Improved Risk Stratification With Addition Of Male Sex (S) To The Elderly International Prognostic Index (S-EIPI) For DLBCL Patients > 60 Years Treated With R-CHOP: An International Collaboration Of The US Intergroup, German High-Grade Non-Hodgkin Lymphoma Study Group and Groupe d’Etude De Lymphome d’Adultes

Abstract Background We have previously reported and validated that the E-IPI, provided better discrimination of overall survival (OS) than the IPI for DLBCL patients > 60 years of age treated with R-CHOP (Advani et al., BJH 2010 and 12-ICML 2013 Abstract 222). Recent reports suggest that males > 60 years treated with R-CHOP have worse outcomes likely related to differences in rituximab clearance (Muller et al., Blood 2012). In this study, we explored if the addition of male sex to the E-IPI further improved risk stratification. Methods DLBCL patients > 60 years treated with R-CHOP on the E4494, RICOVER-60 and GELA 98-5 trials were included. A multivariate analysis was performed to assess whether male sex is an independent prognostic factor for OS in addition to the five E-IPI risk factors, E-IPI score, and E-IPI risk group. Male sex (S) was added as an additional risk factor to the E-IPI (S-EIPI, 0-6) and patients regrouped according to the number of risk factors: low (L)=0-1, low intermediate (LI)=2, high intermediate (HI)=3 and high (H)=4-6 based on the observed OS using Kaplan-Meier curves. C-statistic was used to compare the discrimination ability. The 5 year OS was estimated using the Kaplan-Meier method. Results 1079 patients (E4494, n=267; RICOVER-60, n=610; GELA 98-5, n=202) with a median follow-up of 8.9 years were included. In multivariate analyses, male sex was a significant independent predictor for OS adjusting for all five E-IPI factors, (HR 1.5, p < 0.0001), E-IPI score (HR 1.42, p < 0.001), and E-IPI risk group (HR 1.42, p < 0.001) (Table 1). C-statistic was 0.66 for S-EIPI and 0.64 for EIPI. Incorporation of sex into the E-IPI shifted 35% patients to higher risk groups, including 110 patients into the highest risk group (Table 2). The estimated 5 year OS for the S-EIPI L, LI, HI, and H risk groups was 87%, 70%, 58%, and 40%, respectively (Table 3). Compared to E-IPI, the 95% C.I. did not overlap among S-EIPI risk groups. Conclusion For DLBCL patients >60 years treated with R-CHOP, our results suggest the addition of male sex to the E-IPI may improve categorization of patients into well-defined clinically relevant risk groups. Patients with low risk S-EIPI have an excellent outcome (5 year OS 87%). Patients with high risk S-EIPI have a 5 year OS of only 40% and therapies beyond standard R-CHOP need to be explored. Disclosures: Horning: Genentech: Employment; Roche: Equity Ownership.

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Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.754964 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xue Shi ◽

Xiaoqian Liu ◽

Xiaomei Li ◽

Yahan Li ◽

Dongyue Lu ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

High Risk Group ◽

Stratification System ◽

Risk Stratification System

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.

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A Risk Score Integrating BAALC, ERG and WT1 Expression Can Be Used To Improve Risk Stratification In Acute Promyelocytic Leukemia

Blood ◽

10.1182/blood.v122.21.1323.1323 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1323-1323

Author(s):

Anna Hecht ◽

Florian Nolte ◽

Daniel Nowak ◽

Verena Nowak ◽

Benjamin Hanfstein ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Risk Stratification ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Expression Levels ◽

Improve Risk Stratification

Abstract Introduction With current therapy regimens over 75% of patients with de novo acute promyelocytic leukemia (APL) can be cured. Approaches to further improve patient outcome by stratifying patients at the time of initial diagnosis according to their individual risk and to adjust therapy accordingly have been based on clinical features only. Molecular markers have not been established for risk stratification as yet. Recently, we have shown that high expression levels of the genes brain and acute leukemia, cytoplasmic (BAALC) and ets related gene (ERG) are associated with inferior outcome in APL patients. In addition, data indicate that aberrant expression of the gene Wilms’ tumor 1 (WT1) is a negative prognostic factor with regard to overall survival (OS) after complete remission (CR) and relapse free survival (RFS) in APL. In this study we evaluated the prognostic relevance of a combined score integrating the expression levels of the above mentioned genes to further improve risk stratification in APL patients. Methods Expression levels of BAALC, ERG and WT1 of 62 patients with newly diagnosed APL were retrospectively analyzed in bone marrow mononuclear cells using multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR). Median age of patients was 47 years (range: 19 to 82y). All patients gave informed consent. Patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) study with a treatment of simultaneous ATRA and double induction chemotherapy including high-dose ara-C, consolidation and maintenance chemotherapy. The following gene expression levels were identified as negative risk factors in preceding studies: BAALC expression ≥25th percentile (BAALChigh), ERG expression >75th percentile (ERGhigh) and WT1 expression ≤25th percentile or ≥75th percentile (WT1low/high). A risk score was developed as follows: for the presence of one of the mentioned risk factors one scoring point was assigned to a respective patient, i.e. a maximum of 3 points (one point for BAALChigh, ERGhigh and WT1low/high, respectively) and a minimum of 0 points (i.e. presenting with none of the aforementioned risk factors) could be allocated to one patient. Accordingly, patients were divided into four risk groups: 7 patients scored 0 points (= low risk), 27 patients scored 1 point (= intermediate 1 risk), 19 patients scored 2 points (= intermediate 2 risk) and 9 patients scored 3 points (= high risk). Subsequently, OS, RFS and relapse free interval (RFI) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the four risk groups (p<0.05). Results The integrative risk score divided patients into four groups with significantly different outcome. The low risk group showed a RFS of 100% at 10 years of follow-up compared to the intermediate 1 risk group with 81%, the intermediate 2 risk group with 58% and the high risk group with a RFS of 42% only (median survival: 4.6y) (p=0.02). In accordance, the RFI differed significantly between the four groups: low risk 100%, intermediate 1 risk 100%, intermediate 2 risk 89% and high risk 71% (p=0.049). There was no statistically significant difference between the 4 groups with regard to OS in the entire patient cohort. However, there was a clear trend towards a difference in OS in patients who achieved a CR after induction therapy: low risk 100%, intermediate 1 risk 81%, intermediate 2 risk 68% and high risk 53% survival at 10 years of follow-up (p=0.09). Conclusion Integration of expression levels of the genes BAALC, ERG and WT1 into a scoring system identifies 4 risk groups with significantly different outcome with regard to RFS and RFI. It might be a promising approach to guide therapeutic decisions in patients with APL. However, multivariate analyses and validation of these data in an independent patient cohort is warranted. Disclosures: No relevant conflicts of interest to declare.

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Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211061948 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110619

Author(s):

Xiao Chang ◽

Junqiang Chen ◽

Wencheng Zhang ◽

Jinsong Yang ◽

Shufei Yu ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

High Risk ◽

Risk Stratification ◽

Competing Risks ◽

Risk Group ◽

Postoperative Radiotherapy ◽

Risk Groups ◽

Individual Risk ◽

Independent Risk Factors

Background: A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC). Methods: The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort ( n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort ( n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group. Results: Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively ( p < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved. Conclusion: The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

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Novel risk stratification criteria of metastatic renal cell carcinoma (mRCC) patients (pts) treated with immune checkpoint inhibitors (ICI).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16068 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16068-e16068 ◽

Cited By ~ 1

Author(s):

Dylan J Martini ◽

Yuan Liu ◽

Julie M. Shabto ◽

Bradley Curtis Carthon ◽

Greta Russler ◽

...

Keyword(s):

Risk Stratification ◽

Checkpoint Inhibitors ◽

Recursive Partitioning ◽

Multivariable Analysis ◽

Regression Tree ◽

Progression Free Survival ◽

Risk Groups ◽

C Statistic ◽

Kaplan Meier ◽

Risk Grouping

e16068 Background: IMDC risk criteria is the gold standard for predicting outcomes for mRCC pts. We developed novel risk groups for mRCC pts treated with ICI. Methods: We performed a retrospective review of 100 ICI-treated mRCC pts at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression-free survival (PFS) were used to measure outcomes; OS was the primary outcome. We obtained baseline monocyte-to-lymphocyte ratio (MLR), body mass index (BMI), and metastatic (met) sites. We created a new variable (D_met) that combines number and sites of met: 0 = < 2 met sites; 1 = ≥ 2 met sites without liver metastases (mets); 2 = ≥ 2 met sites with liver mets. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS. Recursive partitioning and regression tree analyses were used for risk stratification. Discrimination of the risk score was measured by Uno C-statistics. Results: The pts were 66% males, 78% clear cell RCC (ccRCC), and 71% received anti-PD-1 monotherapy. Very poor risk pts (MLR ≥ 0.93 or MLR < 0.93, BMI < 24, and D_Met = 2) had significantly shorter OS and PFS than good risk pts (MLR < 0.93, BMI ≥ 24, and D_Met = 0) in univariable and multivariable analysis (UVA and MVA, Table). The Uno C-statistic for our risk grouping criteria compared to IMDC is 0.687 vs 0.566 (p = 0.061) for OS and 0.594 vs 0.541 (p = 0.78) for PFS. Conclusions: Risk grouping using MLR, BMI, and number and sites of mets may predict survival in mRCC pts treated with ICI. These results should be validated in a larger, prospective study. [Table: see text]

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Prognostic Significance of Reduced BCAS4 expression in Bone Marrow Cells of Patients with Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2019-124738 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4258-4258

Author(s):

Masayuki Shiseki ◽

Mayuko Ishii ◽

Mari Ohwashi ◽

Kentaro Yoshinaga ◽

Naoki Mori ◽

...

Keyword(s):

Risk Factors ◽

Bone Marrow ◽

Mononuclear Cells ◽

Bone Marrow Cells ◽

Risk Groups ◽

Older Age ◽

Expression Level ◽

Expression Of Genes ◽

Kaplan Meier ◽

Lysosome Related Organelles

Deletion of long arm of chromosome 20 (del(20q)) is commonly observed in myelodysplastic syndromes (MDS). Reduced expression of genes located within the common deleted region (CDR) of del(20q) due to haploinsufficiency may play a role in molecular pathogenesis of MDS. In the previous study, we examined expression of genes located within the CDR which we determined using array-CGH, in bone marrow mononuclear cells in MDS patients with or without del(20q), indicating that BCAS4 expression was significantly reduced in bone marrow cells in MDS patients with or without del(20q). The BCAS4 gene, which was identified as a fusion transcript expressed in MCF7 cells, encodes 23kD protein. Although function of BCAS4 protein remains unclear, it could be a member of "cappuccino" family, which belong to lysosome-related organelles. Abnormality of genes encoding lysosome-related organelles cause variety of congenital disorders, including the Hermansky-Pudlak syndromes, which is characterized by oculocutaneous albinism and bleeding tendency due to platelet dysfunction as a result of lysosome abnormalities. In the present study we investigated clinical implication of BCAS4 expression level in MDS patients. Mononuclear cells separated from bone marrow samples taken at the time of MDS diagnosis were used for analysis. Written informed consent was obtained from patients before study. To analyze BCAS4 expression, quantitative RT-PCR was performed using cDNA from mononuclear cells as template by the TaqMan probe method (Applied Biosystems) with co-amplification of the endogenous control gene, human GAPDH (Applied Biosystems). Samples from 103 MDS patients, 64 males and 39 females with median age of 67 years (range: 20-91 years), with (n=14) or without (n=89) del(20q), were examined in the present study. Patients were classified as RCUD (n=12), RCMD (n=55), RARS (n=9), RAEB-1 (n=10), and RAEB-2 (n=13), according to WHO 2008 classification, and in RAEB-T (n=4) according to FAB classification. They also were categorized in four IPSS risk groups, low risk (n=30), intermediate-1 risk (n=46), intermediate-2 risk (n=18), and high risk (n=9). There was no significant difference in relative BCAS4 expression level between patients with del(20q) and those without del(20q), and among WHO subtypes. Higher IPSS risk groups (INT-2 and High) showed trend in association with reduced BCAS4 expression compared with lower IPSS risk groups (Low and INT-1) (P=0.104). We analyzed impact of BCAS4 expression on overall survival (OS). Based on BCAS4 expression level, 103 patients were divided into four groups, highest (Q1), intermediate (Q2, Q3), and lowest (Q4) quartiles. The Kaplan-Meier analysis demonstrated that Q4 showed significantly worse OS compared with remaining quartiles (Q1-Q3) (log-rank test, P=0.0031). The estimated 2-year OS rates in Q1-3 group and Q4 group were 75.1% and 48.9%, respectively. According to the COX proportional hazards model, univariate analysis showed lower BCAS4 expression (Q4 vs Q1-Q3) was associated with worse OS (hazard ratio 3.43, 95%CI 1.89-6.11, P=0.0001) as well as older age (65 years or older vs less than 65 years), and higher IPSS risk groups (INT-2 and High vs Low and INT-1). Multivariate analysis indicated that lower BCAS4 expression showed trend for association with worse OS (hazard ratio 1.90, 95%CI 0.96-3.64, P=0.0651) by analyzing with two variables (older age and higher IPSS groups). Next, we investigated whether OS is predicted by combination of three variables, BCAS4 expression level, IPSS risk groups, and age at diagnosis. We defined lower BCAS4 expression (Q4), higher IPSS (INT-2 and High), and older age (65 years or older), as risk factors. The Kaplan-Meier analysis showed that survival curves were well separated according to number of risk factors (0, 1, and 2 or more) (P<0.0001). The estimated 1-year, 2-year, and 5-year survival rates were 100%, 100%, and 86.5% in patients without risk factor, 75%, 70.2%, and 51.7% in patients with one risk factor, and 54%, 34.3%, and 11.4% in patients with two or more risk factors. The present study demonstrated that reduced BCAS4 expression is associated with inferior clinical outcome, indicating that BCAS4 expression level could be a useful prognostic marker in MDS, especially by combination with IPSS risk and patients age at diagnosis. Disclosures Tanaka: Bristol-Myers Squibb: Research Funding.

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Validation of Postpartum Hemorrhage Admission Risk Factor Stratification in a Large Obstetrics Population

American Journal of Perinatology ◽

10.1055/s-0040-1712166 ◽

2020 ◽

Author(s):

Halley Ruppel ◽

Vincent X. Liu ◽

Neeru R. Gupta ◽

Lauren Soltesz ◽

Gabriel J. Escobar

Keyword(s):

Risk Factors ◽

Risk Assessment ◽

High Risk ◽

Blood Loss ◽

Postpartum Hemorrhage ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Hemorrhage Risk ◽

Present On Admission

Abstract Objective This study aimed to evaluate the performance of the California Maternal Quality Care Collaborative (CMQCC) admission risk criteria for stratifying postpartum hemorrhage risk in a large obstetrics population. Study Design Using detailed electronic health record data, we classified 261,964 delivery hospitalizations from Kaiser Permanente Northern California hospitals between 2010 and 2017 into high-, medium-, and low-risk groups based on CMQCC criteria. We used logistic regression to assess associations between CMQCC risk groups and postpartum hemorrhage using two different postpartum hemorrhage definitions, standard postpartum hemorrhage (blood loss ≥1,000 mL) and severe postpartum hemorrhage (based on transfusion, laboratory, and blood loss data). Among the low-risk group, we also evaluated associations between additional present-on-admission factors and severe postpartum hemorrhage. Results Using the standard definition, postpartum hemorrhage occurred in approximately 5% of hospitalizations (n = 13,479), with a rate of 3.2, 10.5, and 10.2% in the low-, medium-, and high-risk groups. Severe postpartum hemorrhage occurred in 824 hospitalizations (0.3%), with a rate of 0.2, 0.5, and 1.3% in the low-, medium-, and high-risk groups. For either definition, the odds of postpartum hemorrhage were significantly higher in medium- and high-risk groups compared with the low-risk group. Over 40% of postpartum hemorrhages occurred in hospitalizations that were classified as low risk. Among the low-risk group, risk factors including hypertension and diabetes were associated with higher odds of severe postpartum hemorrhage. Conclusion We found that the CMQCC admission risk assessment criteria stratified women by increasing rates of severe postpartum hemorrhage in our sample, which enables early preparation for many postpartum hemorrhages. However, the CMQCC risk factors missed a substantial proportion of postpartum hemorrhages. Efforts to improve postpartum hemorrhage risk assessment using present-on-admission risk factors should consider inclusion of other nonobstetrical factors.

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Determination of Risk Factors for Venous Thromboembolism by an Adapted Caprini Scoring System in Surgical Patients

Journal of Personalized Medicine ◽

10.3390/jpm9030036 ◽

2019 ◽

Vol 9 (3) ◽

pp. 36 ◽

Cited By ~ 5

Author(s):

Bui My Hanh ◽

Le Quang Cuong ◽

Nguyen Truong Son ◽

Duong Tuan Duc ◽

Tran Tien Hung ◽

...

Keyword(s):

Risk Factors ◽

Risk Assessment ◽

Venous Thromboembolism ◽

Scoring System ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Assessment Model ◽

Surgical Patients ◽

Risk Scoring

Venous thromboembolism (VTE) is a frequent preventable complication among surgical patients. Precise risk assessment is a necessary step for providing appropriate thromboprophylaxis and reducing mortality as well as morbidity caused by VTE. We carried out this work to define the rate of VTE postoperatively, following a Caprini score, and to determine VTE risk factors through a modified Caprini risk scoring system. This multicenter, observational, cohort study involved 2,790,027 patients who underwent surgery in four Vietnamese hospitals from 01/2017 to 12/2018. All patients who were evaluated before surgery by using a Caprini risk assessment model (RAM) and monitored within 90 days after surgery. The endpoint of the study was ultrasound-confirmed VTE. Our data showed that the 90-day postoperative VTE was found in 3068 patients. Most of VTE (46.97%) cases were found in the highest risk group (Caprini score > 5). A total of 37.19% were observed in the high risk group, while the rest (15.84%) were from low to moderate risk groups. The likelihood of occurring VTE was heightened 2.83 times for patients with a Caprini score of 3–4, 4.83 times for a Caprini score of 5–6, 8.84 times for a score of 7–8, and 11.42 times for a score of >8, comparing to ones with a score of 0 to 2 (all p values < 0.05). Thus, the frequency of postoperative VTE rises substantially, according to the advanced Caprini score. Further categorizing patients among the highest risk group need delivering more appropriate thromboprophylaxis.

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Hypoalbuminemia Is An Independent Prognostic Factor In Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v116.21.4001.4001 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4001-4001

Author(s):

Maria Corrales-Yepez ◽

Mohamed A. Kharfan-Dabaja ◽

Jeffrey Lancet ◽

Alan F. List ◽

Eric Padron ◽

...

Keyword(s):

Prognostic Factor ◽

Serum Albumin ◽

Serum Albumin Level ◽

Risk Group ◽

Risk Groups ◽

Albumin Level ◽

Refractory Anemia ◽

Lower Serum ◽

Kaplan Meier ◽

Low Serum

Abstract Abstract 4001 Background: Low serum albumin level is known to be an adverse prognostic factor in patients with malignancies such as multiple myeloma. We previously reported that severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic stem cell transplant (AHCT) was an independent predictor of non-relapse and overall mortality in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) (Kharfan-Dabaja et al Biol Blood Marrow Transplant. 2010 Jul). In this study we examined prognostic value of serum albumin level in patients with MDS. Methods: Data were analyzed from the Moffitt Cancer Center (MCC) MDS database with chart review verification. The primary objective was to examine the role of serum albumin at time of presentation to MCC as a prognostic marker for overall survival (OS). Patients were divided into 3 groups of serum albumin levels (≤ 3.5, 3.6–4.0 and > 4.0 g/dl). The Kaplan–Meier method was used to estimate median OS. The log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox proportional hazards regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 844 patients were captured by the MCC MDS database. The median age was 69 years. MDS subtypes were coded as refractory anemia (RA) (n=98;12%), refractory anemia with ring sideroblasts (RARS) (n=76;9%), del(5q) (n=20;2.4%), refractory cytopenia with multi-lineage dysplasia (RCMD) (n=96;11%), refractory anemia with excess blasts (RAEB) (n=255;30%), therapy related MDS (n=22;2.6%), and MDS-NOS (n=275; 33%). The distribution of IPSS risk groups was: 18.7% Low risk, 42.9% Intermediate-1 (Int-1), 19.9% Int-2, 5.3% High risk, and 13.2% unknown. Baseline characteristics for the three patient groups defined by serum albumin level are summarized in (Table-1). There was no difference in red blood cell transfusion dependency (RBC-TD) rate between the 3 groups (p=0.21). The median OS for all patients was 36 months (95% confidence interval (CI) 31.5–40.5 mo). Age, IPSS risk group, RBC-TD, Serum ferritin were statistically significant prognostic factors in univariable analysis. The median OS was 19 mo (95%CI= 14.9–23.1 mo), 35 mo (95%CI= 28.7–41.3 mo), and 53 mo (95%CI= 44.7–61.3 mo) for patients with serum albumin levels ≤ 3.5 g/dl, 3.6–4.0 g/dl, > 4.0 g/dl, respectively. (Figure-1) (p= <0.005). After adjustment for age, RBC-TD, OS was statistically significantly inferior among MDS patients with lower serum albumin (Hazard Ratio (HR) = 0.79.; 95%CI= 0.69–0.90; p= 0.001), and higher-risk IPSS group (HR=1.67; 95%CI=1.48-1.87; p= <0.005). The overall rate of AML transformation was 29.2%. Rate of AML transformation was higher in patients with lower serum albumin, 38% in patients with serum albumin ≤ 3.5 g/dl, 30% for patients 3.6–4.0 g/dl, and 23% in patients with serum albumin > 4.0 g/dl (p-value 0.005). Among patients in the Low/Int-1 IPSS risk group, the median OS was 28 mo (95%CI=15.7-40.3 mo), 48 mo (95%CI=38.8-58.0 mo), and 60 mo (95%CI=47.6-72.4 mo) for patients with serum albumin levels ≤ 3.5 g/dl, 3.6–4.0 g/dl and > 4.0 g/dl, respectively (p=0.003). Among patients in the Int-2/High IPSS risk group, the median OS was 16 mo (95%CI 13.3–15.7 mo), 22 mo (95%CI 18.0–26.0 mo), and 21 mo (95%CI 8.8–33.2 mo) respectively for patients with serum albumin levels ≤ 3.5 g/dl, 3.6–4.0 g/dl and > 4.0 g/dl, respectively p=0.03). Conclusion: In this retrospective analysis of a large single institution MDS database, serum albumin is found to be an independent prognostic factor for OS and AML transformation in MDS patients. The prognostic power of low serum albumin was greatest among patients with Low/Int-1 IPSS risk group, but remained an independent variable across all risk groups. Serum albumin may also be a surrogate marker of general health, co- morbidities, and performance status. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v118.21.4128.4128 ◽

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.

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A Risk Score to Predict CMV Viremia within the First 100 Days after Allogeneic Stem Cell Transplantation Based on Pre-Transplant Parameters

Blood ◽

10.1182/blood.v124.21.3877.3877 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3877-3877

Author(s):

Feras Alfraih ◽

John Kuruvilla ◽

Naheed Alam ◽

Anna Lambie ◽

Vikas Gupta ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

High Risk ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Cmv Infection ◽

Allogeneic Hsct ◽

Very High

Abstract Introduction: Cytomegalovirus (CMV) is a major infectious complication following allogeneic hematopoietic stem cell transplantation (HSCT). Risk of CMV infection varies between patients and individualized strategies for monitoring and therapy for CMV are needed. In this study, we attempted to establish a clinical score based on patient and transplant characteristics in order to predict the probability for early CMV viremia (CMV-V) within the first 100 days after HSCT. Methods: A total of 548 patients were evaluated after receiving HSCT between 2005 and 2012 at Princess Margaret Cancer Centre. CMV sero-negative recipients with CMV sero-negative donors (R-D-) were excluded. CMV-V was diagnosed in peripheral blood samples obtained on two occasions either by PCR (>200 IU/ml) or antigenemia testing (>2 positive cells/100000). A total of 378 patients were included into the study. Uni- and multivariable analyses were performed to identify risk factors for CMV-V. A weighted score was assigned to each factor based on the odds ratios determined by the multivariable analysis. A total score was calculated for each patient and used for assignment into one of 4 risk categories, the low risk (score 0-1), the intermediate (score 2-3), the high (score 4-5) and the very high (score 6-8). Median age for all patients was 51 years (range 17-71) and 173 (46%) were female. Matched related donors were used for two hundred fifteen patients (57%). Two hundred forty-three patients (64%) were transplanted for myeloid and 108 (29%) for lymphoid malignancies. One hundred thirteen patients (30%) were CMV sero-positive with a negative donor (R+D-) while 191 (51%) were recipient and donor CMV sero-positivity (R+D+). Graft versus host disease (GVHD) prophylaxis included CSA/MMF (n=200, 52%), and CSA/MTX (n=178, 48%). Myeloablative conditioning regimens were administered to 220 patients (58%), 158 patients (42%) were treated with a reduced intensity regimen. Three hundred-thirty seven patients (89%) received peripheral blood stem cells as a stem cell source. In vivo T cell depletion (TCD) with alemtuzumab was used in 138 (37%). Results: CMV-V occurred in 246 (64%) patients by day 100 post HSCT. The impact of patient and HSCT characteristics on the risk of CMV-V was assessed by multivariable analysis. The significant factors were CMV sero-status R+D- and R+D+, TCD, GVHD prophylaxis with MMF administration of myeloablative preparative regimens (Table 1). Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT CMV-V rates on the 4 new risk categories amounted to 93% in the very high-risk, 78% in high-risk, 41% in intermediate-risk and 11% in low-risk group (Fig 1). The risk score was also predictive for the occurrence of multiple CMV-V reactivations with rates of 71%, 45%, 19% and 4% for the very high, high, intermediate and low-risk groups, respectively. The overall survival (OS) rate at 2 years was 33%(n=56) in the very high-risk group compared to 50% in other-risk groups (n=147) (P=0.01) (Fig 2). Non-relapse mortality (NRM) was 53% in the very high-risk versus 33% in other-risk groups (P<0.001). However, there was no difference on cumulative incidence of relapse between the groups (P=0.3). The cumulative incidence of grades 1-4 acute GVHD, grades 2-4, grades 3-4 at day 120 and overall chronic GVHD at 2 years was 68%, 47%, 25% and 39% in very high-risk group versus 65%, 52%, 21% and 52% in other-risk groups, suggesting slightly lower incidence of chronic GVHD in very high-risk vs other-risk groups. Conclusion: We present a new clinical scoring system to stratify the risk of early CMV viremia after allogeneic HSCT based on patients and HSCT characteristics. Identifying the risk for each patient would facilitate decision making with respect to strategies including CMV prophylaxis, pre-emptive treatment or inclusion into clinical trials, as well directing the CMV monitoring policy post-transplant. In addition, the risk score was associated with higher risk of overall mortality and NRM in the very high-risk versus other-risk groups. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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