P14.11 Severe treatment-induced myelosuppression is more frequent in female malignant glioma patients and associated with reduced overall survival

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii39-ii40
Author(s):  
P S Zeiner ◽  
K Filipski ◽  
M Forster ◽  
M Voss ◽  
E Fokas ◽  
...  

Abstract BACKGROUND An association of treatment-related myelotoxicity with female gender has been previously suggested. However, a systematic analysis of the prognostic relevance of radiochemotherapy-related cytopenia involving the different blood cell lineages is lacking. MATERIAL AND METHODS We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy (RCT) in 493 glioma patients. Histological grading, molecular pathology, surgical procedures and median overall survival (OS) were recorded. The extent of cytopenia was correlated with gender and outcome. RESULTS Treatment-induced severe cytopenia (leuko-, lympho-, neutro- and thrombocytopenia) occurred much more often in female than in male glioma patients (40.8 vs. 13.9%, p-value <0.0001). In female patients with IDH-wildtype high-grade astrocytomas there was a negative correlation of severe leuko-, lympho- and thrombocytopenia during temozolomide RCT with OS (36 vs. 54, 37 vs. 54 and 36 vs. 57 weeks, respectively; all p-values <0.05). In male patients there was also a trend for this unfavorable effect. Additionally, severe cytopenia correlated with reduced temozolomide dose exposure during RCT (all p-values <0.05 in total cohort) and reduced dose exposure was independently associated with worse OS (p-values <0.05 in the total and female cohort). CONCLUSION Our data confirm that women are at higher risk for treatment-induced cytopenia during RCT which is associated with a significant decrease in OS. From our data, it appears plausible that reduced temozolomide dose exposure during RCT is at least in part responsible for this finding. Immunosuppression of patients with severe cytopenia may be an independent contributor to adverse outcome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 789-789
Author(s):  
Laine Elliott ◽  
Allison E. Ashley-Koch ◽  
Jude Jonassaint ◽  
Jennifer Price ◽  
Jason Galloway ◽  
...  

Abstract Priapism, a painful and prolonged erection, has been reported to occur in 30–45% of male patients with sickle cell disease (SCD). However, little is known about the pathological processes and genetic risk factors that contribute to the occurrence of priapism. The identification of genetic variables that are associated with priapism may therefore help define both critical pathophysiologic mechanisms not otherwise apparent, as well as patients at increased risk. We examined genetic variation in our sample of 199 unrelated, adult (>18 years), male patients with Hb SS and Hb Sβ0-thalassemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation, and cell signaling. Additionally, we examined genes involved in NO biology (NOS2, NOS3, SOD1, SLC4A1). Finally, we also examined polymorphisms in the KLOTHO gene, which has previously been associated with priapism. We examined a total of 389 SNPs in 48 candidate genes. Except for the gene encoding the β2 adrenergic receptor, SNP genotyping was performed by TaqMan, using Assays-on-Demand or Assays-by-Design genotyping products (Applied Biosystems). Allele tests were used to detect genetic associations with priapism. Strong evidence of association was found for SNP rs7526590 in the transforming growth factor-β receptor, type III (TGFBR3) gene (p=.00058), SNP rs10244884 in the aquaporin (AQP1) gene (p=.00068), and SNP rs3768780 in the integrin αV (ITGAV) gene (p=0.00090). A second ITGAV SNP (rs3768778), in linkage disequilibrium (r2=.59) with the first, also showed association with priapism (p=.00888). The A1 subunit of coagulation factor XIII (F13A1) had four SNPs (hcv1860621, rs1032045, rs1674074, rs381061) with p-values less than 0.010 (p-values = 0.00156, 0.00415, 0.00648, and 0.00712, respectively). The linkage disequilibrium among these F13A1 SNPs is negligible (r2 <.15). We also adjusted for multiple testing using the Benjamini-Hochberg procedure (significance threshold <.10). SNP rs7526590 in TGFBR3, SNP rs10244884 in AQP1 and SNP rs3768780 in ITGAV each had a false discovery rate (FDR) p-value of .09834. SNP rs1674074 in F13A1 had an FDR p-value of .12733. The other SNPs in F13A1 had large FDR p-values, close to .30. We did not detect an association between priapism and genetic variation in the Klotho gene, as was previously reported by Nolan et al. (2005). Specifically, SNPs rs2249358, rs211234 and rs211239 showed a virtually identical distribution of genotypes for individuals with and without a history of priapism. However, our population is not identical to the previous study, which included patients as young as 10 years old. In conclusion, our data support the hypothesis that genetic variation is associated with risk for priapism among males with SCD and suggest that genes involved in the TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 529-529
Author(s):  
Dale Kesley Robertson ◽  
Chao Zhang ◽  
Yuan Liu ◽  
Theresa Wicklin Gillespie ◽  
Omer Kucuk ◽  
...  

529 Background: In most settings median overall survival (OS) is longer for non-Hispanic whites relative to non-Hispanic blacks with metastatic renal cell carcinoma (mRCC). However, absence of nephrectomy has been a predictor of shorter OS for both groups. The primary objectives of this study were to define the reasons why patients with mRCC do not undergo nephrectomy and to correlate absolute contraindications to surgery with race and OS. Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University and the AVAMC after obtaining institutional authorizations. Reasons for not undergoing nephrectomy were categorized as absolute, relative or no contraindication to nephrectomy. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: See Table. The median OS (months) by nephrectomy status was 15.9 (6.8 – 24.7) vs. 41.8 (25.6 – 49.4), p value 0.0003, for patients at Emory with no nephrectomy vs. nephrectomy, respectively. The corresponding AVAMC values were 15.5 (8.5 – 29.5) vs. 45.2 (30.3 – 100.9), p value 0.0002. Conclusions: The number of patients with absolute contraindications to nephrectomy varied widely by race and institution, yet absence of nephrectomy was the predominant predictor of shorter OS in both settings. [Table: see text]


2018 ◽  
Vol 12 (1) ◽  
pp. 68-74
Author(s):  
Ketlin Helenise dos Santos Ribas ◽  
Valdenilson Ribeiro Ribas ◽  
Silano Souto Mendes Barros ◽  
Valéria Ribeiro Ribas ◽  
Maria da Glória Nogueira Filizola ◽  
...  

ABSTRACT Young's early maladaptive schemas questionnaire (YSQ-S3) is used to understand psychological aspects. Objective: EMSs were evaluated in patients with migraine. Methods: Sixty-five subjects were evaluated using the YSQ-S3 under standard conditions in a room with air conditioning at 22 ± 2°C. The subjects were stratified by morbidity (migraine), gender (male/female) and age (18-29 / 30-39 / 40-55). Controls (without migraine), n = 27 and patients (with migraine), n = 38, men (n = 19) and women (n = 46); participants aged 18-29 years, n = 34, aged 30-39 years, n = 14 and aged 40-55 years, n = 17. Data were analyzed using the Chi-square test, with p-values <0.05. Results were expressed as percentages in contingency tables. Results: There was a significant association between migraine and female gender (84.21%; p-value <0.05, Table 1), between hypervigilance and inhibition, and unrelenting standards (56.52%; p-value <0.0.014, Table 2) and female gender with migraine. Moreover, there was a significant association between hypervigilance and inhibition, and unrelenting standards (73.68%; p-value <0.0001) and self-punishment (84.21%; p-value <0.0001) in patients with migraine of both genders (Table 3). Conclusion: The individuals with migraine had a psychological profile of being overly demanding with themselves and others and self-punishing, where this was more frequent in women.


2020 ◽  
Vol 21 (15) ◽  
pp. 5395 ◽  
Author(s):  
Dominique Scherer ◽  
Heike Deutelmoser ◽  
Yesilda Balavarca ◽  
Reka Toth ◽  
Nina Habermann ◽  
...  

An individual’s inherited genetic variation may contribute to the ‘angiogenic switch’, which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study. Odds ratios and 95% confidence intervals (CI) were estimated from unconditional logistic regression to test for genetic associations with CRC risk. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% CIs for survival. Multiple testing was adjusted for by a false discovery rate. No variant was associated with CRC risk. Variants in EFNB2, MMP2 and JAG1 were significantly associated with overall survival. The association of the EFNB2 tagging SNP rs9520090 (p < 0.0001) was confirmed in two validation datasets (p-values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in JAG1 (p-value 0.0003) and rs2241145 in MMP2 (p-value 0.0005) showed the same direction of association with overall survival in the first and second validation sets, respectively, although they did not reach significance (p-values: 0.09 and 0.25, respectively). EFNB2, MMP2 and JAG1 are known for their functional role in angiogenesis and the present study points to novel evidence for the impact of angiogenesis-related genetic variants on the CRC outcome.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1356-1356
Author(s):  
Carolina Velez-Mejia ◽  
Rodolfo Garza Morales ◽  
Qianqian Liu ◽  
Joel E Michalek ◽  
Adolfo Enrique Diaz Duque

Abstract Background Follicular lymphoma (FLy) is one of the most common subtypes of Non-Hodgkin Lymphomas (NHL) (Cancer EpidemiolPMC4323749). In prior studies, better progression-free survival has been noted in Hispanics (HI), however, further characterization of this ethnic minority needs to be addressed (Ann Lymphoma PMC5877479). This result is consistent with previous research explaining the development of NHL as an heterogeneous process where unique outcomes for races have been noted (Cancer PMID: 22434428). This is the first combined statewide population-based study of Texas (TX) and Florida (FL) evaluating ethnic differences for HI vs Non-Hispanics (NH) comparingdemographics, socioeconomic, clinical and survival patterns of patients diagnosed with FLy. The value of using these states relies on the fact that the percentage of HI in TX and FL are 39.7% and 26.4%, respectively (US Census 2020). Material and Methods This is a retrospective analysis of patients diagnosed with FLy recorded in the Texas Cancer Registry and the Florida Cancer Data System from 2006-2017. Inclusion criteria was histopathologic proven FLy. Patients were divided into HI and NH for comparison. Standard demographic, socioeconomic, clinical, and survival variables were reviewed. All statistical testing was determined using Fisher's Exact test, Pearson's Chi-square test, T-test or Wilcoxon test, as appropriate. Survival time was measured using the day of diagnosis to last date of follow up or death. Survival distribution were calculated based on Kaplan-Meier curves. Results From 2006-2017, 20,497 patients (HI n=3,176, NH n=17,321) were diagnosed with FLy (Table 1, Table 3). In TX, the median age at diagnosis for HI was 60 years (y) vs 64 y for NH [p-value &lt;0.001]. In FL, it was 62 y and 67 y, respectively [p-value &lt;0.001]. In both states, female sex predominated for HI and NH. In TX, the bracket of poverty index that prevailed for HI was 20-100% while for NH was 10-19.9% [p-value &lt;0.001]. In FL, the largest number of HI and NH were in the 10-19.9% bracket [p-value &lt;0.001]. In TX, both HI and NH were more likely be with government-sponsor insurance, however, up to 15% of HI did not have insurance vs 4% in NH [p-value &lt;0.001]. This was also the case in FL, however their number of uninsurance corresponded to 6% and 2% respectively. In TX, the largest number of HI and NH patients were diagnosed at stage III-IV with 49% and 42% respectively [p-value &lt;0.001]. In FL, for these stages it corresponded to 43% and 37% for HI and NH [p-value &lt;0.001]. In TX, treatment at diagnosis showed a similar pattern for HI and NH, choosing mainly no treatment followed by multiple chemotherapy agents [p-value &lt;0.001]. In FL, this trend was also seen. In both states and for HI and NH, most of the patients did not undergo transplant or radiation. In TX, the median overall survival for HI was 9.2 y vs 8.6 y for NH; the survival probability at 2, 5 and 10 y for HI corresponded to 0.835, 0.701 and 0.453, while for NH it was 0.850, 0.703 and 0.354, respectively; and the overall survival probability at 10 y had no statistically significant difference [p-value 0.44] (Table 2, Graph 1). In FL, the median overall survival for HI was not reached vs NH at 10.1 y; the survival probability for HI at 2, 5 and 10 y was 0.871, 0.777 and 0.601, while for NH it was 0.845, 0.709 and 0.506, respectively; and the overall survival probability at 10 y was statistically significant [p-value &lt;0.0001] (Table 4, Graph 2). Conclusions This large two statewide population-based study identified statistical differences in oncological outcomes comparing HI and NH in patients diagnosed with FLy. HI diagnosed with FLy have higher survival at 10 y, and this difference was statistically significant in FL. Moreover, statistical significance was noted in demographic, sociodemographic and disease characteristics. Additional research should be carried out to identify the variables that drive this difference since advance stage, lack of insurance or treatment at diagnosis do not seem to be influencing it. There may be a combination of lifestyle factors (alcohol, cigarette, diet, other), occupational hazards, autoimmune diseases or protective mechanisms, infectious diseases exposures and unique epigenetic interactions that may explain why HI live longer when diagnosed with FLy. Figure 1 Figure 1. Disclosures Diaz Duque: Incyte: Consultancy; Morphosys: Speakers Bureau; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Consultancy; ADCT: Consultancy.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Leyla Bojanini Molina ◽  
Joel E Michalek ◽  
Qianqian Liu ◽  
Adolfo Enrique Diaz Duque

Background Hepatosplenic T-Cell lymphoma (HSTCL) is an aggressive type of lymphoma with extremely low incidence. It has a high fatality rate with a 5-year overall survival (OS) of &lt;10% (Am J Surg Pathol, PMID: 26872013). Although there is no therapy that has proven to produce sustained remission, recent studies suggest improvement in outcomes with allogeneic stem cell transplant (allo-SCT) (Leukemia, PMID: 25234166). Clinical characteristics and therapeutic outcomes have been previously reported; however, documentation of outcomes in minorities such as Hispanics (HI) are lacking. Given the growth of the HI population in the US it is imperative to understand the difference in outcomes and patterns of care (CA Cancer J Clin, PMID: 30285281). The present study aims to fill this gap in the literature; therefore, the present population-based study evaluates the impact of ethnicity in clinical outcomes for HSTCL. Material and Methods We retrospectively searched for cases of HSTCL recorded in the Texas Cancer Registry. Inclusion criteria included and established pathologic diagnosis of HSTCL using the International Classification of Diseases for Oncology Third Edition (ICD-O-3) code list. Patients were divided between HI and non-Hispanics (NH). Demographic, socioeconomic, clinical and survival outcomes were recorded. Statistical analysis included Fisher's Exact test, Pearson's Chi-square test, T-test or Wilcoxon test. Survival analysis was calculation in years from date of primary diagnosis to date of death or last date of follow up. Survival distributions were described with Kaplan-Meier curves, and long rank testing was used to assess significance of variation in median survival with ethnicity. All statistical testing was two-sided with a significance level of 5%. The R language [R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria] was used throughout. Results From 2006-2016, a total of 25 patients were diagnosed with HSTCL; 23 (92%) were NH and 2 (7%) were HI [&lt;0.0001]. The median age at diagnosis was 46 for HI and 48 for NH. It was predominantly seen in males for both HI and NH. The patients mostly self-identified as white (HI: n=2, Nh: n=16), and there were 7 (30%) NH patients that self-identified as black. For HI, one patient was in the bracket of poverty indicator of 10-19.9% and the other one was in the 20-100%; for the NH patients the bracket that prevailed was 10-19.9% [p-value 0.56]. Both HI patients had private insurance (PI); insurance status on NH patients included 7 (33.3%) with PI, 5 (23.8%) with Medicare, and 7 (33.3%) was unknown [p-value 0.64]. The majority of HI and NH patients were located in the metropolitan, non-border area. Stage at diagnosis for NH was mostly III-IV; one HI had a stage III-IV HSTCL and the other was unstaged [p-value 1.0]. From a therapeutic standpoint, the majority of HI and NH patients received chemotherapy, with 13 patients (HI: n=2, NH: n=11) receiving multiple agents as first-line therapy [p-value 0.84]. From the two groups, only 3 (13%) NH patients underwent allo-SCT [p-value 0.014]. The majority of HI and NH did not undergo radiation (Figure 1A). The median overall survival was 0.5 years in HI and 0.6 in NH. The survival probability at 2 years for HI and NH was 0.5 (CI=0.16, 1) and 0.29 (CI=0.15, 0.56) respectively; at 5 years for HI was 0.5 (CI 0.16, 1) and for NH was 0.23 (CI=0.10, 0.51) (Figure 1B). The overall survival probability at 10 years was not statistically different for HI vs NH [p-value 0.53] (Figure 1C). Conclusions Survival analysis shows that HSTCL is usually fatal with a median overall survival of less than a year, and no difference in survival probability at 10 years for both HI and NH. The majority of patients in our study were non-Hispanic white males. A significant finding was that NH patients had access to allo-SCT as opposed to the HI patients. No statistically significant difference in survival was noted depending on the insurance or poverty levels. No other demographics or sociocultural variables seemed to have an impact in outcomes. The main limitation of our study is our sample size that limits generalizability and power of our statistical analysis. Further studies using multiple cancer registries are warranted to assess the clinical characteristics and survival outcomes in HI with HSTCL. Disclosures Diaz Duque: ADCT Therapeutics: Research Funding; Molecular Templates: Research Funding; AstraZeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Seattle Genetics: Speakers Bureau; Verastem: Speakers Bureau; AbbVie: Speakers Bureau.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5029-5029
Author(s):  
Jinming Song ◽  
Mohammad Hussaini ◽  
Lynn C. Moscinski ◽  
Ling Zhang ◽  
Xiaohui Zhang ◽  
...  

Background: DNMT3A and SF3B1 are two of the most commonly mutated genes in myeloid neoplasms. DNMT3A mutations have been found to be associated poor prognosis in acute myeloid leukemia (AML), while SF3B1 mutations have been reported to be associated with favorable prognosis in myelodysplastic syndrome (MDS). Studies exploring the clinical significance of DNMT3A and SF3B1 co-mutation are limited and conflicting. Furthermore, the previous studies did not control for the presence of other co-mutated genes, which could be confounding factors. Materials and Methods: 4390 in-house patients with confirmed or suspected myeloid neoplasms were tested by Next Generation Sequencing (NGS) (up to 54 gene panel). From these, we identified 68 patients with only DNMT3A mutation, 61 patients with only SF3B1 mutation, and 23 patients with only SF3B1/DNMT3A co-mutation, for a total of 152 patients. Patient demographics, diagnosis, cytogenetic abnormalities, and overall survival time were collated and analyzed. Results: Patients with SF3B1 mutation alone or SF3B1/DNMT3A double mutations were found to be significantly older (median age of 76 and 75, respectively) than patients with isolated DNMT3A mutation (median age of 66, p values = 0.00016 and 0.00174 respectively). Patients with SF3B1/DNMT3A double mutations or isolated SF3B1 mutations occurred more commonly in MDS. They occurred less frequently in acute myeloid leukemia (AML) (1.63% and 21.74% respectively) than isolated DNMT3A mutation (41.76%, p values < 0.00001 and p = 0.00529 respectively). Patients with double mutations demonstrated increased ring sideroblasts (100%) at a rate similar to patients with isolated SF3B1 mutation (92.16%), which are unsurprisingly higher than patents with DNMT3A mutation alone (8%, p value < 0.000001). The patients with SF3B1 mutation alone or SF3B1/DNMT3A co-mutation were less likely to have poor cytogenetics and more likely to have intermediate cytogenetics than patients with DNMT3A mutation alone. Finally, patients with sole SF3B1 mutation or SF3B1/DNMT3A co-mutation showed significantly longer median survival time (26.60 months and 19.93 months respectively) and better overall survival curve (Figure 1) than patients with DNMT3A mutation alone (8.32 months, p value = 0.001 and 0.01078 respectively), for all the patients in this study as well as for patients with only myelodysplastic syndrome. Conclusion: Patients with SF3B1/DNMT3A double mutations showed a prognosis similar to patients with isolated SF3B1 mutation and better clinical outcomes than patients with isolated DNMT3A mutation. This suggests that the favorable prognosis of SF3B1 mutation in MDS or AML patients is not abrogated by the concurrent presence of a DNMT3A mutation. Figure 1 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3502-3502
Author(s):  
John Delmonte ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
Francis J. Giles ◽  
...  

Abstract The t(6;9)(p23;q34) is found in <1% of acute myeloid leukemia (AML). This translocation generates a fusion between the dek gene at 6p23 and the can gene at 9q34, with unclear role in leukemogenesis. Few patients (pts) have been described, usually with multilineage dysplasia, bone marrow (BM) basophilia, frequent FLT3 mutations, younger age at diagnosis and poor outcome. We searched the M.D. Anderson leukemia database to identify all pts diagnosed with t(6;9)(p23;q34) from 1993–2007. Clinical, laboratory, hematopathologic, and molecular data were reviewed. We identified 21 pts (18 AML, 2 MDS, 1 CMML) with t(6;9)(p23;q34) among 2,389 pts with AML and 597 pts with MDS seen over this period, representing 1% of all pts. Median age was 51 years (range, 20–82), 12 were female, median WBC 15.1 x109/L (range, 0.5–60.1), peripheral blast 12% (range, 0–86), hemoglobin 9.5 (range, 5.3–12.3), and platelet count 43 (range, 6–203). BM characteristics included median blast 62% (range, 7–87) and 2/21 (10%) pts with basophilia. The t(6;9)(p23;q34) translocation was the only cytogenetic abnormality in 13 (62%) pts; 8 (38%) had other chromosomal aberrations, often trisomy 8 (n=3). 8/12 (67%) pts tested for FLT3 mutations had an internal tandem duplication (ITD). Induction therapy was cytarabine-based (n=16), nucleoside analog/anthracycline-based (n=1), hypomethylating agent (n=1), and supportive care (n=3). 13/18 (72%) treated pts achieved CR, 6 (33%) were refractory, and 1 (6%) died during induction. Median CR duration was 53 weeks (wk) (range, 11–160) and 9/13 (69%) pts relapsed. 3/4 (75%) pts underwent stem cell transplant in 1st CR; two pts were FLT3-ITD negative. 5 pts who relapsed received salvage chemotherapy followed by stem cell transplant, but all subsequently died [median overall survival 45 wk (range, 28–121)]. Median overall survival (OS) for the entire group was 62 wk (range, 1–180). We then compared the t(6;9) AML pts to others treated in the same time period, grouped as: diploid (excluding APL), favorable (defined as inv 16 or t(8;21)), poor-risk (defined as -5 or -7), and other cytogenetic abnormalities. The t(6;9) AML subset was significantly younger (median 51 yrs) than the diploid (63 yrs) (p=0.001), poor-risk (63 yrs) (p<0.001), and other (62 yrs) (p=0.003) groups, but similar to favorable (44 yrs)(p=0.57). With regard to CR rate (72%) the t(6;9) AML subset did worse than favorable (91%)(p=0.017), better than poor-risk (40%)(p=0.006), and similar to the diploid (62%)(p=0.373) and other (52%)(p=0.089) groups. The tables show CR duration and OS for each group. In conclusion, AML with t(6;9)(p23;q34) represents a rare entity characterized by younger age at diagnosis, high frequency of FLT3-ITD, and clinical outcome similar to AML with diploid/intermediate risk cytogenetics. In this population, stem cell transplantation in 1st CR should be considered. The addition of FLT3 inhibitors to therapy should also be investigated. Complete Remission 1 year (%) 2 years (%) Median (weeks) p-value t(6;9) 54 35 53 Diploid 56 37 59 0.772 Favorable 79 54 187 0.017 Other 48 30 50 0.682 Poor-risk 22 11 24 0.021 Overall Survival 1 year (%) 2 years (%) Median (weeks) p-value t(6;9) 66 35 67 Diploid 53 34 60 0.741 Favorable 84 67 233 <0.001 Other 41 24 40 0.15 Poor-risk 19 7 19 <0.001


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4501-4501
Author(s):  
Naheed Alam ◽  
Anna Lambie ◽  
Yvette Neme Yunes ◽  
Feras Alfraih ◽  
Eshetu G Atenafu ◽  
...  

Abstract Abstract 4501 Introduction: CMV (Cytomegalovirus) reactivations are a major cause of morbidity and mortality in recipients of hematopoietic cell transplantation (HCT). Risk factors for CMV reactivations have not been fully elucidated. We evaluated first and subsequent CMV reactivations. Methods: Three hundred and forty seven patients transplanted consecutively between year 2005 and 2010 at Princess Margaret Hospital were assessed. CMV monitoring was performed by pp65 antigenemia testing. Positive patients (defined as >1 positive cells per 105 peripheral blood leukocytes examined) were treated preemptively with ganciclovir. 206(59%) patients received HCTs from related and 141(41%) from unrelated donors. 152(44%) were female and 195(56%) male. Graft versus host disease (GVHD) prophylaxis included Cyclosporine (CSA)/Mycophenolate mofetil (MMF) (n=100, 28.8%), CSA/Methotrexate (MTX) (n=101, 29.1%), CSA/CAMPATH (n=139, 40%), other (n=7, 2%). Results: With a median follow up of 15 months, 132 patients (38%) had at least one CMV reactivation. 67(51%) were Recipient (R) +/Donor (D) +, 61(46%) R+/D- and 4(3%) R-/D+. The median time to first reactivation was 35.5 days with a range from 13 – 1052 days. Risk factors for the occurrence of the first CMV reactivation were analyzed using death and relapse as competing risk factors. Older age at transplant (p-value 0.0375), female gender of recipients (p-value-0.0193) and presence of GVHD (p-value-0.0002) were significant factors for first CMV reactivations by univariate analysis. Conditioning regimens (p-value- 0.3294), donor type (p-value 0.1769) and lymphocyte count on the day of reactivation (p-value- 0.2308) were not significantly associated with first CMV reactivation. GVHD prophylaxis showed a trend (p-value- 0.0587). Multivariate analysis confirmed older age at transplant (p-value- 0.0258, odds ratio 1.024, 95%CI [1.003–1.045]), female gender of recipient (p-value- 0.0123, odds ratio 1.838, 95%CI [1.141–2.959]), GVHD prophylaxis with alemtuzumab (p-value 0.0324, odds ratio 2.121, 95%CI [1.148–3.917]) and presence of GVHD (p-value- <0.0001), odds ratio 2.935, 95%CI [1.754–4.910]) as independent variables. The time to first CMV reactivation was shorter in patients with GVHD prophylaxis using alemtuzumab containing regimens (34 days vs 60 days for CSA + MTX and 105 days for CSA + MMF, p= 0.0241), with low lymphocyte counts (<0.75 × 109/L, 42 days vs 112 days, p=0.0015), and presence of GVHD (40 days vs 79 days, p= 0.05). A number of patients experienced second or multiple CMV reactivations (Table 1) with a maximum of 10 reactivations. The median time to a subsequent reactivation from previous was 44 (range 35–127) days. The overall survival of patients that have not reactivated (Fig. 1) was not significantly different from that of patients with either 1 or multiple CMV reactivations (Fig. 2). Conclusion: Age at transplant, female gender of recipients, GVHD prophylaxis and presence of GVHD were identified as risk factors for the first CMV reactivation. The time to first reactivation was influenced by GVHD prophylaxis, lymphocyte count and presence of GVHD. Overall survival was not affected by CMV reactivations. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11569-e11569
Author(s):  
Claire Brady ◽  
Richard Martin Bambury ◽  
Jodie E Battley ◽  
Susan Murray ◽  
Seamus O'Reilly ◽  
...  

e11569 Background: Resection of a single brain metastasis (SBM) in metastatic cancer has been shown to improve overall survival (OS). A previously reported series from MD Anderson of breast cancer patients undergoing SBM resection reported a median overall survival of 19 months. We report our experience of SBM resection for breast cancer. Methods: Retrospective observational study of patients who underwent resection of SBM from breast cancer brain in a tertiary referral centre from 2000-2011. Results: 20 patients underwent SBM resection from 2000-2011. All patients received WBRT after surgery. 2 patients had progressive metastatic disease presenting as brain metastases. Median time from original breast cancer diagnosis to development of SBM was 53 months (range:1-286months). 9 patients had solitary brain metastases (no metastases elsewhere) and 11 patients had synchronous metastases elsewhere. Regarding the primary breast tumour: 41% of patients were ER+, 57% were HER2+ and 25% were triple negative. 1 patient had discordance of ER status between the primary tumour and brain metastasis (changed from ER- to ER+). Median overall survival was 9 months (95% CI: 5-18 months) with 1 year OS of 50%, 2 year OS of 15% and 3 year OS of 5%. Patients treated between 2006-2011 had better median OS than those treated 2000-2005(18 months vs 6 months – p-value not significant). Patients with a solitary brain metastasis had better median OS than those with synchronous extracranial disease (13 months vs 6 months – p-value not significant). An additional 2 patients underwent craniotomy for presumed breast cancer metastasis but histology revealed glioblastoma multiforme. Conclusions: We report on a cohort of patients undergoing metastatectomy for single brain metastasis from breast cancer. Median OS was 9 months but there was a trend towards better survival in patients treated in recent years when compared with those treated from 2000-2005. Improved systemic therapies may account for this difference. Also of note 2 patients undergoing resection for presumed brain metastases were found to have GBM, highlighting the role of tissue diagnosis in patients presenting with a solitary brain lesion.


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