Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients / 中华血液学杂志

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion: De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

Prognostic significance of (18)F-fluorodeoxyglucose positron emission tomography in patients with diffuse large B cell lymphoma undergoing autologous stem cell transplantation / 中华血液学杂志

Objective: To evaluate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ(2)=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ(2)=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ(2)=22.75, P=0.001) and OS (97.1% vs 40.0%, χ(2)=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell's C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell's C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell's C index in OS (Harrell's C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions: Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.

Lymphoma-associated hemophagocytic syndrome: An analysis of clinical features and survival of 27 cases from a single center in China / 肿瘤

Objective: To analyze the clinical features and treatment outcomes of patients with lymphoma-associated hemophagocytic syndrome (LAHS). Methods: Clinical data of 27 patients with LAHS diagnosed at Peking University Cancer Hospital between May 2007 and August 2014 were retrospectively analyzed. Results: Of the 27 patients, there were 18 males and 9 females, with a median age of 32 years (range: 14 to 77). At diagnosis of lymphoma, 17 patients (63.0%) were stage HI/IV, 8 (29.6%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 5≥2, 12 (46.2%) had International Prognostic Index (IPI) score 5≥3. The most common subtype was extranodal natural killer/T cell lymphoma (ENKTCL) (74.1%, 20/27). Three patients presented with hemophagocytic syndrome (HPS) at lymphoma diagnosis, while the other 24 patients developed HPS during lymphoma progression after failure of chemotherapy. The clinical features of HPS were persistent fever (100.0%), splenomegaly (88.9%), hepatomegaly (37.0%), lymph node enlargement (63.0%), cytopenia (100.0%), ferritin increased (92.6%), hypertriglyceridemia (55.6%), hypofibrinogenemia (55.6%), and hemophagocytosis in bone marrow (70.4%). After a median follow-up of 11.0 months (range: 0.3 to 66.0 months), 24 (88.9%) patients died, and 3 survived. The median overall survival (OS) after the diagnosis of lymphoma was 11 months, and the median OS after the diagnosis of HPS was 28 days. One patient receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) remained alive with complete remission for 53 months. Conclusion: The clinical manifestations of LAHS were complex, and the prognosis and survival time remain dismal. More effective therapeutic strategies should be develpoed, and allo-HSCT may provide survival benefts to LAHS.

Clinical characteristics and prognosis analysis of patients with LMP-1 positive Hodgkin's lymphoma after EBV infection / 中国实验血液学杂志

This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.

The efficacy and safety of the DICE regimen in combination with rh-endostatin (Endostar) in the treatment of recurrent or refractory diffuse large B-cell lymphoma: A prospective clinical trial / 肿瘤

Objective: To evaluate the efficacy and safety of the DICE regimen in combination with recombinant human endostatin (Endostar) in patients with recurrent or refractory DLBCL (diffuse large B-cell lymphoma). Methods: DICE regimen were given intravenously for 4 consecutive days, consisting of dexamethasone 10 mg/d, ifosfamide 1 g·m-2·d -1, cisplatin 25 mg·m-2·d-1, and etoposide 60 mg·m-2·d-1. Endostar were given at 7.5 mg/m2 (i.v.) on days 1-14. Cycles were repeated every 3 or 4 weeks. Results: Between January 2009 and September 2011, 15 patients with recurrent or refractory DLBCL were enrolled: 11(73.3%) with primary refractory lymphoma and 4 (26.7%) with recurrent lymphoma. Two patients (13.3%) achieved a complete remission and 2 (13.3%) achieved a partial remission. The overall response rate was 26.7%. The clinical factors of gender (P = 0.011), International Prognostic Index (P = 0.033) and serum lactate dehydrogenase level (P = 0.011) had significant effects on overall response rate. The TTF (median time to treatment failure) and the OS (overall survival) time were 2 and 10 months, respectively. The one-year OS rate and the TTF rate were 46.7% and 26.7%, respectively. Myelosuppression was the major toxicity. WHO grade III/IV leukopenia and granulocytopenia were developed in 11 patients (78.6%). Conclusion: DICE regimen in combination with Endostar was well tolerated and its efficacy was mild in patients with recurrent or refractory DLBCL, probably due to these extremely poor prognostic patients. Copyright © 2013 by TUMOR.

Prognostic value of (18)F-FDG PET/CT after first-line treatment in patients with diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the value of (18)F-FDG PET/CT in detecting residual disease and predicting relapse following first-line treatment in patients with diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical data of 39 patients with DLBCL, who underwent PET/CT scan after first-line treatment, were analyzed retrospectively. Kaplan-Meier method was used to analyze the survival of patients.</p><p><b>RESULTS</b>PET/CT findings were interpreted as negative, mild metabolism and positive. Seventeen patients' PET/CT findings were judged as negative, none of them relapsed with a median follow-up of 24.1 months, 13 were judged as mild metabolism, 2 of them relapsed with a median follow-up of 17.1 months. Of the rest 9 findings were judged as positive with a median follow-up of 16.3 months, 4 patients were considered as disease progression according to clinical manifestations and other radiographic results, 2 patients relapsed at the time points of 13.5 and 6.8 months after PET/CT scan respectively, the other 3 patients were diagnosed as negative by biopsy, none of them relapsed at the time points of 5.9, 9.6 and 20.0 months after PET/CT scan respectively. One-year progression-free-survival (PFS) for negative, mild metabolism and positive groups was 100%, 83% and 56%, respectively. Two-year PFS was 100%, 83% and 42%, respectively. Overall survival (OS) at 1 year for negative, mild metabolism and positive groups was 100%, 100% and 89%, respectively. Two-year OS was 100%, 100% and 63%, respectively (P = 0.004).</p><p><b>CONCLUSION</b>DLBCL patients with negative and mild metabolism PET/CT following first-line treatment had good prognosis, who needed no additional therapy. While patients with positive PET/CT had poor prognosis, those patients should receive biopsy before adjusting treatment regimen because of the high false-positive rate.</p>

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma / 癌症

Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.

Plasma levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in patients with newly diagnosed lymphomas / 中国实验血液学杂志

The objective of this study was to detect the expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma.

An analysis of hepatitis B virus infection rate in 405 cases of non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the status of hepatitis B virus (HBV) infection in non-Hodgkin lymphoma (NHL) patients.</p><p><b>METHODS</b>The serum HBV markers in NHL patients were detected by enzyme-linked immunosorbent assay (ELISA). The infection rate of HBV in NHL patients was compared with that in nationwide general population.</p><p><b>RESULTS</b>The positive rates of HBsAg, anti-HBs and anti-HBc in 405 cases of NHL were 11.6%, 39.8% and 47.9%, respectively, which were statistically different from those in general population (P < 0.01). The positive rates of HBsAg, anti-HBs and anti-HBc in B-cell NHL and T-cell NHL were 13.3% vs 7.1% (P = 0.083), 40.6% vs 37.5% (P = 0.567), 53.2% vs 33.9% (P = 0. 001), respectively. The HBV DNA positive rate was 23.7% in 93 cases of NHL, and was 50.0% in 38 cases of HBsAg-positive NHL while 5.5% in 55 cases of HBsAg-negative but HBcAb-positive NHL.</p><p><b>CONCLUSIONS</b>The infection rate of HBV in NHL patients is higher than that in general population, in which occult hepatitis B virus infection can not be ignored. The positive rate of anti-HBc in B-cell NHL is significantly higher than that in T-cell NHL. For NHL patients infected with HBV, prophylactic anti-HBV therapy to prevent viral reactivation should be given before the anti-cancer treatment. Further study in the relationship between HBV and NHL should be carried out in the future.</p>

Study on serum erythropoietin levels in patients with hematologic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To study whether hematologic malignancy patients with anemia have a lower erythropoietin (EPO) response.</p><p><b>METHODS</b>Serum EPO levels were detected by ELISA in patients with hematologic malignancies and with iron deficiency anemia (IDA). Eighty patients with hematologic malignancies, including 13 multiple myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty patients with IDA were studied as the control.</p><p><b>RESULTS</b>Hematologic malignancy patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA, serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) , but no such inverse correlation was found in the hematologic malignancy patients with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were significantly lower in anemic patients with hematologic malignancies than in IDA patients (P = 0.032) , indicating a decreased EPO response in the former group.</p><p><b>CONCLUSION</b>Anemia associated with hematologic malignancy might result from an inappropriately low EPO response. EPO treatment for these patients may be beneficial.</p>

The experimental study on the idiotypic nucleic Acid vaccine constructed from the genomic DNA to lymphoma / 中国实验血液学杂志

This study was to investigate the anti-lymphocytic malignancy immunologic effects induced by two types of the idiotypic nucleic acid vaccines which were constructed from the genomic DNA and RNA of the human B lymphoma cell line respectively. Namalwa cell line and BALB/c mice were used as the models. The gene fragments of the IgH variable region (IgHV), which were obtained from the genomic DNA and RNA of Namalwa cell respectively, were cloned into the eukaryocytic expression vector pcDNA 3.0 to be used as the idiotypic nucleic acid vaccines. After transfecting COS cells with one of vaccines constructed from the genomic DNA by using LipofectAMINE, the result of transcription was identified by using RT-PCR. The experimental mice were immunized by intramuscular injection with two types of vaccines. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The results showed that the nucleic acid vaccine constructed from the genomic DNA can be transcribed in COS cells, the transcription product turned shorter, and the intron region of 86 bp was spliced accurately. When immunizing the mice, two vaccines both induced the anti-idiotypic antibody against Namalwa cell, the anti-idiotypic antibody could be detected since detected since after immunization, and got to the peak of titer on the sixth week. It was concluded that the nucleic acid vaccines against lymphoma can be constructed from both the genomic DNA and RNA.