Linfoma de células B primario de mama en una paciente con sida. Presentación de un caso y revisión de la literatura / Primary B-cell lymphoma of the breast in an AIDS patient. Case report and literature review

Los LNH constituyen la segunda neoplasia más frecuente en pacientes con VIH. Estas neoplasias están ligadas a la inmunodeficiencia, suelen ser de período de latencia prolongado y más frecuentes en hombres. Más del 95% de estas neoplasias son de fenotipo B, de alto grado de malignidad, extranodales y representan la causa de muerte en un 12% al 16% de los casos. El linfoma no Hodgkin primitivo de mama (LPM) es una entidad infrecuente, que representa el 2,2% de todos los linfomas extranodales y el 0,5% de todas las neoplasias malignas de la mama. Se presenta una mujer con sida y linfoma primario de mama. (AU)

NHL is the second most common neoplasm in patients with HIV. It is linked to immunodeficiency, tends to have a long latency period and is more common in men. More than 95% of these neoplasms are of phenotype B, high-grade, extranodal and are the cause of death in 12% to 16% of cases. Primitive non-Hodgkin lymphoma of the breast is a rare entity, accounting for 2.2% of all extranodal lymphomas and 0.5% of all breast malignancies. A woman with AIDS and primary breast lymphoma is presented. (AU)

Satisfação com os cuidados de enfermagem de pacientes oncológicos em uso de antineoplásicos ambulatorial / Satisfaction with nursing care of oncology patients on outpatient antineoplastic drugs / Satisfacción con los cuidados de enfermería en pacientes oncológicos que utilizan fármacos antineoplásicos en régimen ambulatorio

RESUMO Objetivo: avaliar a satisfação do usuário oncológico ambulatorial em uso de antineoplásicos sobre os cuidados de enfermagem. Métodos: estudo transversal com abordagem quantitativa, realizado no Serviço de Quimioterapia de um hospital universitário localizado em Belém-PA - Brasil, com 200 usuários no período de junho de 2019 a junho de 2022, através de entrevista e uso do Instrumento de Satisfação do Paciente. Aplicou-se análise de qui-quadrado de Pearson e considerou-se p-valor ≤0,05. Resultados: os usuários relataram bom índice de satisfação na média geral dos domínios (>90%), destacando o domínio técnico-profissional, seguido do educacional e confiança. As variáveis de esclarecimento sobre as orientações médicas, dar bons conselhos, tomar iniciativa após as respostas dos pacientes foram associadas à satisfação do usuário conforme a topografia do câncer e a disponibilidade da equipe àqueles com diferentes graus de estadiamento. Conclusão: este estudo auxilia gestores na identificação e planejamento de melhorias nas áreas e serviços.

ABSTRACT Objective: Evaluate the satisfaction of outpatient oncology users taking antineoplastic drugs about nursing care. Methods: Exsectional study with a quantitative approach, carried out at the Chemotherapy Service of a university hospital located in Belém-PA - Brazil, with 200 users, from June 2019 to June 2022, through interviews and use of the Patient Satisfaction Instrument. Chi-square analysis, Pearson p-value, and chi-square analysis were applied, and the p-value ≤ 0.05 was considered. Results: Users reported good satisfaction in the overall average of the domains (>90%), highlighting the technical-professional domain, followed by the educational and confidence domains. The variables of clarification of medical guidelines, giving good advice, and taking the initiative after patient responses were associated with user satisfaction according to cancer topography and staff availability to those with different degrees of staging. Conclusion: This study assists managers in identifying and planning improvements in areas and services.

RESUMEN Objetivo: evaluar la satisfacción de los usuarios de oncología ambulatoria que utilizan fármacos antineoplásicos sobre los cuidados de enfermería. Métodos: estudio seccional con enfoque cuantitativo, realizado en el Servicio de Quimioterapia de un hospital universitario situado en Belém-PA - Brasilcon 200 usuarios en el período de junio de 2019 a junio de 2022, mediante entrevista y utilización del Instrumento de Satisfacción del Paciente. Se aplicó el análisis chi-cuadrado de Pearson y el valor p ≤0,05. Resultados: los usuarios declararon una buena satisfacción en la media global de los dominios (>90%), destacando el dominio técnico-profesional, seguido de los dominios educativo y de confianza. Las variables de aclaración sobre las directrices médicas, dar buenos consejos, tomar la iniciativa tras las respuestas de los pacientes se asociaron con la satisfacción de los usuarios según la topografía del cáncer y la disponibilidad del personal ante los distintos grados de estadificación. Conclusión: este estudio ayuda a los directivos a identificar y planificar mejoras en áreas y servicios.

Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Efficacy and safety of intermediate-dose cytarabine in the treatment of children with refractory high risk Langerhans cell histiocytosis / 中华儿科杂志

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m2, twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.

More attention for high-risk pathological features for stage Ⅱ colorectal cancer required / 中华病理学杂志

Stage Ⅱ (T3-4N0M0) accounts for 25% of colorectal cancer and five-year survival is between 70% and 80%. However, 25% of patients develop distant metastases and have a survival rate similar to that of stage Ⅲ disease. However, whether or not to give adjuvant chemotherapy is still a controversial issue. As a result, there has been a lot of interest in the identification of the pathological factors underlying the poor prognosis associated with this stage, in order to establish a firmer basis for the administration of adjuvant chemotherapy. But not all high-risk factors are equal for stage Ⅱ colorectal cancer, variability still exists in the management and outcomes of high-risk patients. Here be introduced and commented on thinking and understanding about its controversy and evolution for the attention of the working pathologist and gastroenterologist doctors.

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.

Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

Significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To evaluate the clinical significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma. Methods:Patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were eligible. All received 2 cycles of pembrolizumab combined with docetaxel and platinum neoadjuvant induction therapy. After two cycles, the efficacy was evaluated, followed by radical chemoradiotherapy or surgery and adjuvant chemoradiotherapy according to the efficacy. The primary endpoints were objective response rate（ORR） ，larynx-preservation（LP） rate at 3 months post-treatment and the adverse reactions during neoadjuvant therapy. Results:From December 2021 to December 2022, 10 patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were enrolled. After 2 cycles of the neoadjuvant therapy, 2 patients achieved complete response（CR）, 7 patients achieved partial response（PR）, 1 patient was stable disease（SD）, objective response rate（ORR） was 90%, and disease control rate（DCR） was 100%. 5 patients received radical chemoradiotherapy, 5 patients received surgery and adjuvant chemoradiotherapy, four of them received partial laryngectomy and partial hypopharyngeal resection surgery, and one of them received total laryngectomy and partial hypopharyngeal resection surgery. All patients were able to withstand adverse reactions of neoadjuvant therapy and successfully completed the whole treatment of HPSCC without grade 3-4 treatment-related adverse reactions. There was no recurrence or metastasis during 3-18 months of follow-up. 1 patient died of severe pneumonia 3 months after the completion of radical chemoradiotherapy. At 3 months after treatment, the larynx-preservation rate was 80%. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy has good short-term efficacy and the adverse reactions were tolerable. It can improve the larynx-preservation rate of patients with locally advanced HPSCC, thus improving the prognosis and quality of life of patients.

Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.

Interim results of a multicenter cohort study for Chinese Children Leukemia Group-acute lymphoblastic leukemia 2018 regimen / 中华儿科杂志

Objective: To summarize the therapeutic effects of Chinese Children Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2018 regimen in children with T cell acute lymphoblastic leukemia (T-ALL) and to find out risk indicators for prognosis. Methods: This study was a prospective multicenter cohort study involving 299 newly diagnosed T-ALL children in 21 Grade A tertiary hospitals nationwide. All patients received CCLG-ALL 2018 regimen and clinical data for treatment efficacy evaluating was collected. Variables associated with event free survival (EFS) rate, overall survival (OS) rate and cumulative recurrence rate were evaluated by Lasso regression analysis (including variables selection, model construction and hazard ratio calculating). Results: A total of 299 newly diagnosed T-ALL children were included, accounting for 9.9% (299/3 026) of all ALL patients. Among these patients, there were 224 males and 75 females, and the age of onset was 7.0 (4.7, 10.6) years. All patients received CCLG-ALL 2018 regimen treatment. After 31.1 (17.3, 43.8) months follow-up, 3-year EFS, 3-year OS and cumulative recurrence rate of them were (83.2±2.7)%, (91.3±1.8)%, and (7.9±1.7)%, respectively. Minimal residual disease (MRD) greater than 10.00% on day 15 of induction therapy was a risk factor for EFS (HR=1.89, 95%CI 1.04-3.44), OS (HR=2.82, 95%CI 1.35-5.92), and cumulative recurrence rate (HR=3.05, 95%CI 1.46-6.34). Compared with the medium-risk group, the high-risk group had higher induction failure rate (5.2% (7/134) vs. 0 (0/145), P=0.016) and lower complete remission rate (88.8% (119/134) vs.97.9% (142/145),P=0.004). Most complications happened during induction therapy (95 cases), and the most common complication was serious infection (158 cases). Conclusions: CCLG-ALL 2018 regimen shows good prognosis. MRD greater than 10.00% on day 15 of induction therapy is a strong risk factor, which can indicate the prognosis in the early stage of the disease and guide the appropriate treatment.

Consensus on the clinical use of CDK4/6 inhibitors for the treatment of hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer (2023 edition) / 中华肿瘤杂志

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have led transformative breakthrough of clinical therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. CDK4/6 inhibitors that have been marketed in China include Ribociclib, Palbociclib, Abemaciclib and Dalpiciclib. For HR-positive HER-2-negative locally advanced and metastatic breast cancer, CDK4/6 inhibitors combined with endocrine therapy have become standard regimen, which can prolong the survival of patients. In the adjuvant treatment stage of early breast cancer, CDK4/6 inhibitors have also achieved positive results and been approved for indications. At present, CDK4/6 inhibitors have been widely used in clinical practice in China. In order to further improve the standardized application of CDK4/6 inhibitors in China, the Breast Cancer Expert Committee of the National Center for Cancer Quality Control and the Professional Committee of Clinical Research of Cancer Drugs of the Chinese Anti-Cancer Association organized the related expert to update the consensus based on the "CDK4/6 inhibitor consensus on clinical application of in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer (2021 edition)" . The updated consensus systematically introduces the pharmacological characteristics, drug monitoring and adverse event management, etc., of CDK4/6 inhibitors to promote the accuracy of clinical decision-making with the ultimate goal to prolong the overall survival of patients and improve the quality of life.

Preliminary Study on the Relationship between the Developmental Stage of Multiple Myeloma Disease and the Results of Bone Marrow Whole Exome Sequencing / 中国实验血液学杂志

OBJECTIVE@#To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients.@*METHODS@#Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened.@*RESULTS@#Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution.@*CONCLUSION@#different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.

The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL).@*METHODS@#The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis.@*RESULTS@#Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high β2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis.@*CONCLUSION@#MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.

Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients.@*METHODS@#Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP).@*RESULTS@#The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05).@*CONCLUSION@#For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

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.

Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML).@*METHODS@#The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed.@*RESULTS@#Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred.@*CONCLUSION@#Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.