Role of Ethnicity in Clinical Outcomes of Patients with Ph-Negative Myeloproliferative Neoplasms

Abstract Abstract 2076 Myeloproliferative neoplasms (MPN) have similar incidence rates across different ethnicities in the United States. However, reported clinical studies rarely address the outcome in patients with different ethnicities. In this study, we retrospectively analyzed 127 patients with a diagnosis of MPN followed at the University of Illinois Hospital between January 2005 and July 2011. Of these patients, 69 were Caucasian and 58 Non-Caucasian (mostly African-American and Hispanic). The median age was 50 years (range: 20–85) in non-Caucasians and 51 years (range: 22–89) in Caucasians. Among 127 patients, 53 had polycythemia vera (PV), 52 essential thrombocythemia (ET), and 22 primary myelofibrosis (PMF). In each disease group, the following parameters were compared at diagnosis between Caucasian and non-Caucasian patients: age/gender, JAK2 V617F mutation status, cytogenetic abnormalities, family history of MPNs, constitutional symptoms, white blood cell (WBC) and platelet count, hemoglobin level, and spleen size. In addition, the two groups were compared for thrombotic or hemorrhagic events, cardiovascular complications, progression of disease, secondary cancer and overall survival. Among 53 PV patients, Caucasians (n=33) had higher WBC counts (11.7 vs. 8.1 ×103 cells/μL, p=0.03) and a greater spleen size (14 vs. 10 cm longitudinal diameter, p=0.03) at diagnosis compared to non-Caucasians (n=20). However, more frequent hemorrhagic (38.9% vs. 6.1%, p=0.003) and cardiovascular (27.8% vs. 3%, p=0.009) complications were seen in the non-Caucasian cohort of patients compared to the Caucasian cohort. Use of hydroxyurea (55% vs. 57%), aspirin (88% vs. 76%), anagrelide (10% vs. 24%), interferon (18% vs. 5%) and anticoagulation (21% vs. 20%) were not significantly different between Caucasians and non-Caucasians. In the ET patients (non-Caucasian: n=27; Caucasian: n=25), there were no significant differences in presenting characteristics, type of therapies, or clinical outcomes between the two groups. The 22 patients with PMF were classified according to the international prognostic scoring system (IPSS) at diagnosis. In 11 non-Caucasian and 11 Caucasian patients, differences of patients at low risk (18% vs. 9%), intermediate-1 (55% vs. 27%), intermediate-2 (27% vs. 55%), or high risk (9% vs. 0%) were not statistically significant. In a multivariate logistic regression analysis, we demonstrated that prior history of thrombosis and older age are independent prognostic factors for subsequent thrombotic or hemorrhagic events (p=0.03 and p=0.003, respectively). Neither WBC at diagnosis nor ethnicity were independent prognostic indicators in this series of patients. With a median follow-up of eight years (range 1–23 years), median overall survival was not reached for PV, ET, or PMF and no significant differences were detected in Caucasian or non-Caucasian groups. Our observations suggest that when given equal access to care, similar clinical outcomes are achieved in Caucasian and non-Caucasian patients with MPNs. Disclosures: No relevant conflicts of interest to declare.

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Myelofibrosis in Real Life: Findings from the French Intergroup of Myeloproliferative Neoplasms (FIM) Registry

Blood ◽

10.1182/blood.v128.22.3128.3128 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3128-3128

Author(s):

Brigitte Dupriez ◽

Sylvie Chevret ◽

Jean-Christophe Ianotto ◽

Francoise Boyer ◽

Pascale Cony-Makhoul ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Spleen Size ◽

Biological Parameters ◽

Advisory Committees ◽

History Of

Abstract Background: Myelofibrosis (MF) is the less frequent Philadelphia-negative myeloproliferative neoplasms (MPN). We have included in a nationwide database primary (P), post-polycythemia (PPV) and post-essential thrombocythemia (PET) MF diagnosed in France since 2005. Methods: Inclusion criteria were: diagnostic of MF after 2005; according strictly to WHO (bone marrow biopsy mandatory); informed consent. The registry was launched in Oct. 2013, and 26 hematology centers included patients (pts). Summary statistics were reported, namely median [Interquartile range, IQR] or percentage. Baseline characteristics were compared across IPSS groups using chi-square test or Mann and Whitney test. Kaplan-Meier survival curves were plotted and compared by the log-rank test. Results: At time of analysis (June 2016) a total of 527 pts were included in the registry, complete baseline data were available in 499 (95%), and follow-up (FU) data in 433 (87%). Median [IQR] age and M/F sex ratio were 71 [63-78] years and 315/184 (1.7), respectively (resp). 301 (60%) pts had PMF, 182 (36%) had secondary MF (including 64 PPVMF and 118 PETMF) and 16 had pre-fibrotic MF. Five percent of pts had a familial history of hematologic malignancy, and 22% a history of thrombosis or hemorrhage. Splenomegaly was present in 386 (77%) with a median [IQR] spleen size of 4 cm [1-8] below costal margin, and was symptomatic in 11% of pts. Constitutional symptoms were present in 107 (21%) (weight loss in 56, night sweats in 61, fever in 14), and ECOG score was 0, 1, 2, and 3 in 53%, 36%, 11% and 0.3% of pts, resp. Median [IQR] Hemoglobin, WBC and platelet counts were 109 g/L [94-122], 9.3 G/L [5.7-16.0] and 257 G/L [138-430], resp. Circulating blast cells were present in 41%, LDH was above normal value in 95% of pts, median EPO level was 54 [11 - 57] U/L. Grade of fibrosis (WHO) was 1, 2, and 3 in 2%, 66% and 32% of pts, resp. Karyotype was done in 321 pts, normal in 173 (54%), abnormal with favorable prognostic value in 89 (30%) and unfavorable in 30 (10%) (29 failures). A total of 461 (92%) pts had molecular testing: 60% were JAK2V617F positive, 4% had MPL and 7% had CALR mutations, and 99 (28%) over the 352 pts with triple testing were triple negative. IPSS risk categories were low, int-1, int-2 and high in 68 (14%), 168 (34%), 158 (32%), and 105 (21%) pts, resp. In addition to constitutional symptoms, there was a significant increase in the prevalence of clinical signs across IPSS categories (from low to high risk): symptomatic spleen (p=0.016) -though no difference in spleen size was found (p=0.18)-, early satiety (p=0.013), ECOG score (p= 0.0001), bone pain (p=0.002). Moreover, among biological parameters, there was an increase across IPSS groups in WBC (p=0.029), LDH (p=0.0007), ferritin (p=0.003), circulating CD34+ cells (p=0.020), EPO level (p=0.035). In contrast, a decrease was seen for hemoglobin and platelets (p=0.0001 for both). Lastly, frequency of grade 3 fibrosis increased with IPSS (p=0.043), while no evidence of difference was found regarding abnormal karyotype and mutational pattern. Median FU was 33 months [9-63 months]. Among those 433 pts with FU data, median FU was 38 months [19-68], and 124 (29 %) pts had died at the time of analysis, including 13%, 17%, 31%, and 40% of pts from the Low, Int-1, Int-2, and High risk groups, resp (p= 0.0001, figure 1). In the 450 pts with treatment data, treatments received during FU included cytoreductive drug (41%), Jak-inhibitors (35%), Interferon alpha (18%), IMIDs (4%). Splenectomy was performed in only 14 (3%) pts. Forty percent of pts received packed red blood cells, and 12% platelets transfusions. 49 (11%) patients participated in a clinical trial, and 27 (6%) were allografted. Conclusion: This is the first analysis of the French MF observatory after inclusion of more than 500 pts diagnosed and treated during the past 10 years. Complete baseline data and follow-up information available for the majority of pts should allow for new studies of outcomes and influence of clinical and biological parameters, as well as reassessment of prognostic models in the era of new targeted therapies. Figure 1 Comparison of overall survival according to IPPS Figure 1. Comparison of overall survival according to IPPS Figure 2 Figure 2. Disclosures Etienne: Pfizer: Speakers Bureau; BMS: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Ugo:Novartis: Membership on an entity's Board of Directors or advisory committees. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Is JAK2 Inducible by Cytotoxic Chemotherapy?

Blood ◽

10.1182/blood.v114.22.4979.4979 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4979-4979

Author(s):

Edmond A. Bendaly ◽

Saud S. Rahman ◽

Samiah Zafar ◽

Karen Haglof ◽

Sherif Ibrahim ◽

...

Keyword(s):

Conflicts Of Interest ◽

Myeloproliferative Neoplasms ◽

Case Reports ◽

Lymphoblastic Leukemia ◽

Myeloproliferative Neoplasm ◽

Cytotoxic Chemotherapy ◽

Jak2v617f Mutation ◽

Platinum Based Chemotherapy ◽

History Of ◽

Increased Susceptibility

Abstract Abstract 4979 Introduction The JAK2V617F mutation accounts for most cases of myeloproliferative neoplasms (MPN). Only a few case reports of MPN following cytotoxic chemotherapy have been reported, and all of them were published prior to the discovery of the JAK2V617F mutation. We report a series of 6 patients who developed a JAK2V617F positive MPN following cytotoxic chemotherapy. Patients From 2006 to 2009, 6 patients with a history of a hematologic or an oncologic malignancy who developed an MPN were identified and their medical records retrospectively reviewed. One patient had acute lymphoblastic leukemia, 1 had Hodgkin lymphoma, 1 had squamous cell carcinoma of the head and neck, 1 had cervical cancer, and 2 had breast cancer. All patients were in remission from their primary malignancies at the time the MPN was diagnosed. Five were females. The median age at diagnosis was 72 years. Median time to development of the myeloproliferative neoplasm was 14 years. Type of chemotherapy exposure, MPN diagnosis and time to MPN in each case is shown in the table below. The JAK2V617F mutation was detected either in the peripheral blood or the bone marrow of all patients. There was no predominance of any specific MPN diagnosis. Patients who received platinum-based chemotherapy developed the MPN sooner than those who received alkylators (6 vs 17.5 years respectively). Treatment consisted of phlebotomy, hydroxyurea, anagrelide, aspirin or a combination as deemed appropriate by the treating hematologist. Conclusion These findings lead us to hypothesize whether the development of JAK2V617F positive MPN may be related to prior exposure to cytotoxic chemotherapy. Exposure to platinum-based chemotherapy may cause the disorder to appear sooner compared with exposure to alkylators. Recently, JAK2V617F positive MPN was found to be strongly associated with a specific constitutional haplotype, 46/11 suggesting increased susceptibility to this mutation. Chromosomal analyses are planned to show whether any of the reported patients exhibit this haplotype. Ref: 1.Jones et al, Nat Genet. 2009 Apr;41(4):446-9. 2009 Mar 15. The authors have no relevant disclosure. Disclosures No relevant conflicts of interest to declare.

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Statins Use Improves the Clinical Outcomes of Salvage Therapy in Relapsed/Refractory CLL

Blood ◽

10.1182/blood.v120.21.3931.3931 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3931-3931

Author(s):

Long Xuan Trinh ◽

Young Kwang Chae ◽

Preetesh Jain ◽

Ohad Benjamini ◽

Xuemei Wang ◽

...

Keyword(s):

Overall Survival ◽

Elderly Patients ◽

Clinical Outcomes ◽

Salvage Therapy ◽

Older Patients ◽

Conflicts Of Interest ◽

Young Patients ◽

The Other ◽

Concurrent Use ◽

The Impact

Abstract Abstract 3931 Introduction - Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. In addition, statins possess anti-inflammatory, immunomodulatory, antioxidant, and cell growth inhibitory properties. In B- CLL cells, statins induce in-vitro apoptosis (Daphne Chapman-Shimshon et-al), suggesting that statins might possess properties. We noticed a high prevalence of dyslipidemia in patients with chronic lymphocytic leukemia (CLL). However the impact of dyslipidemia and its modulation by statins on clinical outcomes of patients with CLL remains unclear. Therefore, we conducted a retrospective analysis to assess the effect of statins in patients with CLL who received salvage (fludarabine, cyclophosphamide and rituximab) FCR chemotherapy. Methods - We analyzed the clinical outcome of relapsed/refractory patients with CLL (n=284) who underwent FCR salvage therapy at our institution between 1999 and 2012. Patients who were uninterruptedly treated with statins at least one month prior to and during salvage therapy (n=35) were assigned to the statins arm, whereas the other arm consisted of 249 patients who were not treated with statins. The Cox proportional hazards regression model was used to assess the association between patient characteristics and progression-free survival (PFS) and overall survival (OS). Actual survival and PFS were estimated using the method of Kaplan-Meier, and OS and PFS were compared among two groups of patients using log-rank test. Results - All pretreatment characteristics of the patients with concurrent use of statins were similar to those who were not treated with statins except for their age. Patients in the statins arm were older: 21 patients (60%) were older than 65 compared to 74 patients of 249 (30%) in the other group (p<0.05). The median OS and PFS of all 284 patients were 3.9 years (95% CI: 3.4–4.5) and 1.74 years (95% CI: 1.6–2.3), respectively. PFS was significantly longer in patients treated with statins. Fifteen of the 35 statin-treated patients (43%) as opposed to only 36 of 249 (14%) in the non-statins group experience no disease progression. Concurrent use of statins significantly prolonged PFS. The median PFS for statin-treated v/s. untreated was 4.6 and 1.7 years, respectively (p<0.05). This significantly improved PFS was consistent in young and elderly patients. In young patients (age < 65) with statins, the median PFS was not reached whereas in patients who were not treated with statins it was 2 years (p<0.05). In older patients (age ≥ 65), PFS was significant longer with concurrent use of statins than without statins; estimated PFS were 2 and 1.6 years, respectively (p<0.05). With the median follow-up of 5 years, the median overall survival was significantly longer in patients treated with statins, with 17 of 35 (49%) patients of the statins group and 59 (24%) of 249 in patients who were not treated with statins alive at the end of study. Concurrent use of statins significantly prolonged OS with an estimated median OS for the two groups of 6.9 years and 3.9 years, respectively (p<0.05). This significantly improved OS was consistent in young and elderly patients. Young patients (age <65) with statins had a significant prolonged survival with an estimated OS of 8.6 years whereas estimated OS in young patients without statins (p<0.05) was only 4 years. In older patients (age ≥65) the median OS was significantly longer with the concurrent use of statins than without statins; estimated OS in the two subgroups were 6.9 and 2.6 years respectively, (p<0.05). Conclusions - In conclusion, concurrent use of statins significantly improved OS, PFS in relapsed/refractory CLL patients treated with salvage FCR therapy. Further studies to determine the role of statins and mechanism of action in patients with CLL are warranted. Disclosures: No relevant conflicts of interest to declare.

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Second Cancers Affect the Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline FCR-Based Therapy.

Blood ◽

10.1182/blood.v120.21.2900.2900 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2900-2900 ◽

Cited By ~ 1

Author(s):

Long Xuan Trinh ◽

Young Kwang Chae ◽

Preetesh Jain ◽

Susan Lerner ◽

Ohad Benjamini ◽

...

Keyword(s):

Overall Survival ◽

Clinical Outcomes ◽

Second Cancer ◽

Second Cancers ◽

History Of ◽

Richter’S Transformation ◽

Richter's Transformation ◽

Prior Malignancy ◽

Melanoma Skin

Abstract Abstract 2900 Increasing use of chemo-immunotherapy in CLL has raised concerns over the carcinogenic effect of FCR regimen. Fludarabine based regimen in relapsed CLL has been reported to be predisposed to a higher risk of other cancers as compared to healthy individual. However, an association between the CLL treatment and the development of other cancers is not evident in the frontline FCR setting. We retrospectively studied the frequency, characteristics, and clinical outcomes of second malignancy in patients with CLL who were treated with frontline FCR-based therapy at University of Texas, MD Anderson Cancer Center from 2004 to 2010. Patients who developed other malignancies after the initiation of FCR-based therapy were considered as patients with second cancer post CLL treatment (n=39). Patients who had history of other malignancies before the initiation of FCR-based therapy were considered as patients with prior malignancy history (n=90). Patients who neither have history of other cancers nor patients developed second cancer during the study period were assigned as patients without second cancer group (n=82). There were 24 patients (n=24) who experienced Richter's transformation post FCR-based therapy. The overall survival (OS) was measured from the initiation of CLL treatment until death from any causes or last follow-up. Progression-free survival (PFS) was measured from the initiation of CLL treatment until disease progression, relapse or death. Kaplan-Meier method was used to estimate outcomes in four groups. Cox-proportional hazard regression model was used to assess the association between patient characteristics and survival outcomes. Pre-treatment characteristics were similar among these groups except for chromosome abnormalities. Ten patients (44%) out of 24 patients with Richter's transformation had TP53 gene mutation (p <0.05). Ninety patients (38%) of 235 patients had prior malignancy history includes non-melanoma skin cancer (n=32, 36%), melanoma (n=12, 13%), prostate cancer (n=15, 17%), colon cancer (n=5, 6%), renal cancer (n=2, 2%) and follicular lymphoma (n=1, 1%). Among 145 patients without prior malignancy history, there were 39 patients (27%) who developed second cancer including other leukemia, and 24 patients (17%) who developed Richter's transformation after the FCR-based therapy. The median time from initiation of FCR-based therapy to the development of Richter' transformation was 13.53 months (range, 1.63 to 40.87). There was no patient with prior history of other malignancies had recurrent cancers during the study. Thirty nine patients who developed second cancer includes non-melanoma skin (n=10, 26%), melanoma (n=2, 5%), head and neck (n=1, 2.5), Merkel cell (n=1, 2.5%), prostate (n=6, 15%), breast (n=1, 2.5%), lung (n=2, 5%) renal (n=1, 2.5%), gastric (n=2, 5%), liver (n=1, 2.5%), Hodgkin (n=1, 2.5%), and therapy-related MDS-AML (n=11, 28%). The estimated median PFS in the whole cohort was 4.57 years (95% CI: 3.678 to 5.462). PFS in patients without second cancer was not reached (NR) compared to 3.31 years (95% CI: 2.178 to 3.542) in patients with second cancer post CLL treatment (p<0.05). PFS in patients with Richter's transformation was 1.02 years (95% CI: .625 to 1.415). The median follow up duration for all 235 patients was 3.29 years (range, 0.08–8.51 years) with total of 61 deaths. The median overall survival in either group of patients with prior malignancy history or in patients without second cancers were not reached (NR) compared with 3.81 years (95% CI: 2.231 to 5.389) in patients with second cancer (p < 0.05). OS in patients with Richter's transformation was 3.84 years (95% CI, 1.434 to 6.246) There were 8 patients (10%) who died among 82 patients without second cancer as compared to 20 patients (49%) who died among 39 patients with second cancer (p <0.05). Second cancers in patients with CLL treated with FCR regimen are significantly associated with inferior clinical outcomes. We observed the high incidence of skin cancer, prostate and Richter's transformation in patients with CLL who underwent treatment with frontline FCR-based therapy. Further studies are warranted to determine the association between FCR regimen and the development of second cancer, especially Richter's transformation. Disclosures: No relevant conflicts of interest to declare.

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Ph-Negative Chronic Myeloproliferative Neoplasms – Population Analysis, a Single Center 10-years’ Experience

Blood ◽

10.1182/blood.v124.21.5556.5556 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5556-5556

Author(s):

Vasily Shuvaev ◽

Irina Martynkevich ◽

Alla Abdulkadyrova ◽

Vera Udaleva ◽

Tatyana Zamotina ◽

...

Keyword(s):

Overall Survival ◽

Risk Stratification ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Risk Group ◽

Myeloproliferative Neoplasms ◽

Population Analysis ◽

Myelogenous Leukemia ◽

Rank Test ◽

Chronic Myeloproliferative Neoplasms

Abstract Objectives and background. Nowadays chronic myeloproliferative neoplasms (MPN) other than chronic myelogenous leukemia undergo renaissance of interest. It results from advances in decryption of molecular mechanisms of pathogenesis and invention of target drugs. Epidemiological information is needed to assess potential effect and additional costs of new diagnostic and therapeutic techniques. The objective of our study was to review experience of MPN diagnostic and treatment in our center for past ten years. Methods. Our institution serves as primary hematological outpatient department for a half of Saint-Petersburg city with about 2 million inhabitants. We reviewed patients' charts to obtain information about incidence, symptoms, diagnostic test results, treatment options and relationship to prognostic factors. Statistical methods included descriptive statistics, nonparametric ANOVA for frequencies comparisons and Kaplan-Meyer method with log-rank test for survival comparisons in Statistica 7.0 package. Results. Since 2004 to 2013 there were 570 newly diagnosed MPN patients (pts) in our center. This group consisted of primary myelofibrosis (PMF) (203 pts; 126 female, 77 male; median age 63 years, range 16-83 years), essential thrombocythemia (ET) (201 pts; 146 female, 55 male; median age 58 years, range 23-78 years), polycythemia vera (PV) (166 pts; 96 female, 70 male; median age 57 years, range 20-85 years). The incidence rates were stable during study period: PMF incidence varied from 0.65 to 1.35 with mean of 1.01 new patient per 100 000 inhabitants per year; ET had incidence from 0.60 to 2.1 with mean of 1.00 and PV had incidence from 0.5 to 1.15 with mean of 0.83. The most prevalent symptoms of disease were: splenomegaly (65.5%), constitutional symptoms (fever, night sweats, weight loss) (31.0%), anemia (36.3%) thrombosis (24.1%) for PMF; fatigue (33.2%), headache and dizziness (25.6%), arthralgia (21.8%), erythromelalgia (15.8%) for ET; plethora (82.5%), headache and dizziness (52.4%), fatigue (31.3%) for PV. JAK2V617F was detected in 49.7% of PMF pts, 57.8% of ET pts and in 97.7% of PV pts. Thrombosis rates according WHO IPSET-thrombosis system risks` groups of ET and PV pts were: low-risk group 3.33% (3/90), intermediate-risk group 11.1% (13/117) and 39.4% (63/160) in high-risk group with highly significant (p<0.0001) differences between risks' groups. There were 169 lethal outcomes in the analysed group (102 PMF; 31 ET; 36 PV). Ten-years overall survival rates were 49.8% in PMF pts, 84.6% in ET pts and 78.3% in PV pts. (fig.1). Overall survival in PMF was significantly influenced by risk stratification as IPSS, DIPSS and DIPSS+. Survival curves according DIPSS+ groups are presented in fig.1. Conclusions. Patients with MPN are presented in substantial number; therefore need much finance for novel therapy introduction. Risk stratification systems has high predictive value. Innovative drugs treatment results should be evaluated in comparison with historical control. Figure1 Overall survival in PMF patients according to DIPPS+ stratification groups. Figure1. Overall survival in PMF patients according to DIPPS+ stratification groups. Disclosures No relevant conflicts of interest to declare.

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Role of ethnicity in thrombotic and hemorrhagic complications of myeloproliferative neoplasms.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18555 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18555-e18555

Author(s):

Andrew Peseski ◽

Antoine Saliba ◽

Hamid Sayar

Keyword(s):

Myeloproliferative Neoplasms ◽

Philadelphia Chromosome ◽

Previous History ◽

Multivariate Logistic Regression Analysis ◽

Vascular Complications ◽

Bleeding Complications ◽

Vascular Events ◽

Hemorrhagic Complications ◽

History Of ◽

Caucasian Patients

e18555 Background: Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known complications of hemorrhage and thrombosis. Age and a previous history of thrombosis are well-documented risk factors for future vascular events. Variations in the rates of these complications among ethnicities and sexes have not been extensively explored. Methods: Our retrospective analysis included 301 adult patients with a diagnosis of MPN without a history of thrombosis or hemorrhagic event seen at the Indiana University Simon Cancer Center between 1992 and 2019. Relationships between ethno-racial backgrounds and vascular complications and disease outcomes were evaluated using multivariate logistic regression analysis and Cox regression models. Results: Two hundred seventy-one patients (90.0%) were Caucasian and 30 patients (10.0%) were non-Caucasian. Non-Caucasian patients were comprised of African America, Asian, and Middle Eastern ethnicities. Median age at diagnosis was 56 years, and 43.9% were male. No association was found between the incidence of thrombotic complications and ethnicity using the log-rank test ( p 0.68). The incidence of hemorrhagic events was significantly increased in non-Caucasian patients (OR = 4.33; 95% CI [1.15 – 16.36], p 0.03). Patients with higher hemoglobin concentration at diagnosis were at a significantly lower risk of bleeding complications (OR = 0.79; 95% CI [0.65 – 0.95], p 0.01). Non-Caucasian patients were at 2.98 times (95% CI [1.19 – 7.44], p 0.02) higher risk when vascular complications were pooled together. Our models also showed that male sex (OR = 0.14; 95% CI [.02 – .98], p 0.048) and a higher platelet count at the time of diagnosis (OR = 0.99; 95% CI [.993 –.999], p 0.03) had a marginally significant association with decreased rate of progression to acute myeloid leukemia. Conclusions: This study suggests that in patients without a history of thrombosis or bleeding, non-Caucasian ethnicity was associated with an increased adjusted risk of hemorrhagic complications in patients with MPN. This observation may inform future studies to further characterize those disparities in outcomes at the genetic or socioeconomic level.

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Myeloid Blastic Transformation of Myeloproliferative Neoplasms – A Review of 113 Cases.

Blood ◽

10.1182/blood.v114.22.3113.3113 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3113-3113

Author(s):

Syed Noor ◽

Wei Tan ◽

Gregory Wilding ◽

Laurie Ann Ford ◽

Maurice Barcos ◽

...

Keyword(s):

Overall Survival ◽

Polycythemia Vera ◽

Myeloproliferative Neoplasms ◽

Alkylating Agents ◽

Allogeneic Transplantation ◽

Prior History ◽

Complex Karyotype ◽

Blastic Transformation ◽

Frequent Use ◽

History Of

Abstract Abstract 3113 Poster Board III-50 Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. Mutations of JAK2V617F were described in the majority of MPN patients but only about half of those undergoing blastic transformation continue to harbor that mutation. We describe a cohort of 23 patients from Roswell Park Cancer Institute (RPCI) and discuss 90 additional cases from the English literature for whom biologic features were described. We also screened our cases for JAK2V617F, JAK2T875N and MPL515L/K. We initially compared our 23 patients to the 90 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (22% vs. 53%; P<0.0001), shorter time from MPN diagnosis to blastic transformation (<5 years to transformation in 68% vs. 40%; p=0.0296), <3 prior therapies (100% vs. 16%; p<0.0001), more frequent use of hydroxyurea (63% vs. 27%; p=0.0056), less frequent use of alkylating agents (5% vs. 54%; p<0.0001) and more frequent use of erythropoietin (11% vs. 0%; p=0.0332). Detection of normal karyotype at the time of blastic transformation was more common in the RPCI population (35% vs. 7%; p=0.0033). The two populations did not differ in regards to age at diagnosis of MPN or blastic transformation, gender, prior use of interferon or karyotype aberrations. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar [3 vs. 5 months; 95% confidence interval (CI) 2 to 5 vs. 3 to 9; p=0.1639]. We therefore looked at the outcome of the entire cohort (n=113). Patients with prior history of essential thrombocythemia survived longer (8.6 months; 95% CI 4.3, 24) than patients with prior history of myelofibrosis (4.5 months; 95% CI 2, 11) or polycythemia vera (3 months; 95% CI 2, 5) (p=0.0224). Further, patients with <3 prior therapies had significantly longer survival (8 vs. 3 months; 95% CI 4 to 11 vs. 2 to 5; p=0.0212). Finally, patients with complex karyotype had significantly shorter survival (3 vs. 5 months; 95% CI 2 to 5 vs. 3 to 10); p=0.0272). No difference in survival was detected based on time from MPN diagnosis to blastic transformation, age, prior hydroxyurea treatment, prior alkylating agents, erythropoietin, or interferon, or presence of non-complex karyotype aberrations. We then evaluated the treatment response among the PRCI patients (n=23). A total of 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and eight did not. The overall survival of those achieving remission was significantly longer than those who did not [13 vs. 3 months; 95% CI 8 to 25 vs. 2 to 4); p<0.0001]. Three patients underwent an allogeneic transplantation and their survival was significantly longer that those who did not [11 vs. 4 months; 95% CI 8 to 57 vs. 3 to 5; p=0.0119]. Samples were available for eight of the patients at disease transformation; JAK2V617F was detected in two and none had T875N or MPL515K/L. In summary, patients with less than three prior therapies and lack of complex karyotype have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long term survival in these patients. Disclosures No relevant conflicts of interest to declare.

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Central Nervous System (CNS) Infiltration Assessment Using Cerebrospinal Fluid Flow Cytometry in Hematologic Malignancies: A Single Center Retrospective Analysis of Clinical Outcomes

Blood ◽

10.1182/blood-2019-127558 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5773-5773

Author(s):

Eduardo Cerello Chapchap ◽

Carolina Feres ◽

Laiz Cameirão Bento ◽

Daniela Schimidell ◽

Rodolfo Patussi Correia ◽

...

Keyword(s):

Central Nervous System ◽

Flow Cytometry ◽

Overall Survival ◽

Nervous System ◽

Clinical Outcomes ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Hematologic Malignancies ◽

Clinical Approach ◽

Cns Disease

INTRODUCTION: The detection of central nervous system (CNS) disease in hematologic malignancies is important to guide optimal therapeutic approach, refine prognosis and understand patient`s unexplained neurologic symptoms. Newer flow cytometry (FC) techniques are emerging, also there are increasingly reports of higher accuracy than routine cytospin. Moreover, these are becoming incorporated more frequently in clinical work up practices. However, there is still uncertainty on clinical approach of CNS-positive patients, detected only by FC. OBJECTIVE: To analyze accuracy and clinical outcomes of CNS disease by cytopsin or FC in patients with hematologic malignancies. MATERIAL AND METHODS: FC cerebrospinal samples and medical charts of 84 consecutive patients evaluated for CNS infiltration by hematologic malignancies from January/2014 to December/2016 were reviewed. Statistical analysis were done with SPSS and STATA softwares. RESULTS: Baseline patients characteristics were: male (62%), median age 53 years; non-hodgkin lymphoma (52%), Acute Lymphoblastic Leukemia (26%), Acute Myeloblastic Leukemia (15,5%), Multiple Myeloma (6,5%); CNS-positivity rates according to each technique were: Cytopsin-/FC- (71,4%), Cytospin+ (14,3%), Cytospin-/FC+ (14,3%); CNS-disease was detected by FC in 32,3%, while for cytospin was 16,7%. Overall survival was 71,4% and relapse rate 38,1% at 2,5 years of median follow-up. Relapsed (HR: 2,76 p0,023) and CNS-positivity (HR: 2,01 p0,037) patients were significantly associated with an inferior overall survival. Also, progression free survival (PFS) of Cytospin-/FC+ was significantly inferior than CNS-negative subgroup (HR: 2,93 p0,022). CONCLUSION: FC sensitivity appears to be higher than classicaly cytospin methods to detect CNS disease, also CNS-positivity was associated with a worse prognosis, as well as in the subset of patients Cytospin-/FC+. Further studies with a more homogeneous cohort and larger sample sizes are needed to validate our findings. Figure Disclosures No relevant conflicts of interest to declare.

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Chromosomal Abnormalities in Transformed Ph-Negative Myeloproliferative Neoplasm Are Independent of the JAK2 and the TET2 Statuses.

Blood ◽

10.1182/blood.v114.22.2900.2900 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2900-2900

Author(s):

Florence Nguyen-Khac ◽

Lucile Couronne ◽

Virginie Eclache ◽

Joris Andrieux ◽

Eric Lippert ◽

...

Keyword(s):

Overall Survival ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

Fusion Gene ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Chronic Phase ◽

Molecular Data ◽

Derivative Chromosome ◽

Phase Duration

Abstract Abstract 2900 Poster Board II-876 Ph-negative myeloproliferative neoplasms: polycythemia vera (PV), essential thrombocythemia (ET) and primitive myelofibrosis (PMF) carry an acquired somatic mutation JAK2V617F in 95% (PV), and in 50 to 60% (ET or PMF) of the patients. Mutations of the TET2 gene have been observed with roughly similar frequencies in the three MPN, irrespective of the presence of JAK2V617F. Evolution to myelofibrosis or acute leukemia may occur with time in MPN patients. Although its molecular bases are poorly understood, the evolution is likely due to the acquisition of additional mutations. To investigate whether cytogenetic abnormalities are distributed differently according to type of transformation and to the JAK2 and TET2 statuses, the Groupe Francophone de Cytogénétique Hématologique has collected 82 patients with transformation of MPN. There were 66 (80%) acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) and 16 (20%) myelofibroses (MF). Of note pipobroman (Pi) treatment seems to be associated with MF, and hydroxyuera (Hu) with AML/MDS evolution in our series. Statistical analyses of clinical, cytogenetic and molecular data are shown Table 1. On the cytogenetical point of view, several points are noteworthy. Some abnormalities were unevenly distributed: there were significantly more -7/del7q and -5/del5q in AML/MDS and tri1q and tri9 in MF. MF and PMF cytogenetic profile looked similar, suggesting a potential link between cytogenetic markers and the phenotype. Although the derivative chromosome der(1;7), observed in 9 patients, is responsible for a loss of 7q, it seemed different from patients with -7/del7q [excluding der(1;7)]. In the -7/del7q group, AML/MDS patients were more numerous than MF patients and the overall survival was shorter compared with the der(1;7) group (22/22 (100%) vs 6/9 (67%) AML/MDS, p=0.02; median: 4 vs 41 months, p=0.0007 respectively). Some specific associations could be observed, such as 17p deletions with 5q deletion (12/30, 40% vs 4/48, 8%, p=0.0007) and 20q deletion with der(1;7) (4/9 (44%) vs11/69 (16%), p=0.03). We detected 24/40 (60%) JAK2V617F and 8/25 (32%) TET2 mutations in transformed MPN, with all possible combinations between the wildtype and mutated forms of both genes. For one post-ET AML patient, JAK2V617F had been observed in a fraction of the granulocytes at the chronic phase. Analysis of blood cDNA obtained at chronic phase showed the same TET2 mutation as observed at acute phase. Because the blast cells were JAK2wt-TET2mut and carried a t(10;16)(q22;q23) affecting the CBFB gene, it is likely that the resulting non-MYH11 CBFB fusion gene transformed a JAK2wt-TET2 mutated progenitor that predominated in the chronic phase. In conclusion, no specific chromosomal abnormality was associated with TET2 or JAK2 mutations. Chromosomal abnormalities were associated with a type of transformation (AML/MDS or MF), suggesting a specific role in the process. In addition, association between some chromosomal abnormalities suggest a specific oncogenic cooperation.Table 1.n=82AML/MDS n=66 MF n=16 p univariate p multivariate Sex F39 (59%)5 (31%)nsnsPV/ET/PMF30/26/1013/3/0nsnsAge at diagnosis of MPN54 [20-82]55.5 [31-69]nsnsChronic Phase (duration, years)12 [2-34]14.5 [3-28]nsnsPrior treatments (n=73*)57*16..No treatment (n=6)60nsnsOne treatment (n=40)33 (58%)7 (44%)nsnsTreatments with Hu (n=57)48 (73%)9 (56%)0.03Treatments with Pi (n=41)26 (46%)15 (93%)0.00060.05Age at transformation66.5[37-92]68 [45-80]nsnsAbnormal karyotype62 (94%)16 (100%)nsnsComplex karyotype45 (68%)7 (44%)nsns-7/del7q28 (42%)3 (18%)0.07ns-7/del7q[without der(1;7)]22 (33%)00.0040.04-5/del5q28 (42%)2 (12%)0.03ns-13/del13q5 (8%)3 (19%)nsns-20/del20q11 (17%)4 (25%)nsns-17/del17p15 (23%)1(6%)nsns+1q14 (22%)9 (56%)0.01ns+95 (8%)4 (25%)0.04ns+811 (17%)3 (19%)nsnsdic17 (26%)3 (19%)nsnsder(1;7)6 (9%)3 (19%)nsnsAmplification MLL0 (0%)nsnsJAK2mut17/31 (55%)7/9 (78%)nsnsTET2mut6/19 (32%)2/6 (33%)nsnsMedian overall survival (months)448<0.00010.001*treatment unknown for 3 patients Disclosures: No relevant conflicts of interest to declare.

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Bone Marrow Biopsy Revision According to WHO Criteria in 272 Patients of the Registro Italiano Trombocitemia (RIT): Preliminary Report On Clinical and Histopathological Implications.

Blood ◽

10.1182/blood.v114.22.4974.4974 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4974-4974

Author(s):

Luigi Gugliotta ◽

Stefano Ascani ◽

Silvia Asioli ◽

Emanuela Boveri ◽

G. Fraternali Orcioni ◽

...

Keyword(s):

Bone Marrow ◽

Preliminary Report ◽

Conflicts Of Interest ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Treatment Rate ◽

Who Criteria ◽

Bone Marrow Trephine Biopsy ◽

Hemorrhagic Events ◽

Wbc Count

Abstract Abstract 4974 Background The bone marrow trephine biopsy (BMB) has a crucial role for the diagnosis of essential thrombocythemia (ET), both according to the PVSG and the WHO criteria. The WHO 2001 criteria enhanced the role of BMB also by distinguishing the true-ET (ET) from the prefibrotic and the early fibrotic chronic idiopathic myelofibrosis. The WHO 2008 criteria, in the JAK2 era, confirmed the diagnostic and prognostic relevance of the histopathological features in ET as well as in the other Ph-neg myeloproliferative neoplasms (MPN). Otherwise, only few validated data are presently available, and the reproducibility in the evaluation of some morphological details is still controversy. Objective To validate ET diagnosis in a large registry-based series of patients by revising the BMB specimens according to the WHO criteria and to evaluate the potential relationship between the histopathological and the clinical parameters at presentation. Methods The hematological centers of the Registro Italiano Trombocitemia (RIT) were invited to participate to this study by sending the BMB specimens (hematoxylin-eosin, Giemsa and silver stains) obtained at diagnosis. The clinic-pathological panel of the RIT (with three hematopathologists as permanent members coordinated by a chairman) performed a centralized revision of the BMB specimens, concomitantly (multiheaded microscopy) and blindly (only patient sex and age were known). The panel described for each case the morphological features and gave a diagnostic conclusion according to WHO criteria as follows: true-ET (ET); or initial primary myelofibrosis (i-PMF) distinguished in prefibrotic PMF (pf-PMF/MF-0) and early fibrotic PMF (ef-PMF/MF-1); or advanced PMF (MF-2 and MF-3); or early polycythemia vera (e-PV); or MPN unclassifiable (MPN-U); or diagnosis other than MPN (No MPN). Results Thirteen centers sent the specimen of BMB at diagnosis of 272 patients registered into the RIT and diagnosed in the years 1986-2002 (group A, cases 66, 24.3%), 2003-2005 (group B, cases 95, 34.9%) and 2006-2008 (group C, cases 111, 40.8%). The patients, 104 (38%) males and 168 (62%) females, had at diagnosis: age over 50 in 64% of cases (median 58); PLT count (109/L) >1000 in16% and <= 600 in 24% of cases (median 789); Hgb level (g/dL) >17 in 1% and <=9 in 5% of cases (median 14.3); WBC count (109/L) >9 in 44% of cases (median 8.6); splenomegaly in 18% of cases. Disease symptoms, thrombotic and hemorrhagic events were reported in 40%, 21%, and 7% of cases, respectively. During the follow-up (median 2.7 years) 65% of patients received cytoreductive drugs (Hydroxyurea 59%, Anagrelide 20%, Interferon 14%, Pipobroman 6.5%, Busulfan 0.5%). The revision of the 272 BMB specimens allowed to the following diagnosis: ET 142 cases, 52.2%; i-PMF 72 cases, 26.5% (distinguished in pf-PMF 19 cases, 7% and ef-PMF 53 cases, 19.5%); e-PV 13 cases, 4.8%; MPN-U 16 cases, 14.3%; No MPN 8 cases, 2.9%. In the patients of groups A, B, and C the rate of ET was increasing (from 44%, to 50% and to 59%, respectively) while the rate of i-PMF was decreasing (from 34%, to 31% and to 18%, respectively); moreover, the rate of e-PV was 0%, 6%, and 6%, respectively. The ET patients compared with the i-PMF patients showed at diagnosis a lower rate of splenomegaly (16/142, 11.3% vs 24/72, 33.3%, p<0.0001), of age >50 years ( 84/142, 59.2% vs 53/72, 73.6%, p<0.03), and a higher rate of PLT count (109/L) <=600 (39/142, 27.5% vs 11/72, 15,3%, p<0.04 ); no significant differences were found between the two groups for sex, Hgb level, WBC count, symptoms, thrombotic and hemorrhagic events. The treatment rate was lower in ET than in i-PMF (ratio 0.7). Conclusion This preliminary report on the revision of the BMB at diagnosis in 272 patients of the Registro Italiano Trombocitemia (RIT) shows that: the rate of true ET is continously increasing (from 44% before 2003 to 59% in the period 2006-2008), with i-PMF rate concomitantly decreasing (from 34% to 18%); the ET patients, compared with the i-PMF ones, were younger, with lower PLT count and with lower rate of splenomegaly, and received a less intensive cytoreductive treatment. Disclosures No relevant conflicts of interest to declare.

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