Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group

Enteropathy‐associated T‐cell lymphoma (EATL) is a rare primary gastrointestinal T‐cell lymphoma. A multicenter study from the Asia Lymphoma Study Group identified 38 EATL patients within a 19‐year period. All cases were type II EATL. Men were affected twice as common as women, at a median age of 59 (23–89) years. None had a history of celiac disease. The sites of involvement were small bowel and stomach (5%), small bowel (63%), small and large bowel (16%), and large bowel (18%). Common presenting features were bowel perforation (34%), pain (32%), and obstruction (21%). Lymphomas showed monomorphic neoplastic lymphoid infiltrates that were CD3⁺ (100%), CD56⁺ (91%), TIA‐1⁺ (96%), CD4^–CD8⁺ (63%), CD4⁺CD8⁺ (19%), CD4^–CD8^– (16%), and CD4⁺CD8^– (3%). Epstein Barr virus was demonstrable in three cases. Despite chemotherapy and/or surgical resection, the overall response and complete response rates were poor at 46% and 38%. The median overall survival (OS) was 7 months and progression‐free‐survival (PFS) 1 month. Five patients underwent hematopoietic stem cell transplantation all were alive. Age and the prognostic index for peripheral T‐cell lymphoma were not prognostically significant. Good performance status was associated with better OS (P = 0.03), and response to initial treatment led to better OS and PFS (P < 0.001). Am. J. Hematol. 87:663–668, 2012. © 2012 Wiley Periodicals, Inc.     

Outcomes of allogeneic or autologous stem cell transplantation followed by maintenance chemotherapy in adult patient with B-ALL in CR1 with no detectable minimal residual disease

Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.     

A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long-term follow-up in newly diagnosed mantle cell lymphoma

Mantle cell lymphoma (MCL) is associated with high relapse rates and poor survival when treated with conventional chemotherapy, with or without rituximab. We report the long-term follow-up of a phase II clinical trial using a new intensive multiagent chemotherapeutic regimen [cyclophosphamide, teniposide, doxorubicin and prednisone (CTAP) alternating with vincristine and high-dose methotrexate and cytarabine (VMAC)] in newly diagnosed MCL. Following 4–6 cycles of CTAP/VMAC induction, patients aged ≤65 years proceeded to consolidative autologous haematopoietic stem cell transplantation (auto-HSCT), while patients ≤55 years who had a HLA-identical sibling received allogeneic-HSCT (busulfan/cyclophosphamide conditioning for both). Twenty-five untreated MCL patients enrolled on the protocol between 1997 and 2002. Among evaluable patients, overall response rate (ORR) was 74% following induction chemotherapy. Seventeen patients received HSCT (autologous-13/allogeneic-4). On intent-to-treat analysis, ORR for patients who received consolidative HSCT was 100% (complete remission 76%). Therapy was well-tolerated with 4% treatment-related mortality (including HSCT). The 5-year event-free-survival (EFS) and overall survival (OS) for all patients was 35% and 50% respectively. Furthermore, at 66-months median follow-up, the 5-year EFS and OS for patients who received consolidative auto-HSCT was 54% and 75% respectively. Patients who received auto-HSCT had improved outcomes compared to no auto-HSCT (EFS P  = 0·001; OS P  = 0·0002). CTAP/VMAC induction followed by consolidative auto-HSCT for newly diagnosed MCL is associated with high ORR and durable survival.     

Tandem high-dose therapy in relapsed and refractory B-cell lymphoma: results of a prospective phase II trial of myeloablative chemotherapy,followed by escalated radioimmunotherapy with <Superscript>131</Superscript>I-anti-CD20 antibody and stem cell rescue

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with ¹³¹I-anti-CD20 antibody (¹³¹I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2–6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with ¹³¹I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.     

Progression-free survival and post-progression survival in patients with advanced gastric cancer treated with first-line chemotherapy

Purpose

The impact of post-progression survival (PPS) on the overall survival (OS) of patients with advanced gastric cancer (AGC) has not yet been reported in detail. We analyzed prospectively collected data from AGC patients who received first-line chemotherapy including fluoropyrimidine plus platinum.

Methods

We partitioned OS into progression-free survival (PFS) and PPS in each patient and analyzed correlations between OS and either PFS or PPS using the Spearman rank correlation coefficient (ρ).

Results

A total of 291 AGC patients met the inclusion criteria with median PFS, PPS, and OS of 5.3, 8.1, and 14.8 months, respectively. PFS and OS for each patient showed a correlation of ρ = 0.75 [95 % confidence interval (CI) 0.69–0.81]. PPS and OS showed a correlation of ρ = 0.87 (95 % CI 0.84–0.91). According to multivariate analysis, performance status at progression, PFS of first-line chemotherapy, and use of second-line chemotherapy were independently associated with PPS.

Conclusions

These results indicate that both PFS and PPS are correlated with OS in first-line chemotherapy for AGC, suggesting the importance of reporting detailed patient characteristics and treatment course after disease progression in clinical trials of first-line chemotherapy for AGC.     

Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1?% (95?% confidence interval, CI, 40.1–68.3?%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8?% (95?% CI 58.0–83.7?%), and the 5-year OS was 41.7?% (95?% CI 27.7–55.6?%). The 2-year progression-free survival rate (PFS) was 37.5?% (95?% CI 23.8–51.2?%), and the 5-year PFS was 25.0?% (95?% CI 12.8–37.3?%). The median progression-free survival was 8.8?months (95?% CI 0–20.3?months), and the median overall survival was 40.6?months (95?% CI 22.6–58.6?months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P?=?0.015). Myelosuppression was the main side effect; the incidence of grade 3–4 anemia was 8.3?%; leukopenia, 37.5?%; and thrombocytopenia, 48.3?%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.     

Prognostic impact of CD200 and CD56 expression in adult acute lymphoblastic leukemia patients

Background: The aim of the study is to determine the prognostic relevance of CD200/ CD56 expression in adult acute lymphoblastic leukemia patients.

Methods: The expression of CD200 and CD56 by blast cells was assessed by flow cytometry before the start of chemotherapy in 70 B-ALL patients.

Results: Positive expression of CD200 was detected in forty-six patients (66%) and CD56 was detected in 7 patients (10%) out of 70 patients, respectively. Only three patients (4.3%) had co-expression for CD200⁺ and CD56⁺. Splenomegaly and thrombocytopenia were frequently observed more in CD200⁺ patients. Increased frequency of CD34⁺ was associated with CD200⁺and CD56⁺ patients. The CD200⁺ and CD56⁺ subgroups of B-ALL patients had inferior OS and disease free survival compared to CD 200^? and CD 56^? patients.

Conclusions: CD200⁺ and/or CD56⁺ positive expression in B-ALL patients at diagnosis is a poor prognostic biomarker. Identification of CD200⁺ and CD56⁺ expression at diagnosis is recommended for a better stratification of adult B-ALL patients.     

Randomized clinical trial of arginine-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing gastric cancer surgery

Purpose

Significant malnutrition exists in a high percentage of patients with gastric cancer. It is, therefore, crucial to establish an effective means to provide nutrition for these patients. This prospective, randomized, double-blinded clinical trial aims to assess the long-term survival of arginine-supplementation enteral nutrition versus standard enteral nutrition in malnourished patients with gastric cancer.

Methods

The control group (36 cases) received postoperative standard enteral nutrition. Meanwhile, the arginine-supplementation group (37 cases) adopted the same nutrition product but enriched with arginine (9.0 g/L). The primary study objective was overall survival (OS). Secondary endpoints were progression-free survival (PFS); serum parameters including total protein, albumin, proalbumin, and transferrin obtained on preoperative day 1, postoperative day 2, and day 12; CD4⁺ and CD8⁺ T cells, natural killer (NK) cells, immunoglobulin M (IgM), and immunoglobulin G (IgG) obtained on preoperative day 1 and postoperative day 7.

Results

No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better OS (P = 0.03, 41 vs. 30.5 months) and better PFS (P = 0.02, 18 vs. 11.5 months). On postoperative day 7, CD4⁺ T cells, NK cells, IgM and IgG levels of the arginine-supplemented group increased prominently and were significantly higher than those of the control group and those on preoperative day 1. There is no significant difference in the serum total protein, albumin, proalbumin, and transferrin levels between the two arms.

Conclusions

Arginine-supplemented enteral nutrition significantly improves long-term survival and restores immunity in malnourished gastric cancer.     

Prognostic value of survivin,X‐linked inhibitor of apoptosis protein and second mitochondria‐derived activator of caspases expression in advanced non‐small‐cell lung cancer patients

Background and objective: Survivin and X‐linked inhibitor of apoptosis protein (XIAP) in vitro mediate cancer cell survival and chemoresistance. Second mitochondria‐derived activator of caspases (Smac), an antagonist of XIAP, has been shown in vitro to increase chemosensitivity. This study examined the prognostic value of survivin, XIAP and Smac in advanced non‐small‐cell lung cancer (NSCLC) patients treated with cisplatin‐containing chemotherapy. Methods: Semi‐quantitative RT‐PCR was used to measure survivin, XIAP and Smac mRNA expression in transbronchial biopsy tumour specimens from 72 patients with advanced NSCLC before commencing chemotherapy. Outcome measures were response to chemotherapy, progression‐free survival (PFS) and overall survival (OS). Results: Low expression of survivin was associated with good response to chemotherapy (P = 0.028). No association was found between XIAP and Smac expression levels and response to chemotherapy (P = 0.224 and P = 0.088, respectively). Patients with low survivin expression or high Smac expression had significantly longer PFS (P = 0.012 and P = 0.029, respectively) and OS (P = 0.007 and P = 0.031, respectively) compared with patients with high expression of survivin or low expression of Smac. XIAP expression was not correlated with PFS or OS. Additionally, PFS and OS in patients with performance status of 0 or 1 and stage IIIB were significantly longer than PFS and OS in patients with performance status (PS) of 2 and stage IV disease. Multivariate Cox regression analyses demonstrated that survivin and clinical stage were independent predictors for PFS and OS. Smac was an independent prognostic factor for OS, but not for PFS. Conclusions: Our findings suggest that the expression levels of survivin and Smac, but not XIAP, predict the survival of patients with advanced NSCLC treated with chemotherapy.     

Clinical impact of radiotherapy for locally advanced pancreatic cancer

Background

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC.

Patients

Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n = 30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n = 28, or gemcitabine, n = 19, as a radiosensitizer) at Aichi Cancer Center Hospital.

Results

Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3–4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy.

Conclusions

Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy.     

Peripheral blood CD45RO+T cells is a predictor of the effectiveness of neoadjuvant chemoradiotherapy in locally advanced rectal cancer

To investigate the relationship between the changes in circulating CD45RO⁺T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO⁺T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO⁺ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO⁺ratio.Circulating CD45RO⁺ratio of 1.07 was determined as the optimal cut-off point and CD45RO⁺ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO⁺ratio-high group was significantly higher than that in the CD45RO⁺ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO⁺ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153–0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082–0.726; P = .011).Circulating CD45RO⁺ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.     

Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations

DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (cn‐AML) patients and associated with poor survival. The role of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in DNMT3A^mut cn‐AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of DNMT3A mutations and explored the role of allo‐HSCT in 308 cn‐AML patients who received consolidation of intensive chemotherapy or allo‐HSCT in our center from March 2005 to May 2014. In the whole cohort, 63 patients (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most frequent variant. DNMT3A^mut patients had shorter overall survival (3‐year OS: 31.9% vs. 52.0%, P = 0.009) and disease‐free survival (3‐year DFS: 21.8% vs. 40.1%, P = 0.004) compared with DNMT3A^wt patients. Based on FLT3/NPM1/CEBPA mutations, 308 cn‐AML patients were divided into favorable/intermediate group (n = 262) and unfavorable group (n = 46). There were no significant differences in 3‐year OS and 3‐year DFS between DNMT3A^mut and DNMT3A^wt patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, DNMT3A mutation remained an independent adverse prognostic factor for the survival. In the DNMT3A^mut cohort, 23 complete remission (CR) patients received allo‐HSCT consolidation and 32 CR patients received chemotherapy consolidation, dramatic differences were observed in 3‐year OS (51.7% vs. 28.9%, P = 0.048) and 3‐year DFS (41.6% vs. 14.9%, P = 0.024) between allo‐HSCT group and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor for cn‐AML patients and allo‐HSCT could improve survival of cn‐AML patients with DNMT3A mutations. Am. J. Hematol. 90:992–997, 2015. © 2015 Wiley Periodicals, Inc.     

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2. The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34+ cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs < or = 13%, P < or = 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation.     

A retrospective analysis of primary gastric diffuse large B-cell lymphoma with or without concomitant mucosa-associated lymphoid tissue (MALT) lymphoma components

Primary gastric diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity that includes patients with (DLBCL/MALT) and without detectable mucosa-associated lymphoid tissue (MALT) lymphoma components (de novo DLBCL). We sought to evaluate the clinical characteristics and outcome of this disease in a large number of cases. Patients with primary gastric DLBCL (n?=?162) seen on 2001–2011 at the Tianjin Medical University Cancer Institute and Hospital and the First affiliated Hospital of Chinese PLA General Hospital were retrospectively reviewed. The distribution of sex, age, Lugano staging, and other main clinical characteristics was similar between the de novo DLBCL and DLBCL/MALT groups (p?>?0.05). However, the proportion of patients with a stage-modified international prognostic index (m-IPI)?≥?2 was higher in the de novo DLBCL (34 %) than the DLBCL/MALT group (17 %) (p?=?0.026). In addition, the Helicobacter pylori infection rates were higher in the DLBCL/MALT (75 %) than the de novo DLBCL group (36 %) (p?<?0.001). Five-year progression-free survival (PFS) and overall survival (OS) estimates were similar for patients in the de novo DLBCL (p?=?0.705) and DLBCL/MALT groups (p?=?0.846). Surgical treatment did not offer survival benefits when compared with chemotherapy for 5-year PFS (p?=?0.607) and OS estimates (p?=?0.554). There were no significant differences in 5-year PFS and OS estimates for patients treated with rituximab–chemotherapy (p?=?0.261) or conventional chemotherapy (p?=?0.227). Non-GCB subtype and m-IPI?≥?2 were independently associated with shorter OS, and advanced stages of lymphoma were independently associated with shorter PFS.     

Hematopoietic stem cell transplantation in Lebanon: first comprehensive report

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.     

Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein-Barr-Virus positive diffuse large B cell lymphoma

Patients with EBV-positive diffuse large B cell lymphoma not otherwise specified (EBV⁺ DLBCL (NOS)) recurrently present with advanced age and reduced performance status. They are therefore insufficiently represented in clinical trials and treatment is likely to differ. Here we assess clinicopathological characteristics, therapeutic variability and clinical outcome in the largest consecutively diagnosed EBV⁺ DLBCL (NOS) cohort published to date (n = 80; median age 70 years; range 19–90). Centralized and systematic haematopathological panel review was performed. By immunohistochemistry 60/80 patients were CD30-positive. Further, we identified nine EBV⁺ DLBCL (NOS) patients with associated or composite peripheral T cell lymphoma at diagnosis or relapse (preceded by clonal T cell populations within the initial DLBCL biopsy in 4/5 cases). Most patients (80%) were treated with R-CHOP-type therapy and 16 patients received none or less intensiveprotocols. Upon univariate analysis both R-CHOP-type therapy (OS: P < 0.0001; PFS: P = 0.0617) and negativity for CD30 (OS: P = 0.0002; PFS: P = 0.0002) showed a protective 66 effect, maintained upon multivariate analysis. In a propensity-score matched analysis with a cohort of non-EBV⁺ DLBCL (NOS) patients, balanced for all revised-international prognostic index factors, we found an EBV-association to hold no significant impact on progression-free and overall survival whilst exhibiting a trend favouring EBV-negativity (OS: P = 0.116; PFS: P = 0.269). Our findings provide insight into the clinical course of EBV⁺ DLBCL (NOS), highlight the ramifications of CD30-expression and underline the superior therapeutic efficacy of R-CHOP immunochemotherapy. Alternative therapies, incorporating tumour biology (e.g. CD30 directed therapies) need to be explored in EBV⁺ DLBCL (NOS) patients. Moreover our data advert to the close relationship between EBV⁺ DLBCL (NOS) and peripheral T cell lymphomas.     

The role of Tα1 on the infective patients after hematopoietic stem cell transplantation

The present study was designed to investigate the effect of thymosin α1 (Tα1) administration in infective recipients of hematopoietic stem cell transplantation (HSCT) for hematologic malignancies. Eight patients were enrolled in our study, including seven allo-HSCT patients and one auto-HSCT patient. These patients were allocated randomly into the treatment group (four cases) and control group (four cases). Tα1 was used in the treatment group to test its effectiveness in infection control. The concentrations of cytokines IFN-γ, IL-2, IL-4, IL-10, and IL-12 were observed, and the levels of CD3⁺, CD4⁺, and CD8⁺ T cells, as well as of CD4⁺/CD8⁺ and CD4⁺/CD25⁺ regulatory T cell (Treg) were measured. When Tα1 was administered for 2 weeks, the concentrations of these cytokines were increased after 1 month in the treatment group. Interestingly, the levels of IFN-γ, IL-2, IL-10, and IL-12 were increased in the treatment group more than those in the control group, whereas there were no significant differences between the treatment and control group in the levels of CD3⁺, CD4⁺, and CD8⁺ T cells, or in CD4⁺/CD8⁺ or CD4⁺/CD25⁺ Treg cells. Notably, Tα1 administration did not cause acute or chronic graft versus host disease (GVHD). We conclude that Tα1 administration is safe and may impact favorably on immune function, and that it may improve resistance to infection and induce immunotolerance without GVHD.     

Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome

Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto- (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, beta2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto- and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT.     

Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R-CHOP

Although ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five-year progression-free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPET^neg → ePET^neg), delayed responder (iPET^pos → ePET^neg), loss-metabolic responder (iPET^neg → ePET^pos), and never-metabolic responder (iPET^pos → ePET^pos). In the autologous haematopoietic stem cell transplantation (auto-HSCT)-fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non-metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto-HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R-CHOP. Therefore, prospective clinical trials of iPET-guided treatment strategies for these patients are warranted.     

Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.