Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis.@*METHODS@#The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed.@*RESULTS@#The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L.@*CONCLUSION@#High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

Recent research on cognitive impairment in children with acute lymphoblastic leukemia / 中国当代儿科杂志

Acute lymphoblastic leukemia (ALL) is the most common malignant neoplastic disease in children. With the continuous improvement in diagnosis and treatment, there has been an increasing number of ALL children who achieve long-term survival after complete remission; however, a considerable proportion of these children have cognitive impairment, which has a serious adverse impact on their learning, employment, and social life. This article reviews the latest research on cognitive impairment in children with ALL from the aspects of the influencing factors, detection techniques, and prevention/treatment methods for cognitive impairment.

Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis.@*METHODS@#The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis.@*RESULTS@#The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24).@*CONCLUSIONS@#The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Efficacy and Recurrence Factors of Veneclax Combined with Aza- citidine in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy of veneclax combined with azacitidine in acute myeloid leukemia(AML) patients and explore the predictors of treatment response and recurrence.@*METHODS@#The clinical data of 30 AML patients who received venetecla combined with azacitidine in the Affiliated Hospital of Southwest Medical University from January 2021 to September 2022 were retrospectively analyzed, composite complete remission (CRc) rate, overall response rate(ORR), and disease free survival(DFS) of patients were observed.@*RESULTS@#After one course of trea- tment, CRc was 16 cases and ORR was 23/30. Patients with TP53 mutation had poor treatment response (P=0.009). After 1-2 courses, 25 patients reached CR/CRi. Finally, 24 patients who obtained CR/CRi were included to observe the duration of remission. 17 patients had relapse, with a median recurrence time of 3.9 (0.6-15.9) months. The Kaplan-Meier curve showed that MRD negative was a favorable factor for maintaining DFS status (HR=0.5647,95%CI:0.2179-1.464,P=0.007), while NRAS mutation was an adverse factor for maintaining DFS (HR=2.036,95%CI:0.6639-6.245,P=0.0003). Univariate combined multivariate cox regression analysis showed that NRAS mutation was an independent risk factor affecting DFS in patients (HR=5.569, P<0.05). In addition, the cases number of early recurrence in MRD negative group (n=8) and MRD non-negative group (n=9) was 0 and 5, respectively, the difference was statistically significant (P=0.012). There were 3 cases of early recurrence in the NRAS mutant group (n=4) and 2 cases in the NRAS wild-type group (n=13), the difference was statistically significant (P=0.022).@*CONCLUSION@#TP53 mutation is a predictor of poor response to veneclax in combination with azacitidine. With the conti-nuation of the combination chemotherapy regimen described above, NRAS mutation is an independent risk factor for DFS in patients. Moreover, the patients with non-negative MRD and NRAS mutations are at high risk of early recurrence.

Clinical Features and Prognostic Factors of Patients with Primary Cutaneous Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma.@*METHODS@#The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed.@*RESULTS@#The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated β2-microglobulin (β2-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056).@*CONCLUSION@#The age, disease stage, β2-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.

Comparison of Cyclosporine A and Cyclosporine A Combined with Corticosteroid in the Treatment of Acquired Pure Red Cell Aplasia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA).@*METHODS@#The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms.@*RESULTS@#96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05).@*CONCLUSION@#CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.

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.

A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML).@*METHODS@#From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m2 intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m2 intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed.@*RESULTS@#Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study.@*CONCLUSION@#For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.

Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Belimumabe comparado à terapia padrão do Sistema Único de Saúde no tratamento da nefrite lúpica nos estágios III, IV e V: revisão rápida / Belimumab compared to standard therapy of the Brazilian Public Health System in the treatment of lupus nephritis in stage III, IV, and V: rapid review

Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

Combinación de antidepresivos vs. aumentación con antipsicóticos atípicos tras no lograr la remisión en la depresión unipolar / Combination of antidepressants vs. augmentation with atypical antipsychotics upon failure to achieve remission in unipolar depression

RESUMEN: Introducción: Lograr la recuperación funcional lo más rápido posible en el tratamiento de la depresión unipolar es un reto que la práctica clínica debe tratar de afrontar en la actualidad, ya que cualquier retraso en lograr la remisión de los síntomas es predictivo de un mayor número de recurrencias y mayores tasas de morbimortalidad. En esta revisión comprensiva, nuestro objetivo es guiar a los clínicos en su elección de aumentar con antipsicóticos atípicos o combinar el fármaco de referencia con un segundo antidepresivo, después de que se haya optimizado la dosis del antidepresivo seleccionado inicialmente y/o se haya cambiado el antidepresivo, sin lograr remisión, o bien cuando solo han obtenido una respuesta parcial después de un tiempo suficiente a una dosis apropiada. Estas decisiones surgen con frecuencia en la práctica clínica diaria. Metodología: Se realizó una búsqueda sistemática en PubMed bajo varias combinaciones clave de palabras, resultando en 230 informes. Después de aplicar los criterios de inclusión y según el título y el resumen, el número final de informes seleccionados para la revisión completa fue de 113. Se respondieron dos preguntas principales con base en estos estudios: 1) ¿Existe evidencia para recomendar claramente la combinación de antidepresivos versus potenciación con antipsicóticos (y el momento correcto para hacerlo) en la depresión unipolar no respondedora, una vez que las estrategias de optimización o de cambio han fallado en obtener la remisión? y 2) ¿Es posible identificar algunas características clínicas para guiar la decisión de combinación de antidepresivos versus potenciación con agentes antipsicóticos? Resultados: Según nuestro análisis, no hay datos disponibles para seleccionar una estrategia de otra de manera clara. Sin embargo, sugerimos favorecer una combinación o estrategia de aumento, basada en un enfoque de "tratamiento contra objetivos dianas" para perfilar al paciente, considerando una o dos características clínicas predominantes que permanecen activas como parte de una depresión mayor con respuesta parcial. Un adecuado análisis de los dominios sintomáticos presentes, una visión crítica de las guías clínicas actuales y de las opciones preferidas, considerar la bipolaridad oculta como uno de los principales diagnósticos diferenciales y adoptar una actitud enérgica pero lúcida en esta etapa del tratamiento son, a nuestro juicio, fundamentales para lograr recuperación ad integrum del paciente.

ABSTRACT Introduction: achieving functional recovery as quickly as possible in the treatment of unipolar depression is a challenge that clinical practice must try to meet nowadays, since any delay in accomplishing remission of the symptoms is predictive of a larger number of recurrences and higher morbidity and mortality rates. In this topical review we aim to guide clinicians in their choice to augment with atypical antipsychotics or to combine the baseline drug with a second antidepressant, after the dose of the antidepressant initially selected has been optimized and/or the antidepressant has been changed, not achieving remission, or resulting only in a partial response after sufficient time at an appropriate dose. These decisions arise frequently in everyday clinical practice. Methodology: a systematic search in PubMed was performed under several key combinations of words, resulting in 230 reports. After applying inclusion criteria and based in title and abstract, the final number of reports selected for full revision were 113. Two main questions were answered based on these studies: 1) Is there evidence to clearly recommend combination of antidepressants vs. augmentation with antipsychotics (and the correct moment to do it) in non-responsive unipolar depression, once optimization or switching strategies have failed to obtain remission? and 2) Is it possible to identify some clinical features to guide the decision of combination of antidepressants vs. augmentation with antipsychotic agents? Results: According to our analysis, there is no data available to select one strategy from another in a clear-cut manner. Nevertheless, we suggest favoring a combination or augmentation strategy, based in a "treating to target" approach to profile the patient, considering one or two predominant clinical features that remain active as part of a major depression with partial response. Proper analysis of the symptomatic domains present, a critical view of current clinical guidelines and preferred options, considering hidden bipolarity as one of the main differential diagnoses and adopting an energetic but lucid attitude at this stage of treatment are, in our view, fundamental for achieving ad integrum patient recovery.

Estado actual y retos futuros en el tratamiento de las enfermedades reumáticas / Current status and future challenges in the treatment of rheumatic diseases

Las nuevas estrategias, que incluyen el diagnóstico y el tratamiento tempranos, el enfoque de tratamiento dirigido a un objetivo, la remisión como ese objetivo principal del tratamiento, la participación de los pacientes en las decisiones terapéuticas, junto con el desarrollo de nuevos tratamientos efectivos, han cambiado las expectativas de los reumatólogos y de los pacientes con enfermedades reumáticas. Todavía existen, sin embargo, importantes desafíos tales como la seguridad a largo plazo de los tratamientos actuales y poder escoger tratamientos más individualizados y eficaces, de forma tal de elegir el mejor tratamiento para cada paciente. El futuro, como en el resto de la medicina, probablemente sea la prevención del desarrollo de enfermedades reumáticas. Discutiremos estos temas en esta revisión. (AU)

New strategies, including early diagnosis and treatment, targeted therapy, remission as the main objective of treatment, patient involvement in therapeutic decision-making, and the development of new effective therapies, have changed the expectations of rheumatologists and patients with rheumatic diseases.There are still serious challenges, such as the long-term safety of current treatments and the ability to make more individualized and effective treatments to choose the best treatment for each patient. The future, as that of the whole of medical science, will probably lie in preventing the development of rheumatic diseases. We will discuss these issues in this review. (AU)

Safety and efficacy of ustekinumab in the treatment of Crohn Disease: a systematic review and meta-analysis

ABSTRACT Background and Aims The present systematic review and meta-analysis was designed to estimate the safety and effectiveness of ustekinumab in the treatment of Crohn disease (CD) in clinical trials and observational studies. Methods We retrieved all the related publications from the PubMed, Cochrane, EBSCO, Google Scholar and EMBASE databases using a systematic search strategy. We only included clinical trials and observational studies that were published in English. Results Only 31 studies that met the eligibility criteria out of the 733 identified studies were included. The overall clinical response rate in the cohort studies was of 0.539 (95% confidence interval [95%CI]: 0.419-0.659), and in the clinical trials it was of 0.428 (95%CI: 0.356-0.501). The pooled clinical remission rate was of 0.399 (95%CI: 0.295-0.503) in randomized control trials (RCTs,) and of 0.440 (95%CI: 0.339-0.542) in cohort studies. The rate of adverse effects was of 0.158 (95%CI: 0.109-0.207) in cohort studies and of 0.690 (95%CI: 0.633-0.748) in RCTs. Conclusion Ustekinumab is effective in the treatment of CD. However, more research is required on the safety profiles because there was considerable variation among the included studies. (AU)

Impact of quality of response on survival outcomes among multiple myeloma patients treated with novel agents - a retrospective analysis

Abstract BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Niš, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.

Comparison between DAS28-ESR and DAS28- CRPus for patients with rheumatoid arthritis: application in a population of southern Brazil

Abstract The Disease Activity Score 28 (DAS28) shows discrepancies when using erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) scores to assess rheumatoid arthritis (RA). This study aimed to verify the agreement between the DAS28-CRP and DAS28-ESR scores in patients with RA from the south of Brazil. A unicentric cross-sectional study was performed (n = 56). The diagnosis of the patients followed the American College of Rheumatology/ European League Against Rheumatism criteria, and their DAS28 were calculated. The DAS28- ESR score was higher than the DAS28-CRP (DAS28-ESR mean 4.8±1.6; DAS28-CRP mean 4.3±1.4) for 83.9% of the patients. The DAS28-CRP and DAS28-ESR scores showed a very strong correlation (Pearson's coefficient = 0.922; P<0.0001, 95% CI +0.87 to +0.95, statistical power 100%). Spearman's correlation coefficient (0.49; P=0.0001, 95% CI +0.25 to +0.67, statistical power 47.54%) showed a moderate correlation between the unique components of the DAS28 formulas. There was agreement between the tests in only 36 of the patients (64.29%). Among the discordant categories, DAS28-ESR overestimated the classification in 16 patients (28.5%). The Kappa coefficient between the categories was 0.465 (SE 0.084, 95% CI +0.301 to +0.630), showing a moderate degree of agreement between the instruments. Although the DAS28-ESR and DAS28-CRP were highly correlated, they differed significantly in terms of patient categorization and should not be used interchangeably

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

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.