Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country

ABSTRACT Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.

Clinical analysis of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia / 中华实用儿科临床杂志

Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Progress of blinatumomab in the treatment of relapsed/refractory acute lymphoblastic leukemia in children / 国际儿科学杂志

In recent years, with the continuous improvement of high-dose combined chemotherapy and deeper understanding of risk factors, the remission rate of childhood acute lymphoblastic leukemia has been gradually improved, but the prognosis of relapsed/refractory acute lymphoblastic leukemia(r/r ALL)is still not optimistic.Hematopoietic stem cell transplantation has become an alternative treatment for these children.With the development of cellular immunotherapy, the prognosis of children with r/r ALL is expected to be improved.Blinatumomab, as a bispecific antibody, is the first cloned antibody to be tested in clinical trials and approved by FDA for Philadelphia chromosome negative(Ph-) r/r ALL.Blinatumomab as a new generation of monoclonal antibody can significantly improve the survival of children with r/r ALL.This article focuses on the mechanism of action, drug resistance, clinical research progress and adverse reactions of Blinatumomab.

Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma / 中国医学科学院学报

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

Advances in the Treatment of Glucocorticoid Resistance and Relapsed Immune Thrombocytopenia --Review / 中国实验血液学杂志

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.

Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).@*METHODS@#The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared.@*RESULTS@#In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×109/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×109/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage.@*CONCLUSION@#Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.

Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.

Effects of Peripheral Blood Stem Cell Transplantation from Haploidentical Versus Matched Sibling Donors on High-risk and Refractory/Relapsed Acute Myeloid Leukemia / 肿瘤防治研究

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies

Acute lymphoblastic leukemia (ALL) is the malignant transformation of lymphoid progenitors that affects both children and adults. Although the outcome of pediatric patients has been improved dramatically, there are still many challenges in the treatment of adults. Patients with primary resistant or relapsed disease have the worst outcome and despite the administration of intensified multi-agents chemotherapies, the outcome of this group remains very poor. Accordingly, the development of novel therapeutic options is considered necessary. Having a comprehensive insight into the pathophysiology of ALL and aberrant signaling pathways is crucial for introducing effective targeted therapies. Combination therapies with new drugs and innovative targeted therapies with the aim of affecting the main aberrant signaling pathways in the disease are considered as new approaches. Here we tried to have a comprehensive review on the potential molecular targets in the treatment of refractory/relapsed ALL and the current therapeutic agents

Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM).@*METHODS@#The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated.@*RESULTS@#After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity.@*CONCLUSION@#BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

Chimeric antigen receptor T cell immunotherapy for refractory and relapsed acute lymphoblastic leukemia: Challenge and Countermeasures / 中华检验医学杂志

Chimeric antigen receptor(CAR)-T cell immunotherapy for refractory and relapsed acute lymphoblastic leukemia (R/R ALL) is one of the breakthroughs in the field of hematological malignant disease treatment. However, several challenges remain, such as immune rejection of allogeneic CAR-T cells, leukemia relapse, as well as could we apply CAR-T cell immunotherapy to ALL patients with positive measurable residual disease and those of newly diagnosed cases. The safety and efficiency of CAR-T therapy will be further improved for patients with ALL only by establishing appropriate strategies to address these challenges.

Clinical efficacy and safety of ixazomib-based therapy in the treatment of relapsed or refractory multiple myeloma / 国际肿瘤学杂志

Objective:To investigate the clinical efficacy and safety of ixazomib-based therapy in patients with relapsed or refractory multiple myeloma (RRMM) .Methods:A retrospective analysis was performed on the efficacy and adverse reactions of 53 RRMM patients treated with a combined regimen containing ixazomib in the Hematology Department of Beijing Jishuitan Hospital from July 8, 2018 to November 30, 2020. Among them, 6 patients received ID regimen (ixazomib + dexamethasone) , 30 patients received ID regimen + immunomodulator, and 17 patients received ID regimen + other chemotherapy drugs.Results:Fifty-three patients with RRMM received ixazomib-based therapy. The median previous treatment line was 3, the median treatment course was 6 (2-30) , and the median follow-up time was 21 months (2-32 months) . The overall response rate (ORR) was 54.7% (29/53) after 2 courses of treatment. Among them, 26.4% (14/53) had very good partial response (VGPR) and 28.3% (15/53) had partial response (PR) . The ORR of the ID regimen group, ID regimen + immunomodulator group and ID regimen + other chemotherapy group were 83.3% (5/6) , 56.7% (17/30) and 41.2% (7/17) respectively, with no statistically significant difference among the three groups ( P=0.208) . The median time to progression (TTP) of 53 patients was 8 months (1-24 months) . The most frequent adverse events of ixazomib treatment were gastrointestinal reactions such as nausea, vomit and diarrhea, with an incidence of 37.7% (20/53) , and the incidence of grade 3-4 was 5.7% (3/53) . The most common hematological adverse events were thrombocytopenia (15.1%, 8/53) , neutropenia (11.3%, 6/53) and anemia (9.4%, 5/53) . Grade 1-2 peripheral neurotoxicity occurred in only 7.5% (4/53) of patients. Conclusion:Ixazomib has good efficacy and safety for the patients with RRMM in the real world.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Cyclophosphamide-glucocorticoids versus lenalidomide-dexamethasone as treatment for multiple myeloma at first relapse after autologous stem cell transplantation - a retrospective analysis

ABSTRACT There have been significant improvements in therapeutic options for relapsed multiple myeloma (MM) over the past two decades, with many novel agents including proteasome inhibitors, immunomodulatory agents, and more recently monoclonal antibodies demonstrating efficacy in this setting. However, there is a paucity of real-world data comparing outcomes seen in patients treated with novel agents as opposed to older agents. We report a historical single center cohort of patients diagnosed with myeloma between the years 1991-2012 in order to explore possible differences in outcomes. A total of 139 patients who underwent stem cell transplantation were included in our study. In our study, 88 patients were treated with cyclophosphamide and steroids alone at relapse whereas 51 patients were treated with Len-Dex. In the multivariate analysis, TTNT was shorter for patients who received Cyclo compared to Len-Dex (HR = 1.74; 95% CI, 1.01-2.99; p = 0.04); however, we could not detect an overall survival benefit (HR = 1.20; 95% CI 0.63-2.29; p = 0.57). Adverse event rates were similar in the two groups. In this retrospective single center analysis, Len-Dex was associated with longer TTNT compared with Cyclo at first relapse following autoSCT in MM; however its effect on overall survival in this setting was less clear.

Progress of targeted therapy in relapsed/refractory acute myeloid leukemia / 白血病·淋巴瘤

At present, the treatment of relapsed/refractory acute myeloid leukemia (AML) is still challenging, and there is no standard treatment for relapsed/refractory AML patients. Current research believes that participating in clinical trials involving small molecule targeted therapy, immunotherapy and epigenetic therapy may be the best choice, but the efficacy and toxicity of clinical trials have not been widely evaluated, and the long-term survival of patients is not clear, so the prognosis of relapsed/refractory AML is still very poor. The future direction of research will focus on novel, effective and targeted treatment combinations, and low toxicity, personalized and accurate treatment strategies. This article reviews the latest progress in targeted therapy for relapsed/refractory AML.

Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure / Journal of Rural Medicine

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.

Quality of Life and Tendency to Aggression Among Relapsed and First Time Substance Abusers: A Comparative Assessment Study

@#Introduction: Drug abuse is a prevalent issue in Malaysia, and a constant struggle to eradicate even among substance abusers who have received prior rehabilitation. Drug abuse has also been known to affect the quality of life of an individual, due to the stigma it carries. This research emphasized on studying the life quality of relapsed and first-time substance abusers in rehabilitation centres including their tendency towards aggression. Methods: A cross-sectional study was conducted to evaluate the current inpatients in Cure & Care Rehabilitation Centres (CCRC) in Peninsular Malaysia. Primary data was acquired using a self-administered questionnaire consisting of socio-demographic (Part A), quality of life (Part B) and aggression related questions (Part C). 417 individuals were selected through purposive sampling from five different centres. A statistical analysis was conducted using independent t-test, single linear regression and Kruskal-Wallis using SPSS version 25.0. Results: An analysis of the data presented no significant association between quality of life and tendency of aggression among relapsed and first time substance abusers (p>0.05). Based on the analysis and the outcome, age influences the level of aggression (p=0.018) while quality of life is affected by education level (p=0.017). Marital status is a factor that affects both the level of aggression (p=0.015) and quality of life (p=0.043). Conclusion: The findings may contribute to law enforcements in reducing violent crimes committed by drug abusers and rehabilitation efforts by rehabilitation centres, by establishing demographic profiles in relation to quality of life and aggression.

Different sites of extranodal involvement may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor T cell therapy / 医学前沿

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P < 0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.