Clonotypic analysis of immunoglobulin heavy chain sequences among 44 patients with Waldenström macroglobulinemia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM).@*METHODS@#Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored.@*RESULTS@#The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants.@*CONCLUSION@#The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients / 医学前沿

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

Primary thymic mucosa-associated lymphoid tissue lymphoma: 7 clinical cases report and a review of the literature / 中华血液学杂志

Objective@#To reveal clinical features, pathological diagnosis, treatment and prognosis of primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma and review literatures.@*Methods@#The clinical characteristics, pathological diagnosis, laboratory texts, treatment and prognosis of 7 cases of primary thymic MALT lymphoma identified at the First Affiliated Hospital of Nanjing Medical University from November 2017 to January 2019 were collected and analyzed.@*Results@#Of 7 primary thymic MALT lymphoma cases, six were female. Patients were often asymptomatic and were found mediastinal mass by chest CT. After mediastinal mass resection, pathologist reported a primary thymic MALT lymphoma. Laboratory tests showed all patients were positive for anti-nuclear antibody, anti-Ro52 antibodies and anti-Sjogren’s syndrome A antibodies, and increased erythrocyte sedimentation rate (ESR) . Four were diagnosed with Sjogren’s syndrome (SS) . After surgery, the patients were given the positron emission tomography computed tomography (PET-CT) scans. All cases received "watch and wait" approach. Up to now, all cases showed good prognoses and none of them relapsed.@*Conclusion@#Primary thymic MALT lymphoma was rare, and it was often associated with autoimmune diseases. Such patients who usually had good prognoses should be followed up closely and avoided excessive treatments if there were no indications of intervention.

Clinical observation of five pediatric-type follicular lymphoma in adult / 中华血液学杂志

Objective@#To investigate the characteristics in pathological diagnosis, clinical features, treatment and prognosis of adult patients with pediatric-type follicular lymphoma (PTFL) .@*Methods@#The clinical and pathological features, laboratory examination, diagnosis and treatment, follow-up results of 5 adult PTFL patients admitted in Jiangsu Province Hospital were retrospectively analyzed, and literature review was conducted in combination with related reports.@*Results@#All 5 patients developed PTFL in their adulthood with a median age of 22 years old (15-33 years) . The initial inanifestation of the disease was local painless lymphadenopathy with no fever, night sweats, emaciation or other systemic B symptoms. Pathological characteristics including typical large follicular structures and high proliferation index were found. Meanwhile, additional clonal rearrangement of immunoglobulin heavy chain gene was observed. However, there was no BCL-2 expression in histochemistry as well as BCL-2 gene abnormality in fluorescence in situ hybridization among these PTFL patients. These adult PTFL patients were all in stage Ⅰ-Ⅱ of the disease. For treatment, they were only treated with local surgical excision after diagnosis while didn’t receive subsequent local radiotherapy or systemic immunochemotherapy. During a median follow-up of 27 months, the 5 cases of PTFL kept in a state of sustained complete remission.@*Conclusion@#Adult-onset PTFL is characterized by high pathological proliferation index, while no BCL-2 expression or BCL-2 gene abnormality. Besides, PTFL is clinically manifested as a localized disease that can achieve a quite good prognosis through local surgical intervention. The aforementioned attributes of PTFL are distinctly different from classic adult follicular lymphoma.

High-dose methylprednisolone with Rituximab and fresh frozen plasma in the treatment of six patients with B-cell lymphoproliferative disorders harboring TP53 abnormalities / 中华血液学杂志

Objective@#To investigate whether high-dose methylprednisolone with Rituximab and fresh frozen plasma (HDMP+RTX+FFP) is an effective therapy for patients with B-cell chronic lymphoproliferative disorders (B-CLPD) with TP53 abnormalities.@*Methods@#Six B-CLPD patients with TP53 abnormalities from May 2008 to May 2012 were prospectively enrolled in the study. The patients were treated with HDMP+RTX+FFP for up to 6 cycles.@*Results@#Of the six B-CLPD patients, there were 4 cases of chronic B-cell lymphoproliferative disorders-unclassified (B-CLPD-U) , 1 B-cell prolymphocytic leukemia (B-PLL) and 1 mantle cell lymphoma (MCL) . After a median 3 courses of treatment, 4 patients achieved complete remission (CR) including 3 with undetectable minimal residual disease (MRD-) . One patient was evaluated as stable disease (SD) and another one patient was in disease progression (PD) . After a median follow-up of 30 (4-56) months, 2 non-responders progressed quickly and died. All of CR patients survived and no one succumbed to disease progression at the last follow-up. The hematopoietic function was significantly improved after the treatment whereas there was also significant decrease in serum IgA, IgG and IgM levels. All patients showed well tolerance to this regimen. The incidence of myelosuppression was low and adverse events (AE) were mainly neutropenia which did not exceed grade 3 and infection. All AE were controllable.@*Conclusion@#HDMP+RTX+FFP is an effective and relatively tolerable therapy for patients with B-CLPD accompanying with TP53 abnormalities.

Survival analysis of 118 chronic lymphocytic leukemia patients with abnormal TP53 gene in the era of traditional immunochemotherapy / 中华血液学杂志

Objective@#To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT.@*Methods@#The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β2-microglobulin (β2-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed.@*Results@#Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β2-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn’t receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences.@*Conclusion@#CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.

The prognostic significance of peripheral lymphocyte/monocyte ratio and PET-2 evaluation in adult Hodgkin’s lymphoma / 中华血液学杂志

Objective@#To evaluate the prognostic value of lymphocyte to monocyte ratio (LMR) and PET scan performed after first two cycles of chemotherapy (PET-2) in Hodgkin’s lymphoma (HL) .@*Methods@#The clinical data of 133 patients with HL diagnosed from January 2007 to March 2016 at the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The X-tile software was used to calculate the optimal cut-off value of LMR. Kaplan-Meier method and Cox regression were used for survival analysis.@*Results@#The median age of 133 HL patients was 33 (18–84) years, and the male to female ratio was 1.9∶1. The optimal cut-off value of LMR was 2.5, and progression free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001) were significantly lower in the LMR<2.5 group than that of LMR≥2.5. Multivariate survival analysis showed that LMR<2.5 was an independent predictor of PFS (P=0.002, HR=2.35, 95%CI 1.36–4.07) and OS (P=0.002, HR=10.36, 95%CI 2.35–45.66) in HL patients. The analysis of PET-2 from 56 HL patients showed that PET-2 positive patients had significantly poorer PFS (P=0.022) . After grouping LMR combined with PET-2, significant differences were found in PFS and OS between the three groups (P values were 0.009 and 0.012) .@*Conclusion@#LMR<2.5 is an independent prognostic factor for patients with HL. PET-2 combined with LMR may have better prognostic value.

Prognostic significance of CLL-IPI for Chinese patients with chronic lymphocytic leukemia / 中华血液学杂志

Objective@#To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients.@*Methods@#Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system.@*Results@#①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β2-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS.@*Conclusion@#CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.

Treatment progress of relapsed and refractory Hodgkin lymphoma / 白血病·淋巴瘤

Hodgkin lymphoma (HL) is a highly curable malignancy for most patients, while the treatment of relapsed and refractory HL is still a difficult and important field. A high dose of chemotherapy with autologous stem cell transplantation is treated as the preferred treatment with a high relapse incidence. The 59th American Society of Hematology Annual Meeting reported the recent progress of the treatment of relapsed and refractory HL, including the improvement of traditional high dose chemotherapy regimens, the new drugs or therapies like brentuximab vedotin, nivolumab, pembrolizumab and ibrutinib, and chimeric antigen receptor T-cell. This review focuses on these advances.

Prognostic value of lymphocyte-to-monocyte ratio in angioimmunoblastic T cell lymphoma / 中华血液学杂志

Objective@#To evaluate the prognostic value of lymphocyte-to-monocyte ratio (LMR) in angioimmunoblastic T cell lymphoma (AITL).@*Methods@#Data of 64 patients diagnosed as AITL at the First Affiliated Hospital of Nanjing Medical University between June 2009 and July 2017, were analyzed retrospectively. Receiver Operator Characteristic (ROC) curve was used to calculate the cutoff value of LMR to divide this cohort of patients into high and low LMR groups. Characteristics between groups were compared by Pearson Chi-square or Fisher exact tests. Kaplan-Meier method and Cox regression were performed to probe prognostic factors associated with progression-free survival (PFS) and overall survival (OS).@*Results@#A total of 64 cases [39 cases male and 25 ones female with the median age of 63 (29-89) years old] were enrolled. The cutoff value of LMR was 3.07. Patients with low LMR showed inferior PFS (9 months vs 13 months, P=0.044) and OS (16 months vs not reached, P=0.014), respectively than those without low LMR during a median follow-up of 33 months (5 to 103 months). Multivariate analysis showed that low LMR was an independent prognostic factor associated with poor outcomes (HR=0.48, 95% CI 0.26-0.92 for PFS, P=0.027; HR=0.38, 95% CI 0.18-0.82 for OS, P=0.013, respectively). Subgroup analysis showed that patients with low LMR and under the situation of high score of Prognostic Index for peripheral T-cell lymphoma, Unspecified (PIT) (2-4) had shorter PFS and OS (P=0.013 and P=0.031, respectively). But in low score of PIT (0-1) group, low LMR seemed to play almost no effects on PFS and OS (P=0.949 and P=0.238, respectively).@*Conclusions@#The disease risk status of patients could be initially assessed according to PIT score and LMR level. Low LMR was demonstrated to be able to predict poor outcome in AITL.

Progress in treatment of peripheral T-cell lymphoma / 白血病·淋巴瘤

Peripheral T-cell lymphoma (PTCL) is a kind of highly aggressive lymphoma which contains a collection of subgroups. The patients with PTCL have poor prognosis under current chemotherapy regimens, so the treatment of PTCL remains a big challenge. Brentuximab vedotin combined with CHP regimen, pralatrexate in combination with romidepsin and other regimens have set up more options for patients with PTCL. Novel agents, such as PI3K inhibitors, which entered into clinical trials, bring good news to PTCL patients.

A retrospective analysis of clinical characteristics and prognostic factors for 124 cases of primary gastric lymphomas / 中华血液学杂志

Objective@#To analyze the clinical characteristics, treatment and prognosis of primary gastric lymphomas (PGL).@*Methods@#A retrospective study was conducted in 124 cases of PGL from July 2009 to January 2016 in our hospital, and the clinical records, pathological and immunohistochemical features were analyzed. The relationship between different factors at diagnosis and prognosis were studied.@*Results@#124 cases of PGL included 93 diffuse large B cell lymphoma (DLBCL) patients, 25 mucosa associated lymphoid tissue (MALT) lymphoma cases, 1 mantle cell lymphoma, 4 peripheral T-cell lymphoma-not otherwise specified, and 1 extra-nodal NK/T-cell lymphoma-nasal type. Of the 93 primary gastric DLBCL (PG-DLBCL) patients, the germinal center B cell-like (GCB) DLBCL were 45 cases, non-GCB DLBCL were 48 cases. 10 cases (10.8%) of 93 PG-DLBCL were transformed from gastric MALT, and 7 cases (7.5%) have bone marrow involvement. Evidence of Helicobacter pylori infection was detected in 21 cases (51.2%) of 41 DLBCL patients and in 10 cases (43.5%) of 23 MALT patients. Univariate analysis revealed that clinical stages (P=0.002) , B symptoms (P=0.001) , international prognostic index (IPI) score (P<0.001) , anemia (P<0.001) , low level of serum albumin level (P=0.001) , high level of lactate dehydrogenase (LDH) (P<0.001) , high β2-microglobulin (P=0.003) , chemotherapy uncombined with rituximab (P=0.006) were factors affecting progression-free survival (PFS). Multivariate Cox regression analysis indicated that clinical stages (HR=5.113, 95% CI 1.087-24.048, P=0.039) and LDH (HR=5.111, 95%CI 1.651-15.827, P=0.005) were independent poor prognosis factors affecting PFS. In the non-GCB group, the PFS was significantly extended (P=0.013) , the OS has no statistical significance (P=0.764). The PFS was significantly shortened in MALT transformed to DLBCL compared with MALT lymphoma patients (P=0.016) , but have no statistical significance compared with DLBCL patients (P=0.373).@*Conclusions@#The types of DLBCL and MALT are more common in PGL. PG-DLBCL is a highly heterogeneous malignant tumor, and advanced clinical stages and high LDH value are associated with poor outcome.

Clinical analysis of 81 cases of malignant lymphoma treated with autologous hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma.</p><p><b>METHODS</b>The clinical data of 81 patients with malignant lymphoma received ASCT from April 1999 to October 2013 were retrospectively analyzed. Of 81 patients, 70 were non-Hodgkin's lymphoma (NHL) and 11 Hodgkin's lymphoma (HL). High dose of etoposide combined with G-CSF was used to mobilize peripheral hematopoietic stem cell. Preconditioning regimen was BEAM (carmustine + cytarabine + etoposide + melphalan).</p><p><b>RESULTS</b>Enough peripheral blood stem cells were collected from all patients. All of the patients after transplantation achieved hematopoietic reconstitution, the median time of the absolute neutrophil count (ANC) recovery to >0.5×10⁹/L time was 10(7-16) d, and the median time of platelet count recovery to >20×10⁹/L was 10(6-17) d. With the follow-up of 23(2-139) months, progression free survival (PFS) was 72.7%, and overall survival (OS) was 88.6%. The median PFS and OS were not reached. Complete remission (CR) before ASCT was an independent prognostic factor of PFS. No transplant related death happened.</p><p><b>CONCLUSION</b>ASCT was a safe and effective method for treatment of malignant lymphoma.</p>