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In recent years, bispecific antibodies (BsAb), including targeting B cell maturation antigen (BCMA) ×CD3 and G protein-coupled orphan receptor class C group 5 member D (GPRC5D) ×CD3, have been extensively studied for relapsed/refractory multiple myeloma (RRMM) patients. Teclistamab (BCMA×CD3) was the first BsAb approved for RRMM in 2022 by Food and Drug Administration (FDA), and elranatamab was approved in 2023. BsAb targeting BCMA×CD3 including alnuctamab, WVT078, ABBV-383, linvoseltamab, and F182112, as well as talquetamab and LBL-034 targeting GPRC5D×CD3 are currently being evaluated in clinical trials. Combining with the reports in the 65th Annual Meeting of the American Society of Hematology (ASH), this paper reviews the progress of BsAb in treatment of RRMM.
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Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
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Cell therapy as represented by chimeric antigen receptor T-cell (CAR-T) therapy has made many breakthroughs in the treatment of multiple myeloma (MM), especially autologous CAR-T targeting B-cell mature antigen (BCMA), bispecific CAR-T and universal CAR-T have achieved good curative effect in many clinical studies of MM. A variety of clinical studies with remarkable results were updated at the 63rd American Society of Hematology Annual Meeting.
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The clinical application of biological immunotherapy such as chimeric antigen receptor T cells (CAR-T) and novel targeted therapy has explored a new therapy for multiple myeloma (MM) treatment. Targeting B-cell maturation antigen (BCMA), allogeneic CAR-T, antibody-drug conjugate (ADC) and bispecific antibody targeting BCMA have achieved remarkable efficacy and safety in many clinical studies. This article introduces the latest immunotherapy for MM at the 62nd American Society of Hematology (ASH) Annual Meeting.
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Objective:To explore the efficacy of rituximab combined with ABVD (epirubicin+ bleomycin+ vindesine +dacarbazine) regimen in treatment of Hodgkin lymphoma (HL) complicated with autoimmune hemolytic anemia (AIHA).Methods:The clinical data of 1 HL patient complicated with AIHA in November 2019 in Henan Cancer Hospital were retrospectively analyzed, and literatures were reviewed.Results:The patient received left cervical lymph node biopsy and bone marrow biopsy, and then lymphoma-related gene mutations and whole genetic genome detection were performed. The patient was diagnosed as HL (tuberous sclerosis in stage Ⅳ) complicated with AIHA. After 6 cycles of rituximab combined with ABVD regimen, the efficacy was evaluated. This patient's anemia was recovered, and HL also achieved complete remission.Conclusions:Rituximab combined with ABVD regimen is effective in treatment of HL patients complicated with AIHA.
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Chimeric antigen receptor T-cell (CAR-T) therapy has made a breakthrough in the treatment of hematological tumors. CAR-T therapy targeting kappa immunoglobulin light chain, CD19 and B-cell mature antigen (BCMA) have been used to treat relapsed/refractory MM (RRMM) patients, and the effect of anti-BCMA CAR-T is the best. However, the negative or positive recurrence of BCMA leads to a short progression-free survival (PFS), the improvement of the chimeric antigen receptor (CAR) structure targeted BCMA, dual-targeted CAR-T and CAR-T combined with small molecular drugs as well as other measures have become the focuses of CAR-T in the treatment of RRMM.
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Objective@#To explore the clinical features of patients with synchronous lymphoma and carcinoma.@*Methods@#The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively.@*Results@#Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence.@*Conclusion@#The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.
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Objective@#To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated.@*Results@#The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived.@*Conclusion@#The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.
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Multiple myeloma (MM), the second malignancy of the hematological system, is still untreatable. With the continuous advent of novel targeted therapies, new treatment strategies for MM patients altered, response rate and mitigation depth have also been greatly improved. At the 59th American Society of Hematology (ASH) Annual Meeting, a number of bio-targeted therapies for MM were updated, especially with the combination of various new agents and cell biology therapy. Combined with reports in the 59th ASH Annual Meeting, this paper summarizes the progress of targeted therapy in MM.
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To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS).Clinical outcome including hematopoietic reconstitution,transplant-related complications,survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT.Hematopoiesis reconstitution was achieved in all the 9 recipients.Four cases developed acute graft-versus-host disease (GVHD),and 1 with chronic GVHD.The median follow-up time after transplantation was 10(4-81) months.Only 2 cases survived,the other 7 died of relapse.The median time of relapse after transplantation was 5(3-19) months.Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS.Relapse after transplantation remains the major factor of mortality.
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Objective To summarize the clinical characteristics,diagnosis,treatment and prognosis of EBV related post-transplantation lymphoproliferative diseases (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical data of 262 cases of allo-HSCT were retrospectively,and EBV-associated PTLD occurred in 9 cases after transplantation with a incidence of 3.44％ (9/262).Of the 9 patients,6 were males and 3 were females,with a median age of 19 years;the primary disease was severe aplastic anemia (SAA) in 6 cases,acute myeloid leukemia in 2 cases and chronic myeloid leukemia in 1 case Results The occurring median time of EBV associated PTLDs was 58 d (44-271 d).The clinical manifestations of most PTLD recipients were recurrent fever with no reaction to any antibiotics,antiadoncus and lymphadenectasis.Of the 9 recipients,6 cases obtained pathological diagnosis,and 3 cases clinical diagnosis.Superficial lymph node and central nervous system (CNS) involved in 8 and 4 recipients,respectively;lung and bone involvement occurred in 2 recipients and 1 case,respectively.The median number of peripheral blood EBV DNA in 9 recipients was 7.21 × 104 copies/ml (6.37 × 103-4.56 × 105 copies/ml) at the time of onset.EBV DNA in peripheral blood was positive in only one ease of 4 CNS recipients.Among 9 recipients after therapy,4 cases were cured and 4 cases were partially effective,and 1 recipient was ineffective After follow-up for 28 months (2-48 months),6 cases died,and 3 survived.Conclusion Incidence of EBV related PTLD in SAA patients undergoing allo-HSCT is relatively higher than leukemia recipients.Reduction or withdrawal of immunosuppressant,Rituximab and low dose of DLI is effective treatment.
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Objective To assess the effectiveness of unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of severe aplastic anemia (SAA),and the difference between URD allo-HSCT and matched sibling donor (MSD) allo-HSCT.Methods According to the source of donors,the SAA patients subject to allo-HSCT were divided into MSD allo-HSCT group (MSD group) and URD allo-HSCT group (URD group) from October 2001 to December 2016 in Henan Cancer Hospital.The efficacy and transplantation related complications were compared between two groups.Results There were no statistically significant differences in hematopoietic reconstitution and graft rejection between two groups.The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was higher in the URD group than in the MSD group (30.76％ vs.8.57％,P =0.026;26.92％ vs.5.71％,P =0.021).However,other transplant-related complications including pulmonary complications and hemorrhagic cystitis,incidence of EBV and CMV reactivation and venous occlusive disease showed no significant difference between two groups.The estimated 5-year over survival was (73.6 ± 8.7) ％ in the MSD group and (72.7 ± 9.5) ％ in the URD group (P =0.878).There was no significant difference in 5-year disease-free survival between two groups (73.6 ± 8.7％ vs.70.3 ± 10.2,P =0.668).Conclusion URD-HSCT is a novel treatment approach and could be considered as first-line therapy in selected patients without MSD.
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Numerous targeted therapies emerged into clinical trials, which improved the response rate and life quality of multiple myeloma (MM) patients. Series latest developments at targeted therapy for MM patients were reported on 58th American Society of Hematology (ASH) Annual Meeting, especially the results of combination with these novel agents showed a major highlight of this meeting. The advances in the novel targeted and biological therapies will be summarized in this paper.
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With the further study on molecular pathogenesis of multiple myeloma (MM),lots of novel targeted therapies emerged into clinical trials,which improved the response rate and life quality of MM patients.In the 56th American Society of Hematology (ASH) annual meeting,a series of special reports about latest developments in targeted therapy for MM patients were published.Efficacy was improved significantly by these reagents,which may provide the new treatment strategies for MM patients.The advances in the novel targeted therapies will be summarized in this paper based on the new reports in the 56th ASH annual meeting.
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Objective To explore the feasibility of establishment of NOD/SCID-mouse model with multiple myeloma by using plasma cells from myeloma patients.Methods The femurs and tibias were removed from the New Zealand white rabbits;the muscles,periosteum and cartilage tissues were cleared.Then each bone was cut into two pieces gently along its middle.The NOD/SCID mice weighing 25 - 30 g (4 - 6 weeks)were anesthetized by intraperitoneal injection;rabbit bone was inserted into the right side of the mouse back and engraftment of the bones was allowed to take place after 4 weeks.The 5000 000 purified plasma cells which expressed CD38 +/CD45 - were immunofluorescence labeled and then injected slowly into the implanted rabbit bone through the distal end.The mice were observed weekly;the plasma cells growth in mice was screened by the living-imaging system and the tumor from the mice was determined by biopsy.Results The implanted rabbit bone survived after 4 weeks.The tumor in mice was observed 2 weeks after the purified myeloma cells were injected into the rabbit bone,and it reached 100 mm3 after 8 weeks.Results of the living-imaging system showed that the myeloma cells had uptake in the rabbit bone after 2 weeks of injection and this phenomenon was more pronounced after 8 weeks of injection (2.4×10 4 vs .1.5× 10 5 ,P < 0.05 ).The tumor infiltrated with numerous plasma cells and osteoclasts increased upon the biopsy. Conclusion Rabbit bone marrow implanted into NOD/SCID mice can effectively support local injection of plasma cells of multiple myeloma patients,and the NOD/SCID-mouse model of myeloma has been established.This model can be used to study in vivo experiments related to myeloma and clinical therapeutic approaches for this disease.
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To assess the efficacy of cotransplantation of haploidentical mesenchymal stem calls (MSC) and hematopoietic stem cells (HSC) in the treatment of refractory severe aplastic anemia, Two child patients with refractory severe aplastic anemia admitted to Henan Institute of Haematology from August 2002 to December 2007 were selected. Adipose tissue-derived MSCs (AMSCs) were separately originated from haploidentical mother and peripheral blood stem calls (PBSCs) from HLA-identical sibling brother or sister of patients. The patient 1 received a cotransplantation of PBSCs and AMSCs (1 × 106/kg) at a dose of 4.5 × 108 mononuclear calls/kg (containing 4.41 × 106 CD34+ calls/kg and 0.11 ×105 CD3+ cells/kg); the patient 2 received a second PBSCT at a dose of 6.5 × 108mononuclear cells/kg (containing 4.62×106 CD34+ cells/kg and 0.12×105 CD3+ cells/kg) and AMSC (1 × 108/kg) from his haploidentical mother. The results show that the cotransplantation was successful. During the two years of follow up, the two patients exhibited good condition, with no other treatment or transfusion dependence.
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The present study retrospectively analyzed 2 patients suffering from refractory pure red cell aplasia after major ABO-incompatible hematopoietic stem cell transplantation who received treatment in the Henan Institute of Haematology between April 2004 and February 2006. Patient 1 was a 25-year-old female with acute lymphocytic leukemia in second remission, and patient 2 was a 16-year-old gid with acute myeloid leukaemia in second remission. The two patients received a transplant of human adipose tissue-dedved mesenchymal stem cells (1.0×106/kg). Both of them acquired rapid recovery from pure red cell aplasia without any side effects. These findings suggest that adipose tissue-dedved mesenchymal stem cells seem to be a promising therapeutic option in patients with refractory pure red cell aplasia after ABO-incompatible hematopoietic stem cell transplantation, in whom conventional treatment fails.
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12-O-tetradecanoylphorbol-13-acetate (TPA) is an activator of protein kinase C (PKC)extracted from the croton oil, it is one of the most powerful inducers of differentiation as well as a powerful tumor promoter. It is used by the study of induction and differentiation generally, because of it can induce the differentiation of tumor cell and promote the lymphocyte transformation and secrete of lymphokine, meanwhile,it is able to induce many kinds of cell of leukemic cell strain like HL-60, HEL and so on, Some literature reported that TPA had the function of differentiation of primary leukemic cell. The article mainly explains the induction and differentiation of leukemic cell by phorbol ester as well as its mechanisms, which to provide the theory evidence for prevention and cure of leukemia.
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BACKGROUND: There is no consistently effective therapy for patients with steroid-refractory acute graft-versus-host disease (GVHD). A variety of alternative approaches have been tested, including antithymocyte globulin, mycophenolate mofetil (MMF), pentostatin, and monoclonal antibodies; however, these treatments have been only modestly successful. OBJECTIVE: To further evaluate the efficacy of human adipose-derived stem cells (ASCs) as the salvage therapy for steroid-refractory acute GVHD. DESIGN: A clinical trial.SETTING: Department of Haematology, Henan Institute of Haematology, Henan Tumor Hospital.PARTICIPANTS: The clinical trial was performed at the Henan Institute of Haematology from September 2002 to August 2005. Eight patients were treated with ASCs for grades Ⅲ-Ⅳ steroid-resistant acute GVHD. The study was approved by the Ethics Committee at Henan Tumor Hospital and informed consent was obtained from patients and ASCs donors before they enrolled.METHODS: Eight patients with steroid-refractory grades Ⅲ-Ⅳ acute GVHD received intravenous infusions of ASCs. The ASCs dose was 1.0×106/kg. Seven patients were treated once and one patients twice. Four patients received ASCs from haplo-identical family donors and four from unrelated mismatched donors. MAIN OUTCOME MEASURES: The efficacy of human ASCs as the salvage therapy for steroid-refractory acute GVHD. RESULTS: No side effects were noted after the ASCs infusions. Acute GVHD disappeared completely in seven of eight patients and six of these seven patients are still alive after the median follow-up of 30 months (range 11-90 months) after the initiation of ASCs therapy. All four surviving patients were in good clinical condition and in remission of their hematological malignancy. Two patients died-one with no obvious response to ASCs died of multiorgan failure and one of relapse of leukemia. CONCLUSION: These results suggest that ASCs is a very promising treatment for severe steroid-resistant acute GVHD.
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BACKGROUND: The treatment of chronic myelogenous leukemia (CML) is revolutionized by the tyrosine kinase inhibitor imatinib mesylate (imatinib). However, resistance to imatinib is increasingly recognized as a clinical problem, the prognosis of patients who develop imatinib resistance is poor, particularly in acute transformation phase of leukemia.OBJECTIVE: To characterize a novel CML cell line and to further elucidate the mechanisms of resistance to STI571.DESIGN: An observational comparative experiment.SETTING: Henan Institute of Haematology, Henan Tumor Hospital.MATERIALS: Thirty female BALB/c nu/nu mice with 5 weeks old were purchased from Animal Center, Chinese Academy of Medical Sciences. STI571 was kindly provided by Novartis (Nuremberg, Germany). VP-16 was purchased from Bristol-Myers Squibb (Munich, Germany); anti-P-gp from Santa Cruz Company, USA; anti-ab1 from BD Biosciences Company, USA. The disposal of experimental animal was coincidence with the ethical standard.METHODS: The experiment was performed in the Henan Institute of Haematology from September 2003 to November 2005. A novel K562 cell line (K562/VP16) was achieved after exposure of the K562 cells to VP16. A small subpopulation (SP K562/VP16) that was capable of excluding Hoechst 33342 in the K562/VP16 cell line was isolated by flowcytometry sorting. The rest of the K562/VP16 cells were classified as non-SP K562/VP16. In order to elucidate the mechanisms involved in K562/VP16 SP cells which became resistant to STI571, the expression of multidrug-resistant gene 1 (MDR1), Bcr-Abl and P-gp was detected in K562, non-SP K562/VP16, or K562/VP16 SP calls, respectively. Furthermore, one thousand cells of K562, K562/VP16 SP and non-SP cells were injected,respectively, intraperitoneally into the right flanks of ten 5-week-old female BALB/c nu/nu mice. The same experiment was repeated twice.MAIN OUTCOME MEASURES: Comparison of STI571 resistance and oncogenicity of non-SP K562/VP16 and K562/VP16 SP cells.RESULTS: The MDR-1 gene expression of the Mr 170 000 P-gp was detected in K562/VP16 non-SP and K562/VP16 SP cells but not in K562 cells. The expression levels of P-gp in the two K562/VP16 cell lines were similar (P ＞ 0.05).The levels of Bcr-Abl and Abl proteins were similar in the K562 cell line and in non-SP K562/VP16 and K562/VP16 SP cells (P ＞ 0.05). Compared with non-SP K562/VP16, the K562/VP16 SP cells were more resistant to STI571, and this resistance could hardly be reversed by many multidrug resistance inhibitors. In addition, in vivo study showed that the K562/VP16 SP cells induced oncogenicity in mice, while the K562/VP16 non-SP cells failed to do so.CONCLUSION: Bcr/abl gene amplification and MDR1 overexpression may not be an important clinical mechanism in the diversity of resistance development to imatinib treatment, and the development of drug resistance by leukemia cells may be at least partly due to a rare SP cells which drives leukemia occurrence and maintenance. So, these SP cells need to be targeted for effective cancer therapy.