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Secondary therapy-related acute megakaryocytic leukemia in childhood acute lymphocytic leukemia: report of one case and review of literature

Xia CHEN ; Ye GUO ; Fang LIU ; Beibei ZHAO ; Li ZHANG ; Shuxu DONG ; Huijun WANG ; Hongju ZHANG ; Yidan XU ; Xiaofan ZHU

Journal of Leukemia & Lymphoma.2020;29(2):107-111. doi:10.3760/cma.j.issn.1009-9921.2020.02.009

Objective:To explore the laboratory characteristics and diagnostic methods for therapy-related acute megakaryocytic leukemia (t-AMKL).Methods:The data of one child with acute lymphoblastic leukemia (ALL) in the Blood Disease Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College in September 2014 was retrospectively analyzed. After inducing remission for more than 43 months, the child was diagnosed as t-AMKL.Results:After the diagnosis of ALL, the child was given chemotherapy with standard childhood ALL regimen. After 43 months, t-AMKL was diagnosed by comprehensive morphology, cytogenetics, and molecular biology. Bone marrow morphology showed that the proportion of primitive cells was 0.44; flow cytometry showed the phenotype was abnormal myeloid primitive cells; the pathology result showed that the abnormal cells weakly expressed CD42b and CD61; the electron microscopy showed platelet peroxidase (PPO)-positive and myeloperoxidase (MPO)-negative; the bone marrow immunohistochemistry showed the positive rate of CD41 was 34%; the child had a complex karyotype. After reviewing his medical history, he was diagnosed as t-AMKL.Conclusion:The t-AMKL is relatively rare, and it is helpful to improve the prognosis of patients by completing the relevant examinations for early diagnosis.

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Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia complicated with EB virus infection

Mengmeng YIN ; Aiguo LIU ; Ai ZHANG ; Yaqin WANG ; Qun HU

Journal of Leukemia & Lymphoma.2020;29(2):102-106. doi:10.3760/cma.j.issn.1009-9921.2020.02.008

Objective:To explore the clinical features and prognosis of childhood acute lymphoblastic leukemia(ALL) complicated with EB virus (EBV) infection.Methods:The results of detection of EBV antibody and EBV-DNA in peripheral blood mononuclear cells of 196 children with ALL diagnosed in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2015 to January 2019 were collected. According to the results, 196 children with ALL were divided into EBV infection group and non-EBV infection group. The hepatomegaly and splenomegaly, chromosome, peripheral blood routine, immunophenotyping, clinical risk, secondary infection during chemotherapy, minimal residual disease (MRD) of day 46 after chemotherapy, karyotype, and prognosis were compared between the two groups. The children were followed up until April 30, 2019.Results:Among 196 children with ALL, EBV infection rate was 72.96% (143/196). The EBV-DNA level [median ( P25, P75)] of peripheral blood mononuclear cells was 3.7×10 3 copies/L(1.6×10 3 copies/L, 8.8×10 3 copies/L). The incidence of hepatosplenomegaly (subcostal ≥ 5 cm) in EBV infection group was higher than that in non-EBV infected group [14.69% (21/143) vs. 3.77% (2/53), χ 2= 4.45, P= 0.035]. There was no significant difference in the number of white blood cells and the incidence of abnormal karyotype between EBV infection group and non-EBV infection group (both P > 0.05). The secondary infection rate in EBV infection group was higher than that in the non-EBV infection group [41.96% (60/143) vs.24.53% (13/53), χ2= 5.03, P= 0.025], and the remission rate of day 46 in EBV-infection group was lower than that in non-EBV infection group [80.42% (115/143) vs. 98.11% (52/53), χ2= 9.60, P= 0.020]. The recurrence rate in EBV-infection group was higher than that in non-EBV infectious group [11.89% (17/143) vs. 1.89% (1/53), χ2= 4.64, P= 0.031], and there was a significant difference in the component ratio of immunophenotyping and clinical risk between the two groups (both P < 0.05). Conclusions:The hepatosplenomegaly in children with ALL complicated with EBV infection is obvious, the secondary infection rate is high, the remission rate is low, the recurrence rate is high, and the prognosis is poor. EBV infection may be related to immunophenotyping and clinical risk in children with ALL, and has nothing to do with the abnormal karyotypes.

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Efficacy and safety of reduced-intensity chemotherapy in children with Down syndrome-related myeloid leukemia

Chengxuan CHEN ; Jian LI ; Hao ZHENG ; Shaohua LE ; Yongzhi ZHENG

Journal of Leukemia & Lymphoma.2020;29(2):112-116. doi:10.3760/cma.j.issn.1009-9921.2020.02.010

Objective:To investigate the efficacy and safety of reduced-intensity chemotherapy in treatment of children with Down syndrome-related myeloid leukemia (ML-DS).Methods:The clinical data of 3 hospitalized children with ML-DS who were diagnosed and treated by Children Oncology Group Trial A2971 chemotherapy regimen in Fujian Medical University Union Hospital from January 2016 to June 2019 were retrospectively analyzed, and the clinical characteristics, efficacy and safety were summarized.Results:The ages of 3 children were 1 year and 6 months, 2 years and 6 months, and 1 year and 10 months. Two cases were acute monocytic leukemia, and 1 case was acute megakaryoblastic leukemia. Two cases were positive for EVI1 gene and 1 case had ASXL1 gene mutation, and all 3 cases had complex karyotype. After one course of induction chemotherapy, all 3 cases achieved complete remission, and the minimal residual disease turned negative. During the induction chemotherapy, all 3 cases had severe myelosuppression, and 2 cases of them suffered from severe pneumonia and 1 case of them suffered from intestinal infection and septic shock.Conclusion:The efficacy of reduced-intensity chemotherapy in children with ML-DS is favorable, but the severe complications such as myelosuppression and infection need to be taken seriously.

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Clinicopathological characteristics of non-Hodgkin lymphoma in Shandong province: analysis of 2 886 cases

Ti WANG ; Qiujing ZHANG ; Yuhong LIU ; Qingqing ZHU ; Jujie SUN ; Jianbo ZHANG ; Jie LIU ; Bao SONG

Journal of Leukemia & Lymphoma.2020;29(2):117-120. doi:10.3760/cma.j.issn.1009-9921.2020.02.011

Objective:To investigate the clinicopathological characteristics of non-Hodgkin lymphoma (NHL) in Shandong province.Methods:The clinicopathological data of 2 886 NHL cases in Shandong Cancer Hospital from January 2002 to December 2017 were retrospectively analyzed, the clinicopathological characteristics of patients were summarized and compared with other regions in China and abroad.Results:The median age of all NHL cases was 52 years old (4-90 years old), and the ratio of male to female was 1.57∶1. The subtypes distribution analysis revealed that B-cell NHL (B-NHL) accounted for 66.7% (1 925 cases) of all cases and T-cell NHL (T-NHL) accounted for 27.3% (788 cases) of all cases. The common subtypes were diffuse large B-cell lymphoma (36.0%, 1 039/2 886), NK/T-cell lymphoma (8.8%, 254/2 886), follicular lymphoma (8.2%, 237/2 886) and peripheral T-cell lymphoma (7.4%, 214/2 886). Of all the cases, the nodal lymphomas accounted for 45.8% (1 322 cases) and the extra nodal lymphomas accounted for 54.2% (1 564 cases); there were 389 patients (13.5%) with stage Ⅰ, 678 patients (23.5%) with stage Ⅱ, 975 patients (33.8%) with stage Ⅲ, and 722 patients (25.0%) with stage Ⅳ. The distribution of NHL subtypes in Shandong province was consistent with the domestic multicenter study. However, T-NHL subtype ratio was significantly higher than the foreign studies.Conclusions:The overall incidence of NHL in Shandong province of China is dominated by middle-aged people, and the proportion of B-NHL is higher than that of T-NHL. The distribution of NHL subtypes in Shandong province of China are different from those in the European and American countries, but are roughly consistent with the domestic multicenter study.

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Analysis of clinical efficacy and prognosis of childhood T-cell acute lymphoblastic leukemia

Ping WANG ; Xiaowen ZHAI ; Hui JIANG ; Hongsheng WANG ; Xiaowen QIAN ; Jun LI ; Hui MIAO ; Yi YU ; Xiaohua ZHU ; Fengjuan LU

Journal of Leukemia & Lymphoma.2020;29(2):95-101. doi:10.3760/cma.j.issn.1009-9921.2020.02.007

Objective:To evaluate the treatment efficacy of children with T-cell acute lymphoblastic leukemia (T-ALL) and to explore the prognostic risk factors.Methods:The clinical and laboratory data of children with newly diagnosed T-ALL in Children's Hospital of Fudan University and Children's Hospital of Shanghai from January 2002 to December 2014 were retrospectively analyzed and compared with children with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) in the same period. The treatment protocols were based on the combination of the Berlin-Frankfurt-Münster (BFM)-ALL regimen with chemotherapy. The treatment response and infection of the children were observed. Cox proportional hazard regression model single-factor and multifactor analysis were used to evaluate the prognostic factors.Results:Seventy-one children with T-ALL and 333 children with B-ALL were enrolled. The clinical features including gender, age, central nervous system leukemia as well as the white blood cell count at first diagnosis were significantly different between the two groups (all P < 0.05). The prednisone good response rates of children with T-ALL were lower than that of B-ALL [78.9% (56/71) vs. 93.4% (311/333), P < 0.01], and the complete remission rates were lower than that of [94.4% (67/71) vs. 99.1% (330/333), P= 0.023]. By the end of follow-up, the relapse rates of children with T-ALL and B-ALL were 20.9% (14/67) and 16.4% (54/330) ( P= 0.369). The children with T-ALL had a shorter time to relapse compared with children with B-ALL [64.3% (9/14) vs. 35.2% (19/54), P= 0.049]. The 5-year overall survival (OS) rates of children with T-ALL and B-ALL were (62.1±6.4)% and (81.3±2.4)% (P < 0.05), and the 5-year event free survival (EFS) rates were (61.0±6.3)% and (71.0±2.7)% (P < 0.05). There was no significant difference in OS and EFS among pro/pre T-ALL, cortical T-ALL and mature T-ALL (both P > 0.05). The difference of EFS curves between children with early T-precursor (ETP)-ALL and non-ETP ALL was statistically significant ( P= 0.044). The most common infection site was respiratory tract [63.9% (186/291)], and the gram-negative bacteria accounted for 43.5% (20/46). Cox univariate analysis showed that prednisone poor response, bone marrow non-remission on day 33 of induction-therapy, relapse and sepsis were prognostic risk factors for children with T-ALL (all P < 0.05), and Cox multivariate analysis showed that the latter three were independent prognostic risk factors (all P < 0.05). Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL, and T-ALL patients are prone to early relapse. The EFS of children with ETP-ALL is poor. Non-remission at the end of induction-therapy, relapse and sepsis are independent risk factors for prognosis.

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Application progress of autologous stem cell transplantation in lymphoma treatment

Lingyan PING ; Yuqin SONG ; Jun ZHU

Journal of Leukemia & Lymphoma.2020;29(2):73-78. doi:10.3760/cma.j.issn.1009-9921.2020.02.002

In recent years, due to the progress of cell-targeted therapy and the presence of a large number of new drugs, the treatment efficacy and survival of many lymphoma patients have improved. As a traditional treatment method, autologous stem cell transplantation (ASCT) still plays an important role in lymphoma treatment. ASCT can be a curable method in some clinical situations. Many clinical studies in recent years have further confirmed the role of ASCT in high-risk aggressive lymphoma and Hodgkin lymphoma. The efficacy of ASCT can be improved by combining antibodies such as brentuximab vedotin, programmed death 1, programmed death ligand 1 or chimeric antigen receptor T cell therapy, and the recurrence risk of ASCT may be decreased.

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Progress of epigenetics of lymphoma

Yunfei SHI ; Yuqin SONG

Journal of Leukemia & Lymphoma.2020;29(2):87-90. doi:10.3760/cma.j.issn.1009-9921.2020.02.005

Followed by increasing accumulation in knowledge of tumor pathogenesis, it is now realized that in addition to chromosome number abnormality, gene translocation and mutation, the important role of epigenetics has become increasingly prominent. Based on the emergence of high-throughput detection methods such as next-generation sequencing technology, the epigenetic (DNA, histone, microRNA, etc.) modification abnormalities in lymphoma can be more comprehensively detected and studied. Those findings show that epigenetic modification has widely affected the pathogenesis, recurrence, progress and drug resistance of lymphoma, which also provide new sights and targets for lymphoma treatment. Based on the relevant abstracts reported on the 61st American Society of Hematology (ASH) Annual Meeting, this article reviews the new progress in epigenetics of lymphoma.

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Novel strategies for treatment of follicular lymphoma

Zhangdi XU ; Wei XU

Journal of Leukemia & Lymphoma.2020;29(2):91-94. doi:10.3760/cma.j.issn.1009-9921.2020.02.006

Follicular lymphoma (FL) is a kind of indolent non-Hodgkin lymphoma(iNHL). Rituximab combined with chemotherapy as the first-line treatment has achieved satisfactory results, but the relapse and progress still reappear after the first-line treatments. In the 61st of American Society of Hematology (ASH) Annual Meeting, more and more novel drugs including EZH2 inhibitor tazemetostat, SYK/JAK inhibitor cerdulatinib, anti-CD3-CD20 antibody mosunetuzumab and programmed death 1 inhibitor nivolumab, etc, and new strategies including rituximab combined with anti-CD20 monoclonal antibody and polatuzumab combined with obinutuzumab and lenalidomide had been reported and brought an ample and promising choices for FL patients.

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Progress in treatment of relapsed/refractory peripheral T-cell lymphoma

Linjun ZHAO ; Yuqin SONG ; Jun ZHU

Journal of Leukemia & Lymphoma.2020;29(2):83-86. doi:10.3760/cma.j.issn.1009-9921.2020.02.004

The peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphoma. The overall prognosis is poor with high risk of relapse after the first-line treatment. The 61st American Society of Hematology (ASH) Annual Meeting has covered many treatment advances of PTCL, especially for relapsed/refractory patients. The main contents include histone deacetylase inhibitors (HDACi), farnesyl transferase (FT) inhibitors, dual inhibitors of SYK/JAK signaling pathway, PI3K inhibition agent, programmed death 1 (PD-1) monoclonal antibody, anti-CD38 monoclonal antibody, and EZH1/2 dual inhibitor. New protocols and drugs have brought hope for relapsed/refractory PTCL patients.

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Application progress of novel Bruton tyrosine kinase inhibitors in B-cell lymphoma

Donglu ZHAO ; Jun MA

Journal of Leukemia & Lymphoma.2020;29(2):79-82. doi:10.3760/cma.j.issn.1009-9921.2020.02.003

The Bruton tyrosine kinase (BTK) inhibitor ibrtinib has excellent results in B-cell lymphoma. However, there are still unmet treatment needs in clinical practice. New BTK inhibitors are highly selective and specific, reducing off-target effects. The overall response rate (ORR) of acalabrutinib combination therapy is more than 90%, and high rates of peripheral blood and bone marrow minimal residual disease (MRD)-negative are obtained. Orelabrutinib is a new domestic BTK inhibitor, the results of a phase Ⅱ study showed that the ORR in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma is 88.5%, and in mantle cell lymphoma is 82.5%. Another new domestic BTK inhibitor zanubrutinib, international multi-center study showed that ORR is 95.9% in relapsed/refractory CLL, and in treatment-na?ve chronic lymphocytic leukemia with del (17p) is 92.2%. In addition, non-covalent BTK inhibitors are also emerging, which are expected to overcome the problem of resistance to BTK inhibitors.

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