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.     

Acute Myeloid Leukemia in Children: Experience from Tertiary Cancer Centre in India

There is paucity of data in pediatric Acute Myeloid Leukemia (AML) from developing countries. We analyzed the outcomes of 65 consecutive patients with pediatric AML treated at our centre from January-2008 to May-2013. The median event free survival (EFS) and overall survival (OS) were 12.6 and 14.6 months respectively. Patients with good-risk cytogenetics had a better EFS (p = 0.004) and OS (p = 0.01). Overall, these results are not comparable to that observed in other centres globally and leaves scope for further improvement. This includes implementing allogeneic bone marrow transplantation as a treatment for all children with high-risk AML.     

Cardiovascular medicine heart failure (CVM-HF) index as prognostic model for candidates to MitraClip therapy

Transcatheter MitraClip repair is a new tool for the management of severe mitral regurgitation in patients at very high risk for conventional surgery. Aim of our study was reporting one-year clinical outcomes in candidates to MitraClip procedures, divided into three groups according to the cardiovascular medicine heart failure (CVM-HF) index. The study population consists of 46 consecutive patients, divided, in accordance with CVM-HF index, as follows: one patient in the low-risk category (group A); 27 patients in the medium-risk (group B) and 18 patients in high-risk category (group C). The primary study endpoint was a combined of all-cause mortality and re-hospitalization rate. Secondary endpoints were all-cause mortality and cardiac mortality. Patients of group B and group C were compared. Regarding the primary endpoint, patients in group C had significantly poorer outcomes than patients in group B, with a 12-month survival freedom from events of 44.4  and 74.1 %, respectively (log-rank test, p = 0.039); survival freedom from cardiac mortality was 100 and 83.3 % in group B and C, respectively (log-rank test, p = 0.027). One-year survival free from re-hospitalization was 74.1 % in group B and 39.9 % in group C (log-rank test; p = 0.036). Survival free from all-cause of mortality was 92.6 and 77.8 %, respectively (log-rank test; p = 0.129). In our initial experience the CVM-HF index showed to be valuable for understanding if the patient with advanced heart failure and functional mitral regurgitation can really benefit by MitraClip therapy.     

Prevalence and Prognostic Impact of CEBPA Gene Mutation (Simplified Assay Technique) in Egyptian Acute Myeloid Leukemia Patients with Normal Cytogenetics

Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), especially in those with a normal cytogenetics. However, few studies were done on Egyptian AML patients and none of them look for easier and less expensive method for CEBPA mutation screening. This study is aimed to investigate the prevalence of CEBPA mutations and its clinical and prognostic impact in Egyptian patients with cytogenetically normal AML (CN-AML). This was done using fragment analysis to assess this method as a cheaper and less laborious screening method compared to sequencing. Fluorescent PCR was done to amplify CEBPA gene in DNA extracted from 40 CN-AML patients. This was followed by fragment analysis of post-PCR products using GeneMapper software for detection of CEBPA mutations. CEBPA gene mutations were found in 7/40 CN-AML patients (17.5 %) and it was significantly associated with lower LDH levels (p = 0.039). All patients with CEBPA mutations achieved clinical remission and none of them showed refractoriness, relapsed, or died by the end of the 2 years study period. Furthermore, those patients demonstrate significantly longer overall and disease free survival than those with wild type CEBPA gene (p = 0.001 and 0.004 respectively). CEBPA mutation has a favorable prognostic impact in CN-AML. Fragment analysis is a good, lees laborious and cheaper method that can be used for CEBPA mutation screening in patients with CN-AML.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG

The 5-year overall survival (OS) in patients ≥?60 years old with acute myeloid leukemia (AML) remains <?10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥?60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P?=?0.045) and OS (7.9 vs. 2.8 months, P?=?0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P?=?0.002). Finally, we performed a cost analysis that estimated savings to be $30,000–45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.     

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.     

Clinical impact of galectin-3 in newly diagnosed t (15;17)(q22;q21)/PML-RARa acute promyelocytic leukemia treated with all-trans retinoic acid and arsenic trioxide-based regimens

Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0.001). Higher galectin-3 levels were closely associated with older ages (p < 0.001), the medical history of psoriasis (p = 0.036), coagulopathy (p = 0.042), and CD34 expression (p = 0.004). Compared with patients with lower galectin-3 levels, those with higher galectin-3 levels had significant shorter overall survival (p = 0.028) and relapse-free survival (p = 0.001). Multivariate analysis showed that serum galectin-3 was an independent unfavorable factor for relapse-free survival in patients with APL treated with all-trans retinoic acid and arsenic trioxide-based frontline therapy. Clinical impact of galectin-3 should be further investigated in patients with APL.     

The Synonymous Isocitrate Dehydrogenase 1 315C&gt;T SNP Confers an Adverse Prognosis in Egyptian Adult Patients with NPM1-/CEBPA-Negative Acute Myeloid Leukemia

Although the clinical features of isocitrate dehydrogenase (IDH) genetic aberrations have been well-characterized in acute myeloid leukemia (AML), definitive information on their prognostic significance is lacking. We aimed to explore the prognostic significance of IDH gene alterations in an Egyptian cohort of adult patients with de novo AML. Diagnostic peripheral blood samples from 51 AML patients were analyzed for the presence of mutations/SNPs in exon 4 of IDH1 and IDH2 genes using polymerase chain reaction amplification followed by direct sequencing. IDH mutational status had no impact on event-free survival (EFS) and overall survival (OS), whereas the presence of IDH1 315C>T SNP was significantly associated with inferior EFS (P = 0.037) and OS (P = 0.034) as compared with wild-type IDH1. IDH1 315C>T SNP but not IDH mutations is associated with unfavorable outcomes, suggesting that AML patients with IDH1 315C>T SNP can represent a new subgroup of patients which allows refined risk stratification.     

Bilateral internal thoracic artery grafting in octogenarians: where are the benefits?

The use of bilateral internal thoracic artery (BITA) grafting for myocardial revascularization is usually discouraged in the very elderly because of increased risk of perioperative complications. The aim of the study was to analyze early and late outcomes of BITA grafting in octogenarians. From January 1999 throughout February 2014, 236 consecutive octogenarians with multivessel coronary artery disease underwent primary isolated coronary bypass surgery at the authors’ institution. Six of these patients underwent emergency surgery and were excluded from this retrospective study; consequently, 135 BITA patients were compared with 95 single internal thoracic artery (SITA) patients according to early and late outcomes. Between BITA and SITA patients, there was no significant difference in the operative risk (EuroSCORE II: 8 ± 7.7 vs. 7.6 ± 6.1 %, p = 0.65). There was a lower aortic manipulation in BITA patients. Hospital mortality (3 vs. 4.2 %, p = 0.44) and perioperative complications were similar except that only BITA patients experienced sternal wound infection (5.2 %, p = 0.022). The mean follow-up was 4.7 ± 3.3 years. There were no differences between the two groups in overall survival (p = 0.79), freedom from cardiac and cerebrovascular deaths (p = 0.73), major adverse cardiac and cerebrovascular events (p = 0.63) and heart failure hospital readmission (p = 0.64). Predictors of decreased late survival were diabetes (p = 0.0062) and congestive heart failure (p = 0.0004). BITA grafting can be routinely used in octogenarians with atherosclerotic ascending aorta without an increase in hospital mortality or major adverse cardiac and cerebrovascular complications. However, there is an increased risk of sternal wound infection without a demonstrable long-term benefit.     

Impact of cachexia on outcomes in aggressive lymphomas

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87–93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into “non-cachectic” (CXI ≥49.8, n = 41) and “cachectic” (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.     

A window of opportunity for abatacept in RA: is disease duration an independent predictor of low disease activity/remission in clinical practice?

The objective of the study was to examine whether disease duration independently predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice. Using the Corrona RA registry (February 2006–January 2015), biologic-naïve patients with RA initiating abatacept with 12-month (±3 months) follow-up and assessment of disease activity (Clinical Disease Activity Index [CDAI]) at initiation and at 12 months were identified. The primary outcome was mean change in CDAI (ΔCDAI) from baseline to 12 months. Secondary outcomes at 12 months included achievement of low disease activity (LDA; CDAI ≤10 in patients with moderate/high disease activity at initiation) and remission (CDAI ≤2.8 in patients with low, moderate or high disease activity at initiation). Linear and logistic regression analyses were performed to examine the relationship between disease duration and response to abatacept. There were 281 biologic-naïve patients with RA initiating abatacept (disease duration 0–2 years, n = 107; 3–5 years, n = 45; 6–10 years, n = 50; >10 years, n = 79). Increased disease duration was associated with older age (p = 0.047), and the median number of prior conventional disease-modifying antirheumatic drugs used was lowest in the 0- to 2-year duration group (p < 0.001). Mean ΔCDAI (SE) ranged from ?10.22 (1.19) for 0–2 years to ?4.63 (1.38) for >10 years. In adjusted analyses, shorter disease duration was significantly associated with greater mean ΔCDAI (p = 0.015) and greater likelihood of achieving LDA (p = 0.048). In biologic-naïve patients with RA initiating abatacept, earlier disease (shorter disease duration) was associated with greater ΔCDAI and likelihood of achieving LDA.     

Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion

Background

The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.

Methods

We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).

Results

Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).

Conclusions

CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

     

Reduced-intensity allogeneic hematopoietic stem cell transplantation combined with imatinib has comparable event-free survival and overall survival to long-term imatinib treatment in young patients with chronic myeloid leukemia

The relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in imatinib era have not been evaluated. The study was designed to compare the outcomes of combination therapy of RIST plus imatinib (RIST + IM) vs. imatinib (IM) alone for young patients with early CP (ECP) and late CP (LCP). Of the patients, 130 were non-randomly assigned to treatment with IM alone (n = 88) or RIST + IM (n = 42). The 10-year overall survival (OS) and event-free survival (EFS) were comparable between RIST + IM and IM groups. LCP, high Sokal score, and no complete cytogenetic response at 3 months were adverse prognostic factors for survival, but only the time from diagnosis to IM was an independent predictor after multivariate analysis. For ECP, IM was similar to RIST + IM, with 10-year EFS rates of 77.2 vs. 81.6% (p = 0.876) and OS rates of 93.8 vs. 87.9% (p = 0.102), respectively. For LCP, both treatments resulted in similar survival, but more patients in the imatinib group experienced events (10-year EFS 40.8 vs. 66.7%, p = 0.047). The patients with higher EBMT risk scores had an inferior survival than those with lower scores (69.2 vs. 92.9%, p = 0.04). We concluded that RIST + IM was comparable to IM in terms of OS and EFS. However, RIST + IM was more affordable than IM alone in a 10-year scale. Thus, RIST + IM could be considered as an alternative treatment option, especially when the patients have low EBMT risk scores and demand a definite cure for CML.     

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.     

Prednisolone plus S-adenosil-<Emphasis Type="SmallCaps">l</Emphasis>-methionine in severe alcoholic hepatitis

Purpose/background

Severe alcoholic hepatitis (AH) is a life-threatening liver disease with a potential of 30–40 % mortality at 1 month. While steroids remain to be a first line therapy, they provide only about 50 % survival benefit. The aim of the study was to evaluate the efficacy of glucocorticoids plus S-adenosylmethionine (SAMe), as compared to glucocorticoids alone, in patients with severe alcoholic hepatitis.

Methods

Forty patients with severe AH were randomized in two groups and enrolled in the prospective trial. Group 1 (n = 20) patients received prednisolone 40 mg/daily per os, and group 2 (n = 20) patients were managed with prednisolone 40 mg/daily per os plus SAMe 800 mg i.v. treatment. Duration was 28 days.

Results

The response rate assessed by Lille model was significantly higher in the prednisolone plus SAMe group (19 of 20; 95 %) than in the prednisolone group (13 of 20; 65 %), p = 0.044. Two (10 %) patients died, both from the prednisolone group. There were no lethal outcomes in the prednisolone plus SAMe group. The Kaplan–Meier method showed no significant differences between the two groups (p = 0.151, log-rank). Hepatorenal syndrome (HRS) occurred in 20 % in the prednisolone group (4 of 20 patients) while no HRS cases were registered in the prednisolone plus SAMe group (p = 0.035).

Conclusions

Management of severe alcoholic hepatitis with prednisolone plus SAMe was associated with better therapy response (p = 0.044) and less frequent HRS occurrence (p = 0.035). Mortality was not significantly lower in the prednisolone–SAMe group than in the prednisolone-only group at 28 days (10 vs. 0 %, p = 0.151).

     

The treatment results of definitive radiotherapy for cervical esophageal cancer: a single-institution experience

Background

Cervical esophageal cancer (CEC) is an uncommon disease. Thus, the clinical data from CEC patients have not been sufficient to establish a standard treatment.

Methods

Forty-six CEC patients who received definitive radiotherapy at our center from January 2003 to December 2014 were enrolled in this retrospective study. The stages of the patients according to the UICC 2002 staging system were as follows: stage I, n = 5; stage IIA + IIB, n = 3; and stage III, n = 38. The median radiation dose was 60 Gy. Thirty-nine patients (84.8%) received concurrent chemotherapy.

Results

The 3-year overall survival rate of the 46 patients was 45.4%. The 3-year laryngectomy-free survival rates of non-T4 (n = 20) and T4 patients (n = 26) were 57.8 and 23.6%, respectively; there was a significant difference (p = 0.010). Among the 35 patients who survived for >1 year after treatment, 29 (82.8%) had mild or no dysphagia and could eat solid foods. Among the 11 patients who died at more than 2 years after treatment, 6 (54.5%) died from distant metastasis. Although the number of cases is small, the results of the log-rank tests for various factors suggest that the performance status, tumor progression (TNM stage, T factor, and N factor), tumor response to definitive radiotherapy, and tumor response to induction chemotherapy might affect the prognosis.

Conclusions

Definitive radiotherapy is a promising organ-preserving treatment for CEC, especially in patients with non-T4 disease. However, new treatment strategies will be required to improve the outcomes of patients with advanced CEC, and confirmatory prospective clinical trials are required.

     

Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis

A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrations, variability of concentrations, and failures to maintain target levels that distinguished patients with low, intermediate, and high risks of acute GVHD (hazard ratios (HR) 1.77, 95%CI 1.36–2.32, p < 0.0001). This model was used to compare 95 patients with CsA and 239 with Tac GVHD prophylaxis. In the multivariate analysis, incorporating PK risk, no differences were observed for grade II–IV acute GVHD (HR 0.73, 95%CI 0.48–1.10, p = 0.13), but grade III–IV acute GVHD was lower in the Tac group (HR 0.47, 95%CI 0.28–0.78, p = 0.004). The observed difference was due to patients with high PK risk (HR 0.377, 95%CI 0.19–0.75, p = 0.005), but not with low and intermediate PK risk (p > 0.05). Patients in the Tac group had better GVHD relapse-free survival (HR = 0.659, p = 0.01) and comparable overall survival (p > 0.05). In conclusion, PK risk should be accounted for in comparisons of GVHD prophylaxis regimens with calcineurin inhibitors, and Tac was superior to CsA in patients with high, but not intermediate and low PK risk.     

Prognostic influence of hepatic margin after resection of colorectal liver metastasis: role of modern preoperative chemotherapy

Purpose

Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status.

Methods

Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database.

Results

Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001).

Conclusion

In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.