Independent Prognostic Factor For Relapse Research Articles

Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes

BackgroundThe development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels of cytokines and clinical features and investigate their impact on the prognosis of patients with DLBCL. MethodsWe conducted a retrospective study of 77 patients with newly diagnosed DLBCL to explore the relationships between different cytokines, adverse clinical features, and poor outcomes. The Mann–Whitney U test was used to compare the cytokine profiles between patients with DLBCL and healthy controls. The Kaplan–Meier method was used to analyze the probability of survival, and the log-rank tests were used to evaluate the differences between survival curves. The Cox proportional hazards regression model was used to performed univariate and multivariate analyses to evaluate prognostic variables for survival analyze. ResultsSerum levels of interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, and IFN-γ were significantly elevated in patients with untreated DLBCL. Serum levels of IL-6 and IL-10 were significantly higher in patients with an International Prognostic Index (IPI) of 3–5, bone marrow involvement, serum levels of LDH ≥ 250 U/L, and β2-microglobulin (β2-MG) levels ≥ 2.3 mg/L. Patients with B symptoms only had higher serum IL-10 levels, whereas patients with a partial response or no response to treatment had significantly elevated serum levels of IL-6 as well as IL-10. Significant positive correlations were observed between the levels of IL-6 and IL-10 with those of β2-MG and LDH. Patients with levels of IL-6 ≥ 4.5 or IL-10 ≥ 5.0 pg/mL, as well as combined elevated IL-6 and IL-10 levels, exhibited shorter progression-free survival and overall survival. Additionally, univariate and multivariate analyses revealed that serum levels of IL-6 ≥ 4.5 pg/mL and IL-10 ≥ 5.0 pg/mL and IPI 3–5 were independent prognostic factors for relapse and survival in patients with DLBCL. ConclusionsPre-treatment serum IL-6 and IL-10 levels in patients with newly diagnosed DLBCL might be powerful markers for determining treatment response and predicting the prognosis of DLBCL.

Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation.

The objective of this study was to investigate the clinical significance of minimal residual disease (MRD) monitoring through Wilms tumor 1 (WT1) gene expression and multicolor flow cytometry (FCM) in patients with chronic myelomonocytic leukemia (CMML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). For this purpose, WT1 gene expression and the CMML-related abnormal immunophenotype were examined using real-time quantitative polymerase chain reaction and FCM, respectively. In total, 59 patients with CMML who underwent allo-HSCT were enrolled in this study. Thirteen cases (22.0%) developed hematological relapse, and 15 patients (25.4%) expired during the follow-up period. Thirty-four patients (37.6%) were positive for WT1 (WT1+), and 44 patients (74.6%) were positive for FCM prior to allo-HSCT. After allo-HSCT, there were 21 WT1+ patients (35.6%) and 10 patients (16.9%) who were positive in FCM (FCM+). Post-transplant WT1+ (post-WT1 0.6+; 50.7% vs. 7.6%, p<.001) and post-transplant FCM+ (post-FCM+; 90.0% vs. 8.8%, p<.001) indicated a higher 3-year cumulative incidence of relapse (CIR) compared with the WT1- or FCM-patients. Multivariate analysis of event-free survival (EFS), overall survival (OS), and CIR showed that the FCM status after transplantation was an independent prognostic factor for relapse (p<.05). Both FCM and WT1 after HSCT were identified as important predictors of recurrence of CMML following transplantation and may be useful in guiding interventions against disease relapse.

El papel pronóstico del SUVmáx basal y cambio del SUVmáx en la PET/TC con18F-FDG en pacientes con cáncer de mama con ganglios positivos que reciben quimioterapia neoadyuvante

ObjectiveThis study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC). MethodsOne hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves. ResultsΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively). ConclusionThe results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC.

The Factors Related to Treatment Failure in Children with Acute Lymphoblastic Leukemia

To analyze the efficacy of CCLG-ALL-2008 protocol and the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). The clinical data of 400 children newly-diagnosed ALL in Children's Hospital of Soochow University from March 1, 2008 to December 31, 2012 was retrospectively analyzed. All the children accepted CCLG-ALL-2008 protocol, and were followed-up until October 2019. The dates of relapse, death and causes of death were recorded. Treatment failure was defined as relapse, non-relapse death, and secondary tumor. Following-up for 10 years, there were 152 cases relapse or non-relapse death, the treatment failure rate was 38%, including 122 relapse (80.3%), 30 non-relapse deaths (19.7%) which included 7 cases (4 cases died of infection and 3 cases died of bleeding) died of treatment (23.3% of non-relapse deaths), 8 cases died of minimal residual disease (MRD) continuous positive (26.7% of non-relapse deaths) and 15 cases died of financial burden (50% of non-relapse deaths). According to the relapse stage, 37 cases (30%) in very early stage, 38 cases (31%) in early stage, and 47 cases (39%) in late stage, while according to the relapse site, 107 cases relapsed in bone marrow, 3 cases in testis, 3 cases in central nervous system (CNS), 5 cases in bone marrow plus testis and 4 cases in bone marrow plus CNS. Bone marrow relapse was the main cause of death in 89 cases, followed by nervous system. Initially diagnosed WBC count (≥50×109/L), T-cell immunophenotype, and MRD-positive at week 12 were the independent risk prognostic factors for relapse in children with ALL, while age (≥10 years), initially diagnosed WBC count (≥50×109/L), M3 bone marrow on day 15, and MRD-positive at week 12 were the independent risk factors due to treatment failure. No secondary tumors were found during the follow-up for 10 years. Relapse is the main cause of treatment failure in children with ALL. The initially diagnosed WBC count, immunophenotype and MRD at week 12 were the independent prognostic factors for relapse of the patients. Financial burden accounts for a large proportion of non-relapse death.

The prognostic role of baseline 18F-FDG PET/CT SUVmax and SUVmax change in patients with node-positive breast cancer receiving neoadjuvant chemotherapy

ObjectiveThis study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC). MethodsOne hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves. ResultsΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (P < .001, P = .033, P = .016, and P = .013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (P = .001 and P = .006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (P = .013 and P = .010, respectively). ConclusionThe results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC.

Prognostic factors for early relapse in non-metastatic triple negative breast cancer - real world data.

Triple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse. Single-centre retrospective analysis of 127 women with TNBC, stage II-III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse. After 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3-22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2-6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1-1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively). In this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.

Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T-cell acute lymphoblastic leukaemia.

Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P=0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P=0·0005) and overall survival (OS) (32·7% vs. 69·7%, P<0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P=0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P=0·046], RFS (HR 2·125, P=0·048) and OS (HR 2·987, P=0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.

High neutrophil-to-lymphocyte ratio is associated with relapse in Graves' disease after antithyroid drug therapy.

Antithyroid drugs (ATDs) are effective in controlling hyperthyroidism due to Graves' disease (GD); however, long-term remission rates are low. The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic marker in many inflammatory diseases. We aimed to evaluate whether NLR can be used as a prognostic marker for relapse in patients with GD after ATD therapy. This retrospective cohort study included 108 patients with newly diagnosed GD who achieved remission after ATD therapy and were followed-up for >12 months after ATD discontinuation. The primary outcome was relapse-free survival (RFS). Patients were classified into two groups according to baseline NLR: low NLR group with NLR < 1.14 (n = 59; 55%) and high NLR group with NLR ≥ 1.14 (n = 49; 45%). During the median follow-up of 6.5 years, disease relapse after a year of ATD withdrawal occurred in 23 (21%) patients. The patients with high NLR had poorer RFS than those with low NLR, and RFS curves were significantly different between the two groups (p = 0.002). In multivariate analysis, a high NLR (OR = 4.22, p = 0.016) was an independent prognostic factor for relapse in patients with GD after adjusting for age, sex, goiter, orbitopathy, thyroid hormone levels, thyrotropin binding inhibiting immunoglobulin titer, and the duration of ATD therapy. This study showed that NLR can be an early and cost-effective prognostic biomarker for relapse in patients with GD after ATD therapy. Further studies are needed to validate the prognostic role of NLR in GD.

Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study.

BackgroundThe clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31‐gene expression profile (DecisionDx‐Melanoma) test has shown promising results.ObjectivesTo evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort.MethodsInclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease‐free survival was determined using Kaplan–Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk).ResultsMedian follow‐up time was 26 months (IQR 22–30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age.ConclusionsThis prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31‐gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow‐up strategies.

Postoperative clinicopathological factors affecting cervical adenocarcinoma: Stages I-IIB.

Currently, cervical adenocarcinoma (ADC) receives the same standard treatment as squamous cell carcinoma, but this treatment regimen is not wholly suited for ADC. The present study was conducted to assess the prognostic role of postoperative clinicopathological factors in patients with stage I–IIB cervical ADC.The study examined 312 patients with stage I–IIB cervical ADC who underwent radical hysterectomy, including pelvic lymphadenectomy, at our institutions between October 2006 and September 2014. Overall survival (OS) and relapse-free survival (RFS) was analyzed by the Kaplan–Meier method. Sites of recurrence were classified as local and distant locations.The 5-year OS and RFS rates were 88.2% and 83.8%, respectively. The 5-year OS rates for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, IIA, and IIB were 100.0%, 90.7%, 82.8%, and 55.6%, respectively. The Cox model identified number of positive pelvic nodes and age at surgery as independent prognostic factors for survival, and number of positive pelvic nodes and postoperative tumor diameter (≥4 cm) as independent prognostic factors for relapse. Cancer recurrence developed in 35 women. The top three recurrence sites were pelvis, vaginal stump, and lung.A more aggressive therapeutic strategy different from current practice in cervical cancer is urgently required for cervical ADC. As a new prognostic factor, postoperative tumor diameter should receive special attention in ADC treatment.

Failure Patterns of Luminal B Breast Cancer Following Postoperative Adjuvant Radiation Therapy

The establishment of surrogate definitions for breast cancer molecular subtypes according to IHC has clinically demonstrated prognostic relevance for improved objective risk profiling and individualization of treatment regimens. Defining and stratifying luminal B subtypes, however, still remains indefinite and is in need of more distinct differentiation due to its heterogeneous clinical and molecular characteristics. This study aims to identify prognostic factors for early relapse in luminal B HER2-negative (LBHER2-) and -positive (LBHER2+) subgroups, and to evaluate failure patterns between the latter and HER2-enriched breast cancer after adjuvant PORT. Medical records of 516 women diagnosed with luminal B or HER2-enriched breast cancer that underwent surgical resection and PORT at Seoul National University Bundang Hospital (SNUBH) from 2003 to 2012 were retrospectively reviewed. Based on available IHC and FISH results, molecular subtypes were defined according to the 2013 St. Gallen International Expert Consensus recommendation as LBHER2- in 258 patients (50.5%), LBHER2+ in 136 patients (26.4%), and HER2-enriched in 122 patients (23.6%). Significant differences were observed between the luminal B subgroups, with LBHER2- demonstrating higher proportions of patients with age younger than 50 years (p=0.012), high histologic grade (p < 0.001), and positive expression of p53 (p=0.007). Patterns of care were also significantly different, with higher rates of systemic therapy omission in LBHER2- patients (p=0.001). After a median follow-up duration of 6.3 years, 10-year OS rates were 87.9% and 97.0% for LBHER2- and LBHER2+, respectively (p=0.062). On multivariable Cox regression analysis, N stage in LBHER2- and N stage and histologic grade in LBHER2+ were identified as independent prognostic factors for relapse within 5 years. When compared with HER2-enriched breast cancer, LBHER2+ expressed lower rates of local recurrence (p=0.046) and brain metastasis (p=0.026). Luminal B breast cancer manifest various patterns of failure among which trends to poorer prognosis is seen in the LBHER2- subgroup. The majority of LBHER2+ patients undergo some form of systemic treatment and demonstrate relatively better clinical outcomes than LBHER2- patients. Further stratification of risk prediction, particularly in the LBHER2- subgroup, and more aggressive systemic treatment are needed to improve treatment outcomes, of which p53 may be a potential marker.

1020P - Clinical impact of atypical phenotypes in adult t cell lymphoma/leukemia among HTLV carriers

Background: ATLL represents a fatal disease epidemiologically linked to chronic infection with human T-cell lymphotropic virus type 1 (HTLV1). The diagnosis is classically described based on morphology, immunophenotype (typically CD7, CD8, CD56, ALK, EBV and PAX5 negatives). Our aim was to describe characteristics and compare outcomes between patients with classical ATLL and those with mature T-cell lymphoma and HTLV1 infection (atypical ATLL). Methods: We reviewed 276 medical records from pts with HTLV1 infection and T-cell lymphomas diagnosed between 2008-2014 at the Instituto Nacional de Enfermedades Neoplasicas (Peru). Groups were divided based on presence of classical characteristics of ATLL, outcomes and survival differences were calculated by log-rank test in the univariate analysis and Cox regression analysis for prognostic factors. Results: From 276 pts, 126 (45%) had classical ATLL phenotype and 150 (54%) were atypical. Mean age was 56 years and 19% were <45y, tuberculosis was presented in 32 pts (11.6%). Pts with classical disease had shorter length of disease (3.5 versus 5.6 months, p = 0.01), more B symptoms (51.6% vs 38.7%), bone marrow (51 vs 28%) and peripheral blood involvement (54 vs 32%) than pts with atypical ATLL. According to Shimoyama classification, acute subtype was most common in classical ATLL (46%), as Lymphoma most frequent subtype in atypical ATLL (54%). Most pts received a CHOP-based chemotherapy (71%) and overall response were 28% for classical ATLL (CR:15%, PR:12%) and 41% for atypical ATLL (CR:25%, PR:16%). At 5 years follow-up, median PFS were 2 months in classical and 4 months in atypical ATLL (HR: 1.30, 95%CI [1.02-1.67], p = 0.036), and median overall survival (OS) were 4 and 7 months for classical and atypical ATLL respectively (HR: 1.51, 95%CI [1.17-1.95], p = 0.002). In multivariate analysis, high levels of calcium and LDH, status performance and neutrophil-to-lymphocite ratio were independent prognostic factors for relapse and death. Conclusions: It seems that there are atypical presentations of adult T cell lymphoma/leukemia with slightly better response to chemotherapy and survival, further studies with integration of viral RNA to neoplastic tissues are needed to confirm this category. Legal entity responsible for the study: Instituto Nacional de Enfermedades Neoplasicas Funding: None Disclosure: All authors have declared no conflicts of interest.

Thymidine kinase 1 expression in ovarian serous adenocarcinoma is superior to Ki-67: A new prognostic biomarker.

Cancer is a disease with abnormally proliferating cells and therefore proliferation rate is an important index for assessing tumour growth. Ki-67 is a commonly used proliferation marker considered to be an unfavourable prognostic marker in some tumors, while Thymidine kinase 1 (TK1) is an interesting proliferation marker because its levels are highly dependent on the growth stage of cells. To define the immunohistochemistry (IHC) expression of the TK1 in patients with ovarian serous adenocarcinoma and establish its potential role as a new biomarker for progressive disease, we analyzed the expression patterns of TK1 and Ki-67 in 109 patients with ovarian serous adenocarcinoma. TK1 and Ki-67 expression both showed a statistically significant correlation to MD Anderson Cancer Center (MDACC) grade, but not to age, tumour size, lymph node metastasis or pathological TNM (pTNM) stages. TK1 expression, MDACC grades, pathological stages and lymph node metastasis correlate to relapse incident rate and overall survival, but Ki-67 does not. Although TK1 expression, MDACC grade, pTNM stage and lymph node metastasis significantly correlate to relapse in the Cox univariate analysis, in the multivariate Cox analysis only TK1 expression and lymph node metastasis were independent prognostic factors. The overall survival also correlated significantly to TK1 expression, MDACC grade, pTNM stage and lymph node metastasis in the Cox univariate analysis. However, only the pTNM stage was found to be an independent prognostic factor for survival in the Cox multivariate analysis. Therefore, though TK1 expression was an independent prognostic factor for relapse, but not for survival, TK1 is a more informative expression than Ki-67 for LI, relapse and overall survival rates. Thus, when TK1 is combined with MDACC grading, pTNM staging and lymph node metastasis, IHC determination of TK1 expression may improve the overall prediction of prognosis in patients with ovarian cancer.

C-KIT- Mutated t(8;21)AML Patients with >3log Reduction of MRD Conferred a Very High Relapse and Need HSCT to Improve Outcome

[Objective] Previous studies showed that c-KIT mutation and <3log reduction of minimal residual disease (MRD) were two poor prognostic markers for acute myeloid leukemia (AML) with t(8;21) . However, How to deal with c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD remains undefined. To answer this question, we performed this study.[Methods] The current retrospective study consisted of 70 newly diagnosed patients with c-KIT- mutated t(8;21)AML during July 2005 and March 2016 in Peking University People's Hospital. Induction treatment included standard 3+7' regimen or HAA regimen. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was recommended to all patients with an available donor after 2-3 cycles of consolidation treatment with high-dose cytarabine(HDAC). Patients without a donor or refusing HSCT received HDAC-based intensive treatment. MRD was determined by RUNX1/RUNX1T1 transcript levels detected by Q-PCR. The last follow-up time was July 2016.[Results] Sixty-nine out of 70 patients achieved complete remission(CR).Two patients relapsed after first cycle of consolidation treatment. There were 60 patients having the results of MRD after 2 cycles of consolidation treatment (Figure 1). Thirty-four patients achieved >3log reduction of RUNX1/RUNX1T1 transcript levels (defined as major molecular remission, MMR). There were 16 and 18 patients finally receiving chemotherapy and allo-HSCT. Twenty-six patients did not achieve MMR, and 12 and 14 patients finally receiving chemotherapy and allo-HSCH, respectively. For patients achieving MMR, the 4-year cumulative incidence of relapse (CIR) and disease-free survival (DFS) were 84.8% vs.6.7% (p<0.001) and 20.6% vs.87.5% (p<0.001) when receiving chemotherapy or allo-HSCT(Figure 2). For patients not achieving MMR, the 4-year CIR and DFS were 100% vs.30.8% (p<0.001) and 0% vs.60% (p<0.001) when receiving chemotherapy or allo-HSCT (Figure 2). Multivariate analysis revealed that MRD status (MMR or non-MMR and treatment choice (HSCT or chemotherapy) were independent prognostic factors for relapse, DFS.[Conclusion] We concluded that c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD conferred a very high relapse and need allo-HSCT to improve outcome. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery

AimSurgery is the only modality of cure in patients diagnosed with neuroendocrine tumours (NETs). The aim of this study was to identify prognostic factors associated with disease relapse in patients with NETs treated by potentially-curative surgery. MethodsSequential patients registered in The Christie European NET Society (ENETS) Centre of Excellence, with grade (G)1 or G2 NETs who had undergone curative surgery (February 2002–June 2014) were included. Investigated prognostic factors for relapse were: age, gender, TNM stage, tumour-localisation, functionality, genetic predisposition, presence of multiple NETs, second malignancy, grade (Ki-67-based), presence of vascular and/or perineural invasion, necrosis, surgical margin (R0/R1), Eastern Cooperative Oncology Group performance status and Adult Comorbidity Evaluation co-morbidity score. ResultsOne hundred and eighty-eight patients were identified [median age of 60 years (range 16–89)]. With a median follow-up of 2.6 years, 43 relapses occurred. The estimated median relapse-free survival (RFS) for the entire cohort was 8.0 years (95% confidence interval [CI] 5.9–10.0 years). In univariate analysis, primary NET location (p = 0.01), ENETS T-(HR-1.4; 95%-CI 1.0–2.0, p = 0.026), N-(HR-2.0, 95%-CI 1.1–3.9, p = 0.026) and M-stage (HR-2.6, 95%-CI 1.1–6.3, p = 0.052), grade (Ki-67%-based) (HR-2.5; 95%-CI 1.4–4.7; p = 0.003) and perineural invasion (HR-2.1; 95%-CI 1.1–3.9; p = 0.029) were prognostic for relapse. Factors remaining significant after multivariable analysis were tumour size (HR-1.67; 95%-CI 1.04–2.70; p = 0.03), nodal involvement (HR-2.61; 95%-CI 1.17–5.83; p = 0.013) and Ki-67 at the time of diagnosis (HR-1.93; 95%-CI 1.24–3.0; p = 0.002). ConclusionSize of tumour, lymph node involvement and Ki-67 were independent prognostic factors for relapse after potentially curative surgery in NET.

Tailored therapy and long-term surveillance of malignant germ cell tumors in the female genital system: 10-year experience.

ObjectiveTo explore the appropriate treatment of malignant germ cell tumor (MGCT) in the female genital system, and to analyze the factors influencing both therapeutic response and survival outcome.MethodsA cohort of 230-Chinese women diagnosed with MGCT of the genital system was retrospectively reviewed and prospectively followed. The demographic and pathological features, extent of disease and surgery, treatment efficiency, recurrence and survival were analyzed.ResultsMGCTs from different genital origins shared a similar therapeutic strategy and response, except that all eight vaginal cases were infantile yolk sac tumors. The patients’ cure rate following the initial treatment, 5-year overall survival and disease-free survival (DFS) were 85.02%, 95.00%, and 86.00%, respectively. Although more extensive excision could enhance the remission rate; it did not improve the patients’ survival. Instead, the level of the medical institution, extent of surgery and disease were independent prognostic factors for relapse (p<0.05). Approximately 20% of patients had recurrent or refractory disease, more than half of whom were in remission following secondary cytoreductive surgery with salvage chemotherapy.ConclusionFertility-sparing surgery with or without standardized PEB/PVB (cisplatin, etoposide/vincristine, and bleomycin) chemotherapy is applicable for female MGCTs of different origins. Comprehensive staging is not required; nor is excessive debulking suggested. Appropriate cytoreduction by surgery and antineoplastic medicine at an experienced medical institution can bring about an excellent prognosis for these patients.

Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis.

Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.

Best treatment option for clinical stage I seminoma patients.

In the present cross sectional study comprising 106 patients, the authors compared a risk adapted therapeutic strategy in patients with CSI seminoma [1]. The patients were distributed to active surveillance (AS) (n = 84) and adjuvant chemotherapy (ACT) (n = 22) with single dose carboplatin groups. The relapse rates between the 2 groups were similar. The authors advocated AS for patients with low risk of relapse and, on the other hand, ACT for those with high risk of relapse. The current management options for CSI seminomas include adjuvant radiotherapy (ART), AS, and ACT. ART has been the preferred treatment modality for a long time, but concerns regarding its side effects, such as risks of cardiovascular disease and secondary malignancies, resulted in a significant change in the concept of ART. Thus, the option of ART has been removed from the current guidelines [2, 3]. Surveillance avoids overtreatment in approximately 85% of patients when appropriate follow-up protocols are used [4]. However, identifying the 15% who may harbor micrometastatic disease should be of utmost importance in patients under AS. Surveillance requires highly compliant patients willing to have multiple abdominal CT scans. The radiation from abdominal CT is not benign, with a lifetime attributable risk of secondary malignancy from 4 scans for an 18 year old patient calculated at 0.64% [5]. ACT has been shown to be non-inferior to ART [6]. In the largest series of ACT, a 4.1% relapse rate was demonstrated with a median time to relapse of 22.7 months among 517 patients [7]. A recent study which investigated the practice patterns for adjuvant therapies for CSI seminoma in the US population has demonstrated that ART has been largely replaced by ACT, rather than AS [8]. However, the authors concluded that the lack of an increase in AS in their cohort might represent overtreatment of the population. Proponents of AS consider ACT a potentially harmful and unnecessary intervention. However, in recent studies, especially low risk patients were selected for AS, whereas high risk patients were given ACT [9]. Due to this reason, such series may possibly be flawed by selection bias in favor of AS, whereas predominantly low risk patients were included rather than high risk ones [10]. The long term side effects of single dose ACT remain unclear; moreover, the use of ACT does not obviate the need for abdominal CT scans, which has been proposed as a concern against AS. A risk adapted treatment strategy seems to be logical for CSI seminoma patients. Although rete testis invasion and primary tumor >4 cm were reported to be independent prognostic factors for relapse, these data have not been validated in prospective studies [11]. Currently, AS has been recognized as the treatment of choice of CSI seminomas in the EAU and American Society of Clinical Oncology guidelines [2, 3].

The relationship between WT1 expression level and prognosis in patients of acute T lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation

目的探讨监测WT1基因在急性T淋巴细胞白血病(T-ALL)患者异基因造血干细胞移植(allo-HSCT)后预后的意义。方法回顾性分析2009年1月至2012年3月在我单位行allo-HSCT，且移植后连续监测WT1基因表达水平的68例T-ALL患者。留取初治，移植前，+30、+60、+90、+180、+270、+360 d骨髓标本，用实时定量聚合酶链反应(RQ-PCR)方法监测WT1基因表达水平，同时经流式细胞术(FCM)监测微小残留病(MRD)。结果①移植后WT1基因低水平表达与较低复发风险相关；②+60、+90 d WT1基因升高与较高累计复发率相关(P<0.001、P=0.003)，与较低的无病生存率(P=0.004、P=0.006)和总生存率相关(P=0.004、P=0.007)；③移植后微小残留病(MRD)阳性是T-ALL移植后复发的独立危险因素；④联合WT1基因和FCM可用于移植后复发的监测。结论+60、+90 d WT1基因升高与T-ALL预后显著相关，应尽早予以干预，减少复发甚至死亡风险。T-ALL移植后WT1基因表达低于0.6%，复发风险较低；WT1基因表达超过0.6％需密切随访，并结合FCM监测，达到MRD阳性标准需临床干预，降低复发率。

Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia.

Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms’s sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432), event free survival (p = 0.667) or overall survival (p = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification.