Independent Validation of the MD Anderson Cancer Center Risk Model for Myelodysplastic Syndromes (MDS), and Comparison to the International Prognostic Scoring System (IPSS) and the World Health Organization-Based Prognostic Scoring System (WPSS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3814-3814 ◽  
Author(s):  
Sarah E Hugo ◽  
Sarah C Bundrick ◽  
Curtis A Hanson ◽  
David P Steensma
Keyword(s):  
Mayo Clinic ◽  
Scoring System ◽  
Proportional Hazards ◽  
Risk Model ◽  
Risk Group ◽  
Prognostic Significance ◽  
World Health ◽  
Cancer Center ◽  
Secondary Mds ◽  
Md Anderson

Abstract Abstract 3814 Poster Board III-750 Introduction The 1997 IPSS remains the most widely used prognostic scoring system for patients with MDS, and it has important strengths, but several other prognostic systems have been proposed recently to overcome some of the well-recognized IPSS limitations. These systems include a new risk model for patients with MDS and CMML – including previously treated patients and those with secondary (treatment-related) MDS – proposed by Kantarjian and colleagues at the MD Anderson Cancer Center (MDACC) (Cancer 2008; 113:1351), as well as the WPSS, proposed by Malcovati and colleagues in Europe (J Clin Oncol 2007; 25:3503) To date, the MDACC risk model has not been validated in a large external independent cohort or directly compared to the WPSS. We assessed the performance of the MDACC model compared to the WPSS and the IPSS in a 12-year Mayo Clinic MDS/CMML cohort. Patients and Methods We reviewed the medical records of 1,503 adult patients (pts; 984 males; median age 71 years, range 17-98) with MDS (n=1,249) or CMML (n=254) evaluated at Mayo Clinic between January 1996 and December 2007. Pediatric pts (age ≤16 and pts with ≥30% marrow blasts were excluded. IPSS and WPSS scores were calculated, and data collected for MDACC risk model assignment (age, performance score, platelet count, hemoglogbin, marrow blast proportion, white blood cell count, karyotype, and transfusion history). Data were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Results The overall median survival was 17.8 months (mos) – 13.7 mos for CMML, 19.1 mos for WHO-defined MDS, and 9.6 mos for RAEB-t – similar to the 14.1 mos observed in the test cohort used to derive the MDACC risk model. Follow-up was complete until death in 1,122 (74.7%) pts. Pts excluded from the cohort stratified using IPSS included 122 patients with CMML and leukocytosis (>12 × 109/L), and 176 pts with secondary MDS/CMML (there were 12 pts with secondary CMML with leukocytosis) – total excluded, 286 pts. Patients excluded from the WPSS cohort included 27 pts with RAEB-t, 254 pts with CMML, and 148 pts with secondary MDS – total excluded, 429 pts. Survival by IPSS risk group was 38.9 mos for Low (n=413), 17.9 mos for Int-1 (n=541), 9.6 mos for Int-2 (n=206), and 6.6 mos for High (n=57). Survival by WPSS risk group was 39.0 months for Very Low (n=352), 26.6 months for Low (n=276), 15.9 months for Intermediate (n=185), 11.2 mos for High (n=221), and 4.9 months for Very High (n=40). Survival by MDACC risk group was 45.6 mos for Low (n=426), 20.0 mos for Int-1 (n=552), 12.3 mos for Int-2 (n=325), and 4.9 mos for High (n=200). When the MDACC risk model was used to classify only the 1,074 pts with conditions for which the WPSS has been validated, survival was 51.4 mos for Low (n=336), 21.2 mos for Int-1 (n=411), 13.3 mos for Int-2 (n=213), and 4.6 mos for High (n=114) (p<0.001 for all comparisons). In a multivariable proportional hazards model, all of the MDACC risk model components except WBC>20 × 109/L retained independent prognostic significance. Conclusions All 3 systems stratify patients accurately, but the MDACC risk model best identifies the lowest-risk patients, and also classifies the broadest group of patients (i.e., primary and secondary MDS, and primary and secondary CMML with or without leukocytosis). The revised IPSS that is currently in development should include the patient factors accounted for by the MDACC risk model, with the possible exception of leukocytosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Prognostic Utility of the Current Risk Models in Predicting Outcomes of Patients (pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agents (HMA)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1935-1935
Author(s):  
Amer M. Zeidan ◽  
Mikkael A. Sekeres ◽  
Guillermo Garcia-Manero ◽  
John Barnard ◽  
Najla H Al Ali ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Scoring System ◽  
Goodness Of Fit ◽  
Risk Group ◽  
Cancer Center ◽  
P Value ◽  
Advisory Committees ◽  
Overall Response ◽  
Md Anderson

Abstract Background: Although HMA (azacitidine [aza] or decitabine [dac]) are standard of care therapies for HR-MDS pts, responses may not be seen for 4-6 months and occur in <50% of treated pts. Moreover, curative hematopoietic cell transplantation (HCT), which is recommended as up-front therapy for HR-MDS, is used in <5% of pts. The ability to identify pts with a low likelihood of benefiting from HMA who instead should receive immediate HCT or experimental treatment approaches is a clinical and research priority. Established MDS prognostic systems include the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) [derived from untreated pt cohorts] and the MD Anderson Prognostic Scoring System (MDAPSS) [derived from treated and untreated pt cohort]. A French Prognostic Scoring System (FPSS) was developed to predict survival among aza-treated HR-MDS pts. We compared the relative prognostic discriminatory power of these models in a large cohort of HMA-treated pts with HR-MDS. Methods: The combined MDS database obtained from six institutions in the MDS Clinical Research Consortium (Moffitt Cancer Center, Cleveland Clinic, MD Anderson Cancer Center, Dana Farber Cancer Institute, Weill Medical College of Cornell University, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins) was used to identify patients with HR-MDS (IPSS intermediate-2 [INT-2] and high) who received HMA therapy (aza or dac). Responses were defined per International Working Group 2006 criteria. Overall response rate (ORR) was defined as the sum of rates of complete response (CR), partial response (PR), hematologic improvement (HI), and marrow CR. Pts with stable disease (SD) and progressive disease (PD) were considered non-responders. Logistic regression models were fitted and tested for association of response with prognostic risk categories using chi-square deviance tests. Overall survival (OS) was calculated from the time of diagnosis to time of death or last follow-up. Kaplan-Meier (KM) curves were generated for OS and the log-rank test was used to compare median OS. Akaike information criteria (AIC) were used to assess the relative goodness of fit of the models. Results: We identified 595 pts with HR-MDS (70.3% with INT-2 and 29.7% with high IPSS) who received HMA as upfront therapy (83% aza, 17% dac). Median follow-up from diagnosis was 13.1 months (M), 95% confidence interval (CI): 11.5-15.1 M. 66% of pts were male, 88% white, 85% were >60 years, and 18% had therapy-related MDS. Median number of HMA cycles was 5.7 (range, 0.7-51) with 75% of pts receiving ≥3 cycles of therapy. Median time from diagnosis to start of HMA therapy was 1.5 M. ORR was 42.1% (CR 25.8%, PR 6.7%, HI-E 3.3%, HI-P 2.3%, HI-N 4.0%) while 57.2% were non-responders (SD 28.6% and PD 28.6%) and 0.7 were un-evaluable. None of the prognostic systems predicted overall response to HMA. Median OS for the entire cohort was 16.3 M (CI, 15.0-17.8 M). Figure 1 shows the KM survival curves and Table 1 shows the median OS, the corresponding CI and associated p-value for the risk categories in each prognostic model. Scores generated using the AIC (n=294) to assess the relative goodness of fit (lower is better) were 2139 (MDAPSS), 2148 (FPSS), 2155 (IPSS-R), and 2174 (IPSS). Conclusions: We report the largest direct comparison of the major MDS prognostic models among HMA-treated patients. None of the models predicted overall response to HMA therapy. Nonetheless, the IPSS-R, MDAPSS, and the FPSS all functioned well to separate HMA-treated pts with HR-MDS into different prognostic groups in terms of survival. The MDAPSS and FPSS appear superior to the IPSS-R and IPSS for survival prediction. HR-MDS pts with poor projected survival with HMA therapy should be considered for up-front HCT or for experimental approaches. Figure 1 Figure 1. Abstract 1935. Table 1 IPSS (n=595) IPSS-R (n=555) FPSS (n=296) MDAPSS (n=508) Risk Group (n) Median OS in months (CI) Risk Group (n) Median OS in months (CI) Risk Group (n) Median OS in months (CI) Risk Group (n) Median OS in months (CI) Low (0) NA Very low (1) NA Low (19) 38.4 (23.1-NR) Low (4) Not reached (NA) INT-1 (0) NA Low (3) 28.1 (27.0-NR) INT (241) 17.8 (15.9-19.6) INT-1 (55) 26.2 (18.8-40.4) INT-2 (418) 16.8 (15.3-18.3) INT (59) 39.1 (23.9-49.6) High (36) 10.6 (7.2-13.4) INT-2 (143) 18.6 (17.4-24.1) High (177) 15.2 (13.4-17.8) High (197) 18.8 (16.8-22.2) High (306) 13.4 (11.8-15.0) Very High (295) 12.2 (11.0-14.1) P-value P=0.014 P<0.0001 P<0.0001 P<0.0001 Disclosures Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees. Garcia-Manero:Novartis Pharma: Research Funding. Steensma:Amgen: Consultancy; Ariad: Equity Ownership; Celgene: Consultancy; Novartis: Consultancy. List:Celgene Corporation: Consultancy.

scholarly journals Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 558-564 ◽  
Author(s):  
B Coiffier ◽  
E Lepage
Keyword(s):  
Performance Status ◽  
Prognostic Significance ◽  
Staging System ◽  
Prognostic Models ◽  
Cancer Center ◽  
Malignant Lymphomas ◽  
Prognostic System ◽  
Ann Arbor ◽  
Md Anderson ◽  
Better Than

Abstract Four prognostic models described for aggressive malignant lymphomas and the classical Ann Arbor staging system were used to compare the survival of 737 patients treated with the LNH-84 regimen. The aim of the study was to determine the optimal prognostic system at the time of diagnosis. Three institutions have described these models after multivariate analyses: the Dana Farber Cancer Institute (DFCI1 and DFCI2), the MD Anderson Hospital (MDAH), and the Memorial Sloan- Kettering Cancer Center (MSKCC). The models were constructed with the following variables: performance status, LDH level, and tumor extension. The latter is the most difficult to assess: it was considered as the number of extranodal sites and the diameter of the largest mass in DFCI1, stage and the diameter of the largest mass in DFCI2, the number of extranodal and extensive nodal sites in MDAH, and the number of nodal sites and their localization in MSKCC. Univariate studies with LNH-84 regimen patients showed all these variables to have major prognostic significance (logrank tests: P less than 10(-4)). All five prognostic systems divided patients into three subgroups: good, intermediate, and poor prognosis. Logrank analyses of survival showed highly significant differences (X2 greater than 90 and P less than 10(- 6)) between the subgroups. No gross difference was found between the models, and none was better than the others. A new, internationally accepted prognostic system for the expression and comparison of treatment results in aggressive malignant lymphomas should include major univariate prognostic parameters and must be reliable and easy to use in clinical practice. Until such time, stage or LDH level are the best alternatives.

Molecular and Prognostic Correlates of Cytogenetic Abnormalities in Chronic Myelomonocytic Leukemia: A Mayo Clinic-French Consortium Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 412-412
Author(s):  
Emnet A Wassie ◽  
Raphael Itzykson ◽  
Terra L Lasho ◽  
Olivier Kosmider ◽  
Christy Finke ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
Risk Model ◽  
Normal Karyotype ◽  
Chronic Myelomonocytic Leukemia ◽  
Older Age ◽  
World Health ◽  
Abnormal Karyotype ◽  
Cytogenetic Abnormalities ◽  
Myelomonocytic Leukemia ◽  
Monosomal Karyotype

Abstract Background: The prognostic significance of cytogenetic abnormalities in chronic myelomonocytic leukemia (CMML) was recently revisited (AJH, 89; 813-818, 2014 and Blood April, 2013). Using a large Mayo Clinic-French Consortium database, we analyzed the molecular and prognostic correlates of cytogenetic abnormalities in CMML. Methods: CMML diagnosis was according to World Health Organization criteria. Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature. Statistical analyses considered clinical and laboratory parameters obtained at time of cytogenetic studies. Results: Spectrum and frequency of cytogenetic abnormalities: A total of 409 patients participated in this study including, 268 (66%) from the Mayo Clinic and 141 (34%) from the French CMML consortium. Of these, 396 (97%) had ≥20 metaphases and 13 (3%) had ten to 19, analyzed. One hundred and fifteen (30%) patients displayed an abnormal karyotype, including 82 (71%) sole, 20 (17%) two and 13 (11%) complex abnormalities. The most common abnormalities were; +8 (23%), -Y (20%), -7/7q- (14%), 20q- (8%), +21 (8%) and der (3q) (8%). Other cytogenetic abnormalities included 5q-, 12p-, 13q- and i(17q), present at a much lower frequency (0.9-4%). Phenotypic correlates: Abnormal vs normal karyotype was associated with older age (p=0.03), hemoglobin<10 g/dL (p=0.0009), white blood cell count (WBC) >15 x 109/L (p=0.02), absolute neutrophil count (ANC) >10 x 109/L (p=0.03), absolute lymphocyte count (ALC) >2.5 x109/L ( p=0.04), peripheral blood (PB) blast ≥1% (p<0.0001), bone marrow (BM) blast ≥10% (p<0.0001) and circulating immature myeloid cells (IMC) (p=0.0003). +8 (p=0.01), +21 (p=0.03) and der (3q) (p=0.03) were associated with hemoglobin <10 g/dL. -Y was associated with older age (p=0.04), lower PB (p=0.04) and BM (p=0.02) blasts. -7/7q was associated with leukocytosis (p=0.005), neutrophilia (p=0.04), and higher PB blasts (p=0.004). 20q- was associated with thrombocytopenia (p=0.04). Molecular correlates: ASXL1 mutations were associated with abnormal karyotype (p=0.04) and SRSF2 with normal karyotype (p=0.02). In comparison to other abnormal karyotypes, the incidence of ASXL1 mutations was lower in –Y (P=0.04) and der(3q) (p=0.03). U2AF1 mutations were associated with monosomal karyotype (p=0.03) and SF3B1 with der (3q) (p<0.0001). Prognostic relevance : Median follow-up was 1.8 years with 244 (60%) deaths and 79 leukemic transformations (19%). A step-wise survival analysis resulted in three distinct cytogenetic risk categories (Figure 1): high (complex and monosomal karyotype), intermediate (all abnormalities not in high or low risk) and low (normal, sole -Y and sole der (3q)); the corresponding median survivals were 0.2 (HR 8.1, 95% CI 4.6-14.2), 1.7 (HR 1.7, 95% CI 1.2-2.3). In multivariable analysis, the particular cytogenetic risk stratification remained significant in the context of Mayo molecular model (p<0.0001), MDAPS (p<0.0001), and the GFM risk model (P<0.0001). The Mayo-French cytogenetic risk model was also effective in predicting leukemic transformation with HR of 10.9 (95% CI 4.2-27.8) for high and 2.2 (95% CI 1.3-3.7) for intermediate risk groups. Conclusion: Cytogenetic abnormalities are seen in approximately 30% of patients with CMML and display significant associations with certain molecular and phenotypic characteristics. We describe a novel cytogenetic prognostic model for both over-all and leukemia free survival in CMML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Exploratory analysis of the effect of ruxolitinib on bone marrow morphology in patients with myelofibrosis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7030-7030 ◽  
Author(s):  
Hans-Michael Kvasnicka ◽  
Juergen Thiele ◽  
Carlos E. Bueso-Ramos ◽  
Kevin Hou ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Exploratory Analysis ◽  
World Health ◽  
Cancer Center ◽  
Jak2 Inhibitor ◽  
Comparable Effect ◽  
Md Anderson ◽  
Health Organization ◽  
Clinical Trial Information

7030 Background: Myelofibrosis(MF) is characterized by splenomegaly, burdensome symptoms, progressive bone marrow (BM) fibrosis, and shortened survival. Ruxolitinib (Rux), an oral, FDA-approved JAK1/JAK2 inhibitor, has demonstrated improvements in spleen volume, symptoms, and survival in patients (pts) with MF. This study was conducted to explore possible effects of long-term Rux treatment on BM morphology in MF. Methods: Trephine biopsies were obtained at baseline, 24 (67 pts), and 48 (17 pts) months (mo) from the cohort of MF patients treated at MD Anderson Cancer Center who participated in a phase I/II trial of Rux (NCT00509899). The clinical outcomes from this trial have been published previously [Verstovsek, NEJM 2010]. Two of the authors (JT and HMK) independently evaluated the World Health Organization (WHO)-defined BM fibrosis grade (0-3). Reviewers were blinded to pts characteristics and outcomes and consensus decided discordant scores. For demonstrative purposes, WHO BM fibrosis grading was also determined for a control cohort of pts treated with hydroxyurea (HU) for 24 (31 pts) and 48 (20 pts) mo. Changes in BM fibrosis grade vs. baseline were calculated for 24 and 48 mo, and categorized as improvement, stabilization, and worsening for each patient. Results: A higher percentage of Rux-treated pts showed stabilization or improvement of BM fibrosis at both 24 and 48 mo than the HU-treated pts. Worsening was greater in the HU-treated cohort at both time points. Conclusions: This exploratory analysis of long-term exposure to Rux in MF provides the first indication that JAK inhibitor therapy may be able to meaningfully retard advancement of BM fibrosis. A comparable effect was not seen with long-term HU therapy. Additional research is needed to further elucidate these findings. Clinical trial information: NCT00509899. [Table: see text]

The positive impact of mentoring on burnout: Organizational research and best practice interventions for cancer hospital employees.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Katelyn Cavanaugh ◽  
Bret Belfer ◽  
Debbie Cline ◽  
Courtney Holladay ◽  
Todd Alan Pickard ◽  
...  
Keyword(s):  
Positive Impact ◽  
World Health ◽  
Mentoring Programs ◽  
Cancer Center ◽  
Informal Mentoring ◽  
Mentoring Relationship ◽  
Positive Effects ◽  
Md Anderson ◽  
Professional Fulfillment ◽  
Mentoring Support

11012 Background: While burnout is not a new concept, combating it is becoming an increasingly important focus for organizations across all industries. Recently, the World Health Organization recognized burnout as an “occupational phenomenon” (WHO, 2019), and it was included in the 11th Revision of the International Classification of Diseases, where it is defined as “a syndrome conceptualized as resulting from chronic workplace stress that has not been successfully managed.” The University of Texas MD Anderson Cancer Center addresses burnout at the institutional level in support of all 22,000 workforce members. One avenue of this work focuses on mentoring. Mentorship, both formal and informal, has demonstrated positive effects to include empirical investigations that demonstrate its benefit in reducing risk of burnout in multiple settings for a variety of audiences (Qian et al., 2014; Thomas & Lankau, 2009; van Emmerik, 2004; Varghese at al., 2020). Although mentoring is not as flashy as other interventions, what the last year has shown is that people need human connection now more than ever. Methods: In order to investigate the relationship between burnout and mentoring in our organization, we analyzed responses to our biennial voluntary employee survey, in which all employees were asked whether they are involved in a mentoring relationship and completed a single-item burnout scale. Results: We analyzed the survey data using a chi-square test and found that employees participating in mentoring relationships were less likely to report burnout than employees who are not participating in a mentoring relationship, χ2 (1, 14,486) = 17.431, p < 0.005. The same pattern held for all types of employees; faculty, classified staff, leaders, clinical employees, and non-clinical employees, indicating that the experience of mentorship may be universal regardless of role, rank, and type of work. We suspect that the benefits of mentoring are bi-directional for mentors and mentees, though this should be investigated directly. Conclusions: Both formal and informal types of mentoring programs exist within MD Anderson to support retention, professional fulfillment, and reduce burnout. All employees have access to a centralized online mentoring platform to find a mentor. Formal mentoring support is also provided through various programs developed for specific professional cohorts, including physicians, advanced practice providers, and registered nurses. In addition, informal mentoring support is offered in the form of employee volunteer wellness champions. Together, these formal and informal mentoring programs have positively influenced burnout across the organization.[Table: see text]

Validation of the Revised International Prognostic Scoring System (R-IPSS) for Patients with Myelodysplastic Syndromes: Therapeutic Implications.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2816-2816 ◽  
Author(s):  
Asmita Mishra ◽  
Najla H Al Ali ◽  
Maria Corrales-Yepez ◽  
Eric Padron ◽  
Ling Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Scoring System ◽  
Prognostic Value ◽  
Risk Model ◽  
Risk Group ◽  
International Prognostic Scoring System ◽  
Cell Transplant ◽  
Kaplan Meier ◽  
Very High

Abstract Abstract 2816 Background: The International Prognostic Scoring System (IPSS) was recently revised under the auspices of MDS foundation as a collaborative international effort. The proposed R-IPSS is suggested to refine the prognostic value of the IPSS. Instead of the 4 original IPSS categories, 5 categories are proposed by R-IPSS. To validate this prognostic model and examine its utility for therapy decisions, we tested the new risk model in a large external single institution patient cohort. Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and chart review. The primary objective was to validate the new risk model. The R-IPSS score was calculated as reported. Patients were divided into 5 prognostic categories (very low, low, intermediate, high and very high risk). The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between the groups. Results: The MCC MDS database captured 1157 patients. Complete data was available for 1029 patients to calculate the R-IPSS score. Median age was 68 years, and the most common WHO subtype was RCMD (29%). Two thirds of patients were low/int-1 IPSS risk, and 44% were int-2 or high risk MDAS. (Table-1). Among those, 729 patients (77%) were RBC transfusion dependent (TD), and 264 (26%) had serum ferritin >1000 ng/l. Six hundred eighteen patients (60%) received hypomethylating agent (HMA). The median duration of follow up was 68 months (mo). Median OS according to IPSS risk score was 90 mo (95%CI 75–105), 44 mo (95%CI 39–46), 18 mo (95%CI 15–21), and 14 mo (95%CI 11–17), for low, int-1, int-2, and high risk categories, respectively (p < 0.005). According to MD Anderson risk Score, the median OS was 108 mo (95%CI 91–126), 55 mo (95%CI 50–60), 25 mo (95%CI 22–28), and 14 mo (95%CI 12–16), for low, int-1, int-2, and high risk respectively (p < 0.005). Using the R-IPSS, 106 (10%), 311 (30%), 247 (24%), 201 (20%), and 164 (16%) were classified as very low, low, int, high, and very high risk. The median OS was 82 mo (95% CI 64–100), 57 mo (95% CI 46–68), 41 mo (95% CI 33–49), 24 mo (95% CI 20–28), and 14 mo (95% CI12–16) for each of the corresponding R-IPSS groups (p <0.005). Table-2 summarizes reclassification of each IPSS risk group by R-IPSS and expected OS accordingly. Among those patients who received HMA, the median OS from time of diagnosis was 76 mo, 55 mo, 42 mo, 25 mo, and 16 mo for very low, low, int, high, and very high risk respectively (p < 0.005). A survival benefit for HMA therapy was only statistically significant in patients with very high risk R-IPSS, with a corresponding median OS of 16 mo with HMA versus 7 mo with no HMA (p< 0.005). OS in patients with very high or high R-IPSS who underwent Allogeneic Stem cell transplant (ASCT) was improved compared to corresponding patients who received non-ASCT management. Patients who had very low, low, and int risk R-IPSS had no apparent OS benefit with ASCT. (Table-3). Conclusion: Our data validates the prognostic value of the proposed R-IPSS, but refines prognostic discrimination only for intermediate risk group of IPSS. Both the R-IPSS and IPSS were valid prognostic models for patients treated with HMA. The benefit of ASCT was restricted to patients with high and very high R-IPSS groups. The utility of the R-IPSS as a tool for therapeutic decisions should be further examined before wide adaptation. Disclosures: No relevant conflicts of interest to declare.

Validation of Alternative Chronic Myelomonocytic Leukemia (CMML)-Specific Prognostic Scoring (CPSS) System in UT MD Anderson Cancer Center Cohort

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3278-3278
Author(s):  
Priyanka Priyanka ◽  
Janhavi Raut ◽  
Patricia S Fox ◽  
Francesco Stingo ◽  
Tariq Muzzafar
Keyword(s):  
Overall Survival ◽  
Scoring System ◽  
Risk Groups ◽  
Risk Classification ◽  
Chronic Myelomonocytic Leukemia ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Md Anderson ◽  
Myelomonocytic Leukemia

Abstract INTRODUCTION: Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm that belongs to the category of myelodysplastic syndrome / myeloproliferative neoplasms (MDS / MPN). The International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS) classification and its revised version (IPSS-R) addressed patients with newly diagnosed, untreated MDS and excluded CMML. While numerous investigators have attempted to devise a prognostic risk scoring system for CMML, no system has been generally accepted for this entity. A CMML-specific prognostic scoring (CPSS) system proposed by Such, et al [Blood. 2013; 11;121(15):3005-15] defines 4 different prognostic risk categories for estimating both overall survival (OS) and risk for AML transformation; the alternative version replaces RBC transfusion dependency with hemoglobin levels. AIM: The aim of the study is to validate the alternative CPSS scoring system on the CMML patient cohort at UT MD Anderson Cancer Center (UTMDACC). METHODS: The databases of the Department of Hematopathology at UTMDACC were searched for patients diagnosed with CMML presenting from 2005 to 2012. Cases were classified by WHO 2008 criteria. Inclusion criteria were: confirmed diagnosis of CMML, age > 18 years, persistent absolute monocyte count >1 × 109/L, marrow blasts < 20%, peripheral blood blasts < 20%. The alternative CPSS score was calculated as a function of WHO subtype, FAB subtype, CMML-specific cytogenetic risk classification, and hemoglobin score. Cox proportional hazards regression was used to model overall survival and time to AML progression from date of diagnosis. For time to AML progression, patients who did not experience AML progression were censored at their date of death or last follow-up. Kaplan-Meier curves were used to estimate survival and the log-rank test was used to test for significant differences by CPSS score. All statistical analyses were performed using SAS 9.3 for Windows. RESULTS: Two hundred and three patients with newly diagnosed, untreated CMML were identified in the clinical databases. These included 132 males and 71 females; median age was 70 (range 55-80) years. 149 had CMML-1 and 54 had CMML-2. A total of 107 deaths and 38 progressions were observed. The median (range) follow-up time for all patients was 1.9 (2 days-10.8) years. The variables that compose the alternative CPSS (WHO subtype, FAB subtype, CMML-specific cytogenetic risk classification, hemoglobin) as well as a description of how the score is calculated are given in Tables 1-2. In univariate Cox models, the alternative CPSS score was a significant predictor of both OS and time to AML progression (Type III p-values <.0001 and 0.0037, respectively). Median survival times for OS were 4.07, 3.32, 2.14, and 1.23 years in the low, intermediate-1, intermediate-2, and high risk groups, respectively. Since less than half the patients progressed, the median time to AML progression could not be estimated for all groups but was 6.40 and 1.60 in the intermediate-2 and high risk groups, respectively. Overall, the alternative CPSS score was highly predictive of both OS and progression free survival (PFS) and clearly delineated the patient risk groups in this sample. CONCLUSIONS: These data reinforce the validity of the alternative CPSS and serve as an additional validation cohort. Table 1. Alternative CMML-specific prognostic scoring system (CPSS) score criteria Variable Each level assigned the following value(sum to get the composite CPSS score): 0 1 2 WHO subtype CMML-1 blasts (including promonocytes) <5% in the PB and <10% in the BM CMML-2 blasts (including promonocytes) from 5% to 19% in the PB and from 10% to 19% in the BM, or when Auer rods are present irrespective of blast count — FAB subtype CMML-MD (WBC <13 × 109/L) CMML-MP (WBC ≥13 × 109/L) — CMML-specific cytogenetic risk classification* Low Intermediate High Hemoglobin ≥10 g/dL <10/dL WBC: white blood cell * CMML-specific cytogenetic risk classification; low: normal and isolated –Y; intermediate: other abnormalities; and high: trisomy 8, complex karyotype (≥3 abnormalities), chromosome 7 abnormalities Table 2. Alternative CPSS: scores used for predicting likelihood of survival and leukemic evolution in individual patient with CMML Risk group Overall CPSS score Low 0 Intermediate-1 1 Intermediate-2 2-3 High 4-5 Figure 1 Overall Survival by alternative CPSS Score Figure 1. Overall Survival by alternative CPSS Score Figure 2 Time to AML Progression by alternative CPSS Score Figure 2. Time to AML Progression by alternative CPSS Score Disclosures No relevant conflicts of interest to declare.

The Efficacy of Current Prognostic Models in Predicting Outcome of Patients with Myelodysplastic Syndromes (MDS) at the Time of Hypomethylating Agent Failure

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3275-3275
Author(s):  
Aziz Nazha ◽  
Rami S Komrokji ◽  
Guillermo Garcia-Manero ◽  
John Barnard ◽  
Cassie Zimmerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Scoring System ◽  
Scoring Systems ◽  
Prognostic Models ◽  
Cancer Center ◽  
Md Anderson ◽  
Prognostic Scoring Systems ◽  
Very High ◽  
Time Of Failure

Abstract Background: Several validated prognostic models exist for patients (pts) with MDS, including the International Prognostic Scoring System (IPSS), the Revised IPSS (IPSS-R), and the MD Anderson Prognostic Scoring System (MDAPSS). All were developed in pts with newly diagnosed MDS, and their prognostic value in subsequent stages of disease, such as at the time of failure of hypomethylating agents (HMAs, azacitidine (AZA) and decitabine (DAC), has not been established. Despite this, the IPSS is often used to determine clinical trial eligibility for pts who fail HMAs and is being considered for drug labeling for this indication. Methods Clinical data were combined from the MDS Clinical Research Consortium institutions (Moffitt Cancer Center n=259, Cleveland Clinic n=221, MD Anderson Cancer Center n=192, Cornell University n=100, Dana-Farber Cancer Institute n=45, and Johns Hopkins n=29). The IPSS, IPSS-R, and MDAPSS were calculated at the time of diagnosis and HMA failure. HMA failure was defined as no response to AZA or DAC following ≥ 4 cycles, loss of response, or progression to acute myeloid leukemia (AML). Responses were defined per International Working Group criteria (IWG 2006). Overall survival was calculated from the time of HMA failure to time of death or last follow up (OSHF). Survival curves were compared using stratified log-rank tests. Akaike information criterion (AIC) was used to compare fits from Cox proportional hazards models. Results A total of 488 pts who failed HMAs and had clinical data available at the time of failure were included in the final analyses. Overall, 406 (83%) were treated with AZA and 82 (17%) with DAC. At diagnosis: median age was 70 years (26-91), median absolute neutrophil count 1.06 k/mL (0.06-36.41), hemoglobin 9.3 g/dL (3.4-38.6), platelets 75 X 103/mL (2-969), and bone marrow blasts 7% (0-28). Prognostic scoring systems at diagnosis included, IPSS: 6 (2%) low, 46 (14%) intermediate-1, 206 (60%) intermediate-2, 83 (24%) high; IPSS-R: 3 (1%) very low, 12 (4%) low, 49 (16%) intermediate, 114 (37%) high, 129 (42%) very high; and MDAPSS: 11 (4%) low, 36 (13%) intermediate-1, 89 (31%) intermediate-2, 149 (52%) high. With median follow up from diagnosis of 18.2 months (mo) (0.7-224.6), median time from diagnosis to HMA start was 1.3 mo (0-162.4). Median number of HMA cycles received was (6, range 4-51): AZA (6, range 4-51), and DAC (4, range 4-21). Median OS from time of diagnosis was 19.5 mo (95% CI, 18.3-22.0). At the time of HMA failure, the median OSHF was 7.1 mo (95% CI, 6.2-7.9). Median OSHF by IPSS (n=311, low 10.9, intermediate-1 11.0, intermediate-2 7.1, high 5.1, p=.005), IPSS-R (n=285, very low 22.4, low 10.3, intermediate 5.6, high 9.4, very high 5.7, p<.0001) and MDAPSS (n=215, low 11.0, intermediate-1 11.3, intermediate-2 9.7, high 5.2, p=.01), Figure 1. Prognostic scoring system comparisons using the subset with all three scores gave AIC values of 1401 (IPSS), 1391 (IPSS-R) and 1393 (MDAPSS), with lower scores indicating a better fit. Conclusion When applying three of the most widely used prognostic scoring systems in MDS to pts at the time of HMA failure, the IPSS-R performed the best, followed by the MDAPSS and the IPSS. No system was ideal, though, and should be used with caution for clinical trial eligibility or drug labeling in MDS pts failing HMAs. Figure 1A. Overall survival by scoring systems: (A) IPSS, (B) IPSS-R, (C) MDAPSS Figure 1A. Overall survival by scoring systems: (A) IPSS, (B) IPSS-R, (C) MDAPSS Figure 1B Figure 1B. Figure 1C Figure 1C. Disclosures Roboz: Novartis: Consultancy; Agios: Consultancy; Celgene: Consultancy; Glaxo SmithKline: Consultancy; Astra Zeneca: Consultancy; Sunesis: Consultancy; Teva Oncology: Consultancy; Astex: Consultancy.

Low Absolute Lymphocyte Count (ALC) at Diagnosis Is An IPSS-Independent Predictor of Poorer Survival in Myelodysplastic Syndromes (MDS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3633-3633
Author(s):  
Nisha L Jacobs ◽  
Shernan G Holtan ◽  
Luis F Porrata ◽  
Svetomir N Markovic ◽  
Ayalew Tefferi ◽  
...  
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Lymphocyte Count ◽  
Scoring System ◽  
Risk Group ◽  
Prognostic Significance ◽  
Multivariate Model ◽  
Low Risk ◽  
Kaplan Meier ◽  
Risk Patients

Abstract Background: The prognostic significance of lymphocyte counts and immune status has been carefully examined in lymphoid malignancies, but the importance of the lymphocyte count in chronic myeloid neoplasms is less clear. In a recent analysis of MDS cases associated with deletion of chromosome 5q (Holtan SG et al AmJHem 2008 Epub 12Jun), we observed that an ALC >1.2 × 109 cells/L at diagnosis is independently associated with improved survival. The prognostic value of ALC in MDS not associated with del(5q) is unknown. Methods: We reviewed the medical records of patients without del(5q) diagnosed with MDS at our institution over a 10-year period and gathered data on complete blood counts and leukocyte differentials, bone marrow findings, and clinical course. Inclusion criteria included diagnosis within 6 months prior to initial consultation at our institution and <20% marrow blasts. Patients were classified according to the International Prognostic Scoring System (IPSS) and the WHO-classification based Prognostic Scoring System (WPSS). Results: The median age of the 503 included patients (360 M, 143 F) was 69 years (range 20–91). Median follow-up was 14 months, and 65% of patients were known to have died with an overall median survival of 36 months. Cytogenetic results as classified by the IPSS were favorable in 326 (65%) patients, intermediate in 112 (22%), and poor in 65 (13%). Both IPSS and WPSS accurately stratified patients, but the WPSS was better at identifying the lowest and highest risk patients. Survival by IPSS risk group was as follows: low-risk disease (n=95, median survival 41.8 months), intermediate-1 (n=285, 23.6 months), 106 with intermediate-2 (n=106, 14.1 months), and high-risk (n=17, 8.05 months). WPSS risk groups included very low risk (n=87; median survival 71.9 months), low risk (n=149, 28.8 months), intermediate risk (n=85, 19.3 months), high risk (n=143, 14.4 months), and very high risk (n=39, 8.8 months). In univariate analysis, factors associated with poorer survival included advanced age (p = 0.0012), higher-risk WHO subtype (p<0.0001), increased marrow blast percentage (p<0.0001), poor-risk karyotype (p<0.0001), higher IPSS score or WPSS score (p<0.0001), lower hemoglobin (p<0.0001), lower MCV (p=0.03), lower ALC (p=0.001), and lower platelets (p=0.001). Factors not associated with survival included sex and ANC. In a multivariate model including only baseline CBC parameters, hemoglobin >10 g/dL (p < 0.001), MCV >96 fl (p = 0.0493), ALC >1.2 × 109/L (p = 0.0449), and platelet count >100 × 109/L (p = 0.0046) were associated with improved survival. A high baseline ALC also maintained independent prognostic significance in a multivariate model against the IPSS (RR 0.746, 95% CI: 0.598, 0.933, p = 0.0099), and the raw WPSS score (RR 0.791, 95% CI 0.633, 0.987, p=0.037) but not the WPSS group (p=0.0794). There was no significant difference in the distribution of IPSS scores between the ALC >1.2 × 109 cells/L and the ALC ≤ 1.2 × 109 cells/L groups, although there were significantly more WPSS high risk patients in the low baseline ALC group (p = 0.0163). The creation of an ALC-modified IPSS score by adding 0.5 point for an ALC ≤ 1.2 × 109 cells/L resulted in a significant increase in median overall survival of the low risk group (41.8 months versus 66.1 months, p < 0.001, Figure 1). Conclusion: ALC is a novel and easily obtained prognostic marker in MDS that provides information complementary to existing prognostic scoring systems. Figure 1. Kaplan-Meier curves based upon IPSS (a) and the ALC-modified IPSS (b), where 0.5 point was added for an ALC ≤ 1.2 × 109 cells/L. Figure 1. Kaplan-Meier curves based upon IPSS (a) and the ALC-modified IPSS (b), where 0.5 point was added for an ALC ≤ 1.2 × 109 cells/L.

Validation of the Lower Risk MD Anderson Prognostic Scoring System for Patients with Myelodysplastic Syndromes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3826-3826 ◽  
Author(s):  
Rami S. Komrokji ◽  
Maria Corrales-Yepez ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Stratification ◽  
Lower Risk ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Refractory Anemia ◽  
Kaplan Meier ◽  
Disease Behavior ◽  
Md Anderson

Abstract Abstract 3826 Background: The International Prognostic Scoring System (IPSS) is the most widely used clinical tool for risk stratification and tailoring treatment in myelodysplastic syndromes (MDS). Outcome of patients stratified as lower risk MDS by IPSS is variable, with a subset of patients experiencing inferior than expected outcomes. Identifying patients with higher risk disease behavior is indispensible for proper implantation of disease altering therapy. The Lower Risk MD Anderson Risk Model (LR-MDAS) is a recently proposed model provides prognostic refinement to identify such patients (Garcia-Manero et al, Leukemia 2008). To validate this model, we tested the new risk model in large external single institution cohort of patients. Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and chart review. The primary objective was to validate the new risk model when applied at time of initial presentation to MCC. The LR-MDAS was calculated as published using the sum of points generated from unfavorable (non-del(5q), non–diploid) cytogenetics, hemoglobin (hgb) <10g/dl, platelet count (plt) <50 k/uL or 50–200k/uL, bone marrow blast % >= 4, and age>= 60 years. Patients were divided into 3 prognostic categories. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between the groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 479 patients with low or int-1 risk IPSS were captured by MCC MDS database. The median age was 69 years, MDS subtypes were coded as Refractory anemia (RA) 113 (24%), refractory anemia with ring sideroblasts (RARS) 73 (15%), MDS with del(5q) 19 (4%), refractory cytopenia with multi-lineage dysplasia (RCMD) 109 (23%), refractory anemia with excess blasts (RAEB) 147 (31%), and MDS-unclassified (U) 18 (4%). IPSS risk groups were low risk in 145 (30%), and intermediate-1 (int-1) 334 (70%). Only 31 patients (7%) had a poor risk karyotype by IPSS. Red blood cell transfusion dependence was documented in 42% (n=202), 22% had elevated serum ferritin ≥ 1000 ng/ml, and 45% (n=217) received azanucleoside treatment. Based on the LR-MDAS, 52 patients (11%) were category 1, 188 (39%) category 2, 232 (48%) category 3, and 7 (2%) were unknown. The median OS from time of referral to MCC for all patients was 32 months (95% CI 27–37 mo), Age, IPSS risk group, serum ferritin, and RBC transfusion dependence were all significant prognostic factors in univariate analysis. The median OS for the corresponding categories was, 1 - not reached (NR), 2– 50 mo (95%CI 33–68 mo), and 3 – 22 mo (95%CI 16–27 mo), from time of MCC referral, respectively. (Figure-1) (P < 0.005). Among 142 patients classified as low risk by IPSS, 25 patients (18%) were category 1 LR-MDAS, 81 (57%) category 2, and 36 (25%) category 3 with corresponding median OS of, NR, 62 month, and 35 month respectively (p=0.002). Among 330 patients risk stratified as int-1 IPSS group, 27 patients where category 1 LR-MDAS, 107 category 2, and 196 category 3 where median OS was NR, 28 months and 20 months, respectively. (p< 0.001) (Figure-2). When we applied IPSS risk stratification among each category of LR-MDAS to assess if IPSS can further refine prognosis within LR-MDAS categories, only in patients classified as Category 2 LR-MDAS the median OS was different among low and int-1 risk IPSS (62 month versus 28 month). (p <0.005). The rate of AML transformation according to LR-MDAS was 4%, 12%, and 20% for category 1,2, and 3, respectively. (p<0.02). In Cox regression analysis higher risk LR-MDAS predicted inferior OS (Hazard ratio (HR) 1.8 (95%CI 1.4–2.3) (p <0.005) independent of IPSS risk group (HR 2 95%CI 1.4–2.8) (p <0.005). Conclusion: Our data validates the prognostic value of the proposed LR-MDAS risk model, demonstrating predictive power for overall survival and AML transformation among low/int-1 risk IPSS. The LR-MDAS is complementary to the IPSS, offering further discrimination to identifying those patients with aggressive disease behavior that merit disease altering therapy. The utility of the model as treatment decision tool should be studied prospectively. Disclosures: No relevant conflicts of interest to declare.

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