshpande Shayu,Tytarenko Ruslana,Yaccoby Shmuel,Hillengass Jens,Thanendrarajan Sharmilan,Schinke Carolina,van Rhee Frits,Zangari Maurizio,Walker Brian A,Barlogie Bart,Morgan Gareth J,Davies Faith E,Weinhold Niels Blood Spatial intratumor heterogeneity is frequently seen in multiple myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. Because biopsy-based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FLs) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches. Here, we investigated the prognostic value of FL size in 404 transplant-eligible, newly diagnosed MM patients. Using diffusion-weighted magnetic resonance imaging with background suppression, we identified the presence of multiple large FLs as a strong prognostic factor. Patients with at least 3 large FLs with a product of the perpendicular diameters >5 cm were associated with poor progression-free survival (PFS) and overall survival (OS; median, 2.3 and 3.6 years, respectively). This pattern, seen in 13.8% of patients, was independent of the Revised International Staging System (RISS), gene expression profiling (GEP)-based risk score, gain(1q), or extramedullary disease (hazard ratio, 2.7 and 2.2 for PFS and OS in multivariate analysis, respectively). The number of FLs lost its negative impact on outcome after adjusting for FL size. In conclusion, the presence of at least 3 large FL is a feature of high risk, which can be used to refine the diagnosis of this type of disease behavior and as an entry criterion for risk-stratified trials. 10.1182/blood-2018-04-842880
    Features of extramedullary disease of multiple myeloma: high frequency of p53 deletion and poor survival: a retrospective single-center study of 834 cases. Deng Shuhui,Xu Yan,An Gang,Sui Weiwei,Zou Dehui,Zhao Yaozhong,Qi Junyuan,Li Fei,Hao Mu,Qiu Lugui Clinical lymphoma, myeloma & leukemia BACKGROUND:Multiple myeloma (MM) is a heterogeneous disease in which most patients have myeloma restricted to the bone marrow, and some patients develop extramedullary disease (EMD) at the time of diagnosis or during follow-up, and show different clinical characteristics and a dismal prognosis. PATIENTS AND METHODS:We studied 834 consecutive MM patients in a single center in China and compared clinical features of patients with and without EMD. RESULTS:In general, the prevalence of EMD was 4.8% at the time of diagnosis and 3.4% during follow-up, with a significant increase in recent years. MM patients with EMD at the time of diagnosis had remarkably greater prevalence of P53 deletion determined using fluorescence in situ hybridization (FISH) analysis (34.5% vs. 11.9%; P = .037) and higher level of lactate dehydrogenase (LDH) (P = .003) compared with patients without EMD. EMD relapse/progression during follow-up was correlated with EMD presentation at diagnosis, immunoglobulin (Ig)D subtype and P53 deletion in FISH analysis, but not previous treatment (thalidomide, bortizomib, or transplantation). With respect to prognosis, multivariate analysis showed that EMD was an independent adverse prognostic factor. The overall survival of patients with and without EMD at diagnosis were 16.5 and 40 months, respectively (P < .001), and the time to disease progression of the 2 groups was 11.5 and 25 months, respectively (P < .001). CONCLUSION:MM patients with EMD at the time of diagnosis showed remarkably greater prevalence of P53 deletion in FISH analysis and higher LDH levels. EMD relapse/progression was correlated with EMD presentation at diagnosis, IgD subtype, and P53 deletion in FISH analysis, but not previous exposure to new drugs or transplantation. The presence of EMD involvement negatively affected survival. 10.1016/j.clml.2014.12.013
    Treatment patterns and clinical outcomes in high-risk newly diagnosed multiple myeloma patients carrying the 17p deletion: An observational multi-center retrospective study. Cohen Yael C,Saranga Avi,Gatt Moshe E,Lavi Noa,Ganzel Chezi,Magen Hila,Avivi Irit,Tadmor Tamar,Suriu Celia,Jarchowsky Dolberg Osnat,Papushado Amitai,Trestman Svetlana,Ram Ron American journal of hematology Del17p is a genomic imbalance occurring in ∼7%-10% of myeloma at diagnosis newly diagnosed myeloma patients (NDMM) and comprises a poor prognostic factor. The goal of this study is to analyze real world data and outcomes among NDMM patients carrying 17p deletion. We report an observational, retrospective, multicenter study. Sixty consecutive patients diagnosed with multiple myeloma in the 8 participating centers diagnosed between 1/2008 and 1/2016 proven to carry 17p deletion by means of fluorescence in situ hybridization (FISH) were identified. Most received a bortezomib-based induction, over half underwent autologous hematopoietic cell transplantation (HCT); 30% of the patients gained early access to new novel agents via clinical trials, access programs or private insurance. Overall response rate (ORR) after induction was 85%; 94% for transplant eligible (TE); and 75% for transplant ineligible (NTE), and declined in subsequent treatment lines, 64% achieved ≥ VGPR. Median overall survival (OS) was 43 months; median progression free survival (PFS) was 11 months, 19 months for TE and 7 for NTE. In multivariate analysis: higher M-Spike, presence of extramedullary disease, and >50% of cells baring del17p were associated with adverse PFS; Autologous HCT and higher hemoglobin were associated with longer PFS; OS was 59 months for patients with early access to newer agents. Older age and higher M-Spike levels were associated with adverse OS, Autologous HCT was associated with favorable OS, 59.7 vs 28.7 months for NTE patients. Despite the improvement achieved with autologous HCT and new novel agents, the prognosis of patients with 17p deletion is still inferior, emphasizing the need for novel approaches. 10.1002/ajh.25098
    Role of FDG-PET/CT in Extramedullary Multiple Myeloma: Correlation of FDG-PET/CT Findings With Clinical Outcome. Tirumani Sree Harsha,Sakellis Christopher,Jacene Heather,Shinagare Atul B,Munshi Nikhil C,Ramaiya Nikhil H,Van den Abbeele Annick D Clinical nuclear medicine PURPOSE:The aim of this study was to describe FDG-PET/CT findings in extramedullary multiple myeloma (EMM) correlating them with clinical outcome. METHODS:In this institutional review board-approved HIPAA-compliant retrospective study, we reviewed the FDG-PET/CT scans of 35 patients with EMM (16 women, 19 men; mean age, 56 years; median follow-up after the diagnosis of EMM, 14 months) out of 156 patients diagnosed with MM at our institute between 2004 and 2012. The distribution and metabolic activity of EMM on the scans were reviewed. Clinical data were extracted from electronic medical records. Statistical analysis was performed to determine differences in outcome based on time of detection and distribution of EMM. RESULTS:Extramedullary multiple myeloma was present at diagnosis in 12 of 35 patients and during disease progression in 23 of 35 patients. Indications for FDG-PET/CT were initial staging (12/35), restaging for disease progression (18/23), or assessment of response to therapy (5/23). Extramedullary multiple myeloma was FDG-avid (mean SUVmax, 8.4; range, 1.2-31), solitary in 10 patients (29%) and multifocal in 25 patients (71%). Two patterns of distribution were noted: direct extension of osseous plasmacytomas in 18 (51%) of 35 patients and hematogeneous/lymphangiogenic dissemination in 33 (94%) of 35 patients. Mean SUVmax in lesions with direct osseous extension was statistically higher than hematogeneous/lymphangiogenic EMM (Mann-Whitney U test, P = 0.03). The most common sites of hematogeneous/lymphangiogenic spread of EMM were lymph nodes (21/35 [60%]), liver (10/35 [29%]), lung (9/35 [26%]), muscles away from bones (7/35 [20%]), and peritoneum/mesentery (7/35 [20%]). There was no statistically significant difference in distribution of EMM at presentation and during disease progression (χ2 test, P > 0.05); 24 (69%) of 35 patients died (median interval after diagnosis of EMM, 7 months). There was no statistically significant difference in outcome for EMM at presentation and during disease progression (log-rank test, P = 0.068). Involvement of any of the following 3 sites: liver, lung, and muscles away from bones, was associated with statistically significant shorter survival (log-rank test, P = 0.0008). CONCLUSIONS:Extramedullary multiple myeloma is more often seen on FDG-PET/CT in the context of a hematogeneous/lymphangiogenic spread pattern and less commonly as a direct extension of osseous plasmacytomas. Extramedullary multiple myeloma has poor outcome whether detected at presentation or during follow-up. Extramedullary multiple myeloma involving the liver, lung, and muscles was associated with shorter survival in our study. 10.1097/RLU.0000000000000902
    AYA-Myeloma: Real-World, Single-Center Experience Over Last 5 Years. Yanamandra Uday,Saini Neha,Chauhan Pooja,Sharma Tanya,Khadwal Alka,Prakash Gaurav,Varma Neelam,Lad Deepesh,Varma Subhash,Malhotra Pankaj Journal of adolescent and young adult oncology INTRODUCTION:Multiple myeloma (MM) is considered as a disease of the old with the reported median age of 60-70 years. The disease occurred a decade earlier in the Indian subcontinent. The literature on MM in adolescents and young adult (AYA) is limited. We studied the disease characteristics and outcomes of the AYA-MM in the real-world setting. PATIENTS AND METHODS:It is a retrospective single-center study conducted at a tertiary care center from North India. Records of all consecutive patients with AYA-MM (15-39 years of age) who were managed from January 1, 2010, to December 30, 2015, were reviewed. Survival was assessed from the date of start of treatment to the last follow-up date or death due to any cause. RESULTS:A total of 415 patients managed for MM were included in the study. The frequency of the AYA-MM was 9.6% (40/415) of whom 5 patients were younger than 30 years. There was male preponderance with a median age of the patients being 38 years. The main presenting features were bone pain (55%), fatigue (45%), extramedullary plasmacytomas (20%), and infections (12%) and referral from the peripheral hospital as renal dysfunction (58%). On the evaluation of patients, hypercalcemia, renal impairment, anemia, and lytic lesions were seen in 24.32%, 30%, 52.5%, and 59.25% of patients, respectively. The majority had the high-risk disease (International Staging System [ISS]-III: 75%). Only 22.5% patients were transplanted. The 3-year median overall survival of the study population was 80.21%. CONCLUSION:AYA-MM patients have a higher prevalence of extramedullary disease and high-risk disease. 10.1089/jayao.2017.0034
    Role of F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Cavo Michele,Terpos Evangelos,Nanni Cristina,Moreau Philippe,Lentzsch Suzanne,Zweegman Sonja,Hillengass Jens,Engelhardt Monika,Usmani Saad Z,Vesole David H,San-Miguel Jesus,Kumar Shaji K,Richardson Paul G,Mikhael Joseph R,da Costa Fernando Leal,Dimopoulos Meletios-Athanassios,Zingaretti Chiara,Abildgaard Niels,Goldschmidt Hartmut,Orlowski Robert Z,Chng Wee Joo,Einsele Hermann,Lonial Sagar,Barlogie Bart,Anderson Kenneth C,Rajkumar S Vincent,Durie Brian G M,Zamagni Elena The Lancet. Oncology The International Myeloma Working Group consensus aimed to provide recommendations for the optimal use of fluorodeoxyglucose (F-FDG) PET/CT in patients with multiple myeloma and other plasma cell disorders, including smouldering multiple myeloma and solitary plasmacytoma. F-FDG PET/CT can be considered a valuable tool for the work-up of patients with both newly diagnosed and relapsed or refractory multiple myeloma because it assesses bone damage with relatively high sensitivity and specificity, and detects extramedullary sites of proliferating clonal plasma cells while providing important prognostic information. The use of F-FDG PET/CT is mandatory to confirm a suspected diagnosis of solitary plasmacytoma, provided that whole-body MRI is unable to be performed, and to distinguish between smouldering and active multiple myeloma, if whole-body X-ray (WBXR) is negative and whole-body MRI is unavailable. Based on the ability of F-FDG PET/CT to distinguish between metabolically active and inactive disease, this technique is now the preferred functional imaging modality to evaluate and to monitor the effect of therapy on myeloma-cell metabolism. Changes in FDG avidity can provide an earlier evaluation of response to therapy compared to MRI scans, and can predict outcomes, particularly for patients who are eligible to receive autologous stem-cell transplantation. F-FDG PET/CT can be coupled with sensitive bone marrow-based techniques to detect minimal residual disease (MRD) inside and outside the bone marrow, helping to identify those patients who are defined as having imaging MRD negativity. 10.1016/S1470-2045(17)30189-4