Myelodysplastic Syndrome (MDS)-Specific Comorbidity Index for Predicting the Impact of Extra-Hematological Comorbidities on Survival of Patients with MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2677-2677 ◽  
Author(s):  
Matteo G Della Porta ◽  
Andrea Kuendgen ◽  
Luca Malcovati ◽  
Esther Zipperer ◽  
Cristiana Pascutto ◽  
...  
Keyword(s):  
Cardiac Disease ◽  
Prognostic Value ◽  
Prognostic Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Allogeneic Transplantation ◽  
History Of ◽  
Transfusion Dependency ◽  
Comorbidity Index ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, who are likely to be affected with extra-hematological comorbidities. Recent findings suggest that proper assessment of comorbidities is useful to predict the outcome of MDS patients receiving allogeneic transplantation. However, the results obtained in this highly selected subset of patients cannot be applied to the whole MDS population. In this study, we evaluated the impact of extra-hematological comorbidities on the natural history of MDS with the aim of developing a specific prognostic index. The patients comprised a “learning cohort”, in which we defined the set of variables to be included in the prognostic model and their weighted scores, and a “validation cohort”, in which we confirmed the prognostic value of the scoring system. The learning cohort included 840 MDS patients diagnosed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, between 1992 and 2006, while the validation cohort consisted of 504 patients seen at the Heinrich-Heine-University Hospital, Duesseldorf, Germany, between 1982 and 2006. All cases were classified according to the WHO criteria. Patients who underwent allogeneic transplantation or intensive chemotherapy were censored at the time of the procedure. One or more comorbidities were present in 455 (54%) patients in the learning cohort at the time of diagnosis: the older the age, the higher the prevalence. Cardiac disease was the most frequent extra-hematological morbidity (25% of patients) and the main cause (63%) of non-leukemic death (NLD). In a Cox multivariable analysis with time-dependent covariates, the onset of a comorbidity significantly affected the risk of NLD (HR=2.29, P<.001) and worsened overall survival (OS, HR=1.51, P=.01). Patients who developed RBC transfusion-dependency had a significantly higher risk of NLD (HR=4.31 P=<.001), cardiac disease and death (HR 4.16 and HR 4.88, respectively; P=<.001). In this group, serum ferritin levels were significantly associated with the risk of cardiac disease and death (P=.001). The onset of cardiac, liver, renal, pulmonary disease and solid tumor were found to independently affect the risk of NLD in a multivariable Cox regression (HR from 3.57 to 1.97; P values from <0.001 to 0.04). Based on these results, we developed a dynamic prognostic model (MDS-specific comorbidity index, MDS-CI) for predicting the effect on NLD and OS of comorbidities either present at the time of diagnosis or occurring during the follow-up. Risk scores for each comorbidity were estimated from the regression coefficients (Table 1). Table 1. MDS-specific comorbidity index (MDS-CI) Comorbidity Score Cardiac disease 2 Moderate-to-severe hepatic disease 1 Severe pulmonary disease 1 Renal disease 1 Solid tumor 1 Risk groups: Low (score 0), Intermediate (score 1–2), High (score >2). MDS-CI allowed us to identify 3 groups of patients with different probability of NLD and OS (P<.001). The prognostic value of the MDS-CI was then evaluated in the validation cohort of patients, where the 3 MDS-CI risk groups showed significantly different probabilities of NLD (P<.001) and OS (P=.005), with a 2-year risk of NLD since diagnosis of 24%, 42% and 61% in the low, intermediate and high risk group, respectively. In summary, extra-hematological comorbidities significantly worsen the natural history of MDS patients, specifically increasing the risk of NLD. In particular, transfusion-dependency and secondary iron overload are associated with a higher risk of cardiac complications. The MDS-CI improves our ability to stratify the outcome of MDS patients and may be a useful tool for clinical decision-making. An accurate evaluation of extra-hematological comorbidity should be part of the prognostic assessment of patients with MDS.

Comorbidity as Prognostic Variable in MDS: Comparative Evaluation of the HCT-CI and CCI in a Core Data Set of 582 Patients of the Austrian MDS Platform.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1648-1648
Author(s):  
Wolfgang R Sperr ◽  
Friedrich Wimazal ◽  
Michael Kundi ◽  
Christian Baumgartner ◽  
Thomas Noesslinger ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Data Set ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Prognostic Variable ◽  
Prognostic Parameter ◽  
Comorbidity Index ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective erythropoiesis, peripheral cytopenia(s), and an increased risk to transform to secondary acute myeloid leukemia (AML). The prognosis in MDS is variable and depends on the variant of disease, other disease-related features, and patient-related parameters. In the present study, the influence of comorbidity on survival and AML evolution was analyzed retrospectively in 582 patients (270 females and 312 males, f/m ratio: 1:1.2) with de novo MDS (observation period: 1985–2007). The median age was 71 years (range 18–96 years). Of the 582 patients, 275 died so far. The median survival (OS) of all patients was 3.12 years, and the median event-free survival (EFS) was 2.3 years. The median AML-free survival (AFS) was not reached. All in all, 127 patients (22%) developed secondary AML after a median time of 9.7 months (range 0.3–116.6 months). Two different scoring systems for comorbidity, the hematopoietic stem cell transplantation comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied. As assessed by log rank test, the overall survival (OS) was found to differ among patients in the three different HCT-CI risk groups (p<0.05) and among patients in the four different CCI risk groups. By univariate analysis, the HCT-CI was found to be of prognostic value for OS and EFS in patients meeting WHO- or FAB criteria (p<0.05). The CCI was also found to be of prognostic value for OS in patients diagnosed according to either WHO or FAB criteria (p<0.05). With regard to EFS, the CCI was a prognostically significant variable only for patients meeting WHO criteria (p<0.05), but not in patients diagnosed according to FAB criteria (p>0.05). Calculating AML-free survival (AFS), neither the CCI nor the HCT-CI were of prognostic significance (p>0.05). To evaluate whether comorbity is an independent prognostic parameter in patients with MDS, multivariate analyses were performed. These analyses included the HCT-CT or the CCI together with IPSS, LDH, and the patients’ age. In these analyses, chronic comorbid conditions were found to be independent prognostic risk factors concerning OS and EFS, but not concerning AFS. Specifically, the HCT-CI was an independent prognostic parameter regarding OS (p<0.05) and EFS (p<0.05) for patients diagnosed according to WHO- or FAB-criteria. In contrast, the CCI was of prognostic significance regarding OS for patients meeting WHO- or FAB-criteria, whereas the CCI was not found to be an independent prognostic factor regarding EFS (p>0.05). Regardless of the score applied (HCT-CI or CCI), the highest predictive value of comorbidity was observed in IPSS low risk patients (p<0.05) concerning OS. Of the other variables included in our multivariate analysis, the IPSS was an independent prognostic parameter for OS, EFS, and AFS. Interestingly, age was an independent prognostic variable for OS and EFS, but not concerning AFS, similar to the impact of comorbidity, whereas LDH was an independent predictive factor concerning EFS and AFS. Together, our data show that comorbidity is an independent risk factor for survival in patients with MDS. Therefore, comorbidity should be considered as an important co-variable in the risk assessment in MDS and in the overall treatment plan in these patients.

A WHO Classification-Based Prognostic Scoring System (WPSS) for Predicting Survival in Myelodysplastic Syndromes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 788-788 ◽  
Author(s):  
Luca Malcovati ◽  
Ulrich Germing ◽  
Andrea Kuendgen ◽  
Matteo G. Della Porta ◽  
Rosangela Invernizzi ◽  
...  
Keyword(s):  
Scoring System ◽  
Prognostic Value ◽  
Prognostic Model ◽  
Who Classification ◽  
Proportional Hazards ◽  
Validation Cohort ◽  
Transfusion Requirement ◽  
Risk Groups ◽  
Proportional Hazards Regression ◽  
Very High

Abstract The WHO classification of myelodysplastic syndromes (MDS) is based on uni- or multi-lineage hematopoietic involvement, blast count and cytogenetic features. We recently confirmed the prognostic value of this classification and demonstrated that cytogenetics and transfusion requirement are the main prognostic factors affecting survival of WHO subgroups (JCO 2005, in the press). The aim of the present study was to define and validate a scoring system for evaluating prognosis in MDS classified according to WHO criteria. The patients comprised a learning cohort, in whom investigations were aimed at defining the set of variables to be included in the prognostic model and their weighted scores, and a validation cohort, in whom we evaluated whether the prognostic value of the scoring system was confirmed. The learning cohort was formed of 467 consecutive patients with a diagnosis of de novo MDS made at the IRCCS Policlinico S. Matteo, Italy, between 1992 and 2002, while the validation cohort consisted of 620 consecutive patients diagnosed at the Heinrich-Heine-University Hospital between 1982 and 2003. All cases were reclassified by independent cytologists according to the WHO criteria. Those patients who were treated with allogeneic stem cell transplantation or chemotherapy, were censored at the time of this therapeutic intervention. Uni- and multivariate analyses were performed by means of Cox proportional hazards regression. The actuarial probabilities of overall survival (OS) and leukemia-free survival (LFS) were estimated using the Kaplan-Meier product limit method. Based on the results of the uni- and multivariate analyses, the most significant variables selected for the prognostic model were WHO subgroups, cytogenetic abnormalities scored according to the IPSS and transfusion requirement. Risk scores for each variable were estimated based on coefficients from the proportional hazards regression (Table 1). Table 1 - WHO-Classification Based Prognostic Scoring System (WPSS) for MDS Prognostic variable Score value 0 1 2 3 WHO category RA, RARS, 5q- RCMD, RCMD-RS RAEB-1 RAEB-2 Karyotype Good Intermediate Poor - Transfusion requirement No Regular - - By summing the score values for the three variables, patients were stratified into five distinct risk groups [very low (score 0), low (1), intermediate (2), high (3–4), very high (5–6)], showing significantly different OS and probability of leukemia evolution (P<.0001). The scoring system was then evaluated in the independent cohort of patients in order to confirm its prognostic value. In this validation cohort, the WPSS groups showed significantly different OS (P<.0001), the median survival in the five risk groups being 136, 63, 44, 19 and 8 months, respectively. The WPSS groups also showed significantly different probabilities of leukemia progression (P<.0001), ranging from a 10-year probability of 7% in the very low risk group to a 50% probability of leukemia evolution reached at 8 months in the very high risk group. In conclusion, we have defined a prognostic scoring system based on WHO subgroups, cytogenetics and transfusion requirement. WPSS improves the capacity of the WHO classification to stratify OS and LFS of MDS patients and therefore may be a useful tool for clinical decision-making.

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.

A Prognostic Model for Predicting the Impact of Comorbidities on Survival of Patients with Myelodysplastic Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2453-2453 ◽  
Author(s):  
Matteo G. Della Porta ◽  
Luca Malcovati ◽  
Erica Travaglino ◽  
Cristiana Pascutto ◽  
Margherita Maffioli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Myelodysplastic Syndromes ◽  
Cardiac Death ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
Increased Risk ◽  
Secondary Iron Overload ◽  
Transfusion Dependency ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, and these patients are likely to have comorbidities. We studied the impact of comorbidities on non-leukemic death (NLD) and overall survival (OS) in MDS patients with the aim of developing a specific prognostic index. Eight hundred forty consecutive patients receiving a diagnosis of MDS at Policlinico San Matteo, Pavia, Italy, between 1992 and 2006 were retrospectively evaluated. One or more comorbidities were present in 455/840 (54%) patients: the older the age, the higher their prevalence (P&lt;0.001). Cardiac disease was observed in 25% of patients, liver disease in 16%, diabetes in 11%, prior solid tumor in 10%, nephropathy and pulmonary disease in 4%. Non-leukemic causes of death included cardiac failure (63%), infection (24%) and hemorrhage (7%). In a Cox analysis with age, sex, WHO category, cytogenetics and transfusion-dependency as time-dependent covariates, the presence of one or more comorbidities significantly affected both the risk of NLD (HR=1.91, P=0.001) and OS (HR=1.51, P=0.01), while it did not influence the risk of leukemic progression. The negative effect of comorbidities on OS was more evident in patients without excess of blasts (HR=1.8 P=0.007), while it retained a borderline significance in patients with more advanced disease (P=0.05). By including comorbidities as distinct entities in multivariable analysis, cardiac failure, liver or pulmonary disease, and solid tumors were found to independently affect the risk of NLD (HR=3.7, HR=2.08, HR=2.07 HR=2.23, respectively; P values from &lt;0.001 to 0.033). Based on results of uni- and multivariable analysis, we developed a prognostic model for predicting the effect of comorbidities on NLD and OS. For each comorbidity, risk scores were estimated from the coefficients of the Cox regression. This MDS-specific comorbidity index (MDS-CI) allowed us to identify 3 groups of patients with different probability of NLD and OS (HR 2.78, P&lt;0.001; HR 1.67 P=0.001), and provided a better stratification than the available non MDS-specific indices. Focusing on WPSS categories [J Clin Oncol2007; 25:3503–10], MDS-CI significantly stratified survival of patients with very-low, low and intermediate risk groups (P&lt;0.001), while it had no effect in high and very-high risk groups. We then investigated the relationship between transfusion-dependency, secondary iron overload and comorbidities. Heart failure (28% vs. 18% P=0.001) and cardiac death (69% vs 55% P=0.03) were significantly more frequent in transfusion-dependent patients. In a Cox analysis with time-dependent covariates, transfusion-dependent patients showed an increased risk of NLD (HR=2.12 P=&lt;0.001), heart failure (HR 1.34 P=0.03), and cardiac death (HR 2.99 P=0.01). The development of secondary iron overload significantly affected the risk of NLD and OS (HR=1.25 and 1.16 respectively, P&lt;0.001), and this effect was maintained after adjusting for transfusion burden. Iron overload specifically increased the risk of developing heart failure (HR=1.17, P&lt;0.001). In summary, the presence of non-hematological comorbidities significantly worsens the survival of MDS patients. Transfusion-dependency and secondary iron overload are associated with an increased risk of cardiac complications and cardiac death. The MDS-CI might be a useful tool for clinical decision making in patients with myelodysplastic syndromes.

Cigarette Smoking Is Associated with Increased Rates of Fungal Infection and Increased Mortality After Allogeneic Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2321-2321
Author(s):  
Brian T. Hill ◽  
Brian J. Bolwell ◽  
Lisa Rybicki ◽  
Mikkael A. Sekeres ◽  
Mary Mansour ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cigarette Smoking ◽  
Fungal Infection ◽  
Allogeneic Transplantation ◽  
Smoking History ◽  
Cell Transplant ◽  
Allogeneic Transplant ◽  
Transplant Outcomes ◽  
History Of ◽  
The Impact

Abstract Abstract 2321 Introduction: Prior reports on the effect of smoking on outcomes of stem cell transplantation (SCT) have demonstrated an increased mortality for smokers but have not examined the incidence of fungal infection1-2. Tobacco cigarettes contain aspergillus spores that could serve as a source of fungal infection in immunocompromised patients after allogeneic SCT3. To determine the impact of smoking on transplant outcomes, we retrospectively analyzed data from patients undergoing allogeneic SCT at the Cleveland Clinic and compared the survival and incidence of fungal infection in patients who have smoked cigarettes with those who have never smoked. Methods: We identified 237 consecutive patients using the following inclusion criteria: age ≥18, and myeloablative allogeneic SCT for hematologic malignancy between 2004 and 2009. Survival was estimated using the Kaplan-Meier method and compared according to prospectively-collected smoking history. Smokers were more likely than nonsmokers to be male (59.0% vs. 45.5%, P = 0.046), caucasian (92.8% vs. 84.4%, P= 0.06) and have an unrelated donor (63.9% vs. 48.1%, P = 0.02) but were similar in terms of median age (45 vs. 46, P = 0.85) and hematopoietic stem cell transplant comorbidity index (36.1% low, 27.7% intermediate, 36.1% high vs. 39.0%, 30.5%, 30.5%, P = 0.68). In addition, we analyzed the incidence of fungal infection in 145 consecutive patients with a diagnosis of acute myeloid leukemia (AML) who underwent allogeneic SCT between 1994 and 2009. We categorized the type of fungal infection as possible, probable or proven using the Revised Infectious Diseases Society of America (IDSA) guidelines. Results: 154 of 237 (65.0%) patients who underwent allogeneic transplant had never smoked and 83 (35%) had a history of at least some cigarette smoking. 4 year survival was 42.3% for nonsmokers and 26.4% for smokers (P = 0.004). Multivariable analysis demonstrated a hazard ratio of 1.56 for overall mortality after allogeneic transplantation for smokers (95% confidence interval 1.10 – 2.22, P = 0.013). A Kaplan-Meir survival curve for smokers and nonsmokers is shown below. Patients with AML who had a history of cigarette smoking had a higher incidence of proven or probable fungal infection after allogeneic SCT than nonsmokers (16.3 % vs. 2.9%, P < 0.001). Conclusion: Cigarette smoking is independently associated with increased mortality after allogeneic SCT. Although the effects of cigarette smoking are likely multifactorial, a significantly higher incidence of fungal infections may contribute to the poorer outcomes of smokers after transplantation. References: 1. Marks, D, et al. The Effect of Smoking on Allogeneic Transplant Outcomes. BBMT. 2009;15(10), 1277–1287. 2. Ehlers, SL et al. al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. BMT, May 2010. 3. Verweij, PE, et al: Fungal contamination of tobacco and marijuana. JAMA. 2000;284(22), 2875. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of the Freiburg and Charlson Comorbidity Indices in Predicting Overall Survival in Elderly Patients with Newly Diagnosed Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Min Kim ◽  
Moon Jin Kim ◽  
Hyun Ae Jung ◽  
Kihyun Kim ◽  
Seok Jin Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Performance Status ◽  
Solid Cancer ◽  
Newly Diagnosed ◽  
History Of ◽  
Comorbidity Index ◽  
And Performance ◽  
The Impact

Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG ≥ 2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and ≥4). FCI was a strong prognostic tool for OS (P>0.001) and predicted clinical outcome better than CCI (P=0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma.

scholarly journals A prognostic score including mutation profile and clinical features for patients with CMML undergoing stem cell transplantation

2021 ◽  
Vol 5 (6) ◽  
pp. 1760-1769
Author(s):  
Nico Gagelmann ◽  
Anita Badbaran ◽  
Dietrich W. Beelen ◽  
Rachel B. Salit ◽  
Friedrich Stölzel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Prognostic Score ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Risk Groups ◽  
Mutation Status ◽  
Comorbidity Index ◽  
The Impact

Abstract The inclusion of mutation status improved risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML). Stem cell transplantation is a potentially curative treatment option, and patient selection is critical because of relevant transplant-related morbidity and mortality. We aimed to evaluate the impact of mutation status together with clinical presentations on posttransplant outcome. Our study included 240 patients with a median follow-up of 5.5 years. A significant association with worse survival was identified for the presence of mutations in ASXL1 and/or NRAS. In multivariable analysis, ASXL1- and/or NRAS-mutated genotype (hazard ratio [HR], 1.63), marrow blasts &gt;2% (HR, 1.70), and increasing comorbidity index (continuous HR, 1.16) were independently associated with worse survival. A prognostic score (CMML transplant score) was developed, and the following points were assigned: 4 points for an ASXL1- and/or NRAS-mutated genotype or blasts &gt;2% and 1 point each for an increase of 1 in the comorbidity index. The CMML transplant score (range, 0-20) was predictive of survival and nonrelapse mortality (P &lt; .001 for both). Up to 5 risk groups were identified, showing 5-year survival of 81% for a score of 0 to 1, 49% for a score of 2 to 4, 43% for a score of 5 to 7, 31% for a score of 8 to 10, and 19% for a score &gt;10. The score retained performance after validation (concordance index, 0.68) and good accuracy after calibration. Predictions were superior compared with existing scores designed for the nontransplant setting, which resulted in significant risk reclassification. This CMML transplant score, which incorporated mutation and clinical information, was prognostic in patients specifically undergoing transplantation and may facilitate personalized counseling.

Prognostic Value of Immunophenotyping in Elderly Patients with Acute Myeloid Leukemia: A Single Institution Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4353-4353
Author(s):  
Claudiu Plesa ◽  
Youcef Chelghoum ◽  
Adriana Plesa ◽  
Mohamed Elhamri ◽  
Isabelle Tigaud ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Antigen Expression ◽  
Risk Groups ◽  
Significant Prognostic Factor ◽  
The Impact ◽  
Acute Myeloid

Abstract The poor prognosis of elderly patients with acute myeloid leukemia (AML) raises the question about the benefit of intensive chemotherapy in these patients. The impact of initial characteristics on prognosis has previously been addressed in elderly paitents, but very few data are available regarding the prognostic value of immunophenotypic characteristics in this setting. We investigated the expression of the membrane antigens CD13, CD15, CD33, and CD34 by flow cytometry in elderly patients with newly diagnosed AML, and analyzed whether these parameters possessed clinical or prognostic relevance, in order to help physicians in their choice of therapy. Immunophenotyping was performed in 273 patients aged 60 years or more (median 69 years). CD13 was expressed in 73%, CD15 in 43%, CD33 in 64%, and CD34 in 66% of cases. Complete remission was obtained in 157 cases (58%). The median overall survival was 8.1 months with a 3-year survival rate of 14%. Three risk groups were defined based on CD34 and CD33 antigen expression: Poor risk in patients with CD34+ CD33+ or CD34− CD33− disease, intermediate risk in patients with CD34+ CD33− disease, and favorable risk in patients CD34− CD33+ disease. Immunophenotype was, after cytogenetics, the most significant prognostic factor in terms of survival in a multivariate analysis (p = 0.03 and p < 0.0001 respectively). When combining immunophenotypic and cytogenetic parameters, patients were classified into four prognostic groups: Group A (3-year survival: 33%) including favorable and normal karyotypes with a favorable immunophenotype; Group B (3-year survival: 28%) including normal karyotypes with an intermediate immunophenotype; Group C (3-year survival: 8%) including intermediate or normal karyotypes with an unfavorable immunophenotype; and Group D (3-year survival: 2%) including all unfavorable cytogenetics. Immunophenotypic characteristics appeared to be a major prognostic factor in this patient population. Using two simple parameters assessed at time of diagnosis, we devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.

Independent Impact of Iron Overload and Transfusion Dependency on Survival and Leukemic Evolution in Patients with Myelodysplastic Syndrome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 640-640 ◽  
Author(s):  
Guillermo Sanz ◽  
Benet Nomdedeu ◽  
Esperanza Such ◽  
Teresa Bernal ◽  
Mohamed Belkaid ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Scoring System ◽  
Prognostic Value ◽  
Multivariate Analyses ◽  
Prognostic Impact ◽  
Transfusion Dependency ◽  
The Impact ◽  
Risk Categories

Abstract Transfusion dependency seems to have a major prognostic impact in patients with myelodysplastic syndrome (MDS) (Malcovati L et al. J Clin Oncol2007;25:3503). Preliminary data also suggest that the development of iron overload could influence outcome (Malcovati L et al. J Clin Oncol2005;23:7594 and Garcia-Manero G et al. Leukemia2008;22:538), but small numbers have precluded a meaningful analysis of the prognostic value of this characteristic. The main aim of this study was to evaluate the independent prognostic value of transfusion dependency (as defined in WHO-based Prognostic Scoring System [WPSS]) and iron overload (defined as serum ferritin level &gt;1,000 ng/mL) in a large series of 2,994 patients (median age, 74 yr) with de novo MDS according to FAB criteria (2,107 MDS according to WHO criteria). Complete transfusional history was available in 2,241 patients (835 transfusion dependent [TD] at diagnosis, 526 TD during follow-up, and 880 non-TD) and serum ferritin levels in 1,634. Karyotyping was successfully performed in 2,074 patients, who could then be classified by the International Prognostic Scoring System (IPSS) as low (861 patients), intermediate-1 (748), intermediate-2 (311), and high-risk (154). The numbers of patients in the five risk categories defined by the WPSS (available for 1,228 patients) were 257 (21%) in very low, 385 (31%) in low, 217 (18%) in intermediate, 271 (22%) in high, and 98 (8%) in very high, closely similar to those reported in the original WPSS series. Actuarial curves of overall survival (OS) and risk of evolution to acute myeloblastic leukemia (AML) were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Multivariate analyses of OS and risk of evolution to AML were performed by Cox proportional hazards regression method, with development of transfusion dependency and iron overload entered as time-dependent covariates. Other variables included in the prognostic factor analyses were age, gender, hemoglobin level, absolute WBC, PMN, and platelet counts, proportion of blasts in blood and marrow, percentage of dysplastic features in the three different hematopoietic cell lines, cytogenetics according to IPSS cytogenetic risk subgroups, FAB and WHO classifications, ferritin, beta-2 microglobulin, erythropoietin, and LDH levels at diagnosis, and IPSS and WPSS risk categories. All the previous variables showed a statistically significant relationship with OS and/or AML risk on univariante analyses. Median OS for TD patients at diagnosis, TD patients during evolution, and non-TD patients was 19, 60, and 96 months, respectively (P&lt;.0001). Multivariate analyses in a set of 902 cases with complete data confirmed that development of iron overload (1st variable selected to enter the model; hazard ratio [HR], 52.4; P&lt;.0001) and transfusion dependency (2nd to enter; HR, 8.8; P&lt;.0001) were strongly associated with OS and added significant independent prognostic information to that afforded by the IPSS and WPSS scores or by other characteristics with universally recognized prognostic value. Further, multivariate analyses of AML transformation risk showed that iron overload (1st to enter; HR, 6.6; P&lt;.0001) and transfusion dependency (2nd to enter; HR, 3.5; P=.003) had also independent impact on that endpoint. These results demonstrate for the first time the independent prognostic value of development of iron overload on OS and AML risk in MDS, confirm the impact of transfusion dependency on those outcomes, and support that the inclusion of both variables in a new prognostic scoring system would add clinically relevant information. They also suggest that avoiding or reducing iron overload by an appropriate chelation therapy could improve OS and reduce the risk of AML transformation in MDS patients.

Transfusion Dependency Is Associated With Inferior Survival Even In Very Low and Low Risk IPSS-R Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1518-1518 ◽  
Author(s):  
Devendra K. Hiwase ◽  
Monika M Kutyna ◽  
Rakchha Chhetri ◽  
Stuart Howell ◽  
Peter B Harrison ◽  
...  
Keyword(s):  
Scoring System ◽  
Lower Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Transfusion Dependency ◽  
The Impact ◽  
Very High ◽  
Rbc Transfusion ◽  
Independent Cohort

Abstract Background The International Prognostic Scoring System (IPSS) is commonly used for predicting the outcome of myelodysplastic syndrome (MDS) patients. Recently, a Revised IPSS (IPSS-R) has been developed to address the limitations of IPSS. IPSS-R identifies five different categories and stratifies patients better than IPSS. Although transfusion dependency is associated with inferior survival outcome, it has not been included in the risk stratification of IPSS-R mainly due to limited availability of transfusion data on patients used for deriving the IPSS-R. Aim To evaluate the impact of RBC transfusion on survival outcome in IPSS-R subgroups and assess the validity of IPSS-R in an independent cohort of patients. Materials and Methods To match the patient selection criteria used for generating the IPSS-R scoring system, primary MDS patients who were not treated with disease modifying agents or stem cell transplantation were included for this analysis. The impact of RBC transfusion on overall survival (OS) was assessed in IPSS-R subgroups. RBC transfusion dependency was defined as transfusion of at least 1 unit/8 weeks for at least 4 months. Results A total of 182 patients were included in this analysis. Their median age was 73 years (21 to 91 years) and 66% patients were male. 106 patients were in the Very Low or Low risk groups (termed ‘lower risk'). The median OS of IPSS-R Very Low, Low, Intermediate, High and Very High risk groups was 87.1, 63.9, 24.5, 17.2 and 7.8 months, respectively (Fig.1. p<0.0001), consistent with previously published results (Greenberg et al, Blood 2012). Of the 182 patients, 115 (63%) patients were RBC transfusion dependent. RBC transfusion dependency was more frequent in Very High (18/18, 100%), High (25/28, 89%) and Intermediate (21/31, 68%) risk groups as compared to lower risk IPSS-R groups: Low (35/67, 52%) and Very Low (17/39, 43%). The mean pre-transfusion Hb was 79.1 ±12.3 gm/L, and the trigger for transfusion was Hb ≤90, >90 to ≤100 and >100 gm/L in 83%, 11% and 6% of episodes, respectively. In a multivariate analysis, RBC-transfusion dependency (HR 3.18; P<0.0001) was associated with poor survival, independent of the IPSS-R category and age at diagnosis (Table 2). The median OS of transfusion-dependent patients (n=115) was significantly lower (23.8 vs. 117.8 months; p<0.0001) than that of transfusion-independent patients (n=67). As the majority of IPSS-R higher risk patients were transfusion dependent, we restricted further assessment to IPSS-R lower risk groups. The median OS between Low and Very Low risk group was not significantly different (87.1 vs Low 63.2 months; p=0.1), hence they were grouped together. The median OS of transfusion-dependent lower risk IPSS-R patients (n=52) was significantly shorter than that of transfusion-independent (n=54) patients (52.7 vs 122.5 months; p=0.001). Conclusions We have demonstrated that transfusion dependency is associated with inferior survival even in Very Low and Low risk IPSS-R group patients. This warrants further refinement of IPSS-R scoring system specifically for lower risk group patients. IPSS-R scoring system is validated in our independent cohort of patients. Disclosures: Hiwase: Novartis Australia: Research Funding; Celgene Australia: Research Funding.

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