Nursing care of 5 children on Blinatumomab therapy with relapsed refractory acute B lymphocyte leukemia / 中国实用护理杂志

To summarize the experience of 5 children with relapsed and refractory acute B lymphocyte leukemia treated with Blinatumomab, during the whole nursing processes, careful nursing was carried out before, during and after infusion. The key points of nursing include: reasonable cooperation with nursing staff and specialized training, design a condition observation form, timely grasp changes in the condition, early identify adverse reactions such as cytokine storms, neurotoxicity, and allergies, and ensure the safety of the children. Through personnel, articles and personalized liquid preparation table, ensure accurate dose, smooth infusion and save hospital expenses ￥3, 846~201, 910 for children. Payattention to the psychological burden of children and their families and attach importance to psychological care. Follow the psychological burden of children and caregivers, and pay attention to psychological nursing. As the results, 3 chidlren successfully completed the first cycle of Blinatumomab. But 2 chidlren interrupted due to the tumor burden. Follow up for 5-12 months showed that 2 cases survived, 1 case died of progressive disease after discharge, and 2 cases died of transplant complications.

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.

Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Progress of minimal residual disease monitoring in adult acute lymphoblastic leukemia / 白血病·淋巴瘤

Acute lymphoblastic leukemia (ALL) is a malignancy originating from B-/T-lineage lymphoid progenitor cells. With the continuous development of new drugs as well as therapeutic regimens, adult ALL patients have improved complete remission rates and overall survival rates, but the survival rate of patients after relapse remains low. The positive minimal residual disease after complete remission is an important reason for relapse. Although minimal residual disease monitoring has been found to be important in predicting patients prognosis in recent years, the uniform stratified treatment protocols have not yet been developed in the clinical practice of adult ALL. This article reviews the prognostic significance of minimal residual disease monitoring at different time points, as well as the progress of removal methods of minimal residual disease.

Blinatumomab as bridging therapy in two children with B-cell acute lymphoblastic leukemia complicated by invasive fungal disease / 中国当代儿科杂志

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.

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.

Cuidados a la persona con cáncer y neutropenia / Caring for the person with cancer and neutropenia

Este trabajo se realizó como respuesta a un problema de la practica en enfermería al haberse realizado en el marco de un producto requerido desde la formación posgradual de la maestría en enfermería con profundización en oncología, buscando aportar y transferir el conocimiento a la sociedad. El trabajo está orientado a la educación que requieren los cuidadores de pacientes adultos con Leucemia linfoblástica aguda de células B CD 19 positivo con cromosoma Philadelphia negativo en situación de recaída o refractariedad al tratamiento o con enfermedad mínima residual positiva y que requieran tratamiento con Blinatumomab. El objetivo fue elaborar una guía práctica de cuidado dirigida a los cuidadores de estos pacientes con la intención de brindar herramientas desde el conocimiento que permitan conocer sobre la enfermedad, el tratamiento, la identificación de los signos y síntomas asociados a eventos adversos por la administración del Blinatumomab descritos en la misma guía, para prevenir o disminuir la ocurrencia de desenlaces fatales en esta población de pacientes. Se contó con la participación de enfermeros profesionales y de cuidadores de pacientes que han administrado y recibido terapia con Blinatumomab respectivamente para identificar las necesidades en educación desde la práctica profesional y el desarrollo de los cuidados. Se diseño un material educativo basado en las orientaciones dadas por la Organización Panamericana de la Salud para la elaboración de material educativo, obteniendo como producto una guía comprensible y útil como instrumento para el desarrollo de procesos educativos con cuidadores de adultos con LLA de células B CD 19 positivo PH negativo R/R o con EMR positiva.

The present work was carried out in response to a problem in nursing practice because it was carried out within the framework of a product required from the postgraduate training of the master's degree in nursing with a deepening in oncology, seeking to contribute and transfer knowledge to society. The work is oriented towards the education required by caregivers of adult patients with Philadelphia chromosome negative CD 19 positive B-cell acute lymphoblastic leukemia in a situation of relapse or refractory to treatment or with positive minimal residual disease and who require treatment with Blinatumomab. The objective was to develop a practical care guide aimed at the caregivers of these patients with the intention of providing tools based on knowledge that allow them to know about the disease, treatment, identification of signs and symptoms associated with adverse events due to the administration of the Blinatumomab described in the same guidelines, to prevent or reduce the occurrence of fatal outcomes in this patient population. Professional nurses and caregivers of patients who have administered and received Blinatumomab therapy, respectively, participated to identify educational needs from professional practice and care development. An educational material was designed based on the guidelines given by the Pan American Health Organization for the elaboration of educational material, obtaining as a product an understandable and useful primer as an instrument for the development of educational processes with caregivers of adults with CD B-cell ALL. 19 positive PH negative R/R or with positive EMR.

Application of allogeneic hematopoietic stem cell transplantation in acute lymphoblastic leukemia in the era of targeted therapy / 白血病·淋巴瘤

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the main curable therapies for patients with acute lymphoblastic leukemia (ALL). This article discusses the status of allo-HSCT for ALL as well as how to combine targeted therapy with allo-HSCT to improve outcomes of ALL in the era of targeted therapy based on the data obtained from the 63rd American Society of Hematology (ASH) Annual Meeting.

Application of Blinatumomab in treatment of pediatric refractory/relapsed B-lineage acute lymphoblastic leukemia in 2 cases / 中华实用儿科临床杂志

The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.

Efficacy and safety of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia / 国际肿瘤学杂志

Blinatumomab, as a novel bispecific antibody targeting CD19 and CD3, can induce T lymphocytes to precisely target CD19 positive B lymphocytes to apoptosis. At present, it is the only bispecific antibody approved for the treatment of hematological malignancies in China. Blinatumomab is effective in the treatment of newly diagnosed, relapsed/refractory, minimal residual disease positive patients with B-cell acute lymphoblastic leukemia (B-ALL) . It can improve the survival of the patients and is well tolerated. The further study of blinatumomab can provide theoretical basis and new ideas for induction therapy, salvage therapy and subsequent hematopoietic stem cell transplantation in patients with B-ALL.

Meta-analysis of clinical efficacy and safety of blinatumomab for acute lymphoblastic leukemia / 中国药房

OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia （ALL）in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ，Embase，Web of Science，the Cochrane Library ，CNKI，Wanfang database and CBM during the inception to February 3，2022，randomized controlled trials （RCTs）and cohort studies of blinatumomab （experimental group ） versus conventional chemotherapy （control group ）in the treatment of ALL were collected. After literature screening and data extraction ，the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0，and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale （NOS）. Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ，involving 3 RCTs and 5 cohort studies ，with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR ＝1.30，95％CI（1.14，1.48），P＜0.000 1]，relapse-free survival rate [RR ＝1.78，95％CI（1.50，2.12），P＜0.000 01]，complete remission rate [RR ＝1.42，95％CI（1.11，1.82），P＝0.006]，the incidence of tremor [RR ＝16.98，95％CI（2.17，133.12），P＝0.007]，and the incidence of cytokine release syndrome [RR ＝14.11， 95％CI（3.43，58.01），P＝0.000 2] in trial group were all significantly higher than control group ，but there was no statistical significance in the incidence of headache between two groups [RR ＝1.31，95％CI（0.66，2.59），P＝0.44]. The incidence of adverse events with grade more than or equal to 3，infection，stomatitis，thrombocytopenia，febrile neutropenia ，anorexia， constipation，diarrhea，abdominal pain ，hypokalemia in trial group were significantly lower than control group （P＜0.05）. The incidence of cough ，rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in the total incidence of adverse events ，sepsis，anemia，leucopenia，neutropenia， lymphopenia，nausea，vomiting，hyperglycemia，hypotension，hypertension，elevated transaminase or epistaxis between two groups（P＞0.05）. Results of subgroup analysis by study type showed that the overall survival rate ，relapse-free survival rate and complete response rate （except for cohort studies ）of patients in trial group were significantly higher than control group in both RCTs and cohort studies （P＜0.05）. The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ，with low incidence of infection and adverse events of digestive system ，but high incidence of tremor ，cough，rash，fever，hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .

Immunogenicity of bispecific antibodies / 中国临床药理学与治疗学

The term bispecific antibody (bsAb) is used to describe antibodies that can recognize and bind two different antigens. Compared with the regular therapeutic antibodies, bsAbs have many advantages, such as higher sensitivity, better specificity, and are able to block multiple disease pathways simultaneously. So far, 3 bispecific antibodies have been marketed and nearly 100 are in clinical development all over the world, showing a broad development prospect. Immunogenicity of bispecific antibodies refers to the fact that the drugs will cause the immune response and produce anti-drug antibodies after entering the body, which may affect the pharmacokinetic and pharmacodynamic properties of the drugs. In this paper, the research progress on the immunogenicity of catumaxomab, blinatumomab and emicizumab was reviewed, with a view to providing reference for the safety, efficacy, and rational clinical application of bispecific antibodies.

Research advances of bispecific antibody drugs in tumor therapy / 中国药科大学学报

@#Tumor immunotherapy is currently the new direction for the treatment of cancer. Bispecific antibody can bind two different antigens, so the development prospect in the field of tumor treatment is very attractive. The most compelling trifunctional antibody and bispecific T-cell engager in bispecific antibodies have been marketed separately, with representative drugs as catumaxomab and blinatumomab, respectively. So far, nearly 100 antitumor bispecific antibody drugs are undergoing clinical trials and in-depth understanding of their mechanisms of action will provide more powerful solutions for cancer treatment. This review summarizes the progress of catumaxomab, blinatumomab and current highly promising bispecific antibody drugs, for the further development and application of tumor therapy.