Long-term clinical and molecular remissions in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation

Long-term clinical and molecular remissions in patients with mantle cell lymphoma (MCL) following high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have been evaluated in only a few studies. Thirty-six patients with MCL received ASCT in our institution (27 patients undergoing first-line therapy, 8 patients undergoing second-line therapy, and 1 patient undergoing third-line therapy). In the case of long-term remission (≥5 years; n?=?8), peripheral blood was tested for minimal residual disease (MRD) by t(11; 14) polymerase chain reaction (PCR) and immunoglobulin heavy-chain (IGH) PCR at the last follow-up. Ten-year overall survival (OS), progression-free survival (PFS), and freedom from progression (FFP) after first-line ASCT were 42 %, 43 %, and 54 %; after second-line ASCT, these were all 0 %. Four-year OS, PFS, and FFP for the first-line cohort were 75 %, 48 %, and 61 %, respectively. Four-year OS, PFS, and FFP after second-line ASCT were 55 %, 30 %, and 30 %, respectively. Treatment-related mortality (3 months after ASCT) was 0 %. The only prognostic factor for OS, PFS, and FFP was treatment line (p?=?0.011, p?=?0.046, and p?=?0.023, respectively). No relapses occurred after 5 years following ASCT. So far, eight patients developed sustained long-term clinical and molecular complete remissions of up to 14.6 years following ASCT in the first treatment line. Sustained long-term clinical and molecular remissions can be achieved following ASCT in the first treatment line and apparently less frequent in the second treatment line.     

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Role of high-dose melphalan with autologous stem cell transplantation in multiple myeloma patients receiving botezomib-containing induction therapy

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.     

Autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma: a retrospective study of the Spanish lymphoma group (GELTAMO)

Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned.     

Clinical impact of bulky mass in the patient with primary extranodal diffuse large B cell lymphoma treated with R-CHOP therapy

Although numerous studies about primary extranodal diffuse large B cell lymphoma (DLBCL) were reported sporadically, the literature of clinical value of immunophenotype and bulky diameter in rituximab era is limited. Ninety-six patients with primary extranodal DLBCL receiving R-CHOP therapy were analyzed to evaluate whether immunophenotype and size of bulky disease are significantly important. The International Prognostic Index was still an important prognostic factor for progression-free survival (PFS) and overall survival (OS; p?=?0.003, p?=?0.027). Difference of survival between germinal center (GC) type and non-GC type was not different (PFS: p?=?0.192; OS: p?=?0.197). In two separated groups according to extranodal maximum tumor diameter (EN-MTD) 7.5 cm as cutoff value for survival, the group of EN-MTD ≥7.5 cm had lower PFS and OS than <7.5 cm (PFS: p?=?0.001; OS: p?=?0.008). In four divided subgroups according to EN-MTD combined with immunophenotype, the subgroup of non-GC type with EN-MTD ≥ 7.5 cm had lower PFS and OS compared with the other subgroups (PFS: p?<?0.001; OS: p?=?0.008). Multivariate analysis revealed that non-GC with EN-MTD ≥ 7.5 cm was an independent prognostic parameter (PFS: HR?=?5.407, 95%CI?=?2.378–12.294, p?<?0.001; OS: HR?=?4.136, 95%CI?=?1.721–9.941, p?=?0.002). Bulky primary extranodal DLBCL would be associated with unfavorable outcome especially in non-GC type.     

High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis

Peripheral T-cell lymphoma (PTCL) carries a poor prognosis with conventional treatment. We retrospectively analyzed data from 45 patients with PTCL who received high-dose therapy and autologous stem cell transplantation (HDT/ASCT) from 1990 to 2008 in our center. Eighteen patients underwent HDT/ASCT in complete remission to induction chemotherapy (CR1), and 27 patients underwent HDT/ASCT in other disease statuses. The median follow-up was 113.5 months (range 52.6–261.0) for surviving patients. The 5-year overall survival (OS) and progression-free survival (PFS) were 64 and 60 %, respectively. The 5-year OS for patients in CR1 and in other disease statuses was 89 and 47 %, respectively (P = 0.002), and 5-year PFS was 83 and 43 % (P = 0.007). In the subgroup excluding anaplastic large cell lymphoma, patients transplanted in CR1 also had significantly better 5-year OS (82 vs. 37 %, P = 0.009) and PFS (82 vs. 33 %, P = 0.008) than those transplanted in other disease statuses. Multivariate analysis showed that CR1 status was the only significant prognostic factor for OS (P = 0.040) and PFS (P = 0.040). These results support the use of HDT/ASCT consolidation in CR1 for PTCL patients. Prospective randomized trials are necessary to confirm the efficacy of this approach.     

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.     

Perinatal and familial risk factors for irritable bowel syndrome in a Swedish national cohort

Objective: Studies of the importance of perinatal factors for the development of irritable bowel syndrome (IBS) are sparse. We conducted a large national cohort study to examine perinatal and familial risk factors for IBS.

Material and methods: A national cohort of 1,963,685 persons who were born in Sweden in 1973–1992 (identified from the Swedish Birth Registry) were followed up for adult (18 years and older) IBS incidence in the Swedish Patient Register through 2010 (maximum age 38 years). There were 24,633 IBS cases in 46,784,296 person-years of follow-up.

Results: After adjusting for potential confounders, significant risk factors for IBS included caesarean (HR?=?1.10, 95% confidence interval [CI] 1.05–1.11, p?p?=?.02), being second in birth order (HR?=?1.04, 95%CI 1.01–1.08, p?=?.01), foetal growth ≥1 SD (HR?=?1.06, 95%CI 1.00–1.11, p?=?.05), young maternal age (<20 years) (HR=?1.09, 95%CI 1.02–1.17, p?=?.02), maternal marital status (divorced/widowed) (HR?=?1.12, 95%CI 1.08–1.17, p?p?=?.01), maternal education of 12–14 years (HR?=?1.06, 95%CI 1.01–1.11, p?=?.03), parental history of IBS (HR?=?1.54, 95%CI 1.42–1.66, p?p?p?=?.02). Protective factors were male sex (HR?=?0.36, 95%CI 0.35–0.37, p?p?=?.03).

Conclusions: In this large cohort study, several perinatal and familial factors were associated with an increased risk of IBS independently, suggesting that perinatal and familial factors may play an important long-term role in the aetiology of IBS.     

Prognostic impact of beta-2 microglobulin in patients with extranodal natural killer/T cell lymphoma

Although serum beta-2 microglobulin (B2M) has been suggested as an independent prognostic factor for several lymphoproliferative diseases, it has rarely been investigated in extranodal natural killer/T cell lymphoma (ENKTL). From a prospectively collected database, 145 patients with ENKTL were identified. Among them, a total of 101 patients were included in the analysis, with exclusion of patients without baseline serum B2M level and those did not receive anticancer therapy. Serum B2M (<3.0 vs. ≥3.0 mg/L) was analyzed for association with overall survival (OS). Seventy-nine (78 %) patients had nasal ENKTL, and 22 (22 %) had extranasal ENKTL. In overall patients, median OS was 26.7 months (95 % confidence interval (CI), not assessable), with a median follow-up of 32.4 months (range, 0.9–155.2 months). While median OS was not reached in patients with nasal ENKTL, extranasal ENKTL group had median OS of 5.1 months (95 % CI, 1.2–8.9 months; p?<?0.001). Baseline serum B2M was significantly associated with OS in patients with nasal ENKTL (p?<?0.001). This was consistent in limited (stages I and II) nasal ENKTL (p?=?0.002) and disseminated (stages III and IV) nasal ENKTL (p?=?0.02). However, there was no difference of OS in extranasal ENKTL patients (p?=?0.69). In multivariate analysis including other prognostic factors, elevated serum B2M was significantly associated with poor OS (hazard ratio (HR)?=?3.8, 95 % CI 1.7–8.2, p?=?0.001, in a model including Korean Prognostic Index, and HR?=?3.6, 95 % CI 1.6–8.2, p?=?0.002, in a model including International Prognostic Index). In patients with nasal ENKTL, baseline serum B2M is a powerful prognostic factor. The prognostic value of B2M was independent of previously established prognostic models. Further investigations are necessary to validate the role of B2M in ENKTL.     

Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation

Purpose

The purpose of this study was to determine whether surgical left atrial appendage (LAA) exclusion performed during mitral valve surgery is associated with a reduction in cerebrovascular events in patients with atrial fibrillation.

Methods

We retrospectively studied patients with atrial fibrillation who underwent mitral valve surgery from 1/1/2001 through 12/31/2014. We screened 1352 patients using ICD-9 codes and included 281 patients in the study. The primary end point was a composite of strokes and transient ischemic attacks occurring within 5 years after surgery. Secondary end points were stroke, transient ischemic attack, and all-cause mortality.

Results

The LAA exclusion group (n?=?188) had a lower prevalence of female gender, hypertension, and diabetes mellitus compared with the non-LAA exclusion group (n?=?93). The CHA₂DS₂VASc scores were comparable between groups (2.6 vs 2.9, P?=?.11), as was anticoagulant use (82.4% vs 85.0%, P?=?.60). Concomitant surgical ablation was performed in 73.9% of patients who underwent LAA exclusion. Nine cerebrovascular events occurred in the LAA exclusion group and 13 in the non-LAA exclusion group (HR 0.30 [0.12–0.75], P?=?.01). There was no difference in all-cause mortality between groups. On multivariate analysis of the primary end point of strokes or transient ischemic attacks, significant variables were LAA exclusion (HR 0.31 [0.12–0.76], P?=?.01) and CHA₂DS₂VASc score (HR 1.44 [1.11–1.87], P?=?.006). The benefit of LAA exclusion was detected only when performed together with surgical ablation (HR 0.27 [0.09–0.72], P?=?.01).

Conclusions

LAA exclusion was associated with fewer cerebrovascular events. However, this benefit was seen only with concomitant surgical ablation.

     

Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study

We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60–64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m² was more frequent in the 60–64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3–4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60–64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60–64.     

Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan

High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17–110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.     

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I² statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR?=?0.57, 95 % CI?=?0.54–0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR?=?0.52, 95 % CI?=?0.48–0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR?=?0.56, 95 % CI?=?0.50–0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR?=?0.94, 95 % CI?=?0.91–0.97, p-value?=?0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR?=?0.92, 95 % CI?=?0.88–0.96, p-value?=?0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR?=?1.09, 95 % CI?=?0.81–1.46, p-value?=?0.58], abdominal pain [16.46 % vs. 14.34 %, OR?=?1.24, 95 % CI?=?0.90–1.72, p-value?=?0.19], and pharyngitis [22.22 % vs. 18.23 %, OR?=?1.12, 95 % CI?=?0.86–1.45, p-value?=?0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.     

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1–8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3–18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1–54.2). Median overall survival (OS) was 30 months (95 % CI 25.6–34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p?<?0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p?<?0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.     

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.     

The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma

The choice of a rituximab-based regimen and the prognostic significance of interim 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in primary mediastinal large B cell lymphoma (PMBCL) are debatable. We evaluated the clinical features and outcomes of 95 consecutive patients with PMBCL who were treated between 1985 and 2009. Forty-three patients received rituximab-based chemotherapy, R-VACOP-B (N?=?30) or R-CHOP21 (N?=?13), whereas 52 patients were treated with VACOP-B (N?=?47) or CHOP21 (N?=?5). Radiotherapy was not given. Patients who received rituximab had a 5-year progression-free survival (PFS) of 79 % and overall survival (OS) of 97 % compared with 58 % (p?=?0.06) and 88 % (p?=?0.2), respectively, without rituximab. Five-year PFS in patients treated with R-VACOP-B, R-CHOP21, VACOP-B, and CHOP21 were 83, 69, 62, and 20 %, respectively (p?=?0.039). However, direct comparison showed that the difference between PFS rates in patients receiving R-VACOP-B compared to R-CHOP21 was not statistically significant (p?=?0.3). None of the standard clinical risk factors predicted for PFS and OS in patients receiving rituximab (R)-chemotherapy. Mid-interim FDG-PET/CT scans were performed in 30/43 patients who received R-chemotherapy. The negative predictive values of mid-PET activity were high (100 % for R-VACOP-B and 86 % for R-CHOP21) while the positive predictive values (PPV) were relatively low (30 and 75 %, respectively). Despite the low PPV, the 5-year PFS for mid-PET-negative patients (N?=?16) was significantly higher (94 %) than that for mid-PET-positive (N?=?14) patients (57 %, p?=?0.015). This retrospective analysis demonstrates that the superiority of VACOP-B over CHOP21 for treatment of PMBCL disappeared once rituximab was added. The potential benefit of using interim PET activity as a guide for continuing therapy in patients with PMBCL remains unclear due to the relatively low PPV.     

Body mass index and bioelectrical impedance phase angle as potentially modifiable nutritional markers are independent risk factors for outcome in allogeneic hematopoietic cell transplantation

Beside many risk factors in patients considered for alloHCT, only body mass index (BMI) as a broad marker of nutritional status has prognostic value in these patients. This is the first prospective study to investigate the validity of further nutritional markers: adjusted BMI, normalized for gender and age; Subjective Global Assessment questionnaire and standardized phase angle, normalized for gender, age and BMI in 105 patients as independent risk factors for outcomes [overall survival (OS), non-relapse mortality (NRM), relapse mortality (RM), progression-free survival (PFS)] until 2 years after alloHCT. In Cox proportional-hazards regression models, we included a variety of accepted risk factors. The two most influential pre-transplant risk factors identified and associated with similarly increased hazard ratios (HR) for OS, RM, and PFS were a low-standardized phase angle (HR?=?1.97, P?=?0.043; HR?=?3.18, P?=?0.017, and HR?=?1.91, P?=?0.039) and advanced disease. Under- and overweight according BMI percentiles (≤10th; ≥90th) revealed associations with increased risk of NRM (HR?=?2.90, P?=?0.018; HR?=?3.02, P?=?0.062), although only low BMI was weakly associated with OS (HR?=?1.82, P?=?0.09). In conclusion, our results demonstrate that pre-transplant phase angle is an independent predictor for 2-year outcomes in these patients. Further investigation is necessary to demonstrate whether the theoretically modifiable phase angle can be increased by physical training combined with nutritional support, and if this improves outcome after alloHCT.     

Efficacy and safety profile of combining agents against epidermal growth factor receptor or vascular endothelium growth factor receptor with gemcitabine-based chemotherapy in patients with advanced pancreatic cancer: A meta-analysis

ObjectivesSeveral clinical trials have been published on gemcitabine-based chemotherapy with or without addition of agents against epidermal growth factor receptor (EGFR) or vascular endothelium growth factor receptor (VEGFR) in patients with advanced pancreatic cancer, however, with diverse results. The objective of this study was to perform a meta-analysis of the published trials.MethodsThe database of CENTRAL, MEDLINE and EMBASE were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated the efficacy and safety profile of adding targeted agents against EGFR or VEGFR to gemcitabine-based chemotherapy in patients with advanced pancreatic cancer. The primary outcome was overall survival (OS) while secondary outcomes included progression free survival (PFS) and overall response rate (ORR). Toxicity profiles were also assessed. Review Manager 5.1 was used to perform the analysis.ResultsResults reported from 6 RCTs involving 2733 patients were included in the analysis. Compared to gemcitabine-based chemotherapy alone, addition of an agent against EGFR resulted in significant longer OS [Hazard ratios (HR) 0.89 (0.79–0.99), p = 0.04] and longer PFS [HR 0.87 (0.79–0.97), p = 0.01], but no significant difference in ORR [RR 1.18 (0.82–1.70), p = 0.36]. The addition of an agent against VEGFR resulted in higher ORR [RR 1.54 (1.03–2.30), p = 0.04], but no advantage in OS [HR 0.95 (0.83–1.09), p = 0.47] or PFS [HR 0.97 (0.77–1.23), p = 0.82].ConclusionsAddition of an agent against EGFR to gemcitabine-based chemotherapy improved OS compared to gemcitabine-based chemotherapy alone in patients with advanced pancreatic cancer, while addition of an agent against VEGFR showed a modest improvement in ORR but not PFS and OS.     

Toxicity and efficacy of autologous hematopoietic cell transplantation in elderly patients with aggressive lymphoma: a historical prospective study

High-dose therapy followed by autologous hematopoietic cell transplantation (HCT) prolongs overall survival in patients under 65 years old with relapsed aggressive lymphoma. We aimed to explore the toxicity and efficacy of HCT in patients over 65 years with aggressive lymphoma compared with younger patients. We compared the transplantation outcomes between patients ≥?65 years (n?=?58) and 55–64 years (n?=?44) with chemosensitive aggressive lymphoma (DLBCL, MCL and TCL) that underwent HCT between 1999 and 2016 in the Tel-Aviv Medical Center. The median age was 68 (range, 65–74) and 61 (range, 55–64) years, respectively. There were no differences in the incidences of grade 3–4 mucositis, documented infections and pulmonary complications between the two groups. There was no difference in the incidences of secondary malignancies, relapse (p?=?.26), non-relapse mortality, (p?=?.77) and overall survival (p?=?.53). Multivariate analysis revealed that smoking was a risk factor for non-relapse mortality, while partial remission and >?2 lines of treatment prior HCT were associated with higher risk for relapse. Psycho-socioeconomic score was associated with prolonged hospitalization after HCT and recurrent hospitalizations. We conclude that patients ≥?65 years old with aggressive lymphoma, compared to younger counterparts, have similar transplantation outcome. Improving habits and psychosocial factors may further improve outcomes in these patients.