Acute Myeloid Leukemia in the Context of Previous History of Cancer with or without Exposure to Chemotherapy or Radiotherapy

Abstract Background: Therapy-related acute myeloid leukemia (AML) is a well-described entity and known to carry a worse prognosis, compared to de novo AML. In the current study, we sought to describe the presenting features and outcome of patients with AML, in the setting of previous history of cancer with or without exposure to chemotherapy or radiotherapy. Methods: A Mayo Clinic database of patients with AML was queried to identify patients with a previous history of cancer, both hematologic and solid tumors. A comparative analysis of presenting features, treatment details and survival were performed between patients with therapy-related AML (Group A) and those with AML and a history of cancer that had been managed with surgery alone (Group B). Results: A total of 250 patients (median age 68 years, range 19-90; 60% males) with AML and a previous history of cancer (both hematologic and solid) were identified; 182 (73%) cases were determined to be therapy-related AML (Group A) while the remaining 68 (27%) did not receive chemotherapy or radiotherapy for their antecedent cancer (Group B) (Table). Among group A patients 106 (58%) were exposed to chemotherapy, 37 (20%) to radiotherapy and 39 (22%) to combination chemotherapy and radiotherapy for their cancer. At the time of AML diagnosis, adverse karyotype was noted in 91 (51%) group A and 12 (19%) group B patients (p<0.0001); the incidence of adverse karyotype in patients exposed to chemotherapy vs radiotherapy alone vs combined chemoradiotherapy was 54% (57/106), 30% (11/37), and 59% (23/39) respectively (p=0.04). Group A patients, compared to those in group B, included more females (46% vs 24%; p=0.001), and more preceding hematologic malignancies (p=<0.0001). Next generation sequencing was performed in 74 patients and the results showed no significant difference between groups A and B (Table). Treatment and outcome in Groups A and B: Intensive and less intensive AML-directed chemotherapy were given to 100 (55%) and 44 (24%) patients in group A and 38 (56%) and 14 (21%) patients in group B (P=0.8). 79 (65%) remissions (complete remission (CR) 42 (29%) and CR with incomplete count recovery (CRi) 37 (26%) were documented in Group A and 37 (71%) remissions (CR: 21 (40%) and CRi=16 (31%) in Group B (P=0.2). After a median follow-up of 8.4 months (range: 0.9-217), 184 deaths were documented: 132 (72.5%) in Group A and 52 (76.5%) in Group B (P=0.5). 52 (36%) patients from Group A and 25 (48%) from Group B relapsed (P=0.1). The median (range) overall survival (OS) rates of patients from Group A was 13 (9-17) months and that of Group B was 14 (10-35) months (P=0.6). The 1-, 3- and 5-year OS rates were 52%, 28%, and 24% in Group A; and 62%, 33%, and 24% in Group B patients (Fig 1). Multivariable analysis identified relapse (HR 2.8, 95% CI 1.7-4.7) and failure to achieve CR/CRi (HR 2.8 95% CI 1.9-4.7) as risk factors for inferior survival (Fig 2a and 2b). The median (range) relapse free survival of patients in Group A was 28 (17 -81) and that of Group B was 27 (14 - 76) months (P=0.9) (Fig 2c). 28 patients underwent allogenic stem-cell transplant (25 in CR1 and 3 in CR2), 23 in Group A and 5 in Group B; the 1-, 3-, and 5-year OS of patients who underwent allogenic stem cell transplant were 88%, 72%, and 72% regardless of the group (Fig 2d). Conclusion: The current study did not find significant differences between AML patients with previous history of cancer with or without exposure to chemo/radiotherapy, in terms of either response to AML-directed therapy or overall or relapse-free survival, despite a higher prevalence of adverse karyotype in therapy-related AML. Figure 1 Figure 1. Disclosures Patnaik: Kura Oncology: Research Funding; Stemline Therapeutics: Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Membership on an entity's Board of Directors or advisory committees. Al-Kali: Astex: Other: Research support to institution; Novartis: Research Funding. Litzow: Pluristem: Research Funding; Actinium: Research Funding; AbbVie: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Jazz: Other: Advisory Board; Omeros: Other: Advisory Board; Biosight: Other: Data monitoring committee.

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Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Blood ◽

10.1182/blood-2021-149640 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3747-3747

Author(s):

Charlotte Doublet ◽

Marie-Sarah Dilhuydy ◽

Emmanuelle Ferrant ◽

Pierre Feugier ◽

Alexandra Fayault ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Oncology Nurses ◽

Advisory Committees ◽

Free Survival ◽

Daily Dose ◽

History Of

Abstract Median age at diagnosis of chronic lymphocytic leukemia is 72 years. However, only few patients over 80 years of age are included in clinical trials, even in those devoted to unfit patients. In order to evaluate both efficiency and safety of venetoclax in this category of patients, we conducted a multicentric retrospective study and collected data from 77 CLL patients from 19 FILO centers who started venetoclax after 80 years of age. Median age at venetoclax initiation was 86 years old (81-97). 63% of patients had a history of heart disease, 62% had renal failure (moderate 59% and severe 3%) and 29% had a history of severe infections. Despite their comorbidities and a CIRS greater than 6 in 70% of cases, their autonomy was preserved with a median performans status of 1 (0-4). In this comorbid geriatric population, pretherapeutic geriatric assessment was only performed in a single patient. The median number of prior therapies was 2 (0-6) with an exposure to a BCR inhibitor in 56% of cases. 11q and 17p deletion were found in 39% and 30% of cases respectively, 39% of patients had a complex karyotype and 30% harbored a TP53 mutation. However, in this real life population, these prognostic factors were only performed in half of patients. IGHV mutational status was only available in 11 patients, and 83% of them had unmutated IGHV. At the time of venetoclax initiation, the tumor lysis syndrome (TLS) risk was moderate in 57% of cases and high in 8% of cases. Venetoclax was administered as a single agent (42%) or in association with rituximab (58%). In total, half of the patients were hospitalized at each dose ramp-up, and only 3 patients were treated on outpatient basis. 82% of the cohort was able to reach the daily dose of 400mg. Half of the patients were included in a phone call monitoring program with oncology nurses to pre-emptively manage side effects and foster therapy adherence. The safety study reported 14% of TLS, with 2 discontinuations of treatment within the first month: one of which led to dialysis and the other to death. As in the previously published studies, 25% of patients had infectious complications, and grade 3 haematological and digestive toxicities were reported in 42% and 22% of cases, respectively. The reduction of the daily dose of venetoclax was necessary for 33%. Permanent discontinuation of venetoclax occurred in 40% of subjects, including 29% of early withdrawal (within the first 3 months). Main reasons for discontinuation were intolerance (21%), CLL progression (21%), death (21%) and scheduled treatment discontinuation (10%). The overall response rate was 86%, consisting of 49% of complete response (unconfirmed by bone marrow biopsy) and 37% of partial response. With a median follow-up of 21months, estimated progression free survival and overall survival were 29 and 38 months respectively. Prior exposure to a BCR inhibitor had no impact on progression free survival. To conclude, venetoclax has a manageable safety profile in elderly patients with comorbidities and can induce prolonged responses. Finally, if additional follow-up by oncology nurses seems to be more and more implemented, the pre-therapeutic onco-geriatric evaluation remains underexploited in this population. Disclosures Ferrant: AstraZeneca: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Other: Travel, Accommodations, Expenses. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Laribi: AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; AbbVie: Other: Personal Fees, Research Funding; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria.

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Phenotypes of JAK2-Mutated Polycythemia Vera and Essential Thrombocythemia with and without Thromboembolic Events: Results of the Hinc-207 (OSHO #91) Study

Blood ◽

10.1182/blood-2020-139366 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 13-13

Author(s):

Tony Hennersdorf ◽

Nadja Jaekel ◽

Susann Schulze ◽

Dietrich Kaempfe ◽

Claudia Spohn ◽

...

Keyword(s):

Risk Factors ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Research Funding ◽

Thrombotic Event ◽

Patient Questionnaire ◽

Allele Burden ◽

History Of ◽

Group A ◽

Group B

Thrombosis is the major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). Age ≥60 years (y) and/or history of thrombosis labels patients (pts) as high-risk for thrombosis. Yet, thrombosis frequently occurs prior to the diagnosis of PV/ET. In a multicenter study of the East German Study Group (HINC-207; OSHO #091), the interaction between age and time occurrence of the first thrombosis as risk factors for thrombosis after diagnosis was studied. Methods After IRB approvals, JAK2 mutated adults with PV or ET were prospectively enrolled in 9 centers and centrally stratified in a one to two ratio (group A: pts with a history of thrombosis; group B: pts without thrombosis) with a pre-planned minimum of 60:120 pts. Based on a longitudinal and cross-sectional design, clinical and laboratory data at diagnosis, last follow-up, and thrombosis (for group A) were collected. Thrombosis prior to diagnosis was labeled as A1 and thrombosis after diagnosis as A2. Thrombosis risk factors were grouped into age-, previous thrombosis-, thrombosis prior to PV/ET-, cardiovascular (CV)-, thrombophilia-, and disease- (JAK2 allele burden, Hct, and WBC) related. Additionally, therapies [aspirin (ASS), anticoagulation, phlebotomy, and cytoreduction] and data from a study-own patient questionnaire were included. All pts signed informed consent. The primary endpoint was the phenotypic diversity in JAK2-mutated ET and PV pts with or without thrombosis. Results From April to Dec, 2019, 246 pts were recruited. Data on 237 pts (median age 62y; 59% females, 58% PV) are available. At diagnosis, pts in group A (n=71, median age 59.5y) tended to be younger than those in group B (n=166, median age 63y) (p=0.07). Yet, 70.4% thrombotic events (venous: median age 46.5y; arterial: median age 57y) occurred in A1 and correlated with younger age (p=0.03). Only 3 pts developed a second event after diagnosis. These were counted in A2 (n=24, median age at thrombosis: 61y). Overall, thrombosis occurred either prior to or within the first 3y after diagnosis in 63/71 (89%) pts. Age>60y could not be identified as a risk factor for thrombosis or type of thrombosis at any time point. The 5 y probability of no thrombotic event after diagnosis in pts >60y was 90.4% vs. 89.2% for pts <60y (p=0.8) and that of a thrombotic event >3y after diagnosis in pts >60y was 3.7% vs. 4.9% for pts <60y (p=0.7). Similarly, A1 did not correlate with A2 (p=0.3). With 1691 patient-years for the entire cohort, the incidence of thrombosis after PV/ET diagnosis was 0.7 for arterial and 0.6 for venous events per 100 patient-years. Smoking was more prevalent in pts >60y (p=0.003) and was not associated with thrombosis. Irrespective of age, hypertension (65%, p=0.03), hyperlipidemia (19%, p=0.008), and diabetes (16.4%, p=0.05) were frequent and correlated with A2 while atrial fibrillation (p=0.03) and inherited thrombophilia risk factors (p<0.00) with A1. JAK2 allele burden (median 19%) and Hct >45% (median 45%) at diagnosis correlated strongly with age >60y (p=0.005) but not with A, A1, or A2, although Hct >45% at diagnosis correlated with A2 in PV (p=0.001). Surprisingly, a Hct >45% at thrombosis was more frequently present in A1 (55%) vs A2 (30%) (p<0.00). Median WBC at diagnosis was higher in B compared to A (p=0.004), strongly associated with age >60y (p<0.00) but not with A2. WBC >15% at thrombosis did not correlate with A. Age rather than thrombosis was the trigger for cytoreduction [82% hydroxyurea (HU) in B pts >60y vs 53% in A pts <60y] (p<0.00). In PV, ASS did not correlate with thrombosis (25% of pts in B did not receive ASS). Cytoreduction, interval between diagnosis and cytoreduction, nor the duration of exposure correlated with thrombosis. Conclusions: The majority of thrombotic events occurred prior to or within the first 3 years after the diagnosis of JAK2 mutated PV/ET and were associated with CV-risk factors rather than older age. Phenotypic features such as Hct >45%, high WBC, and JAK2 allele burden were associated with age >60y and less with thrombosis. Their value as surrogate markers for therapeutic interventions to reduce thrombosis needs to be critically evaluated in larger series. Whether adequate PV/ET- or CV-risk- treatments account for the low rate of CV events after diagnosis (despite a higher incidence of CV-risk factors) compared to the general population could not be answered due to study design and needs to be addressed prospectively. Disclosures Al-Ali: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

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Predictive factors for developing acute cholangitis and cholecystitis in patients undergoing delayed cholecystectomy: a retrospective study

10.21203/rs.2.15258/v1 ◽

2019 ◽

Author(s):

Takashi Miyata ◽

Daisuke Matsui ◽

Yuta Fujiwara ◽

Hiroto Saito ◽

Yoshinao Ohbatake ◽

...

Keyword(s):

Risk Factor ◽

Surgical Outcomes ◽

Intraoperative Complications ◽

Acute Cholangitis ◽

Previous History ◽

Cell Counts ◽

Number Of Patients ◽

History Of ◽

Group A ◽

Group B

Abstract Background We evaluated the risk of acute cholangitis and cholecystitis while waiting for cholecystectomy for gallstones. Methods We retrospectively enrolled 168 patients who underwent cholecystectomy for gallstones after a waiting period and conservative therapy between April 2014 and March 2018 at our hospital. We compared the clinical data from 20 patients who developed acute cholangitis and cholecystitis while waiting for cholecystectomy (group A) with data from 148 patients who did not develop cholangitis and cholecystitis (group B). The risk factors for developing acute cholangitis and cholecystitis and all patients' surgical outcomes were investigated. Results Preoperatively, significant differences in age (68.6 years vs 60.7 years; p= 0.004) and the number of patients with a previous history of acute grade II or III cholecystitis (55.0% vs 10.8%; p< 0.001) and biliary drainage (20.0% vs 2.0%; p= 0.004) were observed between group A and group B, respectively. Preoperative white blood cell counts (13500/µL vs 8155/µL; p< 0.001) and serum C-reactive protein levels (12.6 mg/dL vs 5.1 mg/dL; p< 0.001) were significantly increased, and serum albumin levels (3.2 g/dL vs 4.0 g/dL; p< 0.001) were significantly decreased in group A vs group B, respectively. Gallbladder wall thickening (≥ 5 mm) (45.0% vs 18.9%; p= 0.018), incarcerated gallbladder neck stones (55.0% vs 22.3%; p= 0.005), and abscess around the gallbladder (20.0% vs 1.4%; p= 0.002) were seen significantly more frequently during imaging in group A vs group B, respectively. Furthermore, investigating patients' surgical outcomes revealed a higher conversion rate to open surgery (20.0% vs 2.0%; p= 0.004), longer operation time (137 min vs 102 min; p< 0.001), and a higher incidence of intraoperative complications (10.0% vs 0%; p= 0.014) in group A vs group B, respectively. Conclusions Our results suggest that a history of severe cholecystitis is a risk factor for developing acute cholangitis and cholecystitis in patients waiting for surgery, and a risk factor for increased surgical difficulty.

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Optimal Therapy for Relapsed AL Amyloidosis Post Autologous Stem Cell Transplant

Blood ◽

10.1182/blood-2019-125453 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3171-3171

Author(s):

M Hasib Sidiqi ◽

Abdullah S. S. Al Saleh ◽

Iuliana Vaxman ◽

Angela Dispenzieri ◽

Francis K. Buadi ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Al Amyloidosis ◽

Cell Transplant ◽

Advisory Committees ◽

Free Survival ◽

Treatment Regimens ◽

2Nd Generation

Introduction: There is a paucity of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma. Methods: We conducted a retrospective review of patients who relapsed after receiving autologous stem cell transplant at Mayo Clinic. Patients treated for first relapse between January 2004 and December 2018 were included. Results: Three hundred and twenty-one patients were seen for relapsed AL amyloidosis post ASCT during the study period. Baseline characteristics were typical for a cohort with AL amyloidosis and are listed in Table1. 39% received therapy prior to transplant, conditioning in the majority (75%) was melphalan 200mg/m2. The median progression free survival from transplant (PFS1) was 30.7 months. Of the 321 patients 294 received treatment for relapsed disease. We categorized treatment regimens according to commonly used combinations and drug classes to further analyze outcomes. 34 patients were excluded from this analysis as they either proceeded directly to second ASCT (n=10) or received an atypical regimen not commonly considered for AL amyloidosis (n=24). Five categories of therapy regimens were identified, thalidomide based (n=110), melphalan plus steroids (n=31), 2nd generation immunomodulatory (IMiD) drug +/- alkylator (n=76), proteasome inhibitor (PI) +/- alkylator (n=116), PI plus IMiD (n=16), or daratumumab based (n=9). Disease and treatment characteristics for patients treated with these regimens are listed in Table 2. Patients treated with thalidomide had the shortest PFS1 (17.7 months) but PFS1 was similar for those treated with melphalan plus steroids, PI+IMiD and 2nd generation IMiDs (25.5, 24.3 and 25.6 months respectively). Patients treated with a PI +/- alkylator and daratumumab based regimen had the longest PFS1 (36.7 and 41.9 months respectively). The median duration of therapy was longer in patients treated with a 2nd generation IMiD or daratumumab based regimen (10.2, 12, 6.1, 5.5, 6.2 and 5.9 months for Dara based, 2nd generation IMiD, PI+/- alkylator, PI+IMiD, melphalan plus steroids and thalidomide based respectively). Hematologic response rate was lowest in those treated with melphalan plus steroids or thalidomide based regimens (44% and 55% respectively) and highest for patients treated with a PI+/- alkylator, (Figure 1). Progression free survival from relapsed therapy (PFS2) was longest amongst patients treated with daratumumab based regimens, PI +/- alkylator and 2nd generation IMiDs (not reached, 29.9 and 26.7 months respectively), Figure 2A. Overall survival from time of relapsed therapy favored patients treated with daratumumab based regimens, 2nd generation IMiDs and PI +/- alkylator, Figure 2b). Conclusion: A second generation IMiD based regimen or PI +/- alkylator produce high response rates and prolonged progression free and overall survival for relapsed AL amyloidosis. Patients treated with daratumumab based regimens and those treated with a PI plus IMiD also appear to do well, although numbers were low in our study. Patients treated with melphalan plus steroids or thalidomide based combinations have inferior outcomes and these regimens should be avoided. Disclosures Dispenzieri: Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Annexon: Consultancy. OffLabel Disclosure: Daratumumab off label use for AL amyloidosis.

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A pilot study of preoperative (Pre-op), single-dose ipilimumab (Ipi) and/or cryoablation (Cryo) in women (pts) with early-stage/resectable breast cancer (ESBC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.67 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 67-67 ◽

Cited By ~ 1

Author(s):

Adi Diab ◽

Stephen Barnett Solomon ◽

Christopher Comstock ◽

Majid Maybody ◽

Virgilio Sacchini ◽

...

Keyword(s):

Immune Modulation ◽

Early Stage ◽

Delay Group ◽

Technical Failure ◽

Free Survival ◽

History Of ◽

Group A ◽

Grade 3 ◽

Group B ◽

To Receive

67 Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence free survival in ESBC. In this study, we evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC. Radiographic correlates and intratumoral/serologic immune responses are also explored. Methods: Eligible pts are ≥18y of age with operable ≥1.5 cm invasive ESBC, no history of autoimmune disease and planned mastectomy. Pts are sequentially assigned to receive pre-op: cryo alone (Group-A), ipi alone (B), or ipi with cryo (C). Cryo is administered 7-10d prior to surgery. Ipi is administered 8-15d prior to surgery (1-5d prior to cryo). If at least 5/6 pts in each group proceed with surgery without delay, the regimen will be considered safe/tolerable. Toxicity evaluation continues for 12 wks after ipi administration for Groups B and C. Results: As of May 1, 2013, 7/7 pts were enrolled to Group-A (expanded after a possible technical failure in 1 pt) and 6/6 pts were enrolled to Group-B. The median age was 45y (range 39-69y). All 13 pts in Groups A and B underwent mastectomy without delay. Group C is now accruing with 1/6 patients enrolled and awaiting surgery. 6/7 pts in Group-A and none in Group-B had ischemic tumor necrosis/infarction in the mastectomy tissue. Overall, pre-op cryo or ipi alone have been well tolerated with no study related grade 3/4 adverse events (AE) reported (Table). Conclusions: To date, pre-op cryo or ipi is safe and tolerable in pts with ESBC. A Phase II study of pre-op ipi and cryo in ESBC is planned. Clinical trial information: NCT01502592. [Table: see text]

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Is cancer associated thrombosis (CAT) an underestimated issue in oncology clinical practice? Real-world data regarding long term management of CAT.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e23150 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e23150-e23150

Author(s):

Nikolaos Tsoukalas ◽

Alexandros Bokas ◽

Evangelos Bournakis ◽

Athina Christopoulou ◽

Christos Papandreou ◽

...

Keyword(s):

Clinical Practice ◽

Natural History ◽

Disease Stage ◽

Lower Probability ◽

Bleeding Events ◽

History Of ◽

Group A ◽

Group B ◽

History Of Cancer

e23150 Background: Cancer is associated with thrombosis due to different pathophysiological processes. CAT is the 2nd cause of death in oncology patients and can occur anytime during the natural history of cancer. CAT is not rare complication, can delay anti-cancer therapy and increase health systems costs. Methods: A prospective observational study (Greek Management of Thrombosis-GMaT) conducted by HeSMO in Greek Oncology units for two years aiming to record clinical practice of CAT management. Patients with active cancer who received CAT treatment or thromboprophylaxis were enrolled after signing informed consent. Results: 546 patients were enrolled from 18 oncology units. Primary cancers were: lung 23.9%, pancreas 13.3%, breast 7.6%, colorectal 8.9%, stomach 8.3%, ovarian 7.6% and other 30.5%. 120 patients received LMWH for Venus Thombo-Embolism (VTE) treatment (Group A) and 426 for thromboprophylaxis (Group B). Group A: 89/120 (74.17%) patients continued in 2nd year and 58.6% received CAT treatment (6.9±4.4 months). Only 2 had VTE recurrence in 2nd year (versus 3 in 1st year). 4/120 (3.33%) had bleeding events (grade 1) in 1st year while no bleeding events occurred in 2nd year. Group B: 345/426 (80.98%) patients continued in 2nd year. 126 (30%) had Khorana score ≥3 and 300 (70%) had Khorana score ≤2. In 2nd year, 123 (35.65%) received thromboprophylaxis (7.3±3.7 months) while 79.4% of them were initially treated with High Thrombotic Treatment Agents (HTTA: e.g. platinum, 5-FU) and 83.1% had metastatic disease. In 2nd year, 52.5% received LMWHs at prophylactic dose and 47.5% at therapeutic dose. Overall, 12 (2.82%) had thrombotic events whereas 4 were recorded in 2nd year. Notably, patients treated with therapeutic doses had lower probability to have a thrombotic event (OR: 5.8, 95% CI: 1.7 to 20.5, p < .05). Six (1.41%) bleeding events (grade 1) occurred in 1st year and one (0.81%) in 2nd year. Conclusions: LMWHs can be used for long term CAT management. Therapeutic LMWHs doses as thromboprophylaxis are safe and effective. Khorana score is a useful model for CAT risk assessment but some other factors such as disease stage and HTTA might be taken into account. CAT can occur anytime during the natural history of cancer. Oncologists should be aware about CAT and its negative influences in patients’ prognosis and quality of life.

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Predictive Factors for Survival in Sickle Cell Disease: A Cohort Study Using Etendard Data

Blood ◽

10.1182/blood-2018-99-113767 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 7-7

Author(s):

Laurent Savale ◽

Gylna Loko ◽

François Lionnet ◽

Bernard Maitre ◽

Anoosha Habibi ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Sickle Cell Disease ◽

Board Of Directors ◽

Transthoracic Echocardiography ◽

Research Funding ◽

Cell Disease ◽

Advisory Committees ◽

Group A ◽

Group B

Abstract Introduction The prospective ETENDARD study (NCT00434902) evaluated 398 outpatients with sickle cell disease (SCD) enrolled between February 2007 and March 2009 at referral centers in France. All patients were homozygous for hemoglobin S or had Sβ0 thalassemia. This study estimated the prevalence of pulmonary hypertension (PH) related to SCD to be 6%, based on the presence of a tricuspid regurgitation velocity (TRV) ≥2.5 m/s and a mean pulmonary arterial pressure (mPAP) measured by right-sided heart catheterization (RHC) ≥25 mmHg (Parent et al, New Engl J Med 2011). The long-term prognostic value of TRV≥2.5 m/s according to the level of mPAP measured by RHC has not been clearly established. Methods Using updated 10-year follow up data from the ETENDARD cohort study, we analyzed the overall survival of patients according to their TRV/mPAP status, as follows: patients with a TRV<2.5 m/s (group A), patients with a TRV≥2.5 m/s and a mPAP<25 mmHg (group B), and patients with a TRV≥2.5 m/s and a mPAP≥25 mmHg (group C). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modeling was used to compute hazard ratios (HR) along with their 95% confidence intervals (CI95). Results The 398 enrolled patients were followed-up for a mean time of 106±26 months (median 112 months, interquartile range 106-119). TRV was≥2.5 m/s in 109 patients (27.4%). RHC was performed in 98 of them and confirmed PH diagnosis (mPAP≥25 mmHg) in 24 (6%). Overall survival was significantly decreased in patients with a TRV≥2.5 m/s (groups B/C vs. A; HR=2.5 [CI95 1.3-4.7], p=0.006, Figure 1A). However, after accounting for mPAP level, no statistically significant difference was found between patients with a TRV<2.5 m/s and those with TRV≥2.5 m/s and mPAP<25 mmHg (group A vs. B, log-rank p=0.54), while patients with a TRV≥2.5 m/s and a confirmed diagnosis of PH by RHC (mPAP≥25 mmHg) had a significantly decreased survival in comparison with the two other groups (groups A/B vs. C, p<0.0001, Figure 1B), yielding the following HRs in Cox analysis: HR=1.0 (group A), HR=1.3 (group B, CI95 0.5-3.0, p=0.59] and HR=6.0 (group C, CI95 2.7-13.3, p<0.0001). At time of inclusion, patients with confirmed diagnosis of PH by RHC (group C) were older and characterized by lower 6-min walk distance, higher rate of leg ulcers, lower PaO2 and forced vital capacity, and higher levels of alkaline phosphatase, lactate deshydrogenase and γ-glutamyl transferase (all p<0.05). Clearance of creatinine was significantly lower in both groups with TRV≥2.5 m/s. All these parameters and systemic arterial pressures at time of inclusion were associated with a higher risk of mortality in univariate analysis. Conclusion While an isolated VRT≥2.5 m/s on transthoracic echocardiography was found to be a moderate prognostic factor for overall survival, our findings reveal highly contrasted outcomes depending on the mPAP values measured by RHC. Only the combination of a VRT≥2.5 m/s and a mPAP≥25 mmHg is associated with a worse prognosis, confirming that a RHC is mandatory in case of PH suspicion on transthoracic echocardiography in SCD patients. Disclosures Bartolucci: Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding; Novartis US: Membership on an entity's Board of Directors or advisory committees.

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French National Retrospective Cohort of Hairy-Cell Leukemias: Risk of Second Malignancies after 10 Years of Follow-up

Blood ◽

10.1182/blood-2019-127560 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1537-1537

Author(s):

Jérôme Paillassa ◽

Edouard Cornet ◽

Stephanie Noel ◽

Cecile Tomowiak ◽

Aline Schmidt ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Retrospective Cohort ◽

Hematological Malignancies ◽

Hematological Malignancy ◽

Solid Cancer ◽

Advisory Committees ◽

History Of ◽

History Of Cancer

Introduction: Hairy-cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with a favorable outcome thanks to treatment with purine analogues (PNA) like cladribine and pentostatin. Here, we updated the French national retrospective cohort of HCL after 10 years of follow-up, in order to evaluate the risk of second cancers in these patients. Methods: Data were collected up to June 2018 through a questionnaire sent to the members of the Société Française d'Hématologie, and centralized in the cohort database. We described the second malignancies observed during the follow-up, distinguishing second 'solid' cancers from second hematological malignancies. Then, using a Fine and Gray model, we performed a multivariate analysis in order to identify second cancer risk factors. Finally, to evaluate the excess of cancers in our cohort in comparison with the French general population, we calculated the standardized incidence ratio (SIR). Results: 279 patients (pts) from 19 centers were included in our retrospective cohort. The median age was 59 years old (range 29-88). 21% had an infectious disease at diagnosis, 23% had a familial history of cancer and 11% a personal history of cancer before HCL diagnosis. The median number of lines of treatments was 1 (0-7). PNA (cladribine or pentostatin) were the first therapeutic choice in frontline (75% of pts) and at relapse (69%). With a median follow-up of 127 months (2-413), the median overall survival for the overall study population was 328 months (95% CI 299-357) and the median relapse-free survival (RFS) was 136 months (95% CI 109-163). Pts treated with cladribine or pentostatin in first line had a statistically significant better RFS than pts treated with 'other' treatments (log rank test, p < 0.001). The 10-year cumulative incidence of relapse was 39% (95% CI 33-46). Pts who received treatments other than PNA in first line had a higher risk of relapse (Gray's test, p < 0.001). For pts receiving PNA in first and second lines, there was no difference in outcomes between those who switched PNA and those who did not. In this cohort, we observed 68 second malignancies during the follow-up: 49 solid cancers (most prevalent: prostate and non-melanoma skin cancers) and 19 hematological malignancies (most prevalent: monoclonal gammopathy of undetermined significance (MGUS) and myelodysplastic syndromes (MDS)). The median onset of second cancer, second solid cancer and second hematological malignancy from HCL diagnosis was 81 months, 99 months and 78 months, respectively. The median age at diagnosis of cancer, solid cancer and hematological malignancy was 70, 69 and 77 years old, respectively. Considering death as a competing risk, the 10-year cumulative incidence of cancer, solid cancer and hematological malignancy was 15% (95% CI 11-19), 11% (95% CI 7.2-15), and 5.0% (95% CI 2.8-8.2), respectively. In multivariate analyses, IFN treatment was associated with a decreased risk for all cancers (Fine and Gray regression model, subdistribution Hazard Ratio (sdHR) 0.53 (95% CI 0.29-0.97); p = 0.038), a familial history of cancer was a risk factor for solid cancers (sdHR 2.12 (95% CI 1.15-3.91); p = 0.017), a personal history of cancer was a risk factor for hematological malignancies (sdHR 3.47 (95% CI 1.14-10.55); p = 0.028). Even after excluding non-melanoma skin cancers and MGUS, there was an excess of cancers (SIR = 2.22), solid cancers (SIR = 1.81) and hematological malignancies (SIR = 6.67). Conclusions: In this updated real-world retrospective cohort with a long follow-up and most pts treated with PNA, we highlighted the importance and the excess of second cancers in HCL patients, in particular hematological malignancies. Figure Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Hermine:AB Science: Membership on an entity's Board of Directors or advisory committees. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Troussard:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Research Support; Sysmex: Other: Research Support.

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Sparing Anti-Bacterial Prophylaxis in Acute Myeloid Leukemia during Post Induction Aplasia Does Not Impact on Bacteriemiae Incidence and Early Death: A Retrospective Single Center Study

Blood ◽

10.1182/blood-2018-99-117222 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4001-4001 ◽

Cited By ~ 1

Author(s):

Chiara Frairia ◽

Irene Urbino ◽

Ernesta Audisio ◽

Semra Aydin ◽

Stefano D'Ardia ◽

...

Keyword(s):

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Rectal Swab ◽

Advisory Committees ◽

Gram Negative ◽

Single Center Study ◽

Group A ◽

Group B ◽

Acute Myeloid

Abstract Introduction: Acute myeloid leukemia (AML) patients are at high risk of infections during post chemotherapy neutropenia, especially after induction. The anti-bacterial prophylactic approach raised concerns about the emergence of chemo-resistant pathogens and the increased incidence of Gram negative bacteriaemiae during consolidation therapy. The present study aimed at evaluating the need of anti-bacterial prophylaxis or not during induction. Methods: To address this point, we set up a retrospective single center study enrolling all consecutively newly diagnosed AML patients admitted in our institution; acute promyelocytic leukemia patients were excluded. All patients received an intensive standard induction chemotherapy. Patients were divided in two groups on the basis of anti-bacterial prophylaxis (levofloxacin 500 mg OD during aplasia and until neutrophil recovery or until intravenous antibiotic treatment was needed) given (Group A) or not (Group B). Group A consisted in consecutive patients treated from June 2001 to December 2016 and group B in those consecutively treated from January 2017 to May 2018. Clinical and microbiological data were collected and compared between the two groups. The primary endpoint was the number of bacteriaemiae. Statistical analysis was performed using Chi-square test for categorical variables while continuous variables were compared by Student's t-test; p value of <0.05 was considered significant. Results: A total of 402 consecutive AML patients were enrolled from June 2001 to May 2018. A total of 223 were male while 179 were female, the median age at diagnosis was 54 years (19-76). After induction, a complete remission was achieved in 280 patients (70%), 96 were resistant (24%) and 26 died (6%). Anti-bacterial prophylaxis was administered in 343 patients (group A) while 59 patients experienced aplasia without anti-bacterial prophylaxis (group B). Baseline characteristics were equally distributed among the patients in both groups with the exception of age (median 55 years vs 62 in group A vs B, respectively p<0.0001). In group A, 313 patients developed fever (91%), while 30 (9%) remained afebrile; in the group B, 56 patients developed fever (95%), while 3 (5%) remained afebrile (p=0.3439). The median number of fever days was similar in both groups (group A vs B: median 6 days, range 0-42 and median 5, range 0-17, respectively, p=0.0873). The incidence of bacteriemiae was 25% (n=87) in group A compared to 32% (n=19) in group B (p=0.2708). Considering the total number of bacteriemiae, the incidence of gram-negative infections were 32% (n=28) vs 47% (n=9), wherease gram-positive infections were 68% (n=59) vs 53% (n=10) in the group A vs B, respectively (p=0.2084). Klebsiella pneumonia carbapenemase-producing (KPC) positive blood cultures were detected in two patients in group A, one with KPC positive rectal swab, while in group B there was a case without evidence of KPC on rectal swab. A septic shock was evidenced in 5% (n=17) vs 11% (n=6) of patients with fever during induction in group A and B respectively (p=0.1320). Early induction deaths were similar in both groups with 22 deaths in group A (6%) and 4 in group B (7%), respectively (p=0.9160). In group A, we observed 80 (23%) pneumonia, 53 (15%) respiratory failure and 35 (10%) neutropenic colitis. In group B we observed 17 (29%) pneumonia, 17 (29%) respiratory failure and 18 (29%) neutropenic colitis. Conclusions: Our study showed that omitting levofloxacin prophylaxis did not cause an increase incidence of bacteriaemiae in a homogeneous cohort of AML patients. Neither fever incidence nor duration, septic shocks, early induction deaths and the rate of Gram-negative and Gram-positive cultures were different between the two groups. Our results underline the safety of a prophylaxis sparing approach that may reduce the emergence of drug-resistance Gram-negatives during the consolidation phases. Prospective studies are needed to confirm these data and to assess the impact of prophylaxis during consolidation phase. Disclosures Vitolo: Sandoz: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Prolonged Progression-Free Survival Is Possible in Patients with Diffuse Large B-Cell Lymphoma Receiving > 1 Salvage Therapies before Autologous Stem Cell Transplant

Blood ◽

10.1182/blood.v128.22.5825.5825 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5825-5825

Author(s):

Abigail G Kettle ◽

Jeffrey Switchenko ◽

Oscar Calzada ◽

Anh Thuy Phan ◽

Monique Farone ◽

...

Keyword(s):

Radiation Therapy ◽

Board Of Directors ◽

Salvage Therapy ◽

Research Funding ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Salvage Treatment ◽

Cell Transplant ◽

Advisory Committees ◽

Free Survival

Abstract Introduction While 50-60% of patients with diffuse large B-cell lymphoma (DLBCL) are cured with initial chemoimmunotherapy such as R-CHOP, many patients will relapse and require additional therapy. Historically, autologous stem cell transplant (ASCT) has been utilized in chemo-sensitive patients with relapsed DLBCL although the role of ASCT in patients who require > 1 salvage treatment to achieve remission is less defined due to concerns about the likelihood of long-term remission in that population. We evaluated the outcome of ASCT in patients who required >1 salvage therapy. Methods We included all patients undergoing ASCT for relapsed/refractory DLBCL at our site between 2005-2016 who received > 1 salvage treatment before transplant, with radiation therapy considered a salvage treatment if given after relapse but before ASCT. We collected demographic, clinical, laboratory and pathologic data on all patients. We defined progression-free survival (PFS) as time from ASCT to date of progression or death from any cause and overall survival (OS) as time from ASCT to date of death from any cause. Living patients were censored at the time of their last follow up. Univariate Cox proportional hazards models of PFS and OS were fit and Kaplan-Meier plots were developed to estimate the impact of variables of interest on survival. Results Out of 259 patients undergoing ASCT for DLBCL, 43 received > 1 salvage treatment, the median age was 51 years and 23 patients were male. Twenty patients had stage III/IV disease at diagnosis. The median time to relapse from the time of diagnosis was 9.3 months, and 42% of patients experienced a relapse > 12 months after diagnosis. Twenty-six patients (60%) received radiation as one of their salvage therapies, 25 patients (58%) received R-ICE as their first salvage therapy and 10 (23%) patients received R-ICE as their second salvage treatment. All patients received either 2 (n=39) or 3 (n=4) salvage therapies before ASCT, and the response to the initial salvage therapy received was CR in 4 patients, PR in 14 patients, SD in 1 patient, and PD in 14 patients, with initial response to salvage therapy missing in 10 patients. The median PFS for all patients was 15.9 months and the median OS was 57.2 months (Figure 1a). Receipt of radiation and having disease sensitive to treatment at the time of ASCT were the only factors associated with prolonged PFS and OS. Median PFS has not been achieved in patients who received radiation while patients who did not receive radiation had a median PFS of 4.2 months (HR = 0.36, p = 0.014; Figure 1b). Patients who had a chemo sensitive disease status at transplant had a median PFS of 22.6 months; however, patients with refractory disease at transplant only achieved a median PFS of 3.6 months (HR = 0.30, p=0.008). Remaining factors including conditioning regimen, time to relapse, and number of salvage therapies were not significantly associated with PFS or OS. Conclusions ASCT can result in prolonged PFS/OS in patients requiring > 1 salvage therapy especially in the case of sensitive disease. Radiation as an additional line of therapy is associated with improved PFS/OS, suggesting this can be included to induce remission in patients who fail to achieve CR with initial salvage treatment. While uncommon, patients with chemo-refractory disease can also have durable survival and should not be excluded from transplant. Figure 1a Progression-free survival for all patients with DLBCL receiving > 1 salvage therapy. Figure 1a. Progression-free survival for all patients with DLBCL receiving > 1 salvage therapy. Figure 1b Progression-free survival for all patients with DLBCL receiving > 1 salvage therapy based on receipt of radiation therapy. Figure 1b. Progression-free survival for all patients with DLBCL receiving > 1 salvage therapy based on receipt of radiation therapy. Disclosures Calzada: Seattle Genetics: Research Funding. Flowers:Spectrum, Janssen, Infinity, AbbVie, Acerta, Pharmacyclics, TG Therapeutics: Research Funding; Celgene Corporation: Consultancy, Honoraria; Optum Rx, Seattle Genetics, Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Seattle Genetics: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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