Analysis of Survival Gains in Myelodysplastic Syndromes after a Decade of the Modern Treatment Paradigm

Abstract Introduction: The treatment of myelodysplastic syndromes (MDS) changed after the approval of lenalidomide in 2005, and 2 hypomethylating agents (HMA): azacitidine in 2004 and decitabine in 2006. Erythropoietin-stimulating agents (ESA) and reduced intensity conditioning stem cell transplantation (RIC-SCT) also became more widely utilized around that period. Analyses evaluating potential overall survival (OS) improvements in MDS since 2007 across different cancer registries have shown conflicting results. 'Real-world' survival trends are important to measure the true impact of these treatments outside clinical trials, especially as MDS treatment innovations may not reach all patients. We assessed the temporal change in OS and cancer-specific survival (CSS) of MDS patients in the US over the decade before (2001 - 2006) and after modern treatment options were established (2007 - 2016). Methods: Adult subjects diagnosed with MDS between 2001 and 2016 were identified in Surveillance, Epidemiology, and End Results (SEER), and categorized in 2 groups based on year of diagnosis: 2001 - 2006 (cohort 1) and 2007 - 2016 (cohort 2). MDS histologic risk was classified into low, intermediate, and high, using International Classification of Diseases for Oncology 3 rd Edition (ICD-O-3) codes. Cause of death (COD) reported to State registries (SEER recode) was used to determine CSS, defined as death from MDS or acute myeloid leukemia. Only cases with histologic confirmation of ICD-O-3 codes and complete follow up records were analyzed. Kaplan-Meier estimation was used to summarize unadjusted OS distribution. To assess the association of cohort 2 with OS and CSS gains, follow up duration was restricted to a maximum of 5 years in both cohorts and survival analysis was performed using multivariable Cox-proportional hazards regression model adjusting for age, sex, race, ethnicity, MDS risk, and geographic location. Results: We included a total of 42,217 patients with MDS, 13,633 (30.8%) in Cohort 1 (2001 - 2006) and 30,584 (69.2%) in Cohort 2 (modern treatment era). Subjects in cohort 2 were slightly older (mean age 73.8 vs 73.2 years, p<0.001) and included more males (58.6% vs 56.3%, p<0.001). Cohort 1 included more subjects with low MDS histologic risk (27.8% vs 17.2%) and fewer subjects with high MDS risk (18.4% vs 20.5%) (Table 1). Median OS for low, intermediate, and high risk MDS were 44 months (95%CI, 41.5 - 46.5), 27 months (95%CI, 25.7 - 28.3) and 10 months (95%CI, 9.3 - 10.7) in cohort 1, and 48 months (95%CI 45.9 - 50.1), 26 months (95%CI 25.3 - 26.7) and 11 months (95%CI 10.6 - 11.4) in cohort 2, but these differences were not significant. In the multivariable model adjusted for age, sex, race, ethnicity, MDS risk, and geographic location, cohort 2 was associated with a significantly lower hazard of overall death compared to cohort 1, HR for OS of 0.97 (95%CI, 0.95 - 0.99, p<0.001). Similarly, the modern era of treatment was associated with lower cancer-specific death compared to cohort 1, HR for CCS 0.93 (95%CI, 0.89 - 0.93, p=0.038). MDS histologic risk was the strongest factor associated with higher risk of overall and cancer-specific death. Other factors significantly associated with worse OS and CSS were advancing age, male sex, Hispanic ethnicity and unmarried status (Table 2). When analysis was restricted to patients with high risk MDS, cohort 2 was associated with a lower hazard of cancer-specific death, HR for CSS 0.90 (95%CI, 0.84 - 0.94, p=0.006), but no significant difference in overall death, HR for OS 0.96 (95%CI, 0.91 - 1.02, p=0.17). Discussion: In a SEER analysis, we found that the modern paradigm of MDS treatment, including access to lenalidomide, HMA, ESA and RIC-SCT, is associated with only modest survival gains at the population level. Across all MDS risk groups, improvements in cancer-specific death were larger than those seen for overall death and, in high risk MDS, a significant gain in CSS did not translate into longer OS. These data suggest there is a need for targeting non-cancer excess mortality in patients with MDS, who usually present with a high comorbidity burden. Strategies to optimize medical conditions coexisting with MDS and better supportive care may help consolidate the gains associated with currently available MDS-directed therapies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Transfusion Practices in Myelodysplastic Syndromes: Preliminary Results of An Epidemiologic and Economical Study

Blood ◽

10.1182/blood.v118.21.4336.4336 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4336-4336

Author(s):

Matthieu Filloux ◽

Adrien Chauchet ◽

Yvan Beaussant ◽

Chrystelle Vidal ◽

Franck Leroux ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Transfusion Requirement ◽

Conflicts Of Interest ◽

Age Groups ◽

Iron Chelation ◽

Low Risk ◽

Economic Study ◽

Transfusion Threshold ◽

Significant Difference

Abstract Abstract 4336 Background Despite the improvements and promises of novel agents (demethylating and erythropoiesis stimulating agents), red blood cells (RBC) and platelets transfusion remains frequent and essential in the management of myelodysplastic syndromes (MDS). Reducing patients’ dependence to transfusion is a major outcome, linked with the disease prognosis, patients’ quality of life and economical issues. Few data in the literature have described transfusions practices and requirements in MDS patients. We report here an epidemiological study of the transfusion practices in our center and try to build an economical evaluation of direct transfusions costs. Design and Methods We conducted a retrospective, descriptive study including all new patients diagnosed with MDS in the department of haematology of Besan□ on between 2006 and 2009. Patients were classified as high risk (HR) MDS when IPSS was ≥ 1.5, and as low risk (LR) when IPSS was ≤ 1. We compared HR and LR groups and four categories of age (≤68; [68–76]; [76–83] and >83 years) according to transfusion data. The economic study compared direct costs of RBC transfusions and erythroipoiesis-stimulating agents for LR and HR patients, including the costs of hospital stays. Materials, transport, medical examinations, doctors’ and nurses’ wages and iron chelation were not considered in this analysis. T-test and χ2-test were used for comparisons. Results 205 patients were analysed, median age at diagnosis was 74.3 years (table 1), with a predominance of men (sex ratio 1.33). IPSS score was available for 75% of patients (n=154), 111 LR patients and 43 HR patients. Median follow-up was 32 months [10–57]. Twenty-three patients (11%) developed a secondary acute leukaemia and 11 (5%) received allogeneic stem cell transplantation. At diagnosis, hemoglobin (Hb) level was not significantly different between HR and LR patients. Platelets level was lower in the HR vs LR (109 vs. 178 G/L respectively, p<0.0001). 60.5% of patients (n=124/205) received labile blood products during the follow-up, more frequently RBC than platelets (87.5% vs. 12.5% respectively). The mean Hb threshold at transfusion was 8.1 g/dl without any significant difference between neither age groups nor IPSS; age did not influenced transfusion requirement (Table 2). In comparison to HR patients, LR patients were less transfused (55 vs. 79%, p<0.006, table 2), and had longer mean intervals between transfusions (32.5 vs. 16.9 days, p<0.001). Furthermore, a progressive shortening of transfusion intervals was observed for both groups along the time; this progression was faster for HR patients. The anti-erythrocyte immunization rates, excluding anti-RH or anti-Kell, was 6.7%. Economical analysis showed that annual costs of RBC transfusion were 11,409 euros in LR patients and 21,945 euros in HR patients versus 11,492 euros for EPO. Conclusion In our study, neither transfusion requirement nor transfusion threshold were correlated with age, whereas both were affected by IPSS. Furthermore, age did not appear to be a predictive factor concerning the transfusion dependence. Despite its limits, the economic study reveals that EPO and transfusion's annual costs are similar in low risk patients. Updated data will be presented on EPO and 5-azacytidine use in our cohort to assess their impact on transfusion practices. Disclosures: No relevant conflicts of interest to declare.

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A Comparison Study Between Allogeneic and Autologous Hematopoietic Stem Cell Transplant for High-Risk Peripheral T-Cell Lymphomas (PTCL)

Blood ◽

10.1182/blood.v128.22.5845.5845 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5845-5845 ◽

Cited By ~ 2

Author(s):

Haiwen Huang ◽

Qiangli Wang ◽

Zhengming Jin ◽

XiaoWen Tang ◽

Huiying Qiu ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Term Survival ◽

Hematopoietic Stem ◽

Significant Difference

Abstract Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (13-55) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 with ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 with angioimmunoblastic T-cell lymphoma (AITL). Twenty-one (21/60) received allo-HSCT and thirty-nine patients (39/60) received auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients were partial remission (PR) and 18/60 patients were not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients received auto-HSCT. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients received auto-HSCT. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS for auto-HSCT and allo-HSCT were 61% and 60% (P = 0.724). The 5-year OS for auto-HSCT and allo-HSCT were 62% and 61% (P = 0.724). There were no statistically significant differences between the auto-HSCT and allo-HSCT. And the cumulative TRM of allo-HSCT and auto-HSCT were 16.5% and 0 (P=0.250) within 5-years after transplantation. At the end of the last follow-up, 7 patients relapsed in auto-HSCT group and 2 patients relapsed in allo-HSCT group, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively. Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. The effect of allo-HSCT may be better for NR patients. Disclosures No relevant conflicts of interest to declare.

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Postoperative craniospinal radiotherapy of medulloblastoma in children and young adults

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0306226g ◽

2003 ◽

Vol 131 (5-6) ◽

pp. 226-231

Author(s):

Ivana Golubicic ◽

Jelena Bokun ◽

Marina Nikitovic ◽

Jasmina Mladenovic ◽

Milan Saric ◽

...

Keyword(s):

High Risk ◽

Brain Stem ◽

Wilcoxon Test ◽

Time Interval ◽

Tumor Removal ◽

Shunt Placement ◽

Craniospinal Radiotherapy ◽

Number Of Patients ◽

Significant Difference

PURPOSE The aim of this study was: 1. to evaluate treatment results of combined therapy (surgery, postoperative craniospinal radiotherapy with or without chemotherapy) and 2. to assess factors affecting prognosis (extend of tumor removal, involvement of the brain stem, extent of disease postoperative meningitis, shunt placement, age, sex and time interval from surgery to start of postoperative radiotherapy). PATIENTS AND METHODS During the period 1986-1996, 78 patients with medulloblastoma, aged 1-22 years (median 8.6 years), were treated with combined modality therapy and 72 of them were evaluable for the study end-points. Entry criteria were histologically proven diagnosis, age under 22 years, and no history of previous malignant disease. The main characteristics of the group are shown in Table 1. Twenty-nine patients (37.2%) have total, 8 (10.3%) near total and 41 (52.5%) partial removal. Seventy-two of 78 patients were treated with curative intent and received postoperative craniospinal irradiation. Radiotherapy started 13-285 days after surgery (median 36 days). Only 13 patients started radiotherapy after 60 days following surgery. Adjuvant chemotherapy was applied in 63 (80.7%) patients. The majority of them (46 73%) received chemotherapy with CCNU and Vincristine. The survival rates were calculated with the Kaplan-Meier method and the differences in survival were analyzed using the Wilcoxon test and log-rank test. RESULTS The follow-up period ranged from 1-12 years (median 3 years). Five-year overall survival (OS) was 51% and disease-free survival (DFS) 47% (Graph 1). During follow-up 32 relapses occurred. Patients having no brain stem infiltration had significantly better survival (p=0.0023) (Graph 2). Patients with positive myelographic findings had significantly poorer survival compared to dose with negative myelographic findings (p=0.0116). Significantly poorer survival was found in patients with meningitis developing in the postoperative period, with no patient living longer than two years (p=0.0134) (Graph 3). By analysis of OS and DFS in relation to presence of the malignant cells in liquor, statistically significant difference, i. e. positive CSF cytology was not obtained, which was of statistical importance for survival (p=0.8207). Neither shunt placement nor shunt type showed any impact on survival (p=0.5307 and 0.7119, respectively). Children younger than three years had significantly poorer survival compared to those older than 16 years (p=0.0473). Although there was a better survival rate in females than in males this was not statistically significant (p=0.2386).The analysis results of treatment showed that significantly better survival occurred in patients in whom total or subtotal tumor removal was possible (p=0.0022) (Graph 4). Patients who started radiotherapy within two months after surgery have better survival, but again this was not statistically significant, probably due to the small number of patients receiving delayed radiotherapy (p=0.2231)(Graph5). CONCLUSION Based on this factors standard and high risk group could be defined. Combined chemotherapy should to be investigated particularly for high risk subgroup. Future research should be done to define new therapeutic modalities (gene therapy, compounds active in tumor antiangiogenesis etc).

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EPID-16. INTEGRATION OF EHR AND CANCER REGISTRY DATA TO CONSTRUCT A PEDIATRIC NEURO-ONCOLOGY SURVIVORSHIP COHORT AND IMPROVE LONG-TERM FOLLOW-UP CARE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.202 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii322-iii322

Author(s):

David Noyd ◽

Claire Howell ◽

Kevin Oeffinger ◽

Daniel Landi ◽

Kristin Schroeder

Keyword(s):

Cancer Registry ◽

Late Effects ◽

Care Delivery ◽

Clinic Visit ◽

Registry Data ◽

Cancer Registry Data ◽

Significant Difference ◽

Race Ethnicity

Abstract BACKGROUND Pediatric neuro-oncology (PNO) survivors suffer long-term physical and neurocognitive morbidity. Comprehensive care addressing late effects of brain tumors and treatment in these patients is important. Clinical guidelines offer a framework for evaluating late effects, yet lack of extended follow-up is a significant barrier. The electronic health record (EHR) allows novel and impactful opportunities to construct, maintain, and leverage survivorship cohorts for health care delivery and as a platform for research. METHODS This survivorship cohort includes all PNO cases ≤18-years-old reported to the state-mandated cancer registry by our institution. Data mining of the EHR for exposures, demographic, and clinical data identified patients with lack of extended follow-up (>1000 days since last visit). Explanatory variables included age, race/ethnicity, and language. Primary outcome included date of last clinic visit. RESULTS Between January 1, 2013 and December 31, 2018, there were 324 PNO patients reported to our institutional registry with ongoing analysis to identify the specific survivorship cohort. Thirty patients died with an overall mortality of 9.3%. Two-hundred-and-sixteen patients were seen in PNO clinic, of which 18.5%% (n=40) did not receive extended follow-up. Patients without extended follow-up were an average of 3.5 years older up (p<0.01); however, there was no significant difference in preferred language (p=0.97) or race/ethnicity (p=0.57). CONCLUSION Integration of EHR and cancer registry data represents a feasible, timely, and novel approach to construct a PNO survivorship cohort to identify and re-engage patients without extended follow-up. Future applications include analysis of exposures and complications during therapy on late effects outcomes.

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Reducing Preventable Readmissions in a Neurosurgical Patient Population at an Academic Medical Center

Neurosurgery ◽

10.1093/neuros/nyz310_434 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Shayan Moosa ◽

Lindsay Bowerman ◽

Ellen Smith ◽

Mindy Bryant ◽

Natalie Krovetz ◽

...

Keyword(s):

High Risk ◽

Patient Population ◽

Medical Center ◽

Academic Medical Center ◽

Readmission Rates ◽

Academic Medical ◽

Neurosurgical Patient ◽

Neurosurgical Patients ◽

Significant Difference

Abstract INTRODUCTION Hospital readmissions are extremely costly in terms of time and resources and negatively impact patient safety and satisfaction. In this study, we performed a Pareto analysis of 30-day readmissions in a neurosurgical patient population in order to identify patients at high-risk for readmission. Using this information, we implemented a new practice parameter with the goal of reducing preventable readmissions. METHODS Patient characteristics and causes for readmission were prospectively collected for all neurosurgical patients readmitted to an academic medical center within 30 d of discharge between July and October 2018. A program was then initiated where postoperative neurosurgical spine patients were contacted by phone at standardized intervals before their 2-wk follow-up appointment, with the purpose of more quickly addressing surgical concerns and/or coordinating care for general medical issues. Finally, 30-d readmission rates were compared between the initial 4-mo period and January 2019 through April 2019. RESULTS Prior to intervention, the largest group of readmitted patients included those who had undergone recent spinal surgery (16/47, 34%). Among spine readmissions during this time, 47% were readmitted before their two-week follow-up appointment, 67% lived over 50 miles from the medical center, and 40% were Medicare-insured. There was a statistically significant difference in the mean rate of spine readmissions per month in the periods before (7.0%) and after (3.0%) the program onset (P = .029, 57% decline). The total number of surgically and medically related spine readmissions decreased between the pre- and postintervention periods from 10 to 3 (70%) and 3 to 1 (67%), respectively. CONCLUSION Our data suggests that a large number of neurosurgical readmissions may be prevented by the simple process of early follow-up and consistent communication via telephone. Readmission rates may be further reduced by standardizing the coordination of postoperative general medical follow-up and providing thorough wound care teaching for high-risk patients.

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Pre-Enucleation Chemotherapy in Advanced Intraocular Retinoblastoma. Central America Follow Up: AHOPCA II

Journal of Global Oncology ◽

10.1200/jgo.2016.004440 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 75s-75s

Author(s):

Sandra Luna-Fineman ◽

Soad L. Alabi ◽

Mauricio E. Castellanos ◽

Yessika Gamboa ◽

Ligia Fu ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Central America ◽

Conflicts Of Interest ◽

Risk Group ◽

High Risk Group ◽

Globe Rupture ◽

Neo Adjuvant Chemotherapy ◽

Standard Risk

Abstract 57a Purpose: A significant percentage of patients in Central America present with buphthalmos, carrying a high risk of globe rupture and orbital contamination. In 2007, AHOPCA introduced chemotherapy before enucleation in children with buphthalmos. Methods: Patients with advanced intraocular disease were considered standard-risk and underwent enucleation. Those with diffuse invasion of choroid, postlaminar optic nerve, or anterior chamber invasion received 4-6 cycles of adjuvant chemotherapy (vincristine, carboplatin, etoposide). Patients with buphthalmos or perceived to be at risk for abandonment were considered high-risk, given 2-3 cycles of chemotherapy before enucleation to compete 6 cycles regardless of pathology. All cases were discussed via online meetings. Results: From 2007 to 2014, 396 patients were enrolled; 240 had IRSS stage I (174 unilateral). 143 had upfront enucleation, 95 had pre-enucleation chemotherapy, 1 is pending enucleation and 1 abandoned before enucleation. The standard-risk group 69 had risk pathology and 76 had no risk factors; 125 had no events, 5 abandoned 11 relapsed/progressed and 2 died of toxicity. Of 95 high-risk group, 8 abandoned, 20 relapse/progressive, 6 had toxic deaths and 61 are alive at last follow-up (median time of 4 years). Of high risk group, 55 were unilateral, 82% are alive. At 7 years OS (abandonment-censored) was 95±0.02 and 79±0.04 for standard-risk and high-risk (p=0.008). Conclusion: AHOPCA addressed advanced intraocular disease with an innovative approach. In eyes with buphthalmos and patients with risk of abandonment, neo-adjuvant chemotherapy is effective, when followed by post-enucleation chemotherapy. This approach avoids ocular rupture and intensified therapy, and reduces refusal/abandonment rate. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.

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Hodgkin Lymphoma Outcomes: Can We Expect Ethnic Parity in a Hispanic Prevalent Population?

Blood ◽

10.1182/blood-2019-129058 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4056-4056

Author(s):

Michelle Janania Martinez ◽

Prathibha Surapaneni ◽

Juan F Garza ◽

Tyler W Snedden ◽

Snegha Ananth ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Conflicts Of Interest ◽

Relative Survival ◽

Complete Response ◽

Statistical Testing ◽

P Value ◽

Hispanic Population ◽

Significant Difference ◽

The Mean

BACKGROUND It is estimated that 8110 persons will be diagnosed with Hodgkin Lymphoma (HL) in the US during 2019, but the advent of new treatment options has increased the cure rate to at least 80%. It has been reported that the rates of HL are lower in the adolescent and young adult (AYA) Hispanic population but significantly higher in the Hispanic population older than 65. The relative survival estimates are stated to be similar between AYA Hispanics (HI) and non-Hispanics (NH) but for ages 65-84, HI have a significantly higher mortality rate. Pediatric studies have suggested that ethnicity plays a role in outcomes in patients with HL but there is limited data in the adult population. There is an unmet need in the field, where dossiers on underrepresented ethnic minorities need to be carefully considered and compared to existing data. Therefore, our study aims to compare survival outcomes in Hispanics vs Non-Hispanics with HL, who were treated at the only NCI designated cancer center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 116 cases of HL; all the patients received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ethnicity, comorbidities, insurance status, stage, BM and extranodal involvement, treatment received, outcome at 3 and 5 years and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 116 patients with HL, of which 73 were HI (63%), 43 NH (36%) and 1 not specified (1%). In regard to race, 92% identified as Caucasian, 4% as African American, 3% other and 1% Asian. The median age at diagnosis was 37.4, (SD 15.13). There were 49 females (42%) and 67 males (58%). The most common funding source was commercial insurance N=54 (47%), followed by a hospital payment plan N=30 (26%), Medicare N=16 (14%), unfunded N=13 (11%) and Medicaid N=3 (2%). Most prevalent co-morbidities were HTN N=28 (24%) and diabetes mellitus N= 23(20%); 50% of patients had no co-morbidities (N=63).At diagnosis ECOG of 0-1 was seen in 108 patients (93%); 8 were Stage I (7%), 39 stage II (33%), 32 stage III (28%), and 37 stage IV (32%). EBV was positive in 26 patients (22%). There were 15 patients that were HIV positive (13%), 54% with CD4 count <200, and 12 (75%) on antiretroviral therapy at diagnosis. Median PFS was 853.85 days (SD 912.92). We excluded patients who were lost to follow up or had not reached 3/5 years. At 3 year follow up there was: complete response in 37 HI (74%) vs 22 NH (92%); disease progression in 8 (16%) vs 0 (0%); death in 5 (10%) vs 2 (8%), respectively (p-value= 0.094). At 5 year follow up there was: complete response in 30 HI (77%) vs 17 NH (90%); progressive disease in 2 (5%) vs 0 (0); death 7 (18%) vs 2 (11%), respectively (p-value = 0.619). At the end of 2018, 41 HI (84%) were alive compared to 22 NH (88%) [p-value 0.74]. CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, HI patients with HL have no statistically significant difference in outcome when compared to NH patients. Disclosures No relevant conflicts of interest to declare.

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Comparing Toxicities and Survival Outcomes with Total Therapy 4 (TT4) for 70-Gene (R70)-Defined Low-Risk Multiple Myeloma (MM) to Results Obtained with Total Therapy 3 Protocols TT3A and TT3B

Blood ◽

10.1182/blood.v116.21.368.368 ◽

2010 ◽

Vol 116 (21) ◽

pp. 368-368 ◽

Cited By ~ 3

Author(s):

Elias J. Anaissie ◽

Frits van Rhee ◽

Antje Hoering ◽

Sarah Waheed ◽

Yazan Alsayed ◽

...

Keyword(s):

High Risk ◽

Conflicts Of Interest ◽

Low Risk ◽

Phase Iii ◽

Survival Outcomes ◽

Phase Iii Trial ◽

Baseline Characteristics ◽

Total Therapy ◽

Timing Of Onset

Abstract Abstract 368 Background: TT3, incorporating bortezomib and thalidomide with induction prior to and consolidation after melphalan 200mg/m2-based transplants and 3 year maintenance with VTD (year 1) and TD (years 2+3) in TT3A and with VRD for 3 years in TT3B resulted in a high CR rate of ∼60% and, in the 85% of patients with GEP-defined low-risk MM, 5-yr OS/EFS of 80%/78%; 5-year CR duration estimate was 88%. Patients and Methods: Phase III trial TT4 for low-risk MM randomized patients between standard (S) and light (L) arms. TT4-L applied 1 instead of 2 cycles of induction therapy with M-VTD-PACE prior to and 1 instead of 2 cycles of consolidation with dose-reduced VTD-PACE after tandem transplantation. M-VTD-PACE comprised melphalan, bortezomib, thalidomide, dexamethasone and 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide. TT4-S applied standard single dose melphalan 200mg/m2, while TT4-L used a 4-day fractionated schedule of melphalan 50mg/2 on days 1–4. VRD maintenance for 3 years was identical in both arms. Here we report, for both TT4 arms combined, on grade >2 mucosal toxicities, applying CTCAE version 3.0, and on efficacy (CR, EFS, OS) in relationship to TT3 in low-risk MM. At the time of analysis, median follow-up on TT4 is 10.7 months and on TT3A/B 62.3/33.4 months. To facilitate comparisons between trials with different follow-up times, TT3 data were backdated to follow-up time comparable to TT4 as of this reporting time. Results: Baseline characteristics were similar in TT3 (n=364) and TT4 (n=165) in terms of B2M both >=3.5mg/L and >5.5mg/L, and elevated levels of CRP, creatinine, and LDH. Presence of cytogenetic abnormalities (CA) overall and in terms of CA13/hypodiploidy was similar in both. Fewer TT4 patients had ISS-1 (31% v 43%, P=0.010) and more had hemoglobin <10g/dL (35% v 26%, P=0.029). While neither trial had GEP-defined high-risk in the 70-gene model (R70), the more recently validated R80 distribution showed 7% high-risk in TT4 v 3% in TT3 (P=0.031). DelTP53 was more prevalent in TT4 than TT3 (39% v 10%, P<0.001), and MY favorable subgroup designation pertained to 3% in TT4 v 12% in TT3 (P=0.002). Toxicities are reported per protocol phase. During induction (TT4, n=160; TT3, n=364), grade >2 mucosal toxicities included colitis in 0%/1% (P=0.32), esophagitis/dysphagia in 0%/1% (P=0.33), GI mucositis, NOS in 1%/1% (P=0.99) and stomatitis/pharyngitis in 0%/1% (P=0.99). With transplant-1, (TT4, n=139; TT3, n=344), grade >2 mucosal toxicities included colitis in 3%/1% (P=0.24), esophagitis/dysphagia in 1%/5% (P=0.03), gastritis in 1%/0% (P=0.29), GI mucositis, NOS in 1%/2% (P=0.73) and stomatitis/pharyngitis in 0%/5% (P=0.008); with transplant-2 (TT4, n=105; TT3, n=294), grade >2 mucosal toxicities included colitis in 4%/3% (P=0.77), esophagitis/dysphagia in 0%/2% (P=0.20), GI mucositis, NOS in 2%/3% (P=0.99) and stomatitis/pharyngitis in 0%/1% (P=0.58). With consolidation (TT4, n=85; TT3, n=280), grade >2 mucosal toxicities included colitis in 0%/3% (P=0.36) and GI mucositis, NOS in 0%/1% (P=0.99). Timing of onset and final levels of CR differed substantially between TT4 and TT3 in favor of TT4 (P=0.006); no differences were observed in OS (P=0.36), EFS (P=0.66), and CR duration (P=0.12). Conclusion: TT4 (both arms combined) provided, despite higher proportions of patients with unfavorable characteristics than in TT3, superior CR rate and comparable survival outcomes to TT3's low-risk population. GI toxicities were reduced in TT4 v TT3. Results of TT4 arms will be presented. Disclosures: No relevant conflicts of interest to declare.

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Pediatric Therapy In Adult Acute Lymphoblastic Leukemia: Updated Experience of a Single Centre

Blood ◽

10.1182/blood.v116.21.4338.4338 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4338-4338

Author(s):

Stefania Paolini ◽

Sarah Parisi ◽

Ilaria Iacobucci ◽

Cristina Papayannidis ◽

Maria Chiara Abbenante ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Hematological Toxicity ◽

Induction Phase ◽

Single Centre ◽

Phase Ib ◽

Small Series ◽

Significant Difference

Abstract Abstract 4338 Background. Acute lymphoblastic leukemia (ALL) presents with different outcome in children and adults, with event-free-survival (EFS) rates of 70–80% and 30–40% at 5 years, respectively. This reflects both a different disease biology and different therapeutic approaches. Recently, results apparently improved in young adults/adolescents aged 15–21 years, with de novo ALL, when treated with pediatric intensive regimens rather than with typical adult regimens. Similarly, clinical studies are ongoing in older patients, toxicity related-therapy seeming the limiting issue. Aims. We report a single centre experience on adult ALL patients treated with an intensive pediatric-inspired schedule, designed to assess its tolerability and efficacy. Methods. From November 2007 to June 2010 seventeen ALL patients (M/F=12/5) were treated at our Center according to a modified AIEOP LAL2000 regimen. Treatment consisted of 7 days steroid pre-treatment, and four drugs 78-days induction (phase IA and phase IB) after which high risk (HR) patients were treated with three polychemotherapy blocks, while intermediate (IR) and standard risk (SR) patients went on 8-weeks consolidation and subsequent delayed intensification. Allo-SCT was planned for all patients with HLA-matched donor, as alternative to 2-years maintenance therapy. Median age was 31 years (range, 17–47). According to cytogenetic, response to steroid and minimal residual disease patients were classified into HR (n=7), IR (n=6) and SR (n=4). Results. 15/17 patients completed the induction phase IA, two being out for toxicity (grade IV infection and intestinal occlusion). Twelve (71%) obtained a complete remission (CR); three were refractory. However, one of them subsequently achieved CR after polychemotherapy blocks, for an overall response rate of 76% (13/17). Eleven patients then completed the 28-days induction IB. One patient is ongoing. Median induction duration was 92 days (range 82–136). Delays were mostly due to extra-hematological toxicity, the commonest being gastrointestinal (n=12), infective (n=7) and thrombotic (n=3). Delays were accumulated in both induction phases without significant difference between phase IA (median 18.5 days, range 4–37) and phase IB (median 17 days, range 9–66), despite an absolute number of moderate-severe AE superior in phase-IA versus phase-IB (12 vs 5). After induction, 4/12 patients already received consolidation therapy; 2/4 then received allo-SCT. The median duration of consolidation was 51 days (range 22–94). Conversely, 6/12 patients received polychemotherapy-blocks, one patient went directly on alloSCT and the remaining is ongoing. After polychemotherapy-blocks, five out six patients received allo-SCT. The median CR duration was 13 months (range 1+-42+); two patients relapsed, both after allo-SCT. With a median follow-up of 11 months (range 2–43) 11/17 (65%) patients are alive, 9 in CR (5 undergone allo-SCT). Six patients dead, three in CR for infectious complications, 3 for relapsed/refractory disease. Conclusions. Though in a small series, pediatric-like intensive chemotherapy seemed to be feasible in adult ALL. Extra-hematological toxicity, however, caused significant treatment delays during induction. Finally, the overall outcome appeared promising, though longer follow-up and larger populations are needed to draw definitive conclusions. Acknowledgments. BolognAIL, European LeukemiaNet, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO, Project of Integrated Program (PIO), Programma di Ricerca Regione – Università 2007–2009. Disclosures: No relevant conflicts of interest to declare.

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Home Azacitidine Administration in High Risk Myelodysplastic Syndromes: Favorable Results of a Pilot Study in 48 Patients

Blood ◽

10.1182/blood.v118.21.1719.1719 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1719-1719

Author(s):

Sylvestre Guillevic ◽

Thibault Comont ◽

Jonathan Khalifa ◽

Christian Recher ◽

Daniel Adoue ◽

...

Keyword(s):

Quality Of Life ◽

High Risk ◽

Myelodysplastic Syndromes ◽

Conflicts Of Interest ◽

Age Distribution ◽

Hospital Administration ◽

Number Of Cycles ◽

Home Administration ◽

At Home

Abstract Abstract 1719 Background: Myelodysplastic syndromes (MDS) affect elderly patients. Azacitidine represents the gold standard treatment of high risk MDS. French health organization allows home chemotherapy administration after the first cycle of treatment. We decided to develop a home administration program of this drug. Moreover we hypothesized that this modality of treatment will improve patient's quality of life. Patients and methods: after one cycle in hospitalization, high risk MDS patients who were agree to receive home chemotherapy were included in the study. As recommended each first day of Azacitidine cycle was still administrated at hospital. Due to drug instability a quality statement was created to control all steps of administration (including storage temperature before administration). Feasibility and safety were evaluated. Comparison between home or hospital administration was performed: number of cycles, dose, tolerance, problems of administration. Results: 68 patients were included in the home chemotherapy program, 75% were MDS patients and 48 received Azacitidine. Age distribution was 7 patients 60/69 yrs (14%), 22 patients 70/79 yrs (46%) and 19 patients 80–89 yrs (40%). More than 2000 days of hospitalization were performed at home during a 18-month period. Similar median number of cycles and delays were observed in the two groups as well as same level of adverse events and hospitalizations between 2 cycles. In few cases administration was not possible at home due to unresolved infection, cytopenia or drug availability (excessive time between preparation and distribution). No patient was excluded of this program. Discussion and conclusion: home administration of Azacitidine was safe and feasible. All patients agree to continue this modality of administration and high level of satisfaction was observed. Next step will consist in a randomized study to compare quality of life between home and hospital administration of the drug. For this population of patient home treatment will represent an alternative which could improve quality of life as observed for children in ALL (1) or in colorectal cancer (2). Disclosures: No relevant conflicts of interest to declare.

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