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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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Ferroptosis is an iron-dependent cell death pathway that is different from apoptosis, pyroptosis, and necrosis. The main characteristics of ferroptosis are the Fenton reaction mediated by intracellular free divalent iron ions, lipid peroxidation of cell membrane lipids, and inhibition of the anti-lipid peroxidation activity of intracellular glutathione peroxidase 4 (GPX4). Recent studies have shown that ferroptosis can be involved in the pathological processes of many disorders, such as ischemia-reperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of acute leukemia still need to be more fully and deeply studied. This article reviews the characteristics of ferroptosis and the regulatory mechanisms promoting or inhibiting ferroptosis. More importantly, it further discusses the role of ferroptosis in acute leukemia and predicts a change in treatment strategy brought about by increased knowledge of the role of ferroptosis in acute leukemia.
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Humans , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Ferroptosis , Cell Death , Iron/metabolism , Leukemia, Myeloid, AcuteABSTRACT
Chronic myeloid leukemia (CML) is a malignant hematological disease driven by BCR-ABL fusion protein. The emergence of tyrosine kinase inhibitor (TKI) targeting BCR-ABL has completely changed the treatment pattern of CML. From the approval of the first generation TKI imatinib in 2001 to the emergence of the fourth generation TKI drugs, CML patients have benefited a lot from it. But even so, many CML patients suffer treatment failure due to drug resistance, relapse after drug withdrawal or disease progression, some patients therefore are difficult to obtain long-term remission and still need multi-line TKI treatment. The research and development of new drugs covering more mutation lineages, more optimized treatment strategies and drug withdrawal-related research are still the focus of CML treatment. This article introduces the research progress of CML reported on the 64th American Society of Hematology annual meeting.
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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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Objective:To investigate the long-term efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methods:From January 2010 to June 2017, 113 DLBCL patients admitted to Henan Cancer Hospital who had complete remission (CR) after rituximab combined with chemotherapy were enrolled. Among 113 patients, 40 cases received auto-HSCT as the first-line consolidation treatment after chemotherapy (transplantation group) and 73 cases received chemotherapy only (non-transplantation group). The clinical data of 113 patients were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and OS and PFS were compared between both groups.Results:The 2-, 3- and 5-year OS rates of transplantation group and non-transplantation group were 90.0% vs. 91.8%, 84.9% vs. 80.1%, 80.9% vs. 72.8%, respectively, and the difference in OS was statistically significant of both groups ( P = 0.457); the 2-, 3- and 5-year PFS rates were 85.0% vs. 85.0%, 82.2% vs. 61.8%, 82.2% vs. 60.0%, respectively, and the difference in PFS was statistically significant of both groups ( P = 0.046). None of the patients in the transplantation group experienced early transplantation-related death. Conclusions:In the era of rituximab treatment, the first-line auto-HSCT consolidation therapy could improve the PFS of high-risk DLBCL patients who are sensitive to chemotherapy, and it may improve the OS with a good safety.
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Objective:To investigate the pathogenesis and prognosis of transformation of primary myelofibrosis (PMF) to B-cell acute lymphoblastic leukemia (B-ALL).Methods:The diagnosis and treatment process of a patient transferred from PMF to B-ALL in Affiliated Tumor Hospital of Zhengzhou University in November 2018 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 64-year-old female, she was initially diagnosed with PMF, and then she developed B-ALL 17 months later after receiving treatment of prednisone, danazole, levamisole, aspirin, thalidomide and jaktinib. After induction therapy, the patient received 8 months of continuous remission, and then the reexamination showed relapse. There was no remission after reinduction therapy. The patient gave up treatment and was discharged 2 months later. JAK2 V617F gene mutation was positive before and after leukemia transformation.Conclusions:The patients with transformation of PMF to B-ALL have poor clinical prognosis and short survival time. The possible mechanism of its transformation may be related to additional genetic events or certain high-risk genes. However, the specific mechanism is still unclear, and further investigation of the etiology is needed to seek targeted treatment.
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Objective To investigate the clinical efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) for Hodgkin's lymphoma (HL). Methods We retrospectively analyzed the data of 38 patients with HL who underwent ASCT. Kaplan-Meier and Cox methods were used to analyze the curative effect and prognostic factors after transplantation. Results All 38 transplanted patients obtained hematopoietic reconstitution. The CR rates before and after transplantation were 55.3% and 81.6%, respectively, and the 5-year PFS and OS were 76.1% and 79.0%, respectively. Univariate analysis showed that B symptoms, IPS score, pre-transplant remission status, extranodal invasion, and pretreatment regimen were the factors affecting the prognosis of ASCT in patients with HL. Multivariate analysis showed that B symptom was an independent risk factor affecting 5-year PFS. Conclusion ASCT is effective in the treatment of high-risk, relapsed, and refractory patients with HL. B symptom is an independent risk factor affecting the prognosis of transplantation.
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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 evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.
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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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To analyze the prognostic factors of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphoblastic leukemia (ALL).The clinical data of 33 relapsed patients in 95 ALL patients receiving allo-HSCT were analyzed retrospectively. The median time of relapse was 5.7 (0.7-52.3) months. Extramedullary relapse was recorded in 10 cases (10.5%), bone marrow relapse in 15 cases (15.8%), and both extramedullary and marrow relapse were seen in 8 cases (8.4%). The median time of EMR was 7.4(0.7-52.3) months. The most commonly involved organ was central nervous system, followed by testis and bone. The 3-year OS rate in EMR patients was (33.3±11.1) %. Univariate analysis showed that disease state before transplantation ( P=0.026), extramedullary infiltration before transplantation ( P=0.005), conditioning regimens ( P=0.033) and acute graft-versus-host disease(aGVHD) ( P=0.013) were significantly correlated with EMR. Multivariate analysis suggested that extramedullary infiltration ( RR=5.067, 95 %CI1.542-16.645, P=0.007) and aGVHD( RR=3.585, 95 %CI1.245-10.320, P=0.018) were independent predictive factors of EMR in ALL patients after allo-HSCT.
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Objective:To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV).Methods:A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients′ general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed.Results:In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF.Conclusions:Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients′ age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.
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Objective:To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL).Methods:From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated.Results:Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations ( P<0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) ( P<0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ 2=10.330, P=0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ 2=7.974, P=0.047; EFS: χ 2=10.860, P=0.013). Conclusion:Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.
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Objective@#To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV).@*Methods@#A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients′ general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed.@*Results@#In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF.@*Conclusions@#Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients′ age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.
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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 efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.
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Objective:To observe the efficacy of the serial treatment with autologous hematopoietic stem cell transplantation after bortezomib and dexamethasone-based triple chemotherapy regimen and followed by lenalidomide and intermittent intensive therapy in primary plasma cell leukemia.Methods:A retrospective analysis was made on the clinical data of one patient who was diagnosed as primary plasma cell leukemia with complex karyotype in April 2018 in Henan Cancer Hospital, and the relevant literature was reviewed.Results:The patient received multiple cycles of bortezomib and dexamethasone-based triple chemotherapy regimen, then received autologous hematopoietic stem cell transplantation, lenalidomide and intermittent intensive therapy. The patient eventually achieved complete remission and the progression-free survival time was 18 months until the day before the deadline for this article.Conclusion:The treatment with autologous hematopoietic stem cell transplantation after bortezomib and dexamethasone-based triple chemotherapy regimen and followed by lenalidomide and intermittent intensive therapy may improve the prognosis of patients with primary plasma cell leukemia and prolong the survival time.
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Objective@#To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) containing cladribine sequential busulfan regimen for refractory/relapsed acute myeloid leukemia (AML) .@*Methods@#The clinical data of 12 refractory/relapsed AML patients received allo-HSCT with cladribine sequential busulfan regimen.@*Results@#① Of the 12 patients, 9 were males and 3 females, with a median age of 36 (27-50) years. The donors were identical sibling (3) , matched unrelated (1) and haploidentical family member (9) respectively. Nine patients reached partial remission and other remained no remission after chemotherapy before allo-HSCT. The median previous chemotherapy courses before allo-HSCT were 6 (2-13) . ② Conditioning regimen: Smostine 250 mg·m-2·d-1, d-7; Cladribine 5 mg·m-2·d-1, d-6 to d-2; Cytarabine Arabinoside 2 g·m-2·d-1, d-6 to d-2; Busulfan 3.2 mg·m-2·d-1, d-6 to d-3; Rabbit anti-human thymocyte immunoglobulin (ATG) 1.5 mg·m-2·d-1 (unrelated donor transplantation) or 2.0-2.5 mg·m-2·d-1 (haplo-HSCT) , d-4 to d-1. ③ Of the 12 patients, 11 patients attained complete haploidentical engraftment, one case occurred primary graft failure. The median durations for neutrophils and platelet implantations were 15 (15-21) and 19 (17-30) days respectively. ④After conditioning, no hepatic veno-occlusive diseases were observed, hemorrhagic cystitis occurred in 2 patients, 8 patients had fever, 3 cases experienced acute GVHD grade II, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 8 (4-12) months. Leukemia relapse occurred in 2 patients at time of 6, 12 months after allo-HSCT. The estimated 1-year OS and DFS were (71.1±1.8) % and (62.2±1.8) %, respectively.@*Conclusions@#allo-HSCT with cladribine sequential busulfan regimen was a feasible choice with favorable outcome for refractory/relapsed AML.
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Objective@#To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed.@*Results@#Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade.@*Conclusion@#Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.
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Objective@#To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) .@*Method@#The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases.@*Results@#There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %.@*Conclusion@#The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.