Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Comparisons of clinical characteristics and prognosis between patients with primary and secondary thyroid lymphoma / 中华血液学杂志

Objective: To compare clinical characteristics and prognosis between patients with primary (PTL) and secondary thyroid lymphoma (STL) . Methods: A retrospective analysis was performed on 46 patients with thyroid lymphoma (PTL 19, STL 27) from January 2002 to October 2018. Results: ①PTL group included 4 males and 15 females, with a median age of 57 years. The STL group included 10 males and 17 females, with a median age of 61 years. Diffuse large B-cell lymphoma (DLBCL) was the main pathological subtype in both PTL and STL groups, with 14 cases (73.7%) and 20 cases (74.1%) respectively. In terms of clinical manifestations, goiter was the most common symptom in PTL patients 100.0% (19/19) , while 29.6% (8/27) STL had goiter (P<0.001) . The incidences of increased thyroglobulin antibody (TRAb) /thyroid peroxidase antibody (TPO) were 81.3% (13/16) in PTL group and 43.8% (7/16) in STL group (P=0.028) respectively. Concerning the clinical features of patients, only two PTL patients (10.5%) with advanced Ann Arbor stage (Ⅲ/Ⅳ) , while 21 (77.8%) STL experienced advanced Ann Arbor stage (P<0.001) . Elevated serum β(2)-MG were appeared in 1 (7.1%) PTL and 9 (47.4%) STL patients (P=0.013) , and advanced IPI score (3-5) was more common in STL than PTL (59.3% vs 5.3%, P<0.001) . ②Among the 17 PTL patients who received treatments, 15 (88.2%) achieved remission; as for STL patients received treatments, 23/25 (92.0%) were in remission. The 5-year overall survival (OS) rates of PTL (n=17) and STL groups (n=25) were (87.4±8.4) % and (70.0±13.1) % (P=0.433) respectively. ③The 5-year OS rate in 41 patients with B-cell thyroid lymphoma was (81.1±7.5) %. Univariate analysis showed that IPI score of 3-5 (P=0.040) and high level of serum IL-8 (P=0.022) were significantly associated with poor outcome. Conclusion: DLBCL was the most common subtype in both PTL and STL, and goiter was the major symptom in PTL. IPI score of 3-5 and high level of serum IL-8 were unfavorable prognostic factors for patients with B-cell thyroid lymphoma.

Interstitial pneumonia in patients with diffuse large B-cell lymphoma receiving RCHOP and RCDOP regimens / 中华血液学杂志

Objective: To identify the risk factors and clinical features associated with the interstitial pneumonia in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or rituximab, cyclophosphamide, liposomal doxorubicin, vincristine and prednisone (RCDOP) regimens. Methods: A retrospective study was conducted in 836 patients with DLBCL admitted to the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 114 patients were treated with RCDOP regimen. Using the method of propensity score matching according to age, gender, IPI score of patients, 114 patients treated with RCHOP regimen were selected as controls. Clinical data, including comorbidities, gender, age, B symptoms, international prognostic index (IPI) score, disease stage, serum lactic dehydrogenase (LDH) and β(2) microglobulin (β(2)-MG) level were collected and the risk factors of interstitial pneumonia were further analyzed. Results: The interstitial pneumonia developed more frequently in RCDOP group than RCHOP group (28.95% vs 2.60%, P<0.01) . As the dose of liposomal doxorubicin elevated from 25-30 mg/m(2) to 35-40 mg/m(2), the incidence of interstitial pneumonia accordingly increased from 17.30% to 38.71% (P<0.05) . By multivariate analysis, disease stage was an independent factor of interstitial pneumonitis. Conclusions: Front line regimens containing liposomal doxorubicin in DLBCL patients link to a higher incidence of dose-dependent interstitial pneumonia. Prevention and surveillance should be emphasized in future studies.

Prognostic study of 229 follicular lymphoma patients treated with rituximab combined with chemotherapy / 中华血液学杂志

Objective: To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients. Methods: 229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly. Results: In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumβ(2)- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS. Conclusion: FLIPI2 is the better risk stratification in FL patients in the era of rituximab.

Efficacy of RCDOP regimen in the treatment of patients with diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To investigate the efficacy of RCDOP (Rituximab, cyclophosphamide, liposome doxorubicin, vincristine and prednisone) regimen in patients with de novo diffuse large B-cell lymphoma (DLBCL), especially in those patients with multiple extra-nodal involvement or Bulky diseases. Methods: A total of 87 newly diagnosed DLBCL patients who received RCDOP regimen from October 2012 to October 2017 were enrolled into this study. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test, and χ(2) tests were used for categorical data. Results: Among the 87 DLBCL patients treated with RCDOP regimen, 81 patients achieved complete remission (CR) or partial remission (PR), with ORR as 93.1%. Patients were further classified into groups, according to the risk factors, such as IPI scores, multiple extra-nodal involvement, bulky disease, age>60, tumor Ki-67>80%, elevated serum LDH level and advanced Ann Arbor stage. The progression-free survival (PFS, P=0.084) and overall survival (OS, P=0.515) had no statistical difference among the IPI low risk (0-1 score) group, intermediate risk (2-3 scores) group and high risk (4-5 scores) group. Similarly, no statistical difference were fou nd in PFS and OS of patients with extra-nodal involvements ≥2 (P=0.303 and P=0.624), with bulky disease (P=0.518 and P=0.466), with age>60 (P=0.600 and P=0.183), with elevated serum LDH level (P=0.054 and P=0.880), with advanced Ann Arbor stage (P=0.075 and P=0.286), and with tumor Ki-67 over 80% (P=0.190 and P=0.109), when compared with those of patients without these risk factors. Conclusion: RCDOP can improve the therapeutic effect and prognosis of DLBCL patients with certain high risk factors, such as intermediate and high IPI risks, multiple extra-nodal involvements, bulky disease, age over 60, elevated LDH level, advanced Ann Arbor stage and tumor Ki-67 over 80%.

Prognostic Significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in Follicular Lymphoma Patients Treated with Rituximab Maintenance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in FL patients treated with rituximab maintenance.</p><p><b>METHODS</b>A tatol of 140 newly diagnosed FL patients who received Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy in our department were retrospectively analyzed from December 2002 to December 2014. Among 140 patients with FL 122 patients achieved response, from them 56 patients received R maintenance (RM) every 2 months for median 8 times (RM group) while the rest 66 patients did not receive further anti-lymphoma treatment (non-RM group).</p><p><b>RESULTS</b>There was no statistical difference in age, sex, pathologic grading, staging, FLIPI or FLIPI2 between RM and non-RM groups. The 2-year progression-free survival (PFS) of RM and non-RM groups were 89.7% and 77.6% (P=0.043) while the 2-year overall survival were 100% and 98.6% (P=0.131). FLIPI2 is a significant prognostic model either in the total cohort, RM or non-RM groups (P<0.001 all). In subgroup analysis, RM was able to decrease disease progression in low and intermediate-risk group of FLIPI2, while the 2-year PFS of RM and non-RM groups in high-risk group were similar (55.6% vs 46.9%)(P=0.920).</p><p><b>CONCLUSION</b>FLIPI2 presents robust prognostic significance either in RM or OBS patients, the patients in FLIPI2 low and intermediate-risk group may benefite from RM, but the role of RM in high-risk patients should be further to investigate.</p>

Prognostic analysis of non-cytogenetic factors in elderly adults with acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors in elderly patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>The clinical data of 211 AML patients with age 55 years or over and treated in Shanghai Jiaotong University Medical School affiliated Ruijin Hospital from 2007 to 2011 were collected and analyzed. Multivariate and univariate analysis of clinical data were performed using a Cox regression model and log-rank test, including age, subtype, performance status, white blood cell count, serum LDH and albumin level, and treatment strategy.</p><p><b>RESULTS</b>Acute promyelocytic leukemia (APL) patients had longer survival than other subtypes. To rule out the impact of APL on the prognostic analysis, we conducted multivariate and univariate analysis excluding APL patients. The significant parameters of the univariate analysis were age (P = 0.003), achieving remission (P < 0.01), performance status (P < 0.01), organ dysfunction (P < 0.01), increased WBC counts (P = 0.022), increased LDH level (P = 0.006) and low albumin level (P < 0.01). Multivariate analysis showed that only failure of achieving remission (P < 0.01), poor performance status (ECOG 3-4) (P < 0.01) and increased WBC counts (P < 0.01) were independent prognostic factors. The patients aged 70 years or over had poor overall survival, and no significant difference of OS was observed among patients with age between 55 and 69 years. For patients aged 55 - 69 years received either DA/IA or CAG treatments had longer survival than those with palliative treatments. For those aged 70 years or over, only patients with CAG treatment had significantly longer survival than palliative treatment. For the patients with age less than 70 years and achieving complete remission after induction, intermediate-dose cytarabine consolidation might not improve survival.</p><p><b>CONCLUSION</b>Elderly AML patients should be treated individually. The intermediate-dose cytarabine consolidation might not improve survival of elderly AML patients.</p>

Study of prognostic related factors of elderly patients with T/NK cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prognostic related factors of elderly patients with T/NK cell lymphoma.</p><p><b>METHODS</b>The clinical data of 62 T/NK cell lymphoma patients with age over 60 years and treated in Shanghai Jiaotong University Medical School affiliated Ruijin Hospital from 1999 to 2011 were collected and analyzed. Multivariate and univariate analysis of clinical data were performed using a COX regression model, including stage, performance status, extranodal infiltration, bone marrow involvement and LDH level. According to IPI or PIT systems, survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test.</p><p><b>RESULTS</b>Using the IPI system, the CR rate of the low risk (IPI = 1, n = 7), intermediate-low risk (IPI = 2, n = 22), intermediate-high risk (IPI = 3, n = 13) and high risk (IPI = 4-5, n = 20) groups were 85.7%, 59.1%, 0% and 5.0%, with the median overall survival (OS) of 90.0, 63.9, 10.1 and 5.0 months, respectively. The patients with IPI = 1-2 had significant longer OS than those with IPI = 3-5 (P < 0.01), but no significant difference of OS was observed between IPI = 1 and IPI = 2 (P = 0.3647). As for the PIT system, CR rate of patients with PIT = 1 (n = 18), PIT = 2 (n = 18) and PIT = 3-4 (n = 26) were 61.1%, 44.4% and 3.8%, with the median survival of 90.0, 46.9 and 5.0 months, respectively. Significant difference of OS was found among groups of PIT = 1, PIT = 2 and PIT = 3-4 (P < 0.01). Therefore, PIT index was more effective than IPI in predicting prognosis of elderly T/NK cell lymphoma patients. The significant parameters of the univariate analysis were B symptom (P = 0.025), increased LDH level (P = 0.004), bone marrow infiltration (P = 0.023) and extranodal involvements (P = 0.033). Multivariate analysis showed that only increased LDH level (P = 0.007) and bone marrow involvement (P = 0.016) were the two independent prognostic factors of survival. These two factors were included in PIT index.</p><p><b>CONCLUSIONS</b>PIT is more effective than IPI to predict outcomes of elderly T/NK lymphoma patients.</p>