Hodgkin Lymphoma Variant of Richter Transformation: Morphology, EBV Status, Clonality and Survival Analysis a Retrospective Study of 77 Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2637-2637 ◽  
Author(s):  
Wenbin Xao ◽  
Wayne Chen ◽  
Lynn Sorbara ◽  
Theresa Davies-Hill ◽  
Stefania Pittaluga ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Advanced Age ◽  
Type I ◽  
Type Ii ◽  
Clonal Relationship ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Morphological Patterns

Abstract The classical Hodgkin lymphoma variant of Richter transformation (CHL-RT) occurs rarely in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Two morphological patterns have been described: type I with Hodgkin/Reed-Sternberg (HRS) cells scattered in a CLL background, and type II with typical CHL morphology. HRS cells are frequently positive for EBV and can be clonally related or unrelated to CLL. The clinical significance of the different morphological patterns is unclear. What factors dictate the cellular derivation of the HRS cells remains elusive. We retrospectively reviewed 77 cases of CHL-RT submitted to our consultation service. Clinicopathological characteristics were summarized, EBV status was examined, and clonality was analyzed after microdissection of HRS-cells and CLL cells. Patients with the type I pattern (N=26) had a significantly shorter time to progression from CLL to CHL-RT than those with type II pattern (N=51, 15 vs. 49 months, p<0.0001, see Figure 1A). Consistent with these data, 27% of patients with the type I pattern had a prior CLL history as compared to 73% with the type II pattern. 12% (6/51) of type II cases had extranodal involvement (sites other than bone marrow) while none of type I cases did. Three patients with sequential biopsies progressed from type I to II and 2 had an aggressive clinical course. HRS cells were positive for EBV in 71% (55/77) of patients. Clonality analysis was performed in 33 cases: HRS cells were clonally related to the underlying CLL in 14 cases and unrelated in 19 cases. Among all the features examined, ZAP-70 expression of the CLL cells, but not EBV status or morphological pattern, was strongly correlated with clonal relationship: all 14 clonally related cases were negative for ZAP-70 while 74% (14/19) of the clonally unrelated cases were positive for ZAP-70. Overall median survival after the diagnosis of CHL-RT was 44 months. Advanced age was an adverse risk factor for survival (p<0.05, see Figure 1B). In conclusion, we provide evidence that type I morphology is more likely an early stage of CHL-RT and can progress to type II. The majority of CHL-RT cases are EBV positive. Clonal relationship in RT is determined by ZAP-70 and thus likely IGHV mutational status. Advanced age is associated with inferior survival. Figure 1. A, Time to progress from CLL to CHL-RT. B, Kaplan-Meier analysis of overall survival. Figure 1. A, Time to progress from CLL to CHL-RT. B, Kaplan-Meier analysis of overall survival. Disclosures No relevant conflicts of interest to declare.

Analysis of Genotype, Phenotype and Outcome in a Belgian Cohort of Essential Thrombocythemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5584-5584
Author(s):  
Carla AL Assaf ◽  
Els Lierman ◽  
Florence Van Obbergh ◽  
Timothy Devos ◽  
Johan Billiet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
Jak2 V617f ◽  
Male Gender ◽  
Type I ◽  
Free Survival ◽  
Clinical Complications ◽  
Mutational Status ◽  
Positive Groups

Abstract Bleeding and thrombotic events are major clinical complications of ET, together with progression to myelofibrosis and leukemic transformation (AML). The JAK2 V617F mutation, the thrombopoietin receptor mutation MPL W515K/L and the most recently discovered calreticulin (CALR) mutations are mutually exclusive in ET, account for up to 80-90 % of ET cases and support a novel molecular categorization of ET. In a retrospective study, we have examined the clinical phenotype and outcome of a Belgian cohort of 165 ET patients in relation to their mutational status. 38% of the patients were CALR mutated, 22% and 12% of whom carried Type 1 (p.L367fs*46) and Type 2 (p.K385fs*47) indels respectively. 35% were JAK2 V617F positive, 7% were MPL W515K/L positive, one patient was positive for both CALR and JAK2 V617F mutations, and 20% were triple negative (Fig. 1). We compared the hematological and clinical features between CALR mutant patients and JAK2 V617F positive patients. This revealed that CALR mutant ET is associated with younger age than JAK2 V617F positive ET (median age 56 y (range 23-84) versus 65 y (range 36-94), p<0.001), male gender (58% versus 39%, p=0.03), higher platelet count (988 ± 367*109/L versus 870 ± 291*109/L, p=0.04 (mean ± SD)), lower leukocyte count (9.1 ± 3.2*109/L versus 11.6 ± 5.8*109/L, p<0.001), lower erythrocyte count (4.36 ± 0.9*1012/L versus 4.98 ± 0.65*1012/L, p<0.001), hemoglobin (13.2 ± 1.8 g/dL versus 14.3 ±1.6 g/dL, p=0.001) and hematocrit (40 ± 6.2 % versus 44 ± 4.6 %, p<0.001). Analysis of the CALR mutant group according to the indel type showed that CALR Type 1 deletion is strongly associated with male gender (62%). Contrary to previously published findings, we did not find significant differences between CALR type I and II mutations with regard to age and platelet count.CALR mutant patients had a better overall survival than JAK2 V617F positive patients (mean survival 28 y versus 16 y, p=0.01). However, the better overall survival for CALR mutant ET was restricted to patients less than 60 years old (mean survival 29.2 y versus 18.5 y, p=0.02) while in the age group above 60 years, the overall survival was not significantly different (mean survival 18.3 y versus 13 y, p=0.32) (Fig. 2). In our cohort, no difference in myelofibrosis-free survival or leukemia-free survival was found between the molecular subtypes, although the risk of developing myelofibrosis was unexpectedly higher in the CALR mutant group (18% versus 4%, p=0.01). In contrast to other studies, we found no difference in the frequency of arteriovenous complications. In conclusion, this study on a Belgian cohort supports the notion that CALR mutant ET is phenotypically distinct from JAK2 V617F positive ET, with regard to the clinical and hematological presentation as well as the overall survival. In this cohort, the better overall survival was most marked in ET patients less than 60 y of age. Our study adds to the growing body of evidence that CALR mutant ET is a disease entity distinct from JAK2 V617F positive ET. Figure 1 Distribution of 165 ET patients according to their mutational status. Figure 1. Distribution of 165 ET patients according to their mutational status. Figure 2 Overall survival of CALR mutant and JAK2 V617F positive groups stratified according to age: older than 60 y versus younger than or equal to 60 y. Figure 2. Overall survival of CALR mutant and JAK2 V617F positive groups stratified according to age: older than 60 y versus younger than or equal to 60 y. Disclosures No relevant conflicts of interest to declare.

Defining Outcomes in Hispanic Aggressive Non-Hodgkin Lymphoma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4542-4542
Author(s):  
Lara M Paraskos ◽  
Mariela A. Blum ◽  
Maricer Escalon ◽  
Annapoorna Ferrell ◽  
Erin Kobetz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
The United States ◽  
Treatment Modalities ◽  
P Value ◽  
Non Hodgkin Lymphoma ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Hispanic Patients

Abstract Abstract 4542 Background Multiple studies evaluating outcomes for oncology patients have demonstrated inferior overall survival rates among African-Americans. Hispanics comprise the largest ethnic minority in the United States. Surprisingly outcomes for Hispanic aggressive non-Hodgkin lymphoma (NHL) patients have not been evaluated and are therefore largely unknown. We aim to identify differences in epidemiology, treatment modalities and outcomes of Hispanic patients treated for aggressive NHL at our institution between the years 2000-2004. Methods We reviewed the medical records of 82 patients with aggressive type NHL who were identified using the tumor registry. Exclusion criteria include indolent and highly aggressive lymphomas per WHO classification as well as lymphomas related to AIDS or organ transplantation. Standard statistical analyses, including Kaplan-Meier survival estimates and Chi-squared analysis for group comparisons were used. P value of <0.05 was considered statistically significant. Results Of the 82 patients, 46 were self-reported Hispanic in origin; 36 were non-Hispanic. There were no significant differences with respect to age at diagnosis, LDH level, stage, or complete remission rate. Kaplan-Meier estimate of median overall survival (OS) of the cohort was 3.8 years with no statistically significant differences observed between the Hispanic and non-Hispanic ethnic groups. (P = 0.816). Conclusion Ethnic patterns of disease occurrences have been reported, but responses to treatment and outcome for Hispanic patients have not been established. Interestingly from our preliminary analysis, there appears to be no statistically significant difference in overall survival between Hispanic and non-Hispanic patients. Further evaluation is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals NCOG-02. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii129-ii129
Author(s):  
Emilie Le Rhun ◽  
Patrick Devos ◽  
Johannes Weller ◽  
Katharina Seystahl ◽  
Francesca Mo ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Leptomeningeal Metastasis ◽  
Rank Test ◽  
Type I ◽  
Type Ii ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Negative Prognostic Factor ◽  
Choice Of Treatment

Abstract BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes for choice of treatment and outcome. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20-82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity

2018 ◽  
Vol 28 (3) ◽  
pp. 586-593 ◽  
Author(s):  
Mette Calundann Noer ◽  
Sofie Leisby Antonsen ◽  
Bent Ottesen ◽  
Ib Jarle Christensen ◽  
Claus Høgdall
Keyword(s):  
Cox Regression ◽  
Type I ◽  
Prognostic Impact ◽  
Type Ii ◽  
Regression Analyses ◽  
Differential Impact ◽  
Kaplan Meier ◽  
Prediction Of Survival ◽  
Comorbidity Index ◽  
The Impact

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

Suprasellar Rathke Cleft Cysts; Clinical Presentation and Treatment Outcomes

Neurosurgery ◽  
2011 ◽  
Vol 69 (5) ◽  
pp. 1058-1069 ◽  
Author(s):  
Matthew B. Potts ◽  
Arman Jahangiri ◽  
Kathleen R. Lamborn ◽  
Lewis S. Blevins ◽  
Sandeep Kunwar ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Presentation ◽  
Optic Chiasm ◽  
Magnetic Resonance Images ◽  
Type I ◽  
Type Ii ◽  
Visual Dysfunction ◽  
Kaplan Meier ◽  
Laboratory Results ◽  
Suprasellar Extension

Abstract BACKGROUND Rathke cleft cysts (RCCs), benign remnants of the Rathke pouch typically arising in the sella, sometimes have suprasellar extension. Purely suprasellar RCCs are rarely reported. OBJECTIVE To compare the presentations, surgical outcomes, and pathology of purely suprasellar RCCs and sellar-based RCCs. METHODS We retrospectively reviewed records, magnetic resonance images, laboratory results, and pathology of 151 RCC patients surgically managed at our institution from 1989 to 2009. The RCCs were classified as purely sellar (type I, n = 76), sellar with suprasellar extension (type II, n = 56), or purely suprasellar (type III, n = 19). RESULTS The RCCs with a suprasellar component (types II and III) more commonly presented with visual dysfunction (P &lt; .001). Complete cyst drainage occurred in 89%, 55%, and 38% of type I, II, and III RCCs, respectively (P &lt; .001). Vision improved in 100%, 55%, and 33% and headache improved in 74%, 64%, and 29% of type I, II, and III patients, respectively (P = .02). Temporary or permanent postoperative diabetes insipidus occurred in 5%, 16%, and 21% of type I, II, and III patients, respectively. (P &lt; .001). In a multivariate analysis, RCC type was the only factor predicting recurrence. Kaplan-Meier 3-year recurrence/progression rates were 0%, 16%, and 29% for type I, II, and III RCCs, respectively (P &lt; .001, type I vs II, type I vs III; P = .5 type II vs III). CONCLUSION The RCCs with a suprasellar component are neurosurgically challenging because of their proximity to the optic chiasm and infundibulum. Compared with sellar-based RCCs, RCCs with a suprasellar component more frequently present with visual dysfunction, are more difficult to completely eliminate, recur more frequently, and are associated with higher postoperative endocrine morbidity, and their preoperative visual dysfunction and headache less frequently improve with surgery. These factors must be considered during the treatment of RCCs with a suprasellar component.

Clinical Monoclonal B Lymphocytosis (cMBL), Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Diagnostic Criteria, Features At Diagnosis and Natural History

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5273-5273
Author(s):  
Rodrigo Santacruz ◽  
Julio Delgado ◽  
Tycho Baumann ◽  
Maria Rozman ◽  
Martha Aymerich ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
B Cells ◽  
B Cell ◽  
Cell Count ◽  
Diagnostic Criteria ◽  
Conflicts Of Interest ◽  
Consistent Difference ◽  
Transformation Rate ◽  
Mutational Status

Abstract Introduction CLL, SLL and cMBL are considered to be part of the same spectrum of clonal expansions of CD5+ B cells. Clinically, the transition from one to another of these forms over time is a well recognized event. Diagnostic criteria to separate these disorders have been proposed (IWCLL, 2008; WHO, 2008). Aim To compare presenting and evolving features of three groups of patients with cMBL, Rai 0 CLL or SLL and to ascertain the usefulness of current diagnostic criteria for these disorders. Patients and Methods Retrospective study of clinical, biologic and evolving characteristics of patients diagnosed with cMBL, Rai 0 CLL or SLL according to current criteria (CLL: ≥5x109 clonal B cells/L in peripheral blood; SLL <5x109/L clonal B cells with lymphadenopathy, organomegaly, cytopenia or disease-related symptoms; cMBL <5x109 clonal B cells with no signs or symptoms). Results Baseline characteristics of the patients are shown in the Table. Median age was 68 years (range, 24-94) and 57% of patients were males. Out of 1,093 patients, 79 had cMBL (7.2%), 522 Rai 0 CLL (48%) and 94 SLL (8.6%). Overall, adverse biomarkers such as high LDH (p<0.001), high B2M (p<0.001), increased ZAP70 (p<0.001), high CD38 (p<0.001), unmutated IGHV status (p=0.002), +12 (p=0.02) and 11q- (p=0.01) were significantly more frequent in SLL. In subgroup analyses, the only difference between cMBL and Rai 0 CLL was a higher proportion of cases with mutated IGHV in cMBL (p=0.008). Furthermore, when SLL was compared to Rai I to IV CLL no differences were observed (data not shown). The actuarial risk for transformation from cMBL or SLL to CLL was 4.2% and 4.4 % per year (p=0.5), respectively. Median TTFT was significantly shorter in the SLL group (12 m.) than in Rai 0 CLL (174 m.) or cMBL (244 m.) (p<0.001). Median overall survival was also significantly shorter for SLL (94 m.) compared with Rai 0 CLL and cMBL (153 and 157 m., respectively) (p=0.028). Multivariate analysis of 695 patients (cMBL/Rai 0-CLL/SLL) revealed four variables independently correlated with shorter TTFT: diagnosis of SLL vs. Rai 0 CLL vs. cMBL (HR 2.28; p=0.008), high ZAP70 (HR 4.08; p<0.001), high CD38 (HR 4.68; p=0.001) and increased serum B2M levels (HR 1.54; p = 0.031). Importantly, however, when the multivariate analysis was restricted to patients with cMBL and Rai 0 CLL, variables correlated with TTFT were the clonal B-cell count (HR 3.76; p=0.01), ZAP70 (HR 3.31; p<0.001), and CD38 (HR 4.61; p=0.02). FISH cytogenetics, IGHV mutational status,NOTCH1 or SF3B1 mutations were not included in the analysis because of missing data. Conclusions Disparities in biologic and clinical features of cMBL, CLL and SLL mainly reflect the different tumor burden in this spectrum of CD5+ monoclonal B cell disorders. In this study, the transformation rate from either cMBL or SLL to CLL was around 4% per year. As a result of differences in tumor mass, the need for therapy was shorter in SLL than in Rai 0 CLL and cMBL, and the overall survival poorer. Biologically, the only consistent difference between cMBL and Rai O CLL was a higher proportion of mutated IGHV in cMBL. Clinically, however, no differences in median survival were observed. Moreover, the clonal B cell count was the most reliable predictor of disease outcome in both cMBL and Rai 0 CLL. Therefore, the distinction between cMBL and Rai 0 CLL seems hardly justified. Disclosures: No relevant conflicts of interest to declare.

ASXL1 Mutations in AML: Molecular Biomarker for Secondary AML?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2343-2343
Author(s):  
Jingmei Hsu ◽  
Anita J. Kumar ◽  
Martin P. Carroll ◽  
Noelle V. Frey ◽  
Nirav N. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Myeloproliferative Neoplasm ◽  
Molecular Characteristics ◽  
Intermediate Risk ◽  
Kaplan Meier ◽  
The Impact

Abstract Background: Additional sex combs like transcription factor 1 (ASXL1) is a member of the polycomb group protein. ASXL1 mutation has been implicated in myeloid malignancy transformation. It is hypothesized that mutated ASXL1 leads to the loss of polycomb repressive complex 2 (PRC2) mediated gene repression and subsequent transforming events. Recent studies identify ASXL1 mutation as a poor prognostic marker in patients (pts) with de novo acute myeloid leukemia (AML) who present with intermediate–risk cytogenetic lesions (Patel, NEJM 2012; Schnittger, Leukemia2013). To study the impact of ASXL1 mutations in an unselected AML population, we analyzed clinical and molecular characteristics of patients with untreated AML who express ASXL1 mutation at presentation. Methods: Using next generation sequencing, 254 adult patients with AML seen at the Hospital of the University of Pennsylvania were analyzed for mutations, including ASXL1, using a 33-gene hematologic malignancy panel. Clinical characteristics were obtained from retrospective chart review. Kaplan-Meier estimates were used to calculate overall survival (OS) from time of diagnosis. Living patients were censored at date last seen. Results: ASXL1 mutations were detected in 36/254 (14%) AML pts. There were 29 known pathologic mutations, 1 benign, 1 probable pathologic, and 9 variants of unknown clinical significance (VUS). In 6/36 (16.7%) pts, ASXL1 was the sole mutation identified. Of the 30 pts with additional mutations (Figure 1), 6/30 (20%) pts harbored 2 independent ASXL1 mutations. When the 27 patients with pathologic ASCL mutations were analyzed for co-mutations, TET2 (13/27, 48%) was the most frequent ASXL1 co-mutation. FLT3 (0/27, 0%) and NPM1 (1/27, 3.7%) were notable for their absence. Median age of pts at diagnosis was 69 years (range 23-80). Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) was noted in 9/36 (25%) and 11/36 (30.6%) pts, respectively. Four pts (11.1%) had received chemotherapy and/or radiation therapy for a prior non-myeloid neoplasm. Karyotype was normal in 18/36 (50%) pts, and 7 additional pts had intermediate cytogenetic lesions. There were 7 pts (19.4%) with unfavorable cytogenetics (complex karyotype (3 pts), 7q- (3 pts), and 5q- (1 pt)). Four pts (11.1%) had a favorable karyotype, with t(8;21) in 3 pts and t(15;17) in 1 pt. At presentation, median white blood cell count (WBC) was 6.4x103/uL (1.0 x -103). In pts whose AML transformed from prior MPN, median WBC was 50 X103/uL (3.3-140). Standard induction chemotherapy with an anthracycline and cytarabine was given to 17/36 (47%) pts. An additional 3/36 (8.3%) pts underwent induction therapy with clofarabine. Complete remission (CR) was documented in 14/20 (70%) evaluable pts. Of the remaining pts, 11 received a hypomethylating agent, and 5 received other therapies. Thirty-day treatment mortality for all 36 pts and for 27 pts with known ASXL1 pathologic mutation was 13.4% and 18.5% respectively. Kaplan-Meier estimate showed a median overall survival of 349 days (median follow up of 107 days (range 15-1570)). For the 27 pts with a pathologic ASXL1 mutation, the OS was 276 days (Figure 2, median follow up of 145 days (range 18-1570)). Conclusion: ASXL1 mutations in de novo AML with intermediate-risk cytogenetics is associated with poor clinical outcome in cooperative group trials. Strikingly we demonstrate in a single institution, retrospective analysis that 66.7% of pts who present with ASXL1 mutations in the setting of previously untreated AML had documented MDS, MPN and/or prior chemotherapy/radiation. Further studies are necessary to evaluate if ASXL1 mutation has independent prognostic significance in AML or if it is primarily a marker for secondary leukemia. Figure 1: ASXL1 and co-mutations Figure 1:. ASXL1 and co-mutations Figure 2: Overall survival for AML patients with ASXL1 pathologic mutation Figure 2:. Overall survival for AML patients with ASXL1 pathologic mutation Disclosures No relevant conflicts of interest to declare.

Calreticulin Mutations in JAK2-Negative Myeloproliferative Neoplasms. Experience in Our Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5586-5586
Author(s):  
Maria Jose Penalva Moreno ◽  
Carolina Martinez-Laperche ◽  
Santiago Osorio Prendes ◽  
Elena Buces Gonzalez ◽  
Jose Luis Diez-Martin ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Statistical Correlation ◽  
Type I ◽  
Type Ii ◽  
Multifunctional Protein ◽  
High Clinical Suspicion ◽  
Fluorescent Pcr ◽  
Calr Mutations

Abstract Introduction: Calreticulin (CALR) is a multifunctional protein regulated by calcium that is located in the endoplasmic reticulum. Recently, mutations in the calreticulin gene have been described in patients with the diagnosis of essential thrombocytemia (ET) and primary myelofibrosis (PMF), mainly in JAK2-negative cases. CALR mutations are localized to exon 9 and generate deletions or insertions that lead to a frameshift change resulting in a mutant protein. The detection of these mutations helps in the actual diagnosis of JAK2 mieloproliferative syndromes (MPN). Our aim is to assess the utility of the determination of these mutations in the management of patients with diagnosis of MPN in our center. Patients and methods: This study includes 94 patients with diagnosis of JAK2-negative MPN retrospectively selected following clinical and analytical criteria between 2008 and 2014 in our center (Table 1, 2). CALR mutations were performed with the use of fluorescent PCR following the methods described by Klampf et al. (NEJM, 2013). Results: 94 patients were analyzed, 77 of them had the diagnosis of TE, 8 of PMF and 9 of others disorders of myelodisplastic/mieloproliferative. 22% of the cases of ET had mutations in CALR (Table 1). In these mutations, a total of 53% were type I mutations (52-bp deletion) and 47% were type II mutations (5-bp insertion). Only one mutation was infrequent, a 46-pb deletion. We have found statistical correlation in the number of platelets depending on the presence of the mutation and in the largest number of platelets in type II mutations. 33% of the cases of PMF had mutations in CALR, all of them type I. Among other diseases not included in MPN, one of them had a type I mutation (data not shown). Conclusions: Our results are close to recently published results regarding the frequency of mutation and as the largest number of platelets in type II mutations with respect to mutation type I. This study confirms the importance of CALR mutations determination in the diagnosis of JAK2-negative ET and PMF with high clinical suspicion. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors

2020 ◽  
Author(s):  
Emilie Le Rhun ◽  
Patrick Devos ◽  
Johannes Weller ◽  
Katharina Seystahl ◽  
Francesca Mo ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Leptomeningeal Metastasis ◽  
Rank Test ◽  
Type I ◽  
Type Ii ◽  
Csf Cytology ◽  
Kaplan Meier ◽  
Clinical Magnetic Resonance Imaging ◽  
Magnetic Resonance Imaging Mri

Abstract Background The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. Patients and methods We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. Results Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (p=0.006). Type I patients had inferior outcome than type II patients (p=0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (p=0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (p=0.020) or systemic pharmacotherapy (p=0.0004) was associated with improved outcome in type I LM, but not in type II LM. Conclusion The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

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