Proteomic Pattern-Based Risk Stratification of Outcome Shows Significant Higher Accuracy Compared to HCT-CI in Patients with AML and MDS,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4128-4128
Author(s):  
Christiane E Dobbelstein ◽  
Jochen Metzger ◽  
Elke Dammann ◽  
Uwe Borchert ◽  
Stefanie Buchholz ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
The Other ◽  
Unrelated Donor ◽  
Intermediate Risk ◽  
Significant Difference

Abstract Abstract 4128 Objectives: Allogeneic stem cell transplantation (SCT) is an established treatment for many severe disorders of hematopoiesis. Although SCT has considerable curative potential, its application is limited by transplant-related complications such as infections and graft-versus host disease (GvHD) which could lead to high mortality rates especially in older or less fit patients. Therefore, a careful pre-SCT assessment of risk and benefit is mandatory and different scores have recently emerged as helpful tools. We have previously applied proteomics to identify a specific urinary polypeptide patterns (PP) predictive for developing acute GvHD (aGvHD) (Weissinger EM et al, Blood 2007;109:5511–5519). The aim of this study was to investigate whether the PPs can predict overall outcome after allo-SCT and to compare these findings to those of the hematopoietic cell transplantation comorbidity index (HCT-CI) (Sorror M et al, Blood 2005;106:2912–2919). Methods: In this retrospective analysis from Hannover Medical School, the datasets from all patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who were allo-transplanted from a fully matched donor (matched related/unrelated donor (MRD/MUD)) between 2003–2008 and for whom relevant PP data were available, were included. Pts with a pt-donor HLA-mismatch constellation were excluded from this study. PP data from urine samples which were prospectively collected by day ≥ +7 after allo-SCT were correlated with overall survival (OS), aGvHD, non-relapse mortality (NRM), relapse rate and mortality (RM), and compared to the predictive value of the HCT-CI. Results: PP data were available from 111 pts (97 pts with AML, 14 with MDS; median age 52y; median EBMT score 4; 59 male/52 female; 69 MUD/42 MRD). They were grouped in high (PP-HRG), low (PP-LRG) or intermediate risk groups (PP-IRG). Forty-three pts (39%) belonged to the PP-LRG for aGvHD compared to 47 pts (42%) who were classified PP-HRG. Patient characteristics of PP-LRG and PP-HRG were similar in terms of age, sex and EBMT score (median 4 in both groups). OS compared favorably for the PP-LRG with an OS of 72% vs. 49% for the PP-HRG (p=0.03), also if only reduced intensity conditioning (RIC) was considered (73% vs 42%; p=0.01), respectively. There was a trend for higher incidence of NRM in the PP-HRG compared to PP-LRG (30% vs 14%, p=0.07) for the whole cohort, and a significant higher NRM rate, if only RIC was evaluated (35% vs 11%, p=0.01). However, if risk stratification was based on the HCT-CI, there was no significant difference between high risk (S-HRG) and low risk group (S-LRG) in terms of OS and NRM regardless of intensity of conditioning (OS for whole cohort: 57% vs 45%, p=0.4; OS for RIC: 56% vs 36%, p=0.2; NRM for whole cohort: 20% vs 23%, p=0.8; NRM for RIC: 18% vs 29%, p=0.4). Concerning the PP-IRG, there was a difference in OS between PP-IRG and PP-LRG (38% vs 73%, p=0.02). However, there was no significant difference in OS of the PP-IRG compared to the other PP-based risk groups nor between the HCT-CI based risk groups. Further, NRM did not show a significant difference neither for PP-based nor HCT-CI-based intermediate risk group compared to the other risk groups. Thirty vs 15 pts developed aGvHD in PP-HRG and PP-LRG (64% vs 35%, p<0.01) compared to 48% vs 64% (p=0.2) for S-HRG and S-LRG of the whole cohort, respectively. Incidence of aGvHD differed also significantly in the RIC cohort for PP-HRG and PP-LRG (65% vs 32%, p=0.01), but not for HCT-CI-based risk groups (47% vs 64%, p=0.1). Relapse rates and RM were not significantly different between high and low risk groups, neither for PP-based nor HCT-CI based (whole cohort and RIC subgroup), respectively. Conclusion: Risk stratification according to GvHD-match based PP, which has previously been shown to predict aGvHD, now also allows the identification of patient groups with significantly different OS and NRM. In comparison to the HCT-CI, PP-based prediction shows significantly higher accuracy in this rather homogeneous cohort of patients. Since proteomics is a new method which has been available only at a few centers, further multicenter analyses are essential to determinate the value of PP-based prediction of complications and outcome in SCT. Disclosures: Metzger: Mosaiques Diagnostics GmbH: Employment.

scholarly journals Preclinical markers of carotid atherosclerosis and cardiovascular risk assessed by the ESH/ESC scale (2003, 2007, 2009)

2011 ◽  
Vol 10 (4) ◽  
pp. 14-20 ◽  
Author(s):  
S. Sh. Urazalina ◽  
A. N. Rogoza ◽  
T. V. Balakhonova ◽  
R. P. Myasnikov ◽  
T. E. Kolmakova ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
European Society ◽  
Risk Group ◽  
Intima Media Thickness ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
European Society Of Cardiology

Aim. To assess the degree of cardiovascular (CV) risk adjustment in patients with low and intermediate risk by the SCORE scale, who were further examined in accordance with the European Society of Hypertension/European Society of Cardiology Guidelines (2003, 2007, 2009), and also underwent carotid artery (CA) ultrasound, as an extension of the ambulatory examination protocol. Material and methods. The study included 600 individuals aged 30-65 years (445 women, 155 men), with low to intermediate SCORE-assessed risk, and without diagnosed atherosclerosis or diabetes mellitus. The algorithm of CV risk stratification included SCORE scale, the ESH/ESC Guidelines (2003, 2007, 2009) and duplex CA ultrasound, with intima-media thickness (IMT) and atherosclerotic plaque (AP) assessment. Results. At the first stage of CV risk classification, which included routine examinations only, 73,8 % of the patients remained in the “low-risk” group, 14,5 % remained in the “intermediate-risk” group, and 11,7 % were moved to the “high-risk” group. After taking into account the duplex CA ultrasound results, the “low-risk”, “intermediaterisk”, and “high-risk” groups included 35,7 %, 33,5 %, and 30,8 % of the patients, respectively. In the “low-risk” and “intermediate-risk” groups, most patients had normal blood pressure levels (72,8 % and 83,5 %, respectively), while most patients in the “high-risk” group had arterial hypertension (56,7 %). The reason for moving the patients to the “high-risk” group was visualization of AP in CA (100 %). The percentage of subjects with one AP in this group was 22,7 %. In total, AP were visualized in 358 out of 600 participants (59,6 %). Out of these 358 patients, 26 (7,2 %) had IMT value >0,9 mm. Out of 242 patients without AP in CA, 2 (0,8 %) had IMT value >0,9 mm. Conclusion. At both risk stratification stages, the most prevalent causes of moving the patients to the groups of higher CV risk were dyslipidemia (81,3 % and 92,5 %, respectively), smoking (26,7 % and 22,2 %), abdominal obesity (77,7 %), and metabolic syndrome (98,5 %). The level of CV risk was affected by AP presence to a substantially greater extent than by IMT.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

Computational identification of mutator-derived lncRNA signatures of genome instability for improving the clinical outcome of cancers: a case study in breast cancer

2019 ◽  
Vol 21 (5) ◽  
pp. 1742-1755 ◽  
Author(s):  
Siqi Bao ◽  
Hengqiang Zhao ◽  
Jian Yuan ◽  
Dandan Fan ◽  
Zicheng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Genome Instability ◽  
Risk Group ◽  
Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
A Genome ◽  
Significant Difference

Abstract Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, identification of genome instability-associated lncRNAs and their clinical significance in cancers remain largely unexplored. Here, we developed a mutator hypothesis-derived computational frame combining lncRNA expression profiles and somatic mutation profiles in a tumor genome and identified 128 novel genomic instability-associated lncRNAs in breast cancer as a case study. We then identified a genome instability-derived two lncRNA-based gene signature (GILncSig) that stratified patients into high- and low-risk groups with significantly different outcome and was further validated in multiple independent patient cohorts. Furthermore, the GILncSig correlated with genomic mutation rate in both ovarian cancer and breast cancer, indicating its potential as a measurement of the degree of genome instability. The GILncSig was able to divide TP53 wide-type patients into two risk groups, with the low-risk group showing significantly improved outcome and the high-risk group showing no significant difference compared with those with TP53 mutation. In summary, this study provided a critical approach and resource for further studies examining the role of lncRNAs in genome instability and introduced a potential new avenue for identifying genomic instability-associated cancer biomarkers.

Application of Risk-Adapted Therapy for Acute Myeloid Leukemia to a Population. Effects of Stem Cell Transplantation on Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4449-4449
Author(s):  
Anders Wahlin ◽  
Mats L. Brune ◽  
Rolf Billstrom
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Relapse Free Survival ◽  
Free Survival ◽  
First Remission

Abstract We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died < 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p<0.001) different between the three risk groups. 43% of responding patients were alive in first remission after four years. 4-year relapse-free survival was significantly better for both intermediate risk (67%) and high-risk (41%) with allogeneic/URD transplantation than with autologous transplant or chemotherapy alone. Relapse was observed more often among patients treated with chemotherapy alone (42%, p=0.03) or with autologous transplants (42%, p=0.09) than among patients receiving allogeneic/URD transplants in CR1, 22%. Our results do not support the use of autologous transplantation in AML in first remission.

OUTCOME of Allogeneic Hematopoietic CELL TRANSPLANTATION for AML: A Single CENTER Retrospective ANALYSIS.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4567-4567
Author(s):  
Ioanna Sakellari ◽  
Chrisa Apostolou ◽  
Despina Mallouri ◽  
Anastasia Athanasiadou ◽  
Ioannis Batsis ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Cytogenetic Analysis ◽  
Hematopoietic Cell Transplantation ◽  
Risk Group ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Intermediate Risk ◽  
Term Survival ◽  
Poor Risk

Abstract Abstract 4567 Background: Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for patients (pts) suffering of AML with high risk features at diagnosis and beyond 1st complete remission (CR1) it remains the sole rescue treatment. In this retrospective study we analysed the data of all pts (149) allografted concecutively in our BMT unit for AML from 1991 to 2009. The aim of the study was to estimate the outcome in terms of overall survival (OS), disease free survival (DFS), relapse rate (RR) and non relapse mortality (NRM). Sixty-three pts of a median age 35 (8-63) years suffered from de novo (58), secondary (4) and biphenotypic AML (1) were transplanted in CR1. Cytogenetic analysis was available in 40/63 pts (intermediate 32, poor risk 8). Donors were siblings in 55, relative (1 antigen mismatch) in 3, unrelated (4 mismatched with 1–2 alleles) in 8 pts. Graft source was bone marrow (BM) in 12 and peripheral blood (PB) in 51 pts. Fifty-six received a myeloablative (MA) and 7 non- myeloablative (NMA) conditioning regimen. Eighty-six pts were allografted beyond CR1. Disease status was primary refractory (Prim. Ref) in 42/86, CR2 in 15, 1st refractory after re-induction relapse (Rel1) in 23 and advanced (CR3; Rel2+) in 6 pts. Three pts were retransplanted from the original donor for relapsed disease after alloHCT. In the cohort of pts with disease beyond CR1, cytogenetic analysis was available in 71 (favourable 4, intermediate 53, poor risk 14). Donors were siblings in 58, syngeneic (1 antigen mismatch) in 8, unrelated (3 with mismatch) in 17, unrelated double cord blood (CB) in 1, haploidentical in 5 pts. The majority of the pts received mobilized PB (72) as graft source and myeloablative conditioning regimen (82). Results: For pts transplanted in CR1 OS was 63%, NRM 23%, DFS 60% and RR 21% at 13 years. Seventeen pts transplanted before 2000 had an estimated OS and DFS 59%, RR 9% and NRM 35% whereas for forty-six pts transplanted after 1999 the OS was 64%, DFS 61%, NRM 17% and RR 25% at 9 years. DFS for pts in CR1 with an unrelated donor was 47% and 62% for siblings. Myeloablative regimen resulted in 65% DFS while NMA in lower DFS (21%) due to higher RR. According to cytogenetics OS and DFS were 62% and 64% for the intermediate risk group (n=32), 44% and 45% for the poor risk (n=8) respectively. For the cohort of pts transplanted for Prim. Ref. disease (n=42) OS was 20% (plateau at 3 years), DFS 17% (plateau at 2 years), RR 78% and NRM 34% at 12 years. Despite the small number of pts with poor risk karyotype (n=7) the prognosis seemed to be dismal (DFS and OS 0%) versus 25% and 31% respectively for the intermediate risk group (n=28). For pts transplanted in CR2 (n=15) OS was 51% and DFS 46% (plateau at 1year), RR 43% and NRM 16%. For pts in REL1 (n=23) OS was 15%, NRM 56%, DFS 4% and RR 86%. For the 6 pts transplanted for advanced disease (CR3; REL2+) OS was 17%, DFS 17%, RR 67% and NRM 50%. The 5 pts undergone haploidentical alloHCT (2 Prim. Ref., 2 CR2, 1 CR3) after TBI 8/thiotepa/fludara/ATG had OS and DFS 40% at 8 years. One of 3 pts retransplanted is alive in CR and the rest succumbed to their disease. Discussion: In 2010 when the use of alternative transplantation has been expanted the selection of pts upon the best stratification and the timing of the transplantation still remain open questions. The majority of patients are classified in the intermediate risk group with normal karyotype. According to our experience during the last two decades alloHCT for AML in early disease phase (CR1) can offer the best results and possibly cure in a significant number of patients (60%). Transplantation procedures have been continuously improved over time leading to improvement of the outcome mostly in the era of alternative donor alloHCT. For poor risk pts in CR1 and for all pts with AML beyond CR1 (apart from acute promyelocytic leukemia in molecular remission) alloHCT remains the only treatment option. In this cohort of pts results from our data indicate that pts in CR2 may attain long term survival after alloHCT (OS 51%, NRM 16%). Among pts refractory to induction and salvage treatment therapies (> CR2, Prim Ref., REL) a small proportion of pts (15-20%) may be rescued by alloHCT. Disclosures: No relevant conflicts of interest to declare.

The t(9;11) Confers Good Prognosis in AML Patients Treated with Stem Cell Transplantation As Compared to Non-t(9;11) and Other Adverse-Risk Abnormalities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2527-2527
Author(s):  
Claudia Ulrike Walter ◽  
Fahed Almhareb ◽  
Naeem A. Chaudhri ◽  
Abu Jafar Saleh ◽  
Wahiba Chebbo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Group ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Mll Gene ◽  
Significant Difference ◽  
First Remission ◽  
11Q23 Abnormalities

Abstract Abstract 2527 Background: In contrast to most translocations affecting the MLL gene, the t(9;11) is not associated with a markedly poor prognosis. Several studies revealed a very favorable outcome in the pediatric patient group. In adult AML, the t(9;11) has also been associated with superior survival, at least compared to other 11q23 abnormalities. Therefore, 11q23 rearrangements in adult AML are now often dichotomized into t(9;11) and non-t(9;11), with the former being included in the intermediate-risk group and the latter in the adverse-risk group. The proposed European Leukemia Net (ELN) cytogenetic reporting criteria reflect this division. We investigated whether the outcome of AML patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) with t(9;11) remains significantly different from the rest of the adverse-risk cytogenetic group. Methods: Conventional cytogenetics and FISH data from diagnostic bone marrow of 110 adult AML patients treated with HSCT was reviewed and patients classified according to the recommendations of the European Leukemia Net and included 32 with favorable risk, 60 in the intermediate-risk group, and 18 in the adverse-risk group. FISH confirmed MLL rearrangement in cases with apparent 11q23 abnormalities. We compared outcome of patients with t(9;11) to the group of patients with adverse-risk cytogenetics that included all MLL-positive non-t(9;11) among other cytogenetic abnormalities classified adverse-risk. Our study included 62 (56%) patients treated in first remission (CR1), while most non-CR1 AML patients were treated with HSCT in CR2. Patients were between 14 and 57 years, with median age of 25 years. Results: Of the 110 AML patients, 9 (8%) had MLL gene rearrangement. Of these patients only 5 (4.5% of all patients) had t(9;11). When all patients with MLL rearrangement were considered, there was no significant difference between this group and the patients with adverse-risk cytogenetics in overall survival (OS) or event-free survival (EFS). In contrast, when only patients with the t(9;11) were considered, the t(9;11) patients had significantly longer OS (P=0.02) and EFS (P=0.03) as compared with patients with adverse cytogenetics including all non-t(9;11) MLL-rearranged cases. The outcome of MLL-positive non-t(9;11) patients was similar to the group with adverse-risk cytogenetics. MLL rearrangements in the non-t(9;11) group included t(4;11)(q21;q23), t(6;11)(q27;q23) and a variant t(6;11;7)(q27;q23;q11.2), as well as t(11;17)(q23;q25). The survival for patients with t(9;11) remained significantly longer even when only patients treated with HSCT in first remission were considered, although numbers were small. All five patients with t(9;11) were treated with HSCT in CR1. Conclusions: The data supports the conclusion that MLL-positive t(9;11) AML patients should be classified differently from the rest of the MLL-rearranged cases and should be considered as part of the intermediate-risk group. This classification separating the t(9;11) cases from the rest of the MLL-positive cases should be maintained even when patients are treated with allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2657-2664 ◽  
Author(s):  
Bart L. Scott ◽  
Ted A. Gooley ◽  
Mohamed L. Sorror ◽  
Andrew R. Rezvani ◽  
Michael L. Linenberger ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
High Risk Disease ◽  
Risk Patients

Abstract Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

scholarly journals Total Thyroidectomy Versus Lobectomy for Thyroid Cancer: Single-Center Data and Literature Review

2021 ◽  
Author(s):  
Carla Colombo ◽  
Simone De Leo ◽  
Marta Di Stefano ◽  
Matteo Trevisan ◽  
Claudia Moneta ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Risk Group ◽  
Tertiary Care ◽  
Thyroid Stimulating Hormone ◽  
Low Risk ◽  
The Other ◽  
Intermediate Risk ◽  
Other Hand

Abstract Background Controversies remain about the ideal risk-based surgical approach for differentiated thyroid cancer (DTC). Methods At a single tertiary care institution, 370 consecutive patients with low- or intermediate-risk DTC were submitted to either lobectomy (LT) or total thyroidectomy (TT) and were followed up. Results Event-free survival by Kaplan–Meier curves was significantly higher after TT than after LT for the patients with either low-risk (P = 0.004) or intermediate-risk (P = 0.032) tumors. At the last follow-up visit, the prevalence of event-free patients was higher in the TT group than in the LT low-risk group (95% and 87.5%, respectively; P = 0.067) or intermediate-risk group (89% and 50%; P = 0.008). No differences in persistence prevalence were found among microcarcinomas treated by LT or TT (low risk, P = 0.938 vs. intermediate-risk, P = 0.553). Nevertheless, 15% of the low-risk and 50% of the intermediate-risk microcarcinomas treated by LT were submitted to additional treatments. On the other hand, macrocarcinomas were significantly more persistent if treated with LT than with TT (low-risk, P = 0.036 vs. intermediate-risk, P = 0.004). Permanent hypoparathyroidism was more frequent after TT (P = 0.01). After LT, thyroglobulin (Tg)/thyroid-stimulating hormone (TSH) had shown decreasing trend in 68% of the event-free patients and an increasing trend in the persistent cases. Conclusions Lobectomy can be proposed for low-risk microcarcinomas, although in a minority of cases, additional treatments are needed, and a longer follow-up period usually is required to confirm an event-free outcome compared with that for patients treated with TT. On the other hand, to achieve an excellent response, TT should be favored for intermediate-risk micro- and macro-DTCs despite the higher frequency of postsurgical complications.

scholarly journals Killer Cell Immunoglobulin-like Receptor Ligand Matching Determines the Post-Transplant High Risk Groups Among Patients with Permissive HLA Mismatch in Unrelated Donor Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4566-4566
Author(s):  
Yoo Jin Lee ◽  
Joon Ho Moon ◽  
In Hee Lee ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Killer Cell ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Peripheral Blood Stem Cells

Abstract Background: Human leukocyte antigen (HLA) matching between donor and recipient is a key part of successful allogeneic hematopoietic cell transplantation (allo-HCT). The HCT from the unrelated donor (UD) with one allele/antigen mismatch (MM) can be as beneficial as HCT from perfectly matched donor. For the remaining patients, the donors with permissive mismatches may be the option. In HLA-mismatched transplantation, the patient and donor can also be mismatched for their killer cell immunoglobulin-like receptor (KIR) ligands that recognize allotypic determinants shared by certain HLA class I allele groups. Recent research has accumulated evidence of the role of each HLA locus and KIR ligand MM on clinical outcomes for UD-HCT. However, HCT outcomes of the patients with permissive MM depending on KIR ligand MM (KIR-L-MM) status remain obscure in UD-HCT. In the current study, we identified permissive and nonpermissive MM allele combinations and analyzed the effects of these mismatches in combination of KIR ligand mismatches in patients with acute myeloid leukemia (AML). Methods: A total of 438 patients with AML who underwent allo-HCT from UD from 2007 to 2014 were analyzed. Alleles of patients and donors at the HLA-A, -B, -C, and -DRB1 loci were identified by the high resolution DNA typing. Nonpermissive HLA allele combinations were defined as a significant HLA risk factor for severe acute graft-versus-host disease (aGVHD). KIR-L-MM among patient-donor pairs were searched in the Immuno Polymorphism Database available at www.ebi.ac.uk/ipd/kir. Results: Median age of the patients was 45 (range 15-60) years and 117 patients (40.4%) were female. Eighty-five (19.4%) patients were high risk at the time of HCT. Reduced intensity conditioning was performed in 131 patients (29.9%) and anti-thymocyte globulin was used in 324 patients (74.0%). Primary graft source was peripheral blood stem cells (n=369, 84.2%) and median 6.0 x 106/kg cells were infused. Severe aGVDH occurred in 43 patients (9.8%) and chronic GVHD (cGVHD) in 193 (44.1%). With median follow-up duration of 19 (range, 2-96) months, treatment-related mortality (TRM) occurred in 111 patients (25.3%), relapse in 119 (27.2%) and death in 214 (48.9%). Two-hundred sixty-four patients (60.3%) were HLA full matched in the 4 loci. Mismatches in HLA-A loci observed in 64 patients, HLA-B in 35, HLA-C in 98, and HLA-DRB1 in 60. Five nonpermissive MM pairs in 33 patients were identified as donor/patient pair: A*02:06/A*02:01, C*03:03/C*08:01, C*08:01/C03:04, C*08:01/C*15:02, and DRB1*04:03/DRB1*04:05. Among 98 patients with HLA-C loci MM, 16 patients showed KIR ligand MM (KIR-L-MM) as GvH direction, which was observed in the permissive MM group. Severe aGVHD occurred in 30.4%, 22.4%, 13.4%, and 10.8% in nonpermissive, permissive MM and KIR-L-MM, permissive MM and KIR-L-M, and full match group, respectively (p=0.003). The 3-year overall survival (OS) rate was inferior in permissive MM and KIR-L-MM group (30.0%) compared to full match (53.5%), permissive MM and KIR-L-M (51.8%), and nonpermissive (42.4%) group (p=0.067). The 3-year TRM was higher in permissive MM and KIR-L-MM group (57.5%) than full match (21.0%), permissive MM and KIR-L-M (27.7%), and nonpermissive (33.3%) group (p=0.006). In the multivariate analysis, high risk at HCT (HR 2.087, p<0.001), severe aGVHD (HR 3.851, p<0.001), and cGVHD (HR 0.321, p<0.001) were identified as variables affecting the OS. The following variables adversely affected on TRM: permissive MM and KIR-L-MM group (HR 2.699, p=0.007), severe aGVDH (HR 2.204, p=0.001), and cGVHD (HR 2.052, p<0.001). Non-permissive MM (HR 7.487, p=0.001) and CD34+ cells >6x106/kg (HR 4.113, p=0.017) were high risk factors on severe aGVHD. Conclusion: Permissive MM for HLA could be further classified into high risk groups with regard to TRM by KIR-L matching in UD-HCT. The evaluation of KIR-L matching is warranted to reduce unfavorable outcomes among the patients with permissive MM in UD-HCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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