Clinical presentation and treatment of plasmablastic myeloma-a multicenter retrospective analysis

Clinical presentation and treatment of plasmablastic myeloma-a multicenter retrospective analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Clinical presentation and treatment of plasmablastic myeloma-a multicenter retrospective analysis Zhenhui Lv, Xiaoqing Guo, Junjing Yin, Ping Lu, Xueqiong Wu, Xinxin Xu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8656617/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objective : To report the clinical manifestations, laboratory tests, pathological features, diagnosis and treatment process and outcome of six patients with plasmablastic myeloma (PBM), and the clinical features and diagnosis and treatment methods of PBM were discussed in combination with literature. Methods : Clinical data of patients, such as age of onset, sex, pathological type, cytogenetic characteristics, disease stage, extramedullary disease were analyzed, and the efficacy evaluation and outcome after treatment were observed. Results : Among the 6 patients with PBM, 2 male and 4 female. The median age of the 6 patients was 63 (range 46–68) years. Three cases were newly diagnosed, three cases were found at the time of recurrence. The Ki-67 proliferation index of 5 cases was above 65%. Six cases all developed extramedullary infiltrates. Five cases were positive for 1q21 amplification. Four cases were negative for CD56 and one case was partially positive. Five patients died after multiple cycles of chemotherapy, and one patient is under treatment. Conclusion : PBM has a low incidence, rapid cell proliferation, high tumor burden, multiple high-risk genetic abnormalities, rapid progression and poor prognosis. PBM frequently affects extramedullary sites. There is currently no standard treatment for PBM. CAR-T therapy may be a new option. Allogeneic hematopoietic stem cell transplantation is also the direction of exploration. Multiple myeloma Plasmablastic myeloma Extramedullary disease Case report 1. Introduction Multiple myeloma (MM) is a malignant clonal disease originating from plasma cells. Plasmablastic myeloma (PBM) is an aggressive subtype of MM. This type of myeloma has a very poor prognosis, no effective treatment options, few related reports, and the pathogenesis has not yet been elucidated. We retrospectively analyzed the diagnosis and treatment process of 6 cases of PBM treated in Zibo Central Hospital, Qingdao Municipal Hospital, and Tianjin Medical University Cancer Hospital from January 2021 to August 2023 and reviewed relevant literature. The report is as follows. 2. Methods This study retrospectively collected the clinical data of 6 patients with PBM who were treated in three hospitals. The clinical and laboratory characteristics, intervention measures, and outcomes of the patients were retrospectively analyzed. 3. Results 3.1 Clinical and laboratory characteristics The diagnosis, classification and staging of 6 patients with PBM were all based on WHO criteria. The extramedullary lesions were diagnosed by pathological biopsy, and the chromosomal abnormalities were detected by fluorescence in situ hybridization (FISH) after the enrichment of myeloma cells. The clinical characteristics of 6 patients, such as bone marrow cytology, stage, type, and pathological characteristics at initial diagnosis, are shown in Table 1 . Of the 6 patients with PBM, 3 were found at initial diagnosis and 3 were found in new lesions after disease progression, including 4 women and 2 men, with a median age of 63 (46–68) years. Comprehensive evaluation before treatment showed that 2 cases were IgG-λ type, 2 cases were IgA-κ type, 1 case was IgA-λ type and 1 case was light chain λ type. The disease stages of the 6 patients were DS III and ISS III, among which 1 patient was accompanied by renal insufficiency. Five patients were positive for 1q21 amplification (one patient did not undergo FISH testing due to economic reasons), of which case 2 patient also had P53 deficiency, and case 3 patient had both P53 deficiency and MAF/IGH fusion. All the patients had extramedullary invasion during the course of the disease, and the sites were liver (4 cases), lymph nodes (2 cases), pleura/peritoneum (2 cases), spleen (1 case), brain (1 case), muscle (1 case), kidney (1 case), and soft tissue (1 case). Pathological biopsy showed that CD56 was negative in 4 patients, positive in 1 case and partially positive in 1 case. The Ki-67 proliferation index was above 85% in 4 patients, 65% in case 3 and 30% in case 5 . Table 1 Clinical characteristics of 6 patients with PBM Pat Age Gender Type DS stage ISS stage RISS stage Bone marrow cytology FISH Extramedullary involvement Disease status at diagnosis CD56 Ki67 1 67 Female IgGλ ⅢA Ⅲ - 25% - Liver, pleura, peritoneum Disease progression - 85% 2 60 Male IgAκ ⅢA Ⅲ Ⅲ 15%(blood smear 13%) 1q21+/p53 deficiency Liver, spleen, lymph nodes Disease progression + 85% 3 58 Female IgAκ ⅢA Ⅲ Ⅲ 19.50% 1q21+/p53 deficiency/MAF::IGH Liver, brain, peritoneum Initial diagnosis - 65% 4 68 Female IgAλ ⅢB Ⅲ Ⅲ 50% 1q21+ Liver, muscles, lymph nodes Disease progression Partially + 85% 5 46 Female λ ⅢA Ⅲ Ⅲ 17.50% 1q21+ Soft tissue Initial diagnosis - 30% 6 65 Male IgGλ ⅢA Ⅲ Ⅲ 90% 1q21+/1p32- Kidney Initial diagnosis - 90% Pat—Patient; DS—The Multiple Myeloma Durie-Salmon Staging System; ISS—The Multiple Myeloma International Staging System; RISS—Revised International Staging System; FISH—Fluorescence In Situ Hybridization. 3.2 Interventions and Outcomes In the course of treatment of 6 patients, bisphosphonates or denosumab combined with vitamin D and calcium were used to treat osteolytic lesions. For patients with renal insufficiency, adequate hydration, alkalization, diuresis, reduction of uric acid formation and uric acid excretion were given. In this study, case 4 had high creatinine level but did not require hemodialysis treatment. However, in case 3 , acute renal failure occurred in the end stage, creatinine was elevated with oliguria, and the family refused dialysis. Case 3 had a low blood cell count during the treatment, and was given intermittent supportive treatments such as component transfusions and hematopoiesis stimulation. The treatment and outcomes of 6 patients are shown in Table 2 . Table 2 Treatment process and outcomes of 6 patients with PBM Pat Initial treatment Response Treatment after progression Response Treatment after progression Response Treatment after progression Response Treatment after progression Response Ending OS /m 1 VCD*3, VRD*1, HD-Mel+ASCT, ID*2 VGPR VRD*2 (New drugs are not available for economic reasons) PD VD*1 (Thrombocytopenia, discontinue lenalidomide) PD die 25 2 VRD*4, HD-Mel+ASCT CR D 1 KD + PLD*1 PD Ben + XD*2 PD die 12 3 VCD*1, D 1 KD*2 PD X-D 1 VD*2, Lumbar puncture + intrathecal injection*2 PD Ben + XPD*2 (Combined with COVID-19) PD Venetoclax + ID*1 PD die 8 4 VRD*2 PD KPD*2 PD KPD*2(Refusing to change treatment ) PD D 1 PD*2, Radiation therapy PD Ben + VD PD die 9 5 VRD + EPI*1 - - - - - - - - - In the treatment - 6 X-VRD*4 VGPR Ben + DKD*2 (Combined with COVID-19) PD die 8 Pat—Patient; V—bortezomib; C—cyclophosphamide; D—dexamethasone; R—lenalidomide; HD-Mel—high-dose melphalan; ASCT—autologous stem cell transplantation; I—ixazomib; D 1 —daratumumab; K—carfilzomib; PLD—liposomal doxorubicin hydrochloride; Ben—Bendamustine; X—selinexor; P—pomalidomide; EPI—epirubicin; VGPR—very good partial response; PD—progressive Disease. In terms of treatment, Case 1 did not receive FISH testing at the initial diagnosis due to economic reasons. After 3 courses of VCD regimen, the efficacy evaluation reached VGPR, and hematopoietic stem cells were collected from peripheral blood. Then, a course of VRD was given, and high-dose melphalan pretreatment and autologous hematopoietic stem cell transplantation were performed. The efficacy evaluation reached VGPR 3 months after transplantation, and two courses of ID regimen consolidation treatment were continued. Maintenance treatment was not performed due to economic reasons. Thirteen months later, the patient went to the hospital because of "chest tightness and abdominal distension". Imaging examination showed a large amount of pleural, abdominal and pelvic fluid, and multiple hypodense foci in the liver. Liver puncture biopsy and pleural fluid exfoliative cytopathology suggested plasma cell myeloma ‘plasmablastic type’. Due to economic reasons, she chose the VRD regimen for two courses of treatment, during which she was given thoracocentesis and drainage, and the symptoms of chest tightness and abdominal distension were reduced. Because of thrombocytopenia, lenalidomide was discontinued, and she was given one course of the VD regimen, and the abdominal distension and chest tightness worsened, and the disease progressed again, so she was automatically discharged from the hospital, and died of disease progression outside the hospital. Overall survival was 25 months. Case 2 was initially diagnosed with plasma cell leukemia. After four courses of VRD regimen, the efficacy was evaluated as CR. Sequential high-dose melphalan pretreatment and autologous hematopoietic stem cell transplantation were performed. Three months later, the blood and urine protein electrophoresis were negative, the blood and urine immunofixation electrophoresis were negative, the serum free light chain was normal, and the bone marrow cytology indicated that the efficacy reached CR and MRD was negative. Imaging examinations showed new bone destruction and multiple hypoechoic nodules in the liver. PET-CT showed multiple FDG metabolic activity foci in the liver and spleen, multiple FDG metabolic lymph nodes in the pelvic and abdominal cavity, and multiple bone destruction. Liver puncture biopsy pathology showed plasma cell myeloma ‘plasmablastic type’. After treatment with DKD + PLD regimen, the volume of liver lesions increased, and the progression of the disease was considered. Two courses of Bendamustine + XD regimen were given. The patient developed multiple spontaneous pathological fractures, was discharged automatically, and died out of hospital. Overall survival was 12 months. Case 3 was treated with the VCD regimen before the pathological results of liver puncture biopsy came out at the initial diagnosis. After the treatment, numbness of the lips and eyelids and weakness appeared. The pathological results showed plasmablastic myeloma, and then the DKD regimen was changed. After two courses of treatment, the patient developed headaches, and the brain enhanced MRI showed abnormal enhancement foci in the left frontal lobe and left cerebellar hemisphere. Color Doppler ultrasound showed that the lesions in the liver were enlarged, and the disease was considered to be progressive. Two courses of X-DVD regimen combined with lumbar puncture and intrathecal injection were given, and the headache symptoms were relieved. There was no significant change in liver lesions. Bone marrow cytology showed that myeloma cells accounted for 73%, and the disease was considered to be progressive. Bendamustine + XPD regimen was given, during which the patient was combined with COVID-19 pneumonia. After the second course of Bendamustine + XPD regimen, the patient developed chest tightness, abdominal distension, and progressive increase in abdominal circumference; abdominal CT showed a large amount of ascites and splenomegaly. Ascites exfoliated cell pathology suggested plasmacytoma ‘plasmablastic type’. Considering that the disease was progressing again, Venetoclax + ID regimen was given, and oliguria and progressive increase in creatinine occurred. The family refused further diagnosis and treatment, and the patient died outside the hospital due to disease progression. The overall survival was 8 months. Case 4 The patient had hyperviscosity at the time of initial diagnosis. After receiving plasma exchange, she received two courses of VRD regimen. During the follow-up examination, abnormal density foci were found in the liver. The pathological results of liver puncture biopsy indicated that plasma cell myeloma ‘plasmablastic type’. The disease progression was considered to be combined with extramedullary infiltration. Two courses of KPD chemotherapy were given. On the 5th day of the third course of KPD, a right inguinal mass was found. The patient refused biopsy and requested to continue KPD program. During the fourth course of KPD, the original mass in the right inguinal area increased again, and a new mass appeared, and ultrasound-guided mass aspiration was performed, and the pathology showed that plasma cell myeloma ‘plasmablastic type’ was considered. The disease progressed again, and the first course of DPD regimen was given. During this period, the patient developed a new nodule in the right thigh. The patient refused puncture and requested to continue chemotherapy. During the second course of DPD, the swelling and pain in the right thigh worsened. The mass was punctured under ultrasound guidance. The pathology indicated that plasma cell myeloma ‘plasmablastic type’ was considered. Considering the progression of the disease, the patient declined chemotherapy and was discharged after local radiotherapy. One week later, the patient developed increased pain in the lower back and right thigh, and was treated with bendamustine + VD regimen for 1 cycle, with increased pain in the peripheral body and altered mental status, and Brain MRI showed a mass in the frontal lobe, and the patient's condition deteriorated rapidly outside the hospital and she eventually died. Overall survival was 9 months. Case 5 Patient underwent curettage of left humeral bone tumor and pathological fracture reduction and bone grafting internal fixation due to "left humeral fracture". Postoperative pathology: plasma cell myeloma ‘plasmablastic type’. PET-CT showed diffuse multiple perforation-like and worm-eaten bone destruction in the whole body bones (except the skull), some with soft tissue formation (left iliac bone), and increased FDG metabolic uptake. VRD + EPI chemotherapy was given for one course, and the first course of treatment has been completed. Case 6 Patient underwent thoracic spine surgery due to abnormal lesions in the thoracic spine, and postoperative pathology showed plasmablastic myeloma. Abdominal CT showed multiple soft tissue density shadows in the left kidney. Left kidney puncture biopsy was performed under CT guidance, and postoperative pathology showed: plasma cell tumor. Four cycles of X-VRD regimen were given to evaluate the efficacy as VGPR. After 2 months, the disease progressed, and the bendamustine combined with DKD regimen was used for two courses. During this period, treatment was suspended due to "COVID-19 pneumonia and a large amount of pleural effusion", and the disease progressed and died. The overall survival was 8 months. 4. Discussion Multiple myeloma is a malignant clonal plasma cell disease that originates from terminally differentiated B lymphocytes in the germinal center 1 . PBM is an aggressive subtype of multiple myeloma, with clinical manifestations similar to those of multiple myeloma and almost identical morphological and immunophenotypic characteristics to plasmablastic lymphoma 2 , 3 . Bartl et al. first proposed in 1982 that myeloma cells could be divided into plasmablastic and plasmacytic types based on their morphology 4 . Greipp et al. proposed another classification standard in 1985 5 , which is to divide myeloma cells into 4 types according to the degree of cell maturity: mature, intermediate, immature and plasmablastic. Among them, plasmablastic tumor cells show large nuclei, obvious nucleoli, basophilic or amphoteric cytoplasm, perinuclear translucency, and more nuclear divisions under the microscope, which is similar to the tumor cells of plasmablastic lymphoma 6 . Differentiation of myeloma cells into plasmoblasts often indicates a high degree of malignancy, poor prognosis, and is rare. In 1998, Greipp et al. compared 453 cases of multiple myeloma, including 37 cases of plasmablastic myeloma 7 . The study found that plasmablast morphology was an independent adverse prognostic factor for myeloma. Compared with non-plasmablastic myeloma, the event-free survival (EFS) and overall survival (OS) of plasmablastic myeloma were significantly shorter than those of the control group (median EFS 1.1 years vs 2.7 years, median OS 1.9 years vs 3.7 years, P < 0.01). In 2004, Mai Yujie et al. conducted a retrospective analysis of 432 patients with multiple myeloma and found that the median OS of 18 patients with PBM was significantly lower than that of other types (17 months vs 49 months) 8 . From 2021 to 2023, a total of 6 PBM patients were admitted to the hematology departments of the three hospitals. The median age was 63 years (46–68 years), mainly female, and the DS and ISS stages were both III. Among them, 5 cases were accompanied by positive 1q21 amplification, and 1 case did not undergo FISH testing due to economic reasons. All 6 patients had extramedullary infiltration, mainly in the liver, including 3 newly diagnosed patients and 3 relapsed patients. They were treated with proteasome inhibitors, CD38 monoclonal antibody, autologous hematopoietic stem cell transplantation, selective nuclear export protein inhibitors, combined chemotherapy and other regimens, but the efficacy was low, the remission time was short, and the disease progressed rapidly. Ultimately, 5 patients died, with a median survival of 8 months. 1 patient is currently undergoing treatment. PBM patients account for 8.2% of all MM patients and are characterized by a high Ki67 proliferation index, high bone marrow plasma cell infiltration rate, abnormal karyotype, and often aggressive behavior 7 , 9 . PBM can occur in the bone marrow or extramedullary tissue. There are few reports of cases with extramedullary infiltration, but it often occurs during disease progression or relapse. In 2022, Bo-JungChen et al. retrospectively analyzed 25 PBM cases and found that 15 cases (60%) had extramedullary lesions, of which 9 cases had extramedullary lesions for the first time. The most common sites were soft tissue and/or skin (67%), followed by pleural effusion, lungs, and lymph nodes 10 . In 2015, Michael B. Moller et al. analyzed 194 untreated MM patients and found that plasmablast morphology was associated with adverse clinical features, high proliferation index, high bone marrow plasma cell infiltration rate, and abnormal karyotype del(13q). In this study, it was found that the morphology of plasmablasts and del(13q) were significantly different in karyotype analysis, but it had nothing to do with FISH detection; the reason for the analysis may be that the number of plasma cells was small at that time, resulting in a low positive rate of FISH detection. Data collection is limited. These findings suggest that PBM is an advanced and highly proliferative disease 9 . In 2020, YingLiu et al. described the inconsistency between clonal mature small plasma cells in the bone marrow and cells in extramedullary infiltrating lesions in PBM disease progression and transformation. These transformations may be associated with higher MYC and/or P53 expression, higher Ki-67 proliferation index, frequent mutations in the RAS pathway, MYC gene rearrangement, and more complex genomic abnormalities 11 . In this group of 6 patients, the Ki-67 proliferation index was high, and 4 of them were above 65%, which is consistent with the highly invasive characteristics of PBM. In 2015, Kan et al. reviewed the characteristics of 25 MM patients with extramedullary disease and found that the proportion of plasmablast and proplasmacyte was high, and those with chromosome abnormalities detected by FISH were prone to extramedullary infiltration 12 . Chengcheng Fu et al. analyzed 248 newly diagnosed multiple myeloma (NDMM) patients in 2022. According to FISH detection, 135 patients (54.4%) were accompanied by 1q21 amplification, and most of these patients were accompanied by obvious organ damage and high tumor burden. Among them, patients with 1q21 amplification (> 4 copies) had worse progression-free survival (PFS) than those with 1q21 amplification (3 copies), which is a high-risk cytogenetic factor for poor prognosis of NDMM 13 . Five of the six patients in this group had 1q21 amplification, suggesting that PBM patients are prone to 1q21 amplification in cytogenetics, and the high tumor burden caused by 1q21 amplification may be related to the occurrence of extramedullary infiltration. The pathogenesis of extramedullary disease (EMD) in multiple myeloma is still unclear. Studies have suggested that myeloma cell homing blockage, enhanced invasiveness, extracellular matrix degradation and enhanced angiogenesis may be involved in the occurrence of EMD 14 . However, there are few reports on the correlation between myeloma pathological classification and EMD. CD56, a nerve cell adhesion molecule, has been reported to be related to the localization of myeloma cells in bone marrow stroma. By anchoring myeloma cells to restrict their invasion to the extramedullary, CD56 mediates the homing of tumor cells and plays a role in the growth of myeloma cells in the bone marrow, while myeloma cells lacking CD56 expression are more likely to migrate to extramedullary growth 15 , 16 . CD56 negative myeloma cells are more prone to extramedullary invasion, and the expression of CD56 is negatively correlated with the number of plasma cells in the blood, suggesting that CD56 negative myeloma patients may have a worse prognosis. CD56 expression was negative in 4 of the 6 patients and partially positive in 1 patient, suggesting that PBM with negative CD56 immunophenotype was more prone to extramedullary invasion. The incidence of PBM is low, and there is no consensus on the treatment of newly diagnosed patients. There is no standard treatment for PBM case reports. Currently, it is mostly treated according to multiple myeloma. The main drugs include proteasome inhibitors, traditional chemotherapy, CD38 monoclonal antibodies, etc., with low efficacy and easy disease progression 17 – 20 . There was no significant benefit of autologous hematopoietic stem cell transplantation after high-dose mafaran pretreatment 21 . Two patients in this group underwent autologous hematopoietic stem cell transplantation, but their disease progressed early after transplantation. Allogeneic hematopoietic stem cell transplantation is subject to limitations such as donor source, organ function, and age. NCCN and IMWG only recommend allogeneic hematopoietic stem cell transplantation for high-risk MM patients in well-designed clinical trials 22 . No relevant reports on allogeneic transplantation for PBM have been found. With the development of biological cell therapy, CAR-T cell therapy has been gradually applied to more tumor treatments. BCMA is a protein molecule specifically expressed on the surface of plasma cells, plasmablasts and activated B cells, so it can be used as a target for CAR-T cell therapy of MM. Currently, BCMA-CAR-T treatment of myeloma is in the clinical trial stage. In a phase Ib/II trial, BCMA-CAR-T has shown efficacy in heavily pretreated MM, with an overall response rate of 98% at 28 months, and 83% of patients achieving complete remission 23 . PBM, as a plasma cell tumor, also expresses BCMA, so BCMA-CAR-T therapy may be a new option for PBM patients. However, PBM patients have a high tumor burden and rapid disease progression. Whether enough lymphocytes can be collected to prepare CAR-T cells and how to control cytokine release syndrome are also urgent issues that need to be addressed. 5. Conclusions In summary, the incidence of PBM is low, and the clinical manifestations are similar to those of multiple myeloma, but the cells proliferate rapidly, the tumor burden is high, and there are often abnormal karyotypes. Extramedullary infiltration is prone to occur, and the disease progresses rapidly. Bone marrow cytology and flow immunophenotyping are difficult to diagnose, and they mainly rely on pathological morphology and immunohistochemistry for identification, which is prone to missed diagnosis. At present, the treatment of PBM is still a challenge. In the future, we hope that research progress in cell biological therapy, molecular targeted drugs, and improvements in clinical technology will provide new ideas for the treatment of PBM. Declarations AUTHOR CONTRIBUTIONS Zhenhui Lv, Junjing Yin: Drafting articles, collecting data, analyzing/interpreting data; Xiaoqing Guo, Ping Lu, Xueqiong Wu, Xinxin Xu, Jiaju Wang, Yafei Wang: Collecting data and supporting contributions; Yuping Zhong: Critical review of the intellectual content of the article, obtaining research funds and guidance. FUNDING INFORMATION This research was supported by the Natural Science Foundation of Beijing Municipality (Approval number: Z200020). ETHICS STATEMENT The study was approved by the institutional review board of Zibo Central Hospital (202201023) and was conducted in accordance with the Declaration of Helsinki. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. CONSENT TO PARTICIPATE Informed consent to participate was obtained from the patients/patient's legal guardians[if the patient's age is less than 16]. CONSENT TO PUBLISH Informed consent was obtained from all subjects and/or their legal guardian(s) for the publication of any potentially identifying information and/or images in an online open-access publication. CONFLICTS OF INTEREST STATEMENT The authors declare no conflict of interest. Clinical trial number: not applicable. References Mo JN, Wang XJ, Liu XY. [Plasmablastic plasma cell myeloma: report of a case]. Zhonghua Bing Li Xue Za Zhi. 2022;51:247–9. https://doi.org:10.3760/cma.j.cn112151-20210808-00557 . Eladl E, Chang H. Bone marrow infiltration by plasmablastic neoplasm: plasmablastic myeloma or plasmablastic lymphoma? Blood. 2021;137:1268. https://doi.org:10.1182/blood.2020009735 . Vega F, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol. 2005;18:806–15. https://doi.org:10.1038/modpathol.3800355 . Bartl R, et al. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 06 Mar, 2026 Reviews received at journal 02 Mar, 2026 Reviews received at journal 26 Feb, 2026 Reviews received at journal 24 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers agreed at journal 03 Feb, 2026 Reviewers invited by journal 02 Feb, 2026 Editor invited by journal 02 Feb, 2026 Editor assigned by journal 02 Feb, 2026 Submission checks completed at journal 30 Jan, 2026 First submitted to journal 30 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8656617","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":585389111,"identity":"574111f8-6e65-435c-b985-a0d20b39e677","order_by":0,"name":"Zhenhui Lv","email":"","orcid":"","institution":"Central Hospital of Zibo","correspondingAuthor":false,"prefix":"","firstName":"Zhenhui","middleName":"","lastName":"Lv","suffix":""},{"id":585389117,"identity":"c25eca4b-fbc2-4528-8ec5-611b830db345","order_by":1,"name":"Xiaoqing Guo","email":"","orcid":"","institution":"Qingdao Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqing","middleName":"","lastName":"Guo","suffix":""},{"id":585389123,"identity":"53f8ea22-d83a-4bc7-b69c-12ab141c2028","order_by":2,"name":"Junjing Yin","email":"","orcid":"","institution":"Qingdao Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junjing","middleName":"","lastName":"Yin","suffix":""},{"id":585389127,"identity":"dc9bf18c-7194-4c5f-8c7e-a68c28ffb858","order_by":3,"name":"Ping Lu","email":"","orcid":"","institution":"Central Hospital of Zibo","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Lu","suffix":""},{"id":585389128,"identity":"9a907190-1704-4df9-8dcd-fa999ad61351","order_by":4,"name":"Xueqiong Wu","email":"","orcid":"","institution":"Central Hospital of Zibo","correspondingAuthor":false,"prefix":"","firstName":"Xueqiong","middleName":"","lastName":"Wu","suffix":""},{"id":585389131,"identity":"164b8c26-d130-479e-b148-73aafbfae873","order_by":5,"name":"Xinxin Xu","email":"","orcid":"","institution":"Central Hospital of Zibo","correspondingAuthor":false,"prefix":"","firstName":"Xinxin","middleName":"","lastName":"Xu","suffix":""},{"id":585389133,"identity":"a4e5037f-971d-4476-b211-7226ead0500a","order_by":6,"name":"Jiaju Wang","email":"","orcid":"","institution":"Central Hospital of Zibo","correspondingAuthor":false,"prefix":"","firstName":"Jiaju","middleName":"","lastName":"Wang","suffix":""},{"id":585389134,"identity":"f4dbfea9-6a31-4108-b3d8-56bdf0a850bd","order_by":7,"name":"Yafei Wang","email":"","orcid":"","institution":"Tianjin Medical University Cancer Institute and Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yafei","middleName":"","lastName":"Wang","suffix":""},{"id":585389135,"identity":"86b3346f-f55c-4c75-89a8-9adc48ec77f7","order_by":8,"name":"Yuping Zhong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDACCQhlJy9/+OCDhAob4rUkG85gSzZ4cCaNeC2MDTd4zCQfth0irEN+dvOxh1/b7jAzzm4wq0hgO8DA396dgFcL45xj6caybc/42GUOpN1I4LnDIHHm7Aa8WpglcsykJdsOMzM2JBy7kSDxjMFAIhe/FjaoFsaGA4ltBQkGhwlr4QFqkfwI0nIjmY0hIYEILRISaWnSDOeeJRv2HGOWSDiQxkPQL/Izko9J/ii7YyfP3v/x489/NnL87b34tYAAMy/bAYRLCSoHAcYffw4QVDQKRsEoGAUjGAAAyoRNX0I1BpYAAAAASUVORK5CYII=","orcid":"","institution":"Qingdao Municipal Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yuping","middleName":"","lastName":"Zhong","suffix":""}],"badges":[],"createdAt":"2026-01-21 07:43:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8656617/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8656617/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101881800,"identity":"0e4cb9b3-f63e-4330-b5eb-dcfbb6aba703","added_by":"auto","created_at":"2026-02-04 15:16:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":671253,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8656617/v1/dc3132e5-a281-4823-b150-664f60001ca0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical presentation and treatment of plasmablastic myeloma-a multicenter retrospective analysis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMultiple myeloma (MM) is a malignant clonal disease originating from plasma cells. Plasmablastic myeloma (PBM) is an aggressive subtype of MM. This type of myeloma has a very poor prognosis, no effective treatment options, few related reports, and the pathogenesis has not yet been elucidated. We retrospectively analyzed the diagnosis and treatment process of 6 cases of PBM treated in Zibo Central Hospital, Qingdao Municipal Hospital, and Tianjin Medical University Cancer Hospital from January 2021 to August 2023 and reviewed relevant literature. The report is as follows.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis study retrospectively collected the clinical data of 6 patients with PBM who were treated in three hospitals. The clinical and laboratory characteristics, intervention measures, and outcomes of the patients were retrospectively analyzed.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Clinical and laboratory characteristics\u003c/h2\u003e \u003cp\u003eThe diagnosis, classification and staging of 6 patients with PBM were all based on WHO criteria. The extramedullary lesions were diagnosed by pathological biopsy, and the chromosomal abnormalities were detected by fluorescence in situ hybridization (FISH) after the enrichment of myeloma cells. The clinical characteristics of 6 patients, such as bone marrow cytology, stage, type, and pathological characteristics at initial diagnosis, are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the 6 patients with PBM, 3 were found at initial diagnosis and 3 were found in new lesions after disease progression, including 4 women and 2 men, with a median age of 63 (46\u0026ndash;68) years. Comprehensive evaluation before treatment showed that 2 cases were IgG-λ type, 2 cases were IgA-κ type, 1 case was IgA-λ type and 1 case was light chain λ type. The disease stages of the 6 patients were DS III and ISS III, among which 1 patient was accompanied by renal insufficiency. Five patients were positive for 1q21 amplification (one patient did not undergo FISH testing due to economic reasons), of which case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e2\u003c/span\u003e patient also had P53 deficiency, and case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e3\u003c/span\u003e patient had both P53 deficiency and MAF/IGH fusion. All the patients had extramedullary invasion during the course of the disease, and the sites were liver (4 cases), lymph nodes (2 cases), pleura/peritoneum (2 cases), spleen (1 case), brain (1 case), muscle (1 case), kidney (1 case), and soft tissue (1 case). Pathological biopsy showed that CD56 was negative in 4 patients, positive in 1 case and partially positive in 1 case. The Ki-67 proliferation index was above 85% in 4 patients, 65% in case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e3\u003c/span\u003e and 30% in case \u003cspan refid=\"FPar4\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of 6 patients with PBM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDS stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eISS stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRISS stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eBone marrow cytology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFISH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eExtramedullary involvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDisease status at diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eCD56\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eKi67\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c14\" namest=\"c14\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgGλ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLiver, pleura, peritoneum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgAκ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15%(blood smear 13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1q21+/p53 deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLiver, spleen, lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgAκ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e19.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1q21+/p53 deficiency/MAF::IGH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLiver, brain, peritoneum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eInitial\u003c/p\u003e \u003cp\u003ediagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e65%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgAλ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1q21+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLiver, muscles, lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003ePartially +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eλ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1q21+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSoft tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eInitial diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgGλ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1q21+/1p32-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eKidney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eInitial diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePat\u0026mdash;Patient; DS\u0026mdash;The Multiple Myeloma Durie-Salmon Staging System; ISS\u0026mdash;The Multiple Myeloma International Staging System; RISS\u0026mdash;Revised International Staging System; FISH\u0026mdash;Fluorescence In Situ Hybridization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e\u003cem\u003e3.2 Interventions and Outcomes\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eIn the course of treatment of 6 patients, bisphosphonates or denosumab combined with vitamin D and calcium were used to treat osteolytic lesions. For patients with renal insufficiency, adequate hydration, alkalization, diuresis, reduction of uric acid formation and uric acid excretion were given. In this study, case \u003cspan refid=\"FPar3\" class=\"InternalRef\"\u003e4\u003c/span\u003e had high creatinine level but did not require hemodialysis treatment. However, in case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e3\u003c/span\u003e, acute renal failure occurred in the end stage, creatinine was elevated with oliguria, and the family refused dialysis. Case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e3\u003c/span\u003e had a low blood cell count during the treatment, and was given intermittent supportive treatments such as component transfusions and hematopoiesis stimulation. The treatment and outcomes of 6 patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment process and outcomes of 6 patients with PBM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTreatment after progression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTreatment after progression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTreatment after progression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTreatment after progression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eEnding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOS /m\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c14\" namest=\"c14\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVCD*3, VRD*1, HD-Mel+ASCT, ID*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVGPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVRD*2 (New drugs are not available for economic reasons)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVD*1 (Thrombocytopenia, discontinue lenalidomide)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003edie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVRD*4, HD-Mel+ASCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eD\u003csup\u003e1\u003c/sup\u003eKD\u0026thinsp;+\u0026thinsp;PLD*1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBen\u0026thinsp;+\u0026thinsp;XD*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003edie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVCD*1, D\u003csup\u003e1\u003c/sup\u003eKD*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX-D\u003csup\u003e1\u003c/sup\u003eVD*2, Lumbar puncture\u0026thinsp;+\u0026thinsp;intrathecal injection*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBen\u0026thinsp;+\u0026thinsp;XPD*2 (Combined with COVID-19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVenetoclax\u0026thinsp;+\u0026thinsp;ID*1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003edie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVRD*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKPD*2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKPD*2(Refusing to change treatment )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eD\u003csup\u003e1\u003c/sup\u003ePD*2, Radiation therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBen\u0026thinsp;+\u0026thinsp;VD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003edie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVRD\u0026thinsp;+\u0026thinsp;EPI*1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eIn the treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX-VRD*4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVGPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBen\u0026thinsp;+\u0026thinsp;DKD*2 (Combined with COVID-19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003edie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePat\u0026mdash;Patient; V\u0026mdash;bortezomib; C\u0026mdash;cyclophosphamide; D\u0026mdash;dexamethasone; R\u0026mdash;lenalidomide; HD-Mel\u0026mdash;high-dose melphalan; ASCT\u0026mdash;autologous stem cell transplantation; I\u0026mdash;ixazomib; D\u003csup\u003e1\u003c/sup\u003e\u0026mdash;daratumumab; K\u0026mdash;carfilzomib; PLD\u0026mdash;liposomal doxorubicin hydrochloride; Ben\u0026mdash;Bendamustine; X\u0026mdash;selinexor; P\u0026mdash;pomalidomide; EPI\u0026mdash;epirubicin; VGPR\u0026mdash;very good partial response; PD\u0026mdash;progressive Disease.\u003c/p\u003e \u003cp\u003eIn terms of treatment, Case 1 did not receive FISH testing at the initial diagnosis due to economic reasons. After 3 courses of VCD regimen, the efficacy evaluation reached VGPR, and hematopoietic stem cells were collected from peripheral blood. Then, a course of VRD was given, and high-dose melphalan pretreatment and autologous hematopoietic stem cell transplantation were performed. The efficacy evaluation reached VGPR 3 months after transplantation, and two courses of ID regimen consolidation treatment were continued. Maintenance treatment was not performed due to economic reasons. Thirteen months later, the patient went to the hospital because of \"chest tightness and abdominal distension\". Imaging examination showed a large amount of pleural, abdominal and pelvic fluid, and multiple hypodense foci in the liver. Liver puncture biopsy and pleural fluid exfoliative cytopathology suggested plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo;. Due to economic reasons, she chose the VRD regimen for two courses of treatment, during which she was given thoracocentesis and drainage, and the symptoms of chest tightness and abdominal distension were reduced. Because of thrombocytopenia, lenalidomide was discontinued, and she was given one course of the VD regimen, and the abdominal distension and chest tightness worsened, and the disease progressed again, so she was automatically discharged from the hospital, and died of disease progression outside the hospital. Overall survival was 25 months.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 2\u003c/strong\u003e \u003cp\u003ewas initially diagnosed with plasma cell leukemia. After four courses of VRD regimen, the efficacy was evaluated as CR. Sequential high-dose melphalan pretreatment and autologous hematopoietic stem cell transplantation were performed. Three months later, the blood and urine protein electrophoresis were negative, the blood and urine immunofixation electrophoresis were negative, the serum free light chain was normal, and the bone marrow cytology indicated that the efficacy reached CR and MRD was negative. Imaging examinations showed new bone destruction and multiple hypoechoic nodules in the liver. PET-CT showed multiple FDG metabolic activity foci in the liver and spleen, multiple FDG metabolic lymph nodes in the pelvic and abdominal cavity, and multiple bone destruction. Liver puncture biopsy pathology showed plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo;. After treatment with DKD\u0026thinsp;+\u0026thinsp;PLD regimen, the volume of liver lesions increased, and the progression of the disease was considered. Two courses of Bendamustine\u0026thinsp;+\u0026thinsp;XD regimen were given. The patient developed multiple spontaneous pathological fractures, was discharged automatically, and died out of hospital. Overall survival was 12 months.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 3\u003c/strong\u003e \u003cp\u003ewas treated with the VCD regimen before the pathological results of liver puncture biopsy came out at the initial diagnosis. After the treatment, numbness of the lips and eyelids and weakness appeared. The pathological results showed plasmablastic myeloma, and then the DKD regimen was changed. After two courses of treatment, the patient developed headaches, and the brain enhanced MRI showed abnormal enhancement foci in the left frontal lobe and left cerebellar hemisphere. Color Doppler ultrasound showed that the lesions in the liver were enlarged, and the disease was considered to be progressive. Two courses of X-DVD regimen combined with lumbar puncture and intrathecal injection were given, and the headache symptoms were relieved. There was no significant change in liver lesions. Bone marrow cytology showed that myeloma cells accounted for 73%, and the disease was considered to be progressive. Bendamustine\u0026thinsp;+\u0026thinsp;XPD regimen was given, during which the patient was combined with COVID-19 pneumonia. After the second course of Bendamustine\u0026thinsp;+\u0026thinsp;XPD regimen, the patient developed chest tightness, abdominal distension, and progressive increase in abdominal circumference; abdominal CT showed a large amount of ascites and splenomegaly. Ascites exfoliated cell pathology suggested plasmacytoma \u0026lsquo;plasmablastic type\u0026rsquo;. Considering that the disease was progressing again, Venetoclax\u0026thinsp;+\u0026thinsp;ID regimen was given, and oliguria and progressive increase in creatinine occurred. The family refused further diagnosis and treatment, and the patient died outside the hospital due to disease progression. The overall survival was 8 months.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 4\u003c/strong\u003e \u003cp\u003eThe patient had hyperviscosity at the time of initial diagnosis. After receiving plasma exchange, she received two courses of VRD regimen. During the follow-up examination, abnormal density foci were found in the liver. The pathological results of liver puncture biopsy indicated that plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo;. The disease progression was considered to be combined with extramedullary infiltration. Two courses of KPD chemotherapy were given. On the 5th day of the third course of KPD, a right inguinal mass was found. The patient refused biopsy and requested to continue KPD program. During the fourth course of KPD, the original mass in the right inguinal area increased again, and a new mass appeared, and ultrasound-guided mass aspiration was performed, and the pathology showed that plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo; was considered. The disease progressed again, and the first course of DPD regimen was given. During this period, the patient developed a new nodule in the right thigh. The patient refused puncture and requested to continue chemotherapy. During the second course of DPD, the swelling and pain in the right thigh worsened. The mass was punctured under ultrasound guidance. The pathology indicated that plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo; was considered. Considering the progression of the disease, the patient declined chemotherapy and was discharged after local radiotherapy. One week later, the patient developed increased pain in the lower back and right thigh, and was treated with bendamustine\u0026thinsp;+\u0026thinsp;VD regimen for 1 cycle, with increased pain in the peripheral body and altered mental status, and Brain MRI showed a mass in the frontal lobe, and the patient's condition deteriorated rapidly outside the hospital and she eventually died. Overall survival was 9 months.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 5\u003c/strong\u003e \u003cp\u003ePatient underwent curettage of left humeral bone tumor and pathological fracture reduction and bone grafting internal fixation due to \"left humeral fracture\". Postoperative pathology: plasma cell myeloma \u0026lsquo;plasmablastic type\u0026rsquo;. PET-CT showed diffuse multiple perforation-like and worm-eaten bone destruction in the whole body bones (except the skull), some with soft tissue formation (left iliac bone), and increased FDG metabolic uptake. VRD\u0026thinsp;+\u0026thinsp;EPI chemotherapy was given for one course, and the first course of treatment has been completed.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 6\u003c/strong\u003e \u003cp\u003ePatient underwent thoracic spine surgery due to abnormal lesions in the thoracic spine, and postoperative pathology showed plasmablastic myeloma. Abdominal CT showed multiple soft tissue density shadows in the left kidney. Left kidney puncture biopsy was performed under CT guidance, and postoperative pathology showed: plasma cell tumor. Four cycles of X-VRD regimen were given to evaluate the efficacy as VGPR. After 2 months, the disease progressed, and the bendamustine combined with DKD regimen was used for two courses. During this period, treatment was suspended due to \"COVID-19 pneumonia and a large amount of pleural effusion\", and the disease progressed and died. The overall survival was 8 months.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMultiple myeloma is a malignant clonal plasma cell disease that originates from terminally differentiated B lymphocytes in the germinal center\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. PBM is an aggressive subtype of multiple myeloma, with clinical manifestations similar to those of multiple myeloma and almost identical morphological and immunophenotypic characteristics to plasmablastic lymphoma\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Bartl et al. first proposed in 1982 that myeloma cells could be divided into plasmablastic and plasmacytic types based on their morphology\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Greipp et al. proposed another classification standard in 1985\u003csup\u003e5\u003c/sup\u003e, which is to divide myeloma cells into 4 types according to the degree of cell maturity: mature, intermediate, immature and plasmablastic. Among them, plasmablastic tumor cells show large nuclei, obvious nucleoli, basophilic or amphoteric cytoplasm, perinuclear translucency, and more nuclear divisions under the microscope, which is similar to the tumor cells of plasmablastic lymphoma\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Differentiation of myeloma cells into plasmoblasts often indicates a high degree of malignancy, poor prognosis, and is rare. In 1998, Greipp et al. compared 453 cases of multiple myeloma, including 37 cases of plasmablastic myeloma\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The study found that plasmablast morphology was an independent adverse prognostic factor for myeloma. Compared with non-plasmablastic myeloma, the event-free survival (EFS) and overall survival (OS) of plasmablastic myeloma were significantly shorter than those of the control group (median EFS 1.1 years vs 2.7 years, median OS 1.9 years vs 3.7 years, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). In 2004, Mai Yujie et al. conducted a retrospective analysis of 432 patients with multiple myeloma and found that the median OS of 18 patients with PBM was significantly lower than that of other types (17 months vs 49 months)\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFrom 2021 to 2023, a total of 6 PBM patients were admitted to the hematology departments of the three hospitals. The median age was 63 years (46\u0026ndash;68 years), mainly female, and the DS and ISS stages were both III. Among them, 5 cases were accompanied by positive 1q21 amplification, and 1 case did not undergo FISH testing due to economic reasons. All 6 patients had extramedullary infiltration, mainly in the liver, including 3 newly diagnosed patients and 3 relapsed patients. They were treated with proteasome inhibitors, CD38 monoclonal antibody, autologous hematopoietic stem cell transplantation, selective nuclear export protein inhibitors, combined chemotherapy and other regimens, but the efficacy was low, the remission time was short, and the disease progressed rapidly. Ultimately, 5 patients died, with a median survival of 8 months. 1 patient is currently undergoing treatment.\u003c/p\u003e \u003cp\u003ePBM patients account for 8.2% of all MM patients and are characterized by a high Ki67 proliferation index, high bone marrow plasma cell infiltration rate, abnormal karyotype, and often aggressive behavior\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. PBM can occur in the bone marrow or extramedullary tissue. There are few reports of cases with extramedullary infiltration, but it often occurs during disease progression or relapse. In 2022, Bo-JungChen et al. retrospectively analyzed 25 PBM cases and found that 15 cases (60%) had extramedullary lesions, of which 9 cases had extramedullary lesions for the first time. The most common sites were soft tissue and/or skin (67%), followed by pleural effusion, lungs, and lymph nodes\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. In 2015, Michael B. Moller et al. analyzed 194 untreated MM patients and found that plasmablast morphology was associated with adverse clinical features, high proliferation index, high bone marrow plasma cell infiltration rate, and abnormal karyotype del(13q). In this study, it was found that the morphology of plasmablasts and del(13q) were significantly different in karyotype analysis, but it had nothing to do with FISH detection; the reason for the analysis may be that the number of plasma cells was small at that time, resulting in a low positive rate of FISH detection. Data collection is limited. These findings suggest that PBM is an advanced and highly proliferative disease\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In 2020, YingLiu et al. described the inconsistency between clonal mature small plasma cells in the bone marrow and cells in extramedullary infiltrating lesions in PBM disease progression and transformation. These transformations may be associated with higher MYC and/or P53 expression, higher Ki-67 proliferation index, frequent mutations in the RAS pathway, MYC gene rearrangement, and more complex genomic abnormalities\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In this group of 6 patients, the Ki-67 proliferation index was high, and 4 of them were above 65%, which is consistent with the highly invasive characteristics of PBM. In 2015, Kan et al. reviewed the characteristics of 25 MM patients with extramedullary disease and found that the proportion of plasmablast and proplasmacyte was high, and those with chromosome abnormalities detected by FISH were prone to extramedullary infiltration\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Chengcheng Fu et al. analyzed 248 newly diagnosed multiple myeloma (NDMM) patients in 2022. According to FISH detection, 135 patients (54.4%) were accompanied by 1q21 amplification, and most of these patients were accompanied by obvious organ damage and high tumor burden. Among them, patients with 1q21 amplification (\u0026gt;\u0026thinsp;4 copies) had worse progression-free survival (PFS) than those with 1q21 amplification (3 copies), which is a high-risk cytogenetic factor for poor prognosis of NDMM\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Five of the six patients in this group had 1q21 amplification, suggesting that PBM patients are prone to 1q21 amplification in cytogenetics, and the high tumor burden caused by 1q21 amplification may be related to the occurrence of extramedullary infiltration.\u003c/p\u003e \u003cp\u003eThe pathogenesis of extramedullary disease (EMD) in multiple myeloma is still unclear. Studies have suggested that myeloma cell homing blockage, enhanced invasiveness, extracellular matrix degradation and enhanced angiogenesis may be involved in the occurrence of EMD\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. However, there are few reports on the correlation between myeloma pathological classification and EMD. CD56, a nerve cell adhesion molecule, has been reported to be related to the localization of myeloma cells in bone marrow stroma. By anchoring myeloma cells to restrict their invasion to the extramedullary, CD56 mediates the homing of tumor cells and plays a role in the growth of myeloma cells in the bone marrow, while myeloma cells lacking CD56 expression are more likely to migrate to extramedullary growth\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. CD56 negative myeloma cells are more prone to extramedullary invasion, and the expression of CD56 is negatively correlated with the number of plasma cells in the blood, suggesting that CD56 negative myeloma patients may have a worse prognosis. CD56 expression was negative in 4 of the 6 patients and partially positive in 1 patient, suggesting that PBM with negative CD56 immunophenotype was more prone to extramedullary invasion.\u003c/p\u003e \u003cp\u003eThe incidence of PBM is low, and there is no consensus on the treatment of newly diagnosed patients. There is no standard treatment for PBM case reports. Currently, it is mostly treated according to multiple myeloma. The main drugs include proteasome inhibitors, traditional chemotherapy, CD38 monoclonal antibodies, etc., with low efficacy and easy disease progression\u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. There was no significant benefit of autologous hematopoietic stem cell transplantation after high-dose mafaran pretreatment\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Two patients in this group underwent autologous hematopoietic stem cell transplantation, but their disease progressed early after transplantation. Allogeneic hematopoietic stem cell transplantation is subject to limitations such as donor source, organ function, and age. NCCN and IMWG only recommend allogeneic hematopoietic stem cell transplantation for high-risk MM patients in well-designed clinical trials\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. No relevant reports on allogeneic transplantation for PBM have been found.\u003c/p\u003e \u003cp\u003eWith the development of biological cell therapy, CAR-T cell therapy has been gradually applied to more tumor treatments. BCMA is a protein molecule specifically expressed on the surface of plasma cells, plasmablasts and activated B cells, so it can be used as a target for CAR-T cell therapy of MM. Currently, BCMA-CAR-T treatment of myeloma is in the clinical trial stage. In a phase Ib/II trial, BCMA-CAR-T has shown efficacy in heavily pretreated MM, with an overall response rate of 98% at 28 months, and 83% of patients achieving complete remission\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. PBM, as a plasma cell tumor, also expresses BCMA, so BCMA-CAR-T therapy may be a new option for PBM patients. However, PBM patients have a high tumor burden and rapid disease progression. Whether enough lymphocytes can be collected to prepare CAR-T cells and how to control cytokine release syndrome are also urgent issues that need to be addressed.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn summary, the incidence of PBM is low, and the clinical manifestations are similar to those of multiple myeloma, but the cells proliferate rapidly, the tumor burden is high, and there are often abnormal karyotypes. Extramedullary infiltration is prone to occur, and the disease progresses rapidly. Bone marrow cytology and flow immunophenotyping are difficult to diagnose, and they mainly rely on pathological morphology and immunohistochemistry for identification, which is prone to missed diagnosis. At present, the treatment of PBM is still a challenge. In the future, we hope that research progress in cell biological therapy, molecular targeted drugs, and improvements in clinical technology will provide new ideas for the treatment of PBM.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHOR \u0026nbsp;CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhenhui Lv, Junjing Yin: Drafting articles, collecting data, analyzing/interpreting data; Xiaoqing Guo, Ping Lu, Xueqiong Wu, Xinxin Xu, Jiaju Wang, Yafei Wang: Collecting data and supporting contributions; Yuping Zhong: Critical review of the intellectual content of the article, obtaining research funds and guidance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING \u0026nbsp;INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the Natural Science Foundation of Beijing Municipality (Approval number: Z200020).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS \u0026nbsp;STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the institutional review board of Zibo Central\u003cem\u003e\u0026nbsp;\u003c/em\u003eHospital (202201023) and was conducted in accordance with the\u0026nbsp;Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA \u0026nbsp;AVAILABILITY \u0026nbsp; STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent to participate was obtained from the patients/patient\u0026apos;s legal guardians[if the patient\u0026apos;s age is less than 16].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT TO PUBLISH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all subjects and/or their legal guardian(s) for the publication of any potentially identifying information and/or images in an online open-access publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICTS \u0026nbsp;OF \u0026nbsp;INTEREST \u0026nbsp;STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: not applicable.\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMo JN, Wang XJ, Liu XY. 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J Clin Oncol. 2023;41:1265\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1200/jco.22.00842\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1200/jco.22.00842\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Multiple myeloma, Plasmablastic myeloma, Extramedullary disease, Case report","lastPublishedDoi":"10.21203/rs.3.rs-8656617/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8656617/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To report the clinical manifestations, laboratory tests, pathological features, diagnosis and treatment process and outcome of six patients with plasmablastic myeloma (PBM), and the clinical features and diagnosis and treatment methods of PBM were discussed in combination with literature.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Clinical data of patients, such as age of onset, sex, pathological type, cytogenetic characteristics, disease stage, extramedullary disease were analyzed, and the efficacy evaluation and outcome after treatment were observed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among the 6 patients with PBM, 2 male and 4 female. The median age of the 6 patients was 63 (range 46–68) years. Three cases were newly diagnosed, three cases were found at the time of recurrence. The Ki-67 proliferation index of 5 cases was above 65%. Six cases all developed extramedullary infiltrates. Five cases were positive for 1q21 amplification. Four cases were negative for CD56 and one case was partially positive. Five patients died after multiple cycles of chemotherapy, and one patient is under treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: PBM has a low incidence, rapid cell proliferation, high tumor burden, multiple high-risk genetic abnormalities, rapid progression and poor prognosis. PBM frequently affects extramedullary sites. There is currently no standard treatment for PBM. CAR-T therapy may be a new option. Allogeneic hematopoietic stem cell transplantation is also the direction of exploration.\u003c/p\u003e","manuscriptTitle":"Clinical presentation and treatment of plasmablastic myeloma-a multicenter retrospective analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-04 09:21:10","doi":"10.21203/rs.3.rs-8656617/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-06T23:41:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-02T16:18:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-27T01:34:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-24T18:14:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222728202317295035403383474107433935525","date":"2026-02-06T07:03:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151586034371869438381377817492005832939","date":"2026-02-06T06:30:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"120193420577851576912943691596648645197","date":"2026-02-04T03:32:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-03T04:21:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-03T00:23:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-02T09:51:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-30T12:58:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-01-30T11:23:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec1317bd-0761-4b37-b01f-320fcb95a0a4","owner":[],"postedDate":"February 4th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T23:53:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-04 09:21:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8656617","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8656617","identity":"rs-8656617","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}