Progress of chimeric antigen receptor T-cell in treatment of multiple myeloma / 白血病·淋巴瘤

Chimeric antigen receptor T-cell (CAR-T) immunotherapy targeting B-cell maturation antigen (BCMA) has shown significant efficacy in relapsed/refractory multiple myeloma. With the rapid development of CAR-T therapies, CAR-T therapies targeting BCMA continue to be optimized, and new products such as new targets, dual-targets and universal CAR-T are arriving successively. Data from several relevant clinical studies were updated at the 64th American Society of Hematology Annual Meeting.

Progress of bispecific antibodies in treatment of multiple myeloma / 白血病·淋巴瘤

Multiple myeloma is a malignant disorder of plasma cells. Although the prognosis of MM patients has improved significantly with the widespread use of new targeted drugs such as immunomodulators, proteasome inhibitors and autologous hematopoietic stem cell transplantation, the disease will eventually recur and progress. In recent years, immunotherapy has made breakthroughs in the treatment of MM, chimeric antigen receptor T-cell therapy, antibody conjugate drugs and bispecific antibodies have shown significant effectiveness and good safety at different stages of the disease. Bispecific antibodies, which bind both CD3 on T cells and target molecules on the surface of malignant plasma cells, are effective immunotherapeutic agents for patients with relapsed/refractory MM. This article reviews the research progress of bispecific antibodies in the treatment of MM in conjunction with the reports at the 64th American Society of Hematology Annual Meeting.

Efficacy and safety of switching from brand-name to domestic generic levetiracetam in children with epilepsy / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy.@*METHODS@#A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety.@*RESULTS@#For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (P<0.05). There was no significant change in the frequency of seizures from baseline to 6 months after switching (P>0.05). The incidence of refractory epilepsy in children with no response after switching treatment was significantly higher than that in children with response (P<0.05). Before switching, only 1 child (0.6%) experienced somnolence, while after switching, 3 children (1.9%) experienced mild adverse drug reactions, including dizziness, somnolence, irritability, and bad temper.@*CONCLUSIONS@#Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.

Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma / 中华内科杂志

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population ( P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls ( P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients ( P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively ( P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

Hemophagocytic syndrome as the first presentation of histiocytic necrotizing lymphadenitis: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the diagnosis and treatment of histiocytic necrotizing lymphadenitis (HNL) complicated with hemophagocytic syndrome (HPS).Methods:The clinical characteristics, diagnosis, treatment process, and therapy response of a patient with HNL complicated with HPS admitted to the Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences in March 2019 were retrospectively analyzed, and the literature was reviewed.Results:This 17-year-old female patient had fever with bilateral cervical lymphadenopathy as the first presentation, accompanied by cough and expectoration. After admission, the disease progressed rapidly, and the serum ferritin increased progressively.The regimen of hormone and etoposide was used to control the disease condition. The bone marrow smear revealed atypical lymphocytes and hemophagocytic phenomenon, and the pathological features of HNL in lymph node biopsy were observed. This patient was finally diagnosed as HNL complicated with HPS. The patient's condition was stable at 3-month follow-up after discharge.Conclusions:The clinical manifestations of HNL patients complicated with HPS are similar to other hematologic malignant diseases, and application of multiple laboratory and pathological examination methods can help with early diagnosis. In the event of a progressive rise in serum ferritin, timely application of hormone therapy combined with etoposide if necessary can rapidly control the progression of the disease.

Relationship between prognosis and different surgical treatments of zygomatic defects: A retrospective study / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effect and summarize the characteristics of different treatment methods in repairing zygomatic defect.@*METHODS@#A total of 37 patients with zygomatic defect were reviewed in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from August 2012 to August 2019. According to the anatomical scope of defect, the zygomatic defects were divided into four categories: Class 0, the defect did not involve changes in zygomatic structure or continuity, only deficiency in thickness or projection; Class Ⅰ, defect was located in the zygomatic body or involved only one process; Class Ⅱ, a single defect involved two processes; Class Ⅲa, referred to a single defect involving three processes and above; Class Ⅲb, referred to zygomatic defects associated with large maxillary defects. The etiology, defect time, defect size and characteristics of zygomatic defects, the repair and reconstruction methods, and postoperative complications were collected and analyzed. Postoperative computed tomography (CT) data were collected to evaluate the outcome of zygomatic protrusion. Chromatographic analysis was used to assess the postoperative stability.@*RESULTS@#Among the causes of defects, 25 cases (67.57%) were caused by trauma, and 11 cases (29.73%) were of surgical defects following tumor resection. We performed autologous bone grafts in 19 cases, 6 cases underwent vascularized tissue flap, 5 cases underwent external implants alone, and 7 cases underwent vascularized tissue flap combined with external implants. After the recovery of the affected side, the average difference of the zygomatic projection between the navigation group and the non-navigation group was 0.45 mm (0.20-2.50 mm) and 1.60 mm (0.10-2.90 mm), with a significant difference (P=0.045). Two patients repaired with titanium mesh combined with anterolateral thigh flap had obvious deformation or fracture of titanium mesh; 2 patients with customized casting prosthesis had infection after surgery and fetched out the prosthesis finally.@*CONCLUSION@#Autologous free grafts or alloplastic materials may be used in cases without significant structural changes. Pedicle skull flap or vascularized bone tissue flap is recommended for zygomatic bone defects with bone pillar destruction, chronic inflammation, oral and nasal communication or significant soft tissue insufficiency. Titanium mesh can be used to repair a large defect of zygomatic bone, and it is suggested to combine with vascularized bone flap transplantation.

Research advances on the techniques for diagnosing burn wound depth / 中华烧伤杂志

The accurate diagnosis of burn wound depth is particularly important for evaluating the disease prognosis of burn patients. In the past, the diagnosis of burn wound depth often relied on the subjective judgment of doctors. With the continuous development of diagnostic technology, the methods for judging the depth of burn wound have also been updated. This paper mainly summarizes the research progress in the applications of indocyanine green angiography, laser Doppler imaging, laser speckle contrast imaging, and artificial intelligence in the diagnosis of burn wound depth, and compares the advantages and disadvantages of these techniques, so as to provide ideas for accurate diagnosis of burn wound depth.

Progress of tumor-associated myeloid cells in multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a kind of hematologic malignancy. Although there are lots of therapies for MM, it is still incurable. Except for the drug-resistance, another important reason for the incurability is the immunosuppressive effect derived from interactions between tumor cells and the bone marrow microenvironment, which makes our body cannot clear resident tumor cells completely. As a vital part in the immunosuppressive microenvironment, tumor-associated myeloid cells (TAMC) play an extremely significant role in the immune escape of MM and become the reason for limiting the effectiveness of immunotherapy, furthermore, TAMC have become potential targets for the treatment of MM. This article reviews the composition and the latest progress of the mechanisms of TAMC in the immune microenvironment of MM.

Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .@*METHODS@#Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.@*RESULTS@#Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.@*CONCLUSION@#Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Progress of minimal residual disease detection in multiple myeloma / 白血病·淋巴瘤

In recent years, with the application of a variety of new drugs, the prognosis of patients with multiple myeloma (MM) has been significantly improved, and the survival time has been significantly prolonged, but almost patients will relapse eventually. The persistent existence of minimal residual disease (MRD) is considered to be the root cause of disease recurrence. Therefore, the detection of MRD in MM patients is of great clinical significance, which would contribute to evaluate the efficacy of MM, accelerate clinical trials, dynamic risk stratification, and further guide the treatment strategy. However, until now, there are no standard method and evaluation criteria of MRD detection. This review focuses on the advantages and disadvantages of different methods,clinical applications and future development direction of MRD detection in MM.

Clinical Analysis of Patients with MGUS, Primary Light Chain Amyloidosis, Multiple Myeloma or Multiple Myeloma with Concurrent Amyloidosis / 中国实验血液学杂志

OBJECTIVE@#To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities.@*METHODS@#The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively.@*RESULTS@#Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities.@*CONCLUSION@#Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.

Three-dimensional finite element analysis of traumatic mechanism of mandibular symphyseal fracture combined with bilateral intracapsular condylar fractures / 北京大学学报(医学版)

OBJECTIVE@#To analyze the biomechanical mechanism of mandibular symphyseal fracture combined with bilateral intracapsular condylar fractures using finite element analysis (FEA).@*METHODS@#Maxillofacial CT scans and temporomandibular joint (TMJ) MRI were performed on a young male with normal mandible, no wisdom teeth and no history of TMJ diseases. The three-dimensional finite element model of mandible was established by Mimics and ANSYS based on the CT and MRI data. The stress distributions of mandible with different angles of traumatic loads applied on the symphyseal region were analyzed. Besides, two models with or without disc, two working conditions in occlusal or non-occlusal status were established, respectively, and the differences of stress distribution between them were compared.@*RESULTS@#A three-dimensional finite element model of mandible including TMJ was established successfully with the geometry and mechanical properties to reproduce a normal mandibular structure. Following a blow to the mandibular symphysis with different angles, stress concentration areas were mainly located at condyle, anterior border of ramus and symphyseal region under all conditions. The maximum equivalent stress always appeared on condylar articular surface. As the angle between the external force and the horizontal plane gradually increased from 0° to 60°, the stress on the mandible gradually concentrated to symphysis and bilateral condyle. However, when the angle between the external force and the horizontal plane exceeded 60°, the stress tended to disperse to other parts of the mandible. Compared with the condition without simulating the disc, the stress distribution of articular surface and condylar neck decreased significantly when the disc was present. Compared with non-occlusal status, the stress on the mandible in occlusal status mainly distributed on the occlusal surface, and no stress concentration was found in other parts of the mandible.@*CONCLUSION@#When the direction of external force is 60° from the horizontal plane, the stress distribution mainly concentrates on symphyseal region and bilateral condylar surface, which explains the occurrence of symphyseal fracture and intracapsular condylar fracture. The stress distribution of condyle (including articular surface and condylar neck) decreases significantly in the presence of arti-cular disc and in stable occlusal status when mandibular symphysis is under traumatic force.

Interference of CD38 monoclonal antibody in blood compatibility testing and its countermeasures: A general consensus among experts / 中国输血杂志

With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.

Prenatal diagnosis and clinical analysis of two fetuses with Cat-eye syndrome / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of supernumerary small marker chromosomes (sSMCs) carried by two fetuses.@*METHODS@#Single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis were carried out on cells cultured from the amniotic fluid samples.@*RESULTS@#SNP-array analysis showed both fetuses to be arr[hg19]22q11.1q11.21(16 888 899-18 649 190)×4, with a duplicated 1.7 Mb region (16 888 899-18 649 190) leading to partial tetrasomy of 22q11.1-22q11.21. FISH confirmed that both fetuses were 47,XN,+mar.ish idic(22)(q11.2) (RP11-958H20 ++),which suggested a diagnosis of Cat-eye syndrome (CES). The appearance of abortuses were consistent with the diagnosis of CES.@*CONCLUSION@#Two fetuses with CES were diagnosed by genetic testing. The latter has provided a basis for genetic counseling.

Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease.@*METHODS@#The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes＜5×10/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized.@*RESULTS@#The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×10/L, the levels of LDH and β2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin.@*CONCLUSIONS@#The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.

Application of computer-aided virtual mandibular position in the simultaneous treatment of children with temporomandibular joint ankylosis and jaw deformity / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the feasibility of computer-aided design virtual mandibular position in the simultaneous treatment of children with temporomandibular joint ankylosis (TMJA) and jaw deformity.@*METHODS@#The children with unilateral TMJA were surgically treated from January 2016 to June 2017 in the Department of Oral and Maxillofacial Surgery. The image data of jaw and dentition were imported into the computer software to simulate the surgical procedure. An osteotomy of the affected side was performed to remove ankylosed bone mass. Then the mandible was rotated around the unaffected condyle to eliminate the chin deviation by the virtual plan. An open bite was thus created on the affected side to provide space for vertical midfacial growth. In the virtual mandibular position, the affected ramus was reconstructed with costochondral grafting. Finally, digital occlusal splint was designed and prefabricated by 3D printing. During surgery, temporomandibular joint ankylosis was released and mandibular position was guided in place by the digital occlusal splint. In the new mandibular position, costochondral grafting was completed. After the surgery, the occlusal splint was wired to the mandibular dentition and would be gradually adjusted by grinding off the maxillary side to promote downward growth of the maxilla until the open bite was eliminated. The ramus height and chin deviation were measured before and one week after the surgery to validate the method. Comparisons of the measurements were made by means of a repeatedmeasures analysis of variance (ANOVA) (P=0.05). Pairwise multiple comparisons were conducted using the Bonferroni correction (P=0.05).@*RESULTS@#Five patients were included in this study. Under the guidance of the digital occlusal splint, the mandible could reach the preoperative designed position smoothly in all the cases. The chin deviations were (0.58±0.20) mm in the virtual plan before surgery, and (0.70±0.27) mm after surgery, which were not significant statistically (P>0.05). The ramus heights on the affected side were (48.19±3.20) mm in the virtual plan before surgery, and (48.17±3.62) mm after surgery, which were not significant statistically (P>0.05).@*CONCLUSION@#It is feasible and reliable in the simultaneous treatment of TMJA with jaw deformity under the guidance of virtual mandibular position.

Progress of targeted therapy for multiple myeloma / 白血病·淋巴瘤

With the wide clinical application of proteasome inhibitors (PI), immunomodulary drugs (IMiD) and autologous stem cell transplantation (ASCT), the prognosis of multiple myeloma (MM) patients has been dramatically improved. However, MM is still an incurable disease, becoming relapse or disease progression finally. Therefore, the development of new drugs with varying mechanisms and the improvement of treatment regimens can help to eradicate the tumor clone and deepen the degree of disease remission. Although most new agents are in different stages of clinical trials, the emerging development of novel agents abroad currently has made MM patients obtain deeper and more enduring remission according to the early experimental data, adding the good safety and efficacy of the new drugs, which could bring the promising clinical application. Varieties of novel drugs combined with PI or IMiD could provide new treatment regimens for MM. This paper reviews the recent progress of the targeted novel drugs of MM.

Progress of lenalidomide in treatment of non-Hodgkin lymphoma / 白血病·淋巴瘤

In recent years,several large-scale clinical trials have confirmed that lenalidomide has a certain role in the treatment of non-Hodgkin lymphoma (NHL).Currently,the latest edition of the National Comprehensive Cancer Network (NCCN)guideline (2018.V3) recommend that lenalidomide could be used for multiple subtypes of NHL including diffuse large B-cell lymphoma,mantle cell lymphoma,follicular lymphoma,and marginal zone lymphoma.This article reviews the progress in the application of lenalidomide in NHL.

Role of tumor-associated myeloid cells in the formation of immune microenvironment in multiple myeloma / 白血病·淋巴瘤

Although great progress has been made in the treatment of multiple myeloma (MM), it is still an incurable malignant plasma cell tumor. In addition to the MM cell itself, the bone marrow microenvironment also plays a critically important role to prompt MM cell's survival, growth, and drug resistance. Bone microenvironment reformed by MM cells could not only help the proliferation of MM cells, but also inhibit the killing of the immune system to MM. A variety of cell components and mechanisms participate in the formation of immune microenvironment, including high-profile tumor associated myeloid cells (TAMC). This paper introduces the mechanisms of TAMC in MM immunosuppressive microenvironment.

Advances in clinical treatment and biological features of primary plasma cell leukemia / 白血病·淋巴瘤

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with distinct clinical and biological features.Thanks to the application of novel agents such as proteasome inhibitors (e.g.bortezomib) and immunomodulatory drugs (e.g.thalidomide and lenalidomide),along with stem cell transplantation,the outcome of pPCL has been improved a lot.Despite therapeutic advances,the current understanding of pPCL biology is still limited due to the lack of availability of clinical samples.This review provides the recent progress of the diagnostic and therapeutic options in pPCL.