PR1 Vaccine Elicited Immunological Response after Hematopoietic Stem Cell Transplantation Is Associated with Better Clinical Response and Event-Free Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 577-577 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Eric D. Wieder ◽  
Peter F. Thall ◽  
Xuemei Wang ◽  
Rosa L. Rios ◽  
...  
Keyword(s):  
Clinical Response ◽  
Proportional Hazards ◽  
Chronic Gvhd ◽  
Peptide Vaccine ◽  
Vaccine Trial ◽  
Cox Proportional Hazards ◽  
Topical Steroids ◽  
Event Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Background: PR1 peptide has been established as a human myeloid leukemia-associated antigen. We studied PR1 peptide vaccine in a phase I/II clinical trial in HLA-A2 + patients with AML, MDS and CML. To address whether prior HSCT or prior use immunosuppressive drugs would prevent PR1-induce cytotoxic T lymphocyte (PR1-CTL) immunity after vaccination with PR1 peptide vaccine, we studied the outcome in 20 patients with a prior HSCT, who were treated on the PR1 vaccine trial. Methods: Twenty patients (13 with AML or MDS, 7 with CML) were vaccinated at a median time of 9.5 months (range: 1–220) after HSCT. Sixteen patients had received a prior allogeneic HSCT (12 had allogeneic related, 3 had allogeneic unrelated, and 1 had syngeneic) and 4 patients had a prior autologous HSCT. At the time of vaccination, 5 patients were in CR, and 15 had measurable disease. Patients could not receive systemic immunosuppressive therapy for at least 4 weeks prior to vaccination, and had to be free of acute or chronic GVHD requiring systemic therapy. The vaccine was given subcutaneously every 3 weeks for a total of 3 injections at one of three dose levels: 0.25, 0.5 and 1.0 mg. GM-CSF at a dose of 75 mg was injected subcutaneously into the same site. Immune response to the vaccine (IRV) was defined as > 2-fold increase in PR1-CTL by PR1/HLA-A2 tetramer assay. Results: After a median follow up of 56.5 months (range: 27–89), toxicity was limited to grade I/II injection site reactions in 7 (35%) patients. IRV were observed in 11/20 (55%) patients. Nine of 11 (82%) IRV+ patients versus 1 of 9 (11%) IRV- patients had clinical responses (p = .005). Median event-free survival (EFS) was 23.8 months in IRV+ patients versus 1.9 months in IRV- patients (p=0.03). Median overall survival (OS) in IRV+ patients has not yet been reached vs. 40 months in IRV- patients (p = 0.08). Only 2 patients with pre-existing, limited chronic GVHD experienced a mild exacerbation within 3 months of vaccination, which was controlled with topical steroids. PR1-CTL were enriched in central memory phenotype (TCM) that persisted up to 4 years in clinical responders. Univariate and multivariate Cox proportional hazards analyses showed a low pre-vaccine bone marrow blast count (<10%) was associated with a lower risk of progression (p=0.001 and 0.001, respectively). Type of HSCT, interval between HSCT and PR1 vaccine, PR1 dose level and disease status at HSCT did not have a significant impact on EFS or OS. Conclusion: PR1 vaccine produced PR1-CTL in 11/20 (55%) patients after HSCT. IRV was associated with significantly better clinical response and longer EFS. Figure Figure

scholarly journals Prognostic Factors for Event-Free Survival in Pediatric Patients with Hepatoblastoma Based on the 2017 PRETEXT and CHIC-HS Systems

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1387 ◽  
Author(s):  
Hee Mang Yoon ◽  
Jisun Hwang ◽  
Kyung Won Kim ◽  
Jung-Man Namgoong ◽  
Dae Yeon Kim ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Proportional Hazards ◽  
Hazard Analysis ◽  
Staging System ◽  
Cox Proportional Hazards ◽  
Event Free Survival ◽  
Free Survival ◽  
Tertiary Referral Center ◽  
C Statistic ◽  
Pre Treatment

This study aimed to evaluate the prognostic value of variables used in the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system and the Children’s Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system in pediatric patients with hepatoblastoma. A retrospective analysis of data from the pediatric hepatoblastoma registry of a tertiary referral center was conducted to evaluate the clinical and imaging variables (annotation factors) of the PRETEXT staging system. The primary outcome was event-free survival (EFS). Data from 84 patients (mean age: 2.9 ± 3.5 years) identified between 1998 and 2017 were included. Univariable Cox proportional hazards analysis revealed that PRETEXT annotation factors P (portal vein involvement), F (multifocality of tumor), and M (distant metastasis) showed a significant negative association with EFS. Multivariable Cox proportional hazard analysis showed that factor F was the strongest predictor (HR (hazard ratio), 2.908; 95% CI (confidence interval), 1.061–7.972; p = 0.038), whereas factor M showed borderline significance (HR, 2.416; 95% CI, 0.918–6.354; p = 0.074). The prediction model based on F and M (F + M) showed good performance to predict EFS (C-statistic, 0.734; 95% CI, 0.612–0.854). In conclusion, the PRETEXT annotation factor F was the strongest predictor of EFS, and the F + M model showed good performance to predict EFS in pediatric patients with hepatoblastoma.

Depressive Symptoms

2016 ◽  
Vol 39 (4) ◽  
pp. 539-552
Author(s):  
Muna H. Hammash ◽  
Terry A. Lennie ◽  
Timothy Crawford ◽  
Seongkum Heo ◽  
Misook L. Chung ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Survival Data ◽  
Proportional Hazards ◽  
Heart Association ◽  
Cox Proportional Hazards ◽  
Health Perceptions ◽  
Class Iii ◽  
Event Free Survival ◽  
Free Survival ◽  
The Relationship

Depressive symptoms and poor health perceptions are predictors of higher hospitalization and mortality rates (heart failure [HF]). However, the association between depressive symptoms and health perceptions as they affect event-free survival outcomes in patients with HF has not been studied. The purpose of this secondary analysis was to determine whether depressive symptoms mediate the relationship between health perceptions and event-free survival in patients with HF. A total of 458 HF patients (61.6 ± 12 years, 55% New York Heart Association Class III/IV) responded to one-item health perception question and completed the Patient Health Questionnaire–9. Event-free survival data were collected for up to 4 years. Multiple regression and Cox proportional hazards regression analysis showed that depressive symptoms mediated the relationship between health perceptions and event-free survival. Decreasing depressive symptoms is essential to improve event-free survival in patients with HF.

scholarly journals Usefulness of quantitative 99mTc-pyrophosphate SPECT/CT for predicting the prognosis of patients with wild-type transthyretin cardiac amyloidosis

2022 ◽  
Author(s):  
Kouji Ogasawara ◽  
Shinya Shiraishi ◽  
Noriko Tsuda ◽  
Fumi Sakamoto ◽  
Seitarou Oda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Accuracy Evaluation ◽  
Inferior Wall ◽  
Wild Type ◽  
Event Free Survival ◽  
Free Survival ◽  
Septal Wall ◽  
Quantitative Indices

Abstract Purpose Wild-type transthyretin-related amyloidosis cardiomyopathy (ATTRwt-CM) is an increasingly recognized cause of heart failure especially in elderly patients. The purpose of the present study was to determine retrospectively whether the quantitative indices of 99mTc-pyrophosphate (PYP) SPECT/CT help to predict the prognosis of ATTRwt-CM patients when compared with other clinical parameters. Materials and methods Sixty-eight patients with biopsy-proven ATTRwt-CM who underwent PYP SPECT/CT were enrolled. Baseline clinical characteristics, echocardiographic parameters, and qualitative and/or quantitative indices of planar and SPECT/CT imaging in PYP scintigraphy for each patient were included. For quantitative analysis of SPECT/CT, the accumulation ratio of PYP in the septum, posterior, anterior, lateral, and apex walls to the cavity pool was calculated as the septal wall-to-cavity ratio (Se/C), lateral wall-to-cavity ratio (La/C), anterior wall-to-cavity ratio (An/C), inferior wall-to-cavity ratio (In/C), and apical wall-to-cavity ratio (Ap/C), respectively. Endpoints for prognostic accuracy evaluation were cardiac death or hospitalization due to heart failure. Event-free survival rate was evaluated through Cox proportional hazards regression analysis, providing estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and Kaplan–Meier curves. Results High-sensitivity cardiac troponin T (hs-cTnT), La/C, age, interventricular septal thickness in diastole, and E/e′ ratio in the septal wall were significantly associated with event-free survival (P < 0.05). For a multivariable Cox proportional hazards analysis, hs-cTnT (HR 1.153; 95% CI 1.034–1.286; P < 0.01), La/C (HR 2.091; 95% CI 1.012–4.322; P = 0.046), and age (HR 1.116; 95% CI 1.007–1.238; P = 0.037) were significant independent prognostic factors. Conclusion This study indicated that the quantitative indices of PYP SPECT/CT can help to predict the prognosis of ATTRwt-CM patients.

Abstract 15644: Proinflammatory Diet Independently Predicts Shorter Event-free Survival in Patients With Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Junghee Kang ◽  
Debra K Moser ◽  
Martha J Biddle ◽  
Terry A Lennie
Keyword(s):  
Heart Failure ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Enzyme Inhibitor ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Event Free Survival ◽  
Free Survival ◽  
Phone Calls

Introduction: Inflammation is a common biological process accompanying chronic conditions, such as heart failure (HF) that can be moderated by diet. The association between foods thought to promote inflammation and event-free survival in patients with HF has not been investigated. Hypothesis: The inflammatory potential of individuals’ diets, measured using the dietary inflammatory index (DII), will be associated with event-free survival in patients with HF. Methods: The DII scores were calculated from 4-day food diaries recorded at baseline by 213 patients with HF (age 61±12years, 35% female, 43% NYHA III/IV). Patients were followed for a median of 365 days by monthly phone calls, medical record review, and death records to determine time to all cause-hospitalization or death. The DII scores were dichotomized using median value for the Cox regression model. Hierarchical multivariate Cox proportional hazards model was used to determine whether DII scores predicted event-free survival after controlling for age, gender, body mass index, prescribed angiotensin-converting-enzyme inhibitor, beta-blocker, cholesterol lowering agent, antiinflammatory agent, N-terminal pro B-type natriuretic peptide, comorbidity, depressive symptoms, and the New York Heart Association functional classification. Results: The DII scores independently predicted event-free survival in the model constant ( p = 0.012). Higher DII scores were associated with more than double the risk of an event compared to lower DII scores (HR: 2.28, 95% Confidence Interval =1.21-4.36). Conclusions: Greater intake of foods considered to promote inflammation was associated with shorter event-free survival in patients with HF. These results provide further evidence of the importance of diet to HF outcomes.

scholarly journals Event-Free Survival after 68Ga-PSMA-11 PET/CT in recurrent Hormone-Sensitive Prostate Cancer (HSPC) patients eligible for Salvage Therapy.

2021 ◽  
Author(s):  
Francesco Ceci ◽  
Guido Rovera ◽  
Giuseppe Carlo Iorio ◽  
Alessia Guarneri ◽  
Valeria Chiofalo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salvage Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Psma Pet ◽  
Hormone Sensitive

Abstract Background/AimProstate-Specific-Membrane-Antigen/Positron Emission Tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically-relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. Materials and Methodsthis analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as: death, radiological progression or PSA recurrence after therapy. ResultsOne-hundred and seventy-six (n=176) patients were analyzed (median PSA 0.62 [IQR:0.43–1.00] ng/mL; median follow-up of 35.4 [IQR:26.5-40.3] months). The EFS was 78.8% at one year, 65.2% (2-years), and 52.2% (3-years). Patients with clinically relevant events had a significantly higher median PSA (0.81 [IQR:0.53-1.28] vs 0.51 [IQR:0.36-0.80] ng/mL) and a lower PSAdt (5.4 [IQR:3.7-11.6] vs 12.7 [IQR:6.6-24.3] months) (p<0,001) compared to event-free patients. The Kaplan-Meier curves showed that PSA>0.5 ng/mL, PSAdt≤6 months and a positive PSMA-PET result were associated with a higher event rate (p<0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA> 0.5 ng/mL and PSAdt≤ 6months were statistically significant event-predictors in multi-variate model (p<0.001). ConclusionIn this cohort of HSPC patients prospectively enrolled, low PSA and long PSAdt were significant predictors of event. Furthermore, a lower incidence of events was observed also in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 59-59
Author(s):  
Umang Swami ◽  
Taylor Ryan McFarland ◽  
Benjamin Haaland ◽  
Adam Kessel ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
Risk Of Progression ◽  
The Relationship

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]

scholarly journals GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia

2019 ◽  
Vol 3 (9) ◽  
pp. 1441-1449 ◽  
Author(s):  
Rohtesh S. Mehta ◽  
Shernan G. Holtan ◽  
Tao Wang ◽  
Michael T. Hemmer ◽  
Stephen R. Spellman ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Leukemia ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cox Proportional Hazards ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Grade Iii

Abstract We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy–requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen–mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P &lt; .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation–based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P &lt; .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

MiR-340 Expression As a Prognostic Marker to Guide Clinical Decision-Making in Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2728-2728
Author(s):  
Tingting Shao ◽  
Yuan Feng ◽  
Ninghan Zhang ◽  
Rong Wang ◽  
Ting Pan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hematopoietic Stem ◽  
Proportional Hazards Models ◽  
Chemotherapy Group ◽  
Cox Proportional Hazards Models ◽  
Hoxa Genes ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is an aggressive hematological disease. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and chemotherapy are major treatment regimens for AML. However, prognostic markers cannot guide the decision for a specific treatment, as they are related with a various prognosis regardless of the given treatment. HOXA (homeobox A) genes cluster could promote tumor survival, proliferation, invasion, and increase the resistance of AML. The aim of this study was to screen potential miRNAs (microRNAs) that would target HOXA genes, and evaluate the utility of miRNAs in AML, help patients choose a better treatment between chemotherapy and allo-HCST. Methods: Clinical data and RNA-Seq expression data of selected cases were provided by The Cancer Genome Atlas (TCGA). Genome-wide screening was performed to identify miRNA in a heterogeneous AML population. Univariable Cox proportional hazards models and Multivariable Cox proportional hazards models were employed to identify whether OS and EFS would be affected by other variables. Results: In this study, totally 162 AML patients were recruited. All patients were firstly divided into the chemotherapy and allo-HSCT groups. Subsequently, according to median values of miR-340, patients were divided into miR-340high and miR-340low expressers, respectively. In chemotherapy group, no difference was found in clinical characteristics, such as the median age, FAB subtypes, karyotypes and genes mutation between miR-340high and miR-340low expressers. However, miR-340low expressers often accompanied with high first relapse rate or death rate in one year than high expressers (P=0.012; 82.2% vs 55.6%). To identify the independent prognostic role of miR-340 in chemotherapy group patients, Univariable and Multivariable Cox proportional hazards models were performed. We found that miR-340lowpatients showed shorter OS (P=0.0005; 5-year OS, 35.6% vs. 5.4%) and EFS (P=0.0005) compared with high expressers. In multivariable analysis, miR-340low patients showed reduced OS (P=0.004; HR: 2.07) and EFS (P=0.01; HR: 1.909) after adjusting other co-variates, such as age, WBC count and several genes mutation in chemotherapy group. Therefore, low miR-340 amounts could be an independent adverse bio-marker in AML patients undergoing chemotherapy. However, in the allo-HSCT group, miR-340 expression level was not associated with outcome in AML patients. To further explore the potential of allo-HSCT in overcoming the adverse characteristics of low miR-340 amounts, the whole 162 patients were regrouped into miR-340low and miR-340high groups. Then patients were divided into chemotherapy and allo-HSCT subgroups. Subgroup analysis revealed that miR-340low patients had significantly longer OS (P<0.0001; HR: 0.316; 95%CI: 0.167-0.459) and EFS (P=0.002; HR: 0.391; 95%CI: 0.231-0.622) in allo-HSCT subgroup than in chemotherapy subgroup (Figure 1). However, in cases highly expressing miR-340, no difference in survival events was detected between the two treatment subgroups. These findings indicated, allo-HSCT may overcome the adverse prognostic effects of low mir-340 expression. Therefore, for low miR-340 cases, early allo-HSCT may be a better option. To explore underlying biological functions of miR-340, we examined gene expression signatures related to the miR-340 expression in AML patients. We observed 135 genes expression levels that associated with miR-340 expression, with 61 and 74 showing positive and negative correlations, respectively. Gene Ontology showed that these genes involved in cellular and developmental processes, transcription regulation, immune system process, cell apoptosis and proliferation, myeloid cell differentiation and hematopoietic organ development. Furthermore, miR-340 expression was negatively correlated with HOXA and HOXB cluster levels. Strikingly, HOXA10, HOXB2, MEIS1 and PRDM16 were predicted miR-340 targets according to in silico analysis. The results hint a prospective regulatory mechanism that links miR-340 to HOXA genes associated with AML. Conclusions: Our data indicate that decreased miR-340 expression predicts an adverse prognosis and allo-HSCT may overcome the potential adverse characteristics of low miR-340 expression. Therefore, lower miR-340 cases should be strongly considered for early allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Graft-Versus-Tumor Effect In Patients with Graft-Versus-Host Disease Defined by NIH Consensus Criteria

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2343-2343
Author(s):  
Sung-Eun Lee ◽  
Byung-Sik Cho ◽  
Seung-Ah Yahng ◽  
Ki-Seong Eom ◽  
Yoo-Jin Kim ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Proportional Hazards ◽  
Chronic Gvhd ◽  
Onset Time ◽  
Cox Proportional Hazards ◽  
Time Dependent ◽  
Survival Outcomes ◽  
Proportional Hazards Regression ◽  
Short Course ◽  
Unrelated Donors

Abstract Abstract 2343 Background. The National Institutes of Health consensus criteria (NCC) for chronic graft-versus-host disease (GVHD) are based on clinical manifestations rather than onset time after transplantation. Previous studies about the feasibility of the new criteria have been performed in patients who survived beyond 100 days after transplantation and had GVHD presenting after day 100. In order to investigate and compare the clinical impact of acute and chronic GVHD by NCC on survival, a cohort including patients with GVHD presenting ‘before' as well as ‘after' day 100 is needed. Additionally, a proper statistical tool should be applied to clarify the effect of GVHD on survival outcomes, because the occurrence of GVHD is a well known time-dependent event. In this context, we examined a cohort including all patients who underwent allogeneic stem cell transplantation (SCT) in order to investigate clinical impact of acute or chronic GVHD by NCC on survival outcomes. Methods. We retrospectively investigated 771 patients who underwent allogeneic SCT between January 2002 to December 2008. To study a homogenous cohort, patients received 2 allogeneic SCT and/or donor-lymphocyte-infusion was excluded. We used time-dependent analyses to reveal the effect of GVHD on survival outcomes. In particular, to approach the effects of GVHD as a time-dependent covariate on competing risks [relapse or transplant-related mortality (TRM)], we analyzed cause-specific hazards by Cox proportional hazards regression model (Cartese G, Andersen PK. Biometrical Journal 2009;51:138–158). Results. The median age was 36 years (range, 15–68). Patients had various hematologic malignancies (AML/ALL/CML/MDS/MM, 361/226/86/67/31, respectively) and were transplanted from matched sibling (n=485), well-matched unrelated donors (n=154), partially-matched unrelated donors (n=101), and mismatched unrelated donors (n=31). Conditioning regimens consisted of myeloablative (n=536) and reduced-intensity regimens (n=235). GVHD prophylaxis consisted of cyclosporine and short-course methotrexate for related SCT and tacrolimus and short-course methotrexate for unrelated SCT. Among 771 patients, 540 patients were diagnosed with GVHD after transplantation. According to onset time of GVHD, in 348 patients GVHD developed within 100 days after SCT, whereas in 156 patients GVHD occurred more than 100 days after SCT. Using the NCC, we classified patients as three categories regardless of onset time: (1) acute GVHD (n=215), if patients had only acute features (no chronic features) during the course of GVHD, (2) acute GVHD with following chronic GVHD (n=118), if patients had any chronic features after the occurrence of acute GVHD, and (3) chronic GVHD (n=207), if patients had any chronic features at the onset of GVHD. Multivariate analyses using cause-specific hazards revealed that acute GVHD was significantly associated with lower relapse incidence [HR (95% CI) 0.65 (0.44–0.94), P=0.023]. However, it did not influence disease-free survival (DFS, P=0.602) and overall survival (OS, P=0.294) due to higher TRM in patients with acute GVHD [HR (95% CI) 1.74 (1.15–2.61), P=0.008]. Acute GVHD with following chronic GVHD was also associated with lower relapse incidence [HR (95% CI) 0.31 (0.15–0.66), P=0.002] and higher TRM [HR (95% CI) 2.89 (1.65–5.04), P<0.001], which did not influence DFS (P=0.567) and OS (P=0.820). On the other hand, the occurrence of chronic GVHD significantly reduced relapse rates [HR (95% CI) 0.46 (0.29–0.75), P=0.002] without increasing TRM (P=0.177). Indeed, this effect was translated into improved DFS [HR (95% CI) 0.67 (0.48–0.95), P=0.023]. Conclusions. Our data show that both acute and chronic GVHD by NCC reduced the risk of relapse, demonstrating the presence of graft-versus-tumor (GVT) effect by the occurrence of GVHD and no difference according to the clinical features (acute or chronic) by NCC. However, survival benefit was only observed in chronic GVHD by NCC compared to acute GVHD with/without following chronic GVHD by NCC due to higher TRM. This study represents the first one demonstrating the GVT effect of GVHD defined by NCC in a cohort including GVHD presenting ‘before' as well as ‘after' day 100 using appropriate time-dependent analyses by cause-specific hazards by Cox proportional hazards regression model. Disclosures: No relevant conflicts of interest to declare.

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