Time Changes In Predictive Power Of MDS Prognostic Scores – Effects On Revised Scores Such As The IPSS-R, Impact Of Age

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1544-1544 ◽  
Author(s):  
Michael Pfeilstöcker ◽  
Heinz Tüchler ◽  
Julie Schanz ◽  
Guillermo Sanz ◽  
Guillermo Garcia Manero ◽  
...  
Keyword(s):  
Lower Risk ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Risk Category ◽  
Prognostic Scoring Systems ◽  
Prognostic Power ◽  
Risk Categories ◽  
Over Time

Abstract Introduction New, refined prognostic scoring systems have been established for MDS. Most scores assess prognosis at time of diagnosis assuming stable prediction over time. Earlier studies have shown moderate loss of prognostic power over time in scores using clinical parameters whereas cytogenetic scores maintained prognostic power, scores including comorbidity had shown gain of prognostic power (Pfeilstöcker et al, 2012). The aim of this multicenter retrospective study was to assess the relative stability of the newly developed scoring systems over time, to compare and explain observed time-related losses of prognostic power, and to discuss their clinical implications. Methods This study is based on 7212 untreated (no disease modifying treatment) MDS patients from multiple institutional databases of the IWG-PM, which generated the IPSS-R (Greenberg et al, 2012). Patient characteristics were well comparable with other populations: median age 71 years, male gender 60 %, median overall survival 3.8 years (range 3.7-4.0), median time to AML transformation not reached with 25% of patients transforming to AML after 6.8 years. Patients were diagnosed and classified by FAB and WHO; cytogenetics were classified by original IPSS subtypes and by the recently refined proposal integrated into the IPSS-R (Schanz et al, 2012). The following scores were analysed for their stability over time: IPSS, IPSS-R, WPSS variants, cytogenetic scores, age, performance status and other differentiating features of the IPSS-R. Time variations were described by the Cox-zph-test, and by applying Dxy, a measure of concordance, for censored data at separate observation periods. Results In line with previous observations, loss of prognostic power occurred over time after diagnosis in all scoring systems. While for the entire population the risk between adjacent IPSS-R risk categories differs by ∼80%, for patients observed at least 1 year the increase is ∼66%, and for those observed 4 years it is only ∼25%. The IPSS-R and particularly its age-including version (the IPSS-RA) retained the highest prognostic values compared to all other scoring systems at all time points. Dxy for IPSS-R: at diagnosis 0.43, 1 year 0.35, 2 years 0.27, 4 years 0.14. Including age, as in the IPSS-RA, was associated with less loss of prognostic power over time: Dxy at diagnosis 0.46, 1 year 0.38, 2 years 0.31, 4 years 0.22. For the IPSS and WPSS (available for the latter in only 33% cases), these values were: 0.37, 0.30, 0.22, 0.11 and 0.44, 0.36, 0.29, 0.18 respectively. Considering risk categories, the risk remained fairly constant over time for the lower risk categories in every analyzed scoring system, while the risks in the higher risk categories were especially high in the second half of the first year after diagnosis, diminishing thereafter, thus reducing the prognostic value of these categories over time. To determine whether statistical weights optimized for each time period would alter these results, time-specific weights were applied, which did not demonstrate substantially different prognostic values from the basic model analysis. Particularly good retention of prognostic power was found in the lower risk categories over time. The lesser retention of prognostic power in the higher risk categories appeared related to loss of a larger portion of these patients over time due to their deaths or being censored by their beginning treatment. For the IPSS-R intermediate risk category patients, the prognosis for survival approached the “high” category ∼3 years after diagnosis, while it remained intermediate regarding their risk of AML transformation. Conclusions These data demonstrate that a degree of attrition of prognostic value occurred over time from diagnosis for all of the assessed MDS prognostic scoring systems. The IPSS-R, particularly the age-inclusive IPSS-RA, best retained such prognostic capability over time for the untreated patients analyzed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Neutrophil-to-Monocyte Ratio and Platelet-to-White Blood Cell Ratio Represent Novel Prognostic Markers in Patients with Pancreatic Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Feng Tang ◽  
Penghui Dai ◽  
Qiongqiong Wei ◽  
Ke Gan ◽  
Zijie Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Blood Cell ◽  
White Blood Cell ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Cell Ratio ◽  
Kaplan Meier ◽  
Prognostic Scoring Systems

Background. Inflammation plays an important role in the development of tumors. Several serum based-markers and ratios have been investigated for their prognostic value in pancreatic cancer. However, the prognostic value of the neutrophil-to-monocyte ratio (NMR) and platelet-to-white blood cell ratio (PWR) for patients with pancreatic cancer has scarcely been investigated. Methods. From October 2013 to November 2018, a retrospective cohort study was performed on 269 pancreatic cancer patients without treatment. Receiver operating characteristic curves were generated, and areas under the curve were compared for the evaluation of the discriminatory ability of inflammation-based prognostic scoring systems. Kaplan-Meier curves and the Cox proportional hazard model were employed to analyze the relationships among NMR, PWR, and overall survival (OS). Results. The optimal cutoff values of NMR and PWR were 48 and 6, respectively. In univariate analysis, the survival time of NMR > 48 and PWR ≤ 6 was shorter than that of NMR ≤ 48 and PWR > 6 in patients with pancreatic cancer ( P < 0.001 ). In Cox univariate and multivariate analyses, NMR (hazard ratio (HR), 9.095; 95% confidence interval (CI), 3.64–22.72; P < 0.001 ) and PWR (HR, 8.230; 95% CI, 3.32–20.43; P < 0.001 ) were significantly correlated with OS. Conclusions. The current study demonstrated that NMR and PWR may serve as novel and promising inflammatory prognostic scores for patients with pancreatic cancer. Elevated NMR (>48) and depressed PWR (<6) were independently associated with poor prognosis in patients with pancreatic cancer.

Scoring Systems For Predicting Outcome Of Chronic Myeloid Leukemia In Adults Are Poorly Informative In Pediatric Patients Treated With Imatinib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2725-2725 ◽  
Author(s):  
Meinolf Suttorp ◽  
Ingmar Glauche ◽  
David Gurrea Salas ◽  
Josephine Tabea Tauer ◽  
Christina Nowasz ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Pediatric Patients ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Sokal Score ◽  
Eutos Score ◽  
Risk Categorization ◽  
Risk Categories

Abstract Introduction Imatinib (IM) front-line treatment impressively improved survival of children with chronic myeloid leukemia (CML). In contrast to adult CML, specific scoring systems predicting the treatment response in individual pediatric patients (pts) are still lacking. Here we analyzed a cohort of pediatric pts with CML applying the established prognostic scores for adults in a comparative fashion. We question the value of four scoring systems (Sokal-, Sokal young-, Hasford-, Eutos-Score) especially with regard to grouping individual children differently or homogeneously into a defined risk category. In addition, we analyzed which scoring system would classify most specifically the prognosis of pediatric CML with regard to early molecular response (MR) on IM. Methods A total of 90 pts (male/female: 57/33; median age: 11.6 yrs, range: 1-18) with CML-CP enrolled in the prospective trial CML-PAED-II were included in this analysis. Registry data were collected on standardized forms filled in by the treating physicians. On this basis the Eutos-, Sokal- and Hasford-Scores were calculated using internet resources of the ELN (www.leukemia-net.org/content/leukemias/cml/cml_score), whereas the Sokal young Score (Sy) – a score described specifically for adolescents and younger adults (Sokal JE, Blood 1985;66:1352) – was manually calculated. Pts were grouped using the original three risk categories (low=LR, intermediate=IR, high=HR) or two categories, respectively, for the Eutos-Score (LR or HR). Evaluation of therapeutic response was performed by assessing the MR by measurement of the transcript ratio BCR-ABL1/ABL1 in blood specimen sent to the central reference laboratory at month 3 after start of IM treatment. Measurements were expressed according to the International Scale. Results By Sokal-Score 59/90 pts were classified as LR, 20/90 pts as IR and 11/90 pts as HR. By Hasford Score 57/90 pts were classified as LR, 25/90 pts as IR, and 8/90 pts as HR. By Eutos Score 73/90 pts were classified as LR and 17/90 pts as HR. As the hematocrit value was not collected systematically at diagnosis, this necessary parameter for calculating the Sy-Score was applicable only in 46/90 pts and thus 44/46 pts were classified as LR, 2/46 as IR, and 0/46 as HR. Comparing results of individual pts only 25/46 pts (54%) were categorized homogeneously as LR by applying all 4 scoring systems, while 54/90 pts (60%) were classified as LR if Sy-Score was excluded. Thus, the remaining 21/46 pts (46%) were grouped heterogeneously by applying each of the 4 prognostic scores, and correspondingly 33/90 pts (37%) were classified heterogeneously within different risk categories by the Eutos, Hasford and Sokal Score. Only 3 pts were categorized homogenously as HR by each of the Sokal, Hasford, and Eutos Score and by applying all 4 scoring systems no patient was concordantly classified as HR. When comparing only the Sokal-Score to the Sy-Score, discordant results were obtained in 19/46 (41%) pts. BCR-ABL1/ABL1 transcript ratio could be analyzed quantitatively in 72/90 pts at month 3 after treatment initiation. In this cohort we identified 46/72 good responders (ratio BCR-ABL1/ABL1 <10%) and 26/72 poor responders (ratio >10%). Although the Eutos-score performed best in in a logistic regression analysis with an Odds Ratio OR=3.02 to predict an unfavorable course of IM-treated CML in the HR group, the discrimination did not reach statistical significance (p=0.08). However, by reducing the cut-off point for the Eutos Score from 87 to 64 an OR=4.8 with p=0.004 was achieved, thus indicating that a refined risk categorization appears beneficial. Conclusion Comparing risk categorization by all four scores in individual pediatric pts, results may vary considerably. Keeping in mind that the number of pts analyzed is still small, especially applying the Sy-Score seems not to provide benefit in this cohort with a median age of only 11 years. Contrasting results in adults, in this pediatric cohort the Sokal- and Hasford-Scores did not predict a poor IM treatment response at month 3 while the Eutos Score achieved borderline significance. Thus, there is an urgent need for the development of a more specific pediatric risk score. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Consistency Test between Scoring Systems for Predicting Outcomes of Chronic Myeloid Leukemia in a Saudi Population Treated with Imatinib

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Haneen R. Banjar ◽  
Enaam Alsobhi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Hematological Parameters ◽  
Prognostic Score ◽  
Scoring Systems ◽  
Transcript Level ◽  
Prognostic Scores ◽  
Molecular Response ◽  
Risk Categories

Inconsistency in prognostic scores occurs where two different risk categories are applied to the same chronic myeloid leukemia (CML) patient. This study evaluated common scoring systems for identifying risk groups based on patients’ molecular responses to select the best prognostic score when conflict prognoses are obtained from patient profiles. We analyzed 104 patients diagnosed with CML and treated at King Abdulaziz Medical City, Saudi Arabia, who were monitored for major molecular response (achieving a BCR-ABL1 transcript level equal to or less than 0.1%) by Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR), and their risk profiles were identified using Sokal, Hasford, EUTOS, and ELTS scores based on the patients’ clinical and hematological parameters at diagnosis. Our results found that the Hasford score outperformed other scores in identifying risk categories for conflict groups, with an accuracy of 63%.

scholarly journals Lower risk but high risk

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 428-434
Author(s):  
Amy E. DeZern
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Myelodysplastic Syndromes ◽  
Genetic Information ◽  
Lower Risk ◽  
Molecular Genetic ◽  
Scoring Systems ◽  
International Prognostic Scoring System ◽  
Disease Characteristics ◽  
Prognostic Scoring Systems

Abstract Risk stratification is crucial to the appropriate management of most cancers, but in patients with myelodysplastic syndromes (MDS), for whom expected survival can vary from a few months to more than a decade, accurate disease prognostication is especially important. Currently, patients with MDS are often grouped into higher-risk (HR) vs lower-risk (LR) disease using clinical prognostic scoring systems, but these systems have limitations. Factors such as molecular genetic information or disease characteristics not captured in the International Prognostic Scoring System–Revised (IPSS-R) can alter risk stratification and identify a subset of patients with LR-MDS who actually behave more like those with HR-MDS. This review describes the current identification and management of patients with LR-MDS whose condition is likely to behave in a less favorable manner than predicted by the IPSS-R.

Role Of Hypomethylating Agents For Patients With Lower-Risk Myelodysplastic Syndrome Defined By IPSS and IPSS-R

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2782-2782
Author(s):  
Joon Ho Moon ◽  
Sang Kyun Sohn ◽  
Jae Sook Ahn ◽  
Yeo-Kyeoung Kim ◽  
Hyeoung Joon Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Risk Groups ◽  
International Prognostic Scoring System ◽  
Hypomethylating Agents ◽  
Risk Patients ◽  
Very High ◽  
Prognostic Power

Abstract Background International Prognostic Scoring System (IPSS) is commonly used to distinguish various subgroups of myelodysplastic syndrome (MDS) patients with different prognosis and to make a therapeutic decision. However, the classic IPSS, defining lower-risk as low and intermediate-1 IPSS, seems to be insufficient to discriminate the prognostic groups of lower-risk MDS. Recently, IPSS was updated into the revised score (IPSS-R) to refine the IPSS by reassessing the major predictive features of MDS. The hypomethylating agents (HMA) are usually recommended for patients with lower-risk MDS who is not responsive to other therapies. However the role of HMA for the patients with lower-risk IPSS are still on debate. This study was conducted to find the rationale to treat HMA for the patients with lower-risk IPSS and to know whether IPSS-R further discriminate the prognosis of patients treated with HMA. Methods The data of 334 patients diagnosed with MDS lower-risk defined by IPSS after Jan 2006 were retrospectively reviewed. Lower-risk IPSS was revised into IPSS-R to know whether it could further discriminate the prognosis of this group of patients. The prognosis of lower-risk by IPSS and IPSS-R were analyzed in terms of overall survival (OS) and prognostic power was calculated with time-dependent Cox-hazard models. To define the role of HMA for patients with lower-risk IPSS, we categorized the lower risk patients into No-HMA group, early HMA group (HMA within 2 mo.), and late HMA group (HMA after 2 mo). Results Out of 334 lower-risk patients (39 low and 295 intermediate-1), 195 patients (58.4%) were treated with HMA (azacitidine 163, decitabine 32). Median time to HMA treatment was 43 days (range 0-1778 days). 3yr-OS rate was not significantly different between HMA group (43.1¡¾4.2%) and non-HMA group (62.3¡¾5.9%) (p=0.099). Early HMA treatment (3yr-OS 36.4¡¾5.4%) didn't show survival benefits compared to late HMA group (54.6¡¾6.3%) or no-HMA group (62.3¡¾5.9%) (p=0.003). Plus, HMA response (CR/PR/HI) didn't guarantee OS benefits: 3yr-OS of 45.2¡¾7.4% in responders (CR/PR/HI, n=74) and 43.4¡¾5.0 in non-responders (SD/PD, n=121) (p=0.239). Among 39 patients with IPSS low, 11 patients (28.2%) were revised into IPSS-R very low, 24 (61.5%) into low, 3 (7.7%) into intermediate, and 1 (2.6%) into high. Among 295 patients with IPSS intermediate-1, 4 patients (1.4%) were revised into IPSS-R very low, 84 (28.5%) into low, 133 (45.1%) into intermediate, 71 (24.1%) into high and 3 (1.0%) into very high. IPSS-R could further discriminate the IPSS lower-risk patients with regard to OS: 3yr-OS rates of 100% in very low, 64.5¡¾5.9% in low, 46.1¡¾5.5% in intermediate, 26.1¡¾6.6% in high, and 0% in very high (p<0.001). The survival benefits of HMA for lower risk groups (very low and low) defined by IPSS-R (n=123) was not defined in the current study, where 3yr-OS was 83.8¡¾6.4% in no-HMA group (n=60) vs. 60.5¡¾7.1% in HMA group (n=63) (p=0.198). Conclusion The prognosis of the patients with lower-risk IPSS (low and intermediate-1) were successfully refined by IPSS-R. The IPSS intermediate-1 risk was heterogeneous group, which subdivided into very low to very high by IPSS-R. However, the beneficial effect of HMA for patients with lower-risk MDS, defined by IPSS (low and intermedite-1) and IPSS-R (very low and low), should be elucidated in the future studies. Disclosures: No relevant conflicts of interest to declare.

Do predictive scoring systems have any role in determining treatment strategy for colorectal liver metastases at the individual patient level?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15104-e15104
Author(s):  
H. Malik ◽  
G. Poston
Keyword(s):  
Liver Metastases ◽  
Scoring System ◽  
Colorectal Liver Metastases ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Published Data ◽  
Individual Patient Level ◽  
Patient Level ◽  
The Individual ◽  
Prognostic Scoring Systems

e15104 Background: the literature contains four prognostic scoring systems from large volume series predicting survival after resection for colorectal liver metastases. Our aim was to directly compare these systems in terms of accuracy in predicting survival, and evaluate the role of such systems in determining therapeutic strategies on intention to treat at the individual patient level. Methods: the original published data were reviewed and the median survivals plotted against each point in the scoring system. The best fit line was drawn and the resultant plots enabled calculation of slope of the linear regression line and the square of the Pearson product moment correlation coefficient through data points allowing all four prognostic scoring systems to be directly compared. Results: when the prognostic scores were compared on a common scale, the R-squared values of all the scoring systems were similar with R-squared values of greater than 0.94 in all cases. The Basingstoke Predictive Index however produced the steepest gradient suggesting it can better distribute patients along a wider range of survival. Conclusions: none of the four scoring systems was perfect in their predictive value. It is not surprising that the risk score from MSKCC and Leeds are not as good as the others since they are meant to be preoperative prognostic scores and postoperative scoring system by their nature of having more information should be better. Clearly, future developments in this field must incorporate advances in our understanding of tumor biology. [Table: see text]

scholarly journals Inflammatory prognostic scoring systems are risk factors for surgical site infection following wide local excision of soft tissue sarcoma

2021 ◽  
Author(s):  
Omer M. Farhan-Alanie ◽  
Taegyeong Tina Ha ◽  
James Doonan ◽  
Ashish Mahendra ◽  
Sanjay Gupta
Keyword(s):  
Risk Factors ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Curative Resection ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Increased Risk ◽  
Tumour Location ◽  
Grade 3 ◽  
Prognostic Scoring Systems

Abstract Introduction Limb-sparing surgery with negative margins is possible in most soft tissue sarcoma (STS) resections and focuses on maximising function and minimising morbidity. Various risk factors for surgical site infections (SSIs) have been reported in the literature specific to sarcoma surgery. The aim of this study is to determine whether systemic inflammatory response prognostic scoring systems can predict post-operative SSI in patients undergoing potentially curative resection of STS. Methods Patients who had a planned curative resection of a primary STS at a single centre between January 2010 and December 2019 with a minimum follow-up of 6 months were included. Data were extracted on patient and tumour characteristics, and pre-operative blood results were used to calculate inflammatory prognostic scores based on published thresholds and correlated with risk of developing SSI or debridement procedures. Results A total of 187 cases were included. There were 60 SSIs. On univariate analysis, there was a statistically significant increased risk of SSI in patients who are diabetic, increasing specimen diameter, American Society of Anaesthesiology (ASA) grade 3, use of endoprosthetic replacement, blood loss greater than 1 L, and junctional tumour location. Modified Glasgow prognostic score, C-reactive protein/albumin ratio and neutrophil–platelet score (NPS) were statistically associated with the risk of SSI. On multivariate analysis, ASA grade 3, junctional tumour location and NPS were independently associated with the risk of developing a SSI. Conclusion This study supports the routine use of simple inflammation-based prognostic scores in identifying patients at increased risk of developing infectious complications in patients undergoing potentially curative resection of STS.

scholarly journals Established and novel agents for myelodysplastic syndromes

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Mikkael A. Sekeres ◽  
Aaron T. Gerds
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Hematopoietic Cell Transplantation ◽  
Scoring Systems ◽  
The United States ◽  
Immunosuppressive Drugs ◽  
Novel Agents ◽  
Hypomethylating Agents ◽  
Risk Patients ◽  
Prognostic Scoring Systems

Abstract The myelodysplastic syndromes (MDS) are the most commonly diagnosed myeloid malignancy, with >15 000 new cases identified in the United States yearly. Prognostic scoring systems supplant a formal staging approach and, in general, divide patients into those with lower-risk and those with higher-risk MDS. Although treatment goals for patients with lower-risk disease focus on minimizing transfusions and optimizing quality of life, in higher-risk MDS, the goal is to delay transformation to acute leukemia and to prolong survival. In lower-risk patients, isolated cytopenias are treated with erythropoiesis-stimulating agents or growth factors such as thrombopoietin mimetics. For patients with the del(5q) cytogenetic abnormality or those who fail these initial approaches, lenalidomide may be tried, as can experimental agents. Lower-risk patients with multiple cytopenias may be treated with immunosuppressive drugs or low-dose hypomethylating agents. For patients with higher-risk disease, hypomethylating agents are the preferred initial treatment approach, with evaluation for hematopoietic cell transplantation at diagnosis. Several novel agents are being developed for MDS patients who have failed hypomethylating drugs.

Survival Advantage with Hypomethylating Agents In Patients with Higher Risk Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1859-1859
Author(s):  
Young-Hoon Park ◽  
Je-Hwan Lee ◽  
Kyoo Hyung Lee ◽  
Jung-Hee Lee ◽  
Dae-Young Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Survival Data ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Cox Model ◽  
Immunosuppressive Treatment ◽  
Complete Response ◽  
Risk Category ◽  
Hypomethylating Agents ◽  
Treatment Groups

Abstract Abstract 1859 Background: Two hypomethylating agents, azacitidine and decitabine, are active in myelodysplastic syndrome (MDS) and both drugs have been approved for the treatment of MDS in Korea. In this retrospective analysis, we tried to analyze the effects of hypomethylating agents on the clinical outcomes of the patients with MDS. Methods: A total of 385 patients, who were diagnosed as MDS at the Asan Medical Center between July 1992 and March 2010, were included in this study. We divided the patients into three treatment groups such as hypomethylating therapy (HMT, n=92), intensive chemotherapy (IC, n=15), and supportive care (including low-dose cytarabine and immunosuppressive treatment, SC, n=278). Primary end points of this study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. All survival data were censored at the time of hematopoietic cell transplantation (HCT) to eliminate the influence of HCT on survivals. The difference of survivals was compared using time updated Cox model because times from diagnosis of MDS to treatment (HMT or IC) were various. Results: Baseline clinico-laboratory features were not significantly different between 3 treatment groups (HMT vs. IC vs. SC) in regard to sex, age, WHO subtype, and IPSS risk category. Among 83 patients in the HMT group, 39 (47.0%) attained any response to HMT including complete response, partial response, marrow complete response, and hematologic improvement. Survival data were the followings: OS, HMT vs. IC vs. SC, median 62.5 vs. 16.7 vs. 21.0 months; PFS, median 37.7 vs. 13.8 vs. 17.8 months. Multivariate analyses by stratified time updated Cox model showed that hazard ratio (HR) of HMT compared to SC was 1.029 (95% CI, 0.670–1.582, P=0.895) for OS and 0.539 (95% CI, 0.362–0.803, P=0.002) for PFS. When we performed subgroup analyses in lower risk disease (IPSS Low/Intermediate-1) and higher risk disease (IPSS Intermediate-2/High), the effects of HMT on survivals were different by the risk stratification of MDS. In lower risk MDS, there were no survival benefits of HMT compared to SC (OS, median 53.9 vs. 39.8 months, HR 1.570, P=0.108; PFS, median 37.7 vs. 52.5 months, HR 0.880, P=0.633), whereas both OS and PFS were significantly longer in HMT compared to SC (OS, median 137.9 vs. 5.9 months, HR 0.289, P=0.043; PFS, median 80.2 vs. 0.9 months, HR 0.154, P<0.001). Conclusion: Our data suggested that hypomethylating therapy could improve the survivals (OS and PFS) of the patients with higher risk MDS. Disclosures: No relevant conflicts of interest to declare.

RBC-Transfusion Dependency Improves the Prognostic Value of the Revised-IPSS in MDS Patients: Analysis of South Australian and Dusseldorf MDS Registries

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1998-1998
Author(s):  
Deepak Singhal ◽  
Corinna Strupp ◽  
Rakchha Chhetri ◽  
Monika M Kutyna ◽  
L Amilia Wee ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Validation Cohort ◽  
Prognostic Index ◽  
Scoring Systems ◽  
Risk Groups ◽  
Transfusion Dependency ◽  
Cox Proportional Hazard Regression ◽  
Prognostic Scoring Systems ◽  
Rbc Transfusion

Abstract RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor survival in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International prognostic Scoring System (IPSS-R) includedthree haemoglobincut-offs, which were thought to substitute for RBC-TD. Thus, none of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R, in addition to that offered by haemoglobin levels at diagnosis. South Australian MDS registry (SA-MDS registry) data were used to derive a prognostic index while Dusseldorf registry (Germany) data was used as a validation cohort. Inclusion criteria for this study were: primary MDS not treated with disease-modifying therapy, bone marrow blasts ≤30% and peripheral blasts ≤20%. RBC TD was defined as at least one unit of packed red cells transfused every eight weeks for four months (mos), according to WPSS classification. In this study IPSS-R was calculated at the time of diagnosis and the RBC-TD was continuously reassessed after diagnosis. In South Australian Registry, the prevalence of RBC-TD at diagnosis was 61/295 (20.7%), while the incidence of RBC-TD during follow-up was 64/234 (27.4%; Table I). The poor prognosis associated with RBC-TD was demonstrated in a series of landmark analyses. The median overall survival (OS) of RBC-TD patients was significantly inferior to RBC transfusion independent (RBC-TI) patients at 6mos (18 vs. 64 months; n=255; p < 0.0001), 12mos (24 vs. 71 months; n=231; p < 0.0001) and 24mos (40 vs. 87 months; p < 0.0001; n=173; Fig 1A-C). Subgroup analysis of IPSS-R Low and Intermediate risk groups also showed inferior OS in RBC-TD compared to RBC-TI within each risk category. The adverse prognosis of RBC-TD was substantiated in multivariate analysis using a Cox-proportional regression model. We tested 46 models and in each of the three models with least Akaike Information Criterion (AIC) or minimum AIC difference RBC-TD wasan independent adverse prognostic marker in addition to age, sex, and IPSS-R variables(Wald test; P<0.0001). In the best-fitting model, the IPSS-R variables were used as continuous variables (except IPSS-R cytogenetic risk groups).This Cox-proportional regression model (Table 2) was used to derive a prognostic index using cut-off points determined by Cox's method and was validated in the Dusseldorf cohort. Dusseldorf validation cohort: This cohort consisted of 106 patients (160 start-stop intervals) with a median follow-up of 5.66 years. Cox proportional hazard regression of OS on the prognostic index resulted in a slope coefficient of 0.663 in the validation cohort. This difference in slope could be due to differences between the datasets: e.g. the validation cohort comprised younger patients, more patients with RBC-TD at diagnosis and fewer cases with favourable cytogenetic risk (Table 1). The validation cohort was divided into four prognostic groups using cut-offs determined by Cox's method (derivation dataset). Cox-proportional hazard regression of OS showed significant OS difference between the four prognostic groups (p<0.001) and significantly higher risk of death in groups 3 (p=0.032) and 4 (p=0.007) relative to group 1 (Table 1). Conclusion: Multivariate analysis by Cox proportional hazards regression and serial landmark analysisof dataset clearly demonstrates that development of RBC-TD at any time during the disease course is associated with poor OS, independent of IPSS-R. This was confirmed in the Dusseldorf validation cohort. This is the first report demonstrating that inclusion of RBC-TD can refine the IPSS-R. Furthermore, despite inclusion of three haemoglobin cut-off values in the IPSS-R model, the onset of RBC-TD during follow-up provides additional prognostic value and could be included in future prognostic scoring systems and in treatment decision algorithms for MDS patients. Disclosures Ross: Novartis Pharmaceuticals: Honoraria, Research Funding; BMS: Honoraria.

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