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Application progress of transcriptome sequencing in hematological malignancies

Hongxing LIU ; Xue CHEN ; Fang WANG ; Xiaoli MA ; Lili YUAN ; Panxiang CAO ; Daijing NIE

Journal of Leukemia & Lymphoma.2019;28(12):705-708. doi:10.3760/cma.j.issn.1009-9921.2019.12.001

Transcriptome sequencing (RNA-seq) has unique advantages in analyzing gene fusion, splicing mutations, and gene expression profiles. Single-cell RNA-seq provides powerful tools to reveal cellular heterogeneity in normal and tumor tissues. With the widespread application of high-throughput gene sequencing technology and the rapid reduction in cost, RNA-seq is increasingly used in hematological malignancies research. This article introduces the related research progress in conjunction with reports at the 61st American Society of Hematology Annual Meeting.

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Progress of immune checkpoint inhibitors in treatment of malignant lymphoma

Qingpei GUAN ; Tingting ZHANG ; Xianhuo WANG ; Huilai ZHANG

Journal of Leukemia & Lymphoma.2019;28(12):709-712. doi:10.3760/cma.j.issn.1009-9921.2019.12.002

The immune checkpoint inhibitors (ICI) represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) antibody opened a new era of immunotherapy. However, PD-1/PD-L1 inhibitors have not been approved for indications in the field of malignant lymphoma except for classic Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma. Researchers have actively explored different lymphoma subtypes with single drugs or combined therapy, and achieved certain effect initially. The latest advances of ICI in cHL, B-cell non-Hodgkin lymphoma and T-cell lymphoma and the management of immune-related adverse events are briefly introduced in this paper.

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Diagnosis and treatment progress of follicular lymphoma

Bing XU ; Zhijuan LIN

Journal of Leukemia & Lymphoma.2019;28(12):713-715. doi:10.3760/cma.j.issn.1009-9921.2019.12.003

Follicular lymphoma (FL) is the most common indolent lymphoma. With the improvement of disease awareness and the introduction of various novel drugs, the 5-year overall survival rate has been more than 90% for the majority of FL patients. However, certain subgroups of FL patients, especially patients who progressed within 24 months after starting front-line therapy, still have worse outcome. This article reviews the progress in genetics, prognostic factors and treatment options of FL that reported at the 61st American Society of Hematology Annual Meeting 2019.

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Treatment progress of Hodgkin lymphoma

Jiaqi QIN ; Wei XU

Journal of Leukemia & Lymphoma.2019;28(12):716-718. doi:10.3760/cma.j.issn.1009-9921.2019.12.004

Hodgkin lymphoma (HL) is a highly curable disease, and even in advanced-stage patients, more than 90% of them can achieve long-term survival. Due to its few adverse reactions and good curative effect, the ABVD regimen is currently used as the standard first-line chemotherapy for HL. In order to further improve the efficacy, the new first-line combination therapies and salvage therapeutic regimens for relapsed/refractory HL are continuously updated, such as anti-CD30 monoclonal antibody brentuximab vedotin combined with immune checkpoint inhibitors or chemotherapy, programmed death receptor 1 with chemotherapy or chimeric antigen receptor T-cells are gradually showing their advantages. This article summarizes the treatment progress of HL at the 61st American Society of Hematology Annual Meeting 2019.

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Treatment progress of diffuse large B-cell lymphoma

Weiting WANG ; Wei XU

Journal of Leukemia & Lymphoma.2019;28(12):719-723. doi:10.3760/cma.j.issn.1009-9921.2019.12.005

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). After the treatment of standard chemotherapy R-CHOP regimen, approximately 40% of DLBCL patients fail to respond to treatment or show progress of the disease. At the 61st American Society of Hematology Annual Meeting, multiple studies reported the latest treatment progress of DLBCL, including improving the prognosis of newly diagnosed patients and providing more treatment options for relapsed/refractory DLBCL patients.

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Treatment progress of mantle cell lymphoma

Yimin REN ; Wei XU

Journal of Leukemia & Lymphoma.2019;28(12):724-727. doi:10.3760/cma.j.issn.1009-9921.2019.12.006

Mantle cell lymphoma (MCL) is a subtype of aggressive B-cell non-Hodgkin lymphoma(NHL) with a heterogeneous clinical characteristics, accounting for 3%-10% of adult-onset NHL. With the great advance of novel drugs, the therapeutic options for MCL are constantly updating. The 61st American Society of Hematology Annual Meeting reported the recent treatment progress of MCL including novel drugs,combinations of nonchemotherapeutic agents and chimeric antigen receptor T-cell therapy. This paper focuses on the treatment progress of MCL.

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Clinical effect and safety of dasatinib combined with Chinese Children's Leukemia Group-acute lymphoblastic leukemia 2008 protocol in treatment of childhood Philadelphia chromosome-positive acute lymphoblastic leukemia

Chunxia CAI ; Jian LI ; Shaohua LE ; Hao ZHENG ; Xueling HUA ; Zaisheng CHEN ; Yongzhi ZHENG ; Jianda HU

Journal of Leukemia & Lymphoma.2019;28(12):728-733. doi:10.3760/cma.j.issn.1009-9921.2019.12.007

Objective: To investigate the clinical effect and safety of dasatinib combined with Chinese Children's Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2008 protocol in treatment of childhood Philadelphia chromosome-positive (Ph⁺) acute lymphoblastic leukemia (ALL). Methods: The clinical data of 22 patients with Ph⁺ ALL who were newly diagnosed at the age of less than 15 years old in Fujian Medical University Union Hospital from January 2014 to December 2018 were retrospectively analyzed. All patients were treated with dasatinib combined with CCLG-ALL2008 protocol (high-risk group). The patients were assigned to two groups according to different starting times of oral dasatinib: the dasatinib-induced group (starting from day 15 of induction chemotherapy) and the dasatinib-consolidated group (starting with early consolidated chemotherapy). The early treatment response and 5-year event-free survival (EFS) rate were compared between the two groups. Results: The differences of clinical characteristics and early efficacy of chemotherapy before treatment of dasatinib between the two groups were not statistically significant (both P > 0.05). The complete remission (CR) rate on day 33 of induction chemotherapy was higher in the dasatinib-induced group than that in the dasatinib-consolidated group [100% (10/10) vs. 75% (9/12)], but the difference was not statistically significant (χ ²= 2.895, P= 0.221). The rate of minimal residual disease (MRD) turned negative (<0.01%) on day 33 of induction chemotherapy in the dasatinib-induced group was significantly higher than that in the dasatinib-consolidated group [70% (7/10) vs. 17% (2/12)], and the difference was statistically significant (χ ²= 6.418, P= 0.027). The 3-year EFS rate was higher in the dasatinib-induced group than that in the dasatinib-consolidated group (88.9% vs. 63.5%), but the difference was not statistically significant (P= 0.163). The incidence of grade 3-4 infection in the dashatinib-induced group was lower than that in the dasatinib-consolidated group, and the difference was statistically significant [60% (6/10) vs. 100% (12/12), P= 0.029]. the other grade 3-4 adverse reactions related to the chemotherapy drugs mainly included hematological toxicity, diarrhea, abnormal liver function, edema and pleural effusion, but there was no significant difference between the two groups (all P > 0.05). Conclusions Dasatinib combined with CCLG-ALL2008 protocol in the treatment of children with Ph⁺ ALL has good efficacy and safety. Furthermore, the early use of dasatinib on day 15 of induction chemotherapy can enable patients to achieve deeper remission earlier and improve long-term efficacy.

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Application of metagenomics next-generation sequencing in monitoring Legionella pneumophila infection after allogeneic hematopoietic stem cell transplantation

Lili YUAN ; Huizheng ZHAO ; Jianping ZHANG ; Fang WANG ; Nannan LI ; Xingzhen ZHAO ; Xue CHEN ; Yang ZHANG ; Daijing NIE ; Panxiang CAO ; Mangju WANG ; Ming LIU ; Mingyue LIU ; Hongxing LIU

Journal of Leukemia & Lymphoma.2019;28(12):734-738. doi:10.3760/cma.j.issn.1009-9921.2019.12.008

Objective: To investigate the application of metagenomic next-generation sequencing (mNGS) in detection of the rare or difficult-to-cultivate pathogens. Methods: One patient with acute lymphoblastic leukemia who went through allogeneic hematopoietic stem cell transplantation (allo-HSCT) developed symptoms of infection after transplantation. Conventional microbial culture, polymerase chain reaction (PCR), and mNGS combined with biological information analysis were performed with plasma and cerebrospinal fluid samples, the anti-infective treatment was adjusted according to the test results, and the efficacy was assessed. Results: No suspected pathogens were detected by microbial culture and PCR in the cerebrospinal fluid and plasma samples since the patient developed infection symptoms. However, Legionella pneumophila was analyzed by mNGS in the cerebrospinal fluid specimen on day 23 after allo-HSCT (reads count: 19 655), and it was considered as the principal pathogen after comprehensively evaluating the patient's clinical manifestations and the test results. Then the antimicrobial treatments were adjusted according to the patient's clinical manifestations and laboratory test results, and the number of gene sequences of Legionella pneumophila was monitored by mNGS method. Azithromycin, tigecycline, and other antibiotics effective for Legionella pneumophila were used after detecting this pathogen. A total of 15 mNGS analysis were performed during the 5-month period, and the highest number of Legionella pneumophila sequences monitored in the cerebrospinal fluid was 2 226, the lowest was 253 and eventually turned negative. The clinical symptoms and treatment outcomes were consistent with the mNGS monitoring results. Conclusions The mNGS technology has significant value in detection of the rare and difficult-to-cultivate pathogens. The mNGS technology provides a valuable supplement to microbial culture and PCR methods.

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Clinical observation of priming regimen with pegylated recombinant human granulocyte colony-stimulating factor for treatment of initial treatment elderly patients with acute myeloid leukemia

Mo ZHOU ; Yu SHAO ; Xueyun SHAN ; Chunbin WANG ; Pin WANG ; Naitong SUN

Journal of Leukemia & Lymphoma.2019;28(12):739-742. doi:10.3760/cma.j.issn.1009-9921.2019.12.009

Objective: To evaluate the efficacy and side effects of priming regimen with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the treatment of initial treatment elderly patients with acute myeloid leukemia (AML). Methods: Thirty-five elderly patients with early-stage AML (non-M₃) who received pre-excitation chemotherapy in Yancheng Third People's Hospital from February 2015 to January 2019 were retrospectively analyzed. According to the different granulocyte colony-stimulating factor (G-CSF) in the chemotherapy regimen, 15 cases were in PEG-rhG-CSF group, 6 mg PEG-rhG-CSF was used alone on day 0 by subcutaneous injection; 20 cases were in recombinant human granulocyte colony-stimulating factor (rhG-CSF) group, 200 μg/m² rhG-CSF was used per day from day 0 to day 13 by subcutaneous injection, rhG-CSF was suspended or continued according to the number of white blood cells. In addition, both groups were given priming regimen with cytarabine and arubicin, or cytarabine and harringtonine. The efficacy and adverse reactions of the two groups were compared. Results: In the PEG-rhG-CSF group, there were 5 cases of complete remission, 6 cases of partial remission, 4 cases of non-remission, and 11 cases were effective. In the rhG-CSF group, there were 8 cases of complete remission, 7 cases of partial remission, 5 cases of non-remission, and 15 cases were effective. There was no significant difference in the efficacy between the two groups (χ ²= 0.012, P= 0.911). In terms of adverse reactions, the incidence of infectious fever, bone pain, duration of neutropenia, and duration of thrombocytopenia were not statistically significant (all P > 0.05). Conclusions In the pre-excitation chemotherapy for AML, the clinical efficacy and adverse effects of PEG-rhG-CSF are similar to rhG-CSF. However, the use of PEG-rhG-CSF can simplify the operation and reduce the pain and risk of local infection during chemotherapy.

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Effect of lenalidomide combined with interferon and interleukin-2 for treatment of refractory/relapsed or minimal residual disease-positive acute myelogenous leukemia

Ruihua MI ; Lin CHEN ; Hao AI ; Fangfang YUAN ; Qingsong YIN ; Xudong WEI

Journal of Leukemia & Lymphoma.2019;28(12):743-748. doi:10.3760/cma.j.issn.1009-9921.2019.12.010

Objective: To analyze the efficacy and safety of lenalidomide combined with interferon (IFN) and interleukin-2 (IL-2) for treatment of refractory/relapsed or minimal residual disease (MRD)-positive acute myelogenous leukemia (AML). Methods: Twelve patients with AML who were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from August 2013 to May 2019 were selected. These patients were previously treated with thalidomide combined with IFN and IL-2, and then treated with combined with IFN and IL-2. According to the Frence-American-British (FAB) classification system, there was 1 case of M₀, 1 case of M₁, 4 cases of M_2a, 3 cases of M_2b, 1 case of M_4EO, and 2 cases of M_5b. There were 2 cases with FLT3-ITD mutation-positive, 1 case with c-kit mutation-positive. There were 2 cases in the low-risk group, 7 cases in the intermediate-risk group, and 3 cases in the high-risk group. Three cases were refractory AML, 7 cases were relapsed AML (including 3 cases of recurrence once, 4 cases of recurrence twice; 5 cases of recent recurrence, 2 cases of long-term recurrence), 2 cases were MRD-positive. The efficacy and adverse reactions of 12 cases were evaluated. Results: Twelve patients had received more than one cycle therapy of lenalidomide combined with IFN and IL-2, of which 4 patients achieved morphological complete remission (CR), 2 patients had CR with incomplete recovery of blood cells (CRi), 4 patients had no remission, 1 case had a decrease in MRD, and 1 case had an increase in MRD, and the total effective (CR+ CRi+ partial remission+ MRD decreased) was in 7 cases. There were no adverse reactions such as rash, constipine, bradycardia and peripheral neuritis; six patients had grade Ⅲ or higher experienced myelosuppression. No patients died of complications during the treatment, and the duration of remission of all patients was 2-20 months. Conclusion Lenalidomide combined with IFN and IL-2 for treatment of refractory/relapsed or MRD-positive AML is effective, and it can reduce the MRD value in MRD-positive patients, it could be a new treatment method for AML.

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