Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody

BackgroundWe explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).MethodsAmong 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.ResultsWe frequently observed hNLR in patients with SAR (53% vs. 35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60] vs. 1 [N = 76] vs. 2 [N = 49]: 7.6 vs. 6.4 vs. 2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached vs. 16.8 vs. 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 vs. 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 vs. 3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).ConclusionsWe demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.

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Prognostic impact of immune-related adverse events with nivolumab in patients with advanced gastric cancer: A multicenter retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.347 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 347-347

Author(s):

Yuno Ohya ◽

Takayuki Ando ◽

Akira Ueda ◽

Kohei Ogawa ◽

Iori Motoo ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Practice ◽

Adverse Events ◽

Advanced Gastric Cancer ◽

Retrospective Analysis ◽

Prognostic Impact ◽

Significant Difference ◽

Metastatic Sites ◽

Practice Methods ◽

Ecog Ps

347 Background: Nivolumab was established as one of the standard treatments for previously treated advanced gastric cancer (AGC). The aim of this study is to evaluate the frequency of immune-related adverse events (irAEs) with Nivolumab and its impact on treatment efficacy in clinical practice. Methods: We performed multicenter retrospective analysis, which included 90 patients with advanced gastric cancer who received Nivolumab treatment between October 2017 and September 2019. The frequency of irAEs and its treatment outcome were evaluated, and survival was compared during Nivolumab treatment. Results: The characteristics of 90 patients in this analysis were as follows: median age (range), 68 (36-85); male/female, 56/34; ECOG PS 0-1/≥2, 62/28; number of metastatic sites 1/≥2, 36/56; treatment line 3/≥4, 63/27. Median treatment cycle of nivolumab treatment was 3 (range 1-26). The overall response in 68 patients with target lesions was 6.3% (4/68), and the median PFS and OS was 1.5 and 4.3 months, respectively. IrAEs were observed in 8 patients (8.8%), including grade 4 pneumonitis, grade 2 or 3 adrenal insufficiency, and grade 2 hypothyroidism, encephalitis, and immune thrombocytopenia. Median time to onset of irAEs was 1.3 (range 0.6-10.5) months. Six were treated with systemic corticosteroid therapy, and all irAEs were relieved. The median PFS and OS were 4.7 months (95%CI, 1.2-9.3) and 12.2 months (95% CI, 3.2-not reached) in patient with irAEs, and 1.4 months (95%CI, 1.1-1.9) and 4.1 months (95%CI, 2.6-6.6) in those without, respectively. There was significant difference in the PFS (p=0.005) and OS (p=0.03). Conclusions: Nivolumab was effective and well tolerated even in clinical practice. Development of irAEs may be associated with better outcome of Nivolumab in patients with AGC.

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Pancreatic enzymatic mediastinitis followed by total gastrectomy with splenectomy: report of two cases

Surgical Case Reports ◽

10.1186/s40792-021-01240-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yoko Zaitsu ◽

Takashi Nishizaki ◽

Takuma Izumi ◽

Daisuke Taniguchi ◽

Yuichiro Kajiwara ◽

...

Keyword(s):

Gastric Cancer ◽

Abdominal Surgery ◽

Ct Scan ◽

Pancreatic Fistula ◽

Medical History ◽

Advanced Gastric Cancer ◽

Total Gastrectomy ◽

Upper Body ◽

History Of ◽

Acute Mediastinitis

Abstract Background Acute mediastinitis is a rare disease that rapidly progresses with a high mortality rate. Its most common cause is direct injury of the mediastinum, including iatrogenic causes such as cardiac surgery or upper endoscopy. Enzymatic mediastinitis is a rare complication of a pancreatic fistula caused by the inflammatory digestion of the parietal peritoneum spreading to the mediastinum. Here, we present two cases of enzymatic mediastinitis caused by total gastrectomy with splenectomy. One of them was successfully treated and cured after early diagnosis and transabdominal drainage. Case presentation Case 1 was that of a 60-year-old man (body mass index [BMI] 27) with a medical history of diabetes and hypertension who was diagnosed with advanced gastric cancer in the upper body of the stomach. A total gastrectomy with splenectomy was performed. The patient experienced acute respiratory failure 24 h after surgery. Pulmonary embolism was suspected, so a computed tomography (CT) scan was performed; however, no relevant causes were found. Although he was immediately intubated and treated with catecholamine, he died in the intensive care unit (ICU) 40 h after surgery. Post-mortem findings revealed retroperitonitis caused by a pancreatic fistula spreading towards the mediastinum, causing severe mediastinitis; a review of the CT scan revealed pneumomediastinum. We concluded that the cause of death was enzymatic mediastinitis due to post-gastrectomy pancreatic fistula. Case 2 involved a 61-year-old man (BMI 25) with a medical history of appendicitis who was diagnosed with advanced gastric cancer at the gastric angle between the lesser curvature and the pylorus, spreading to the upper body of the stomach. A total gastrectomy with splenectomy was also performed. The patient had a high fever 3 days after the surgery, and a CT scan revealed pneumomediastinum, indicating mediastinitis. As the inflammation was below the bronchial bifurcation, we chose a transabdominal approach for drainage. The patient was successfully treated and discharged. Conclusion Acute mediastinitis caused by gastrectomy is rare. The acknowledgment of abdominal surgery as a cause of mediastinitis is important. In treating mediastinitis caused by abdominal surgery, transabdominal drainage may be a minimally invasive yet effective method if the inflammation is mainly located below the bifurcation of the trachea.

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Comparison of prognostic impact of anatomic location of the pancreas on postoperative pancreatic fistula in laparoscopic and open gastrectomy

BMC Gastroenterology ◽

10.1186/s12876-020-01476-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jun Kinoshita ◽

Takahisa Yamaguchi ◽

Hiroto Saito ◽

Hideki Moriyama ◽

Mari Shimada ◽

...

Keyword(s):

Gastric Cancer ◽

Pancreatic Fistula ◽

Left Gastric Artery ◽

Postoperative Pancreatic Fistula ◽

Open Gastrectomy ◽

Amylase Level ◽

Prognostic Impact ◽

Anatomic Location ◽

Significant Difference ◽

Preoperative Ct

Abstract Background Postoperative pancreatic fistula (POPF) is a serious complication after gastric cancer surgery. The current study aimed to investigate the significance of the anatomic location of the pancreas as a predictor for POPF in both laparoscopic gastrectomy (LG) and open gastrectomy (OG). Methods In total, 233 patients with gastric cancer were assessed retrospectively. We measured the maximum vertical (P-L height; PLH) and horizontal length (P-L depth; PLD) between the upper border of pancreas and the root of left gastric artery on a preoperative CT in the sagittal direction. The maximum length of the vertical line between the surface of the pancreas and the aorta (P-A length), previously reported as prognostic factor of POPF, was also measured. We investigated the correlations between these parameters and the incidence of POPF in LG and OG groups. Results Among the patients in this study, 118 underwent OG and 115 underwent LG. In LG, the median PLH and P-A length in patients with POPF were significantly longer compared with those without POPF (p = 0.026, 0.034, respectively), but not in OG. There was no significant difference in the median PLD between the patients with or without POPF in both LG and OG. The multivariate analysis demonstrated that PLH (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.57–11.3, P = 0.004) and P-A length (OR 4.06, 95%CI 1.05–15.7, P = 0.042] were independent factors for predicting POPF in LG. However, intraoperative blood loss (OR 2.55, 95%CI 1.05–6.18, P = 0.038) was extracted as an independent factor in OG. The median amylase level in the drained fluid (D-Amy) were significantly higher in patients with high PLH(≥12.4 mm) or high P-A length (≥45 mm) compared with those with low PLH or low P-A length in LG. However, there were no differences in the D-Amy levels by PLH or P-A length in OG patients. Conclusions The anatomic location of the pancreas is a specific and independent predictor of POPF in LG but not in OG. PLH is a simple parameter that can evaluate the anatomic position of the pancreas, and it may be useful for preventing POPF after LG.

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Comparison of prognostic impact of anatomic location of the pancreas on postoperative pancreatic fistula in laparoscopic and open gastrectomy

10.21203/rs.3.rs-53308/v3 ◽

2020 ◽

Author(s):

Jun Kinoshita ◽

Takahisa Yamaguchi ◽

Hiroto Saito ◽

Hideki Moriyama ◽

Mari Shimada ◽

...

Keyword(s):

Gastric Cancer ◽

Pancreatic Fistula ◽

Left Gastric Artery ◽

Postoperative Pancreatic Fistula ◽

Open Gastrectomy ◽

Amylase Level ◽

Prognostic Impact ◽

Anatomic Location ◽

Significant Difference ◽

Preoperative Ct

Abstract Background: Postoperative pancreatic fistula (POPF) is a serious complication after gastric cancer surgery. The current study aimed to investigate the significance of the anatomic location of the pancreas as a predictor for POPF in both laparoscopic gastrectomy (LG) and open gastrectomy (OG). Methods: In total, 233 patients with gastric cancer were assessed retrospectively. We measured the maximum vertical (P-L height; PLH) and horizontal length (P-L depth; PLD) between the upper border of pancreas and the root of left gastric artery on a preoperative CT in the sagittal direction. The maximum length of the vertical line between the surface of the pancreas and the aorta (P-A length), previously reported as prognostic factor of POPF, was also measured. We investigated the correlations between these parameters and the incidence of POPF in LG and OG groups. Results: Among the patients in this study, 118 underwent OG and 115 underwent LG. In LG, the median PLH and P-A length in patients with POPF were significantly longer compared with those without POPF (p=0.026, 0.034, respectively), but not in OG. There was no significant difference in the median PLD between the patients with or without POPF in both LG and OG. The multivariate analysis demonstrated that PLH (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.57–11.3, P=0.004) and P-A length (OR 4.06, 95%CI 1.05–15.7, P=0.042] were independent factors for predicting POPF in LG. However, intraoperative blood loss (OR 2.55, 95%CI 1.05–6.18, P=0.038) was extracted as an independent factor in OG. The median amylase level in the drained fluid (D-Amy) were significantly higher in patients with high PLH(≥12.4 mm) or high P-A length (≥45 mm) compared with those with low PLH or low P-A length in LG. However, there were no differences in the D-Amy levels by PLH or P-A length in OG patients. Conclusions: The anatomic location of the pancreas is a specific and independent predictor of POPF in LG but not in OG. PLH is a simple parameter that can evaluate the anatomic position of the pancreas, and it may be useful for preventing POPF after LG.

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Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer

Cancers ◽

10.3390/cancers12061689 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1689 ◽

Cited By ~ 1

Author(s):

Bianca Grosser ◽

Meike Kohlruss ◽

Julia Slotta-Huspenina ◽

Moritz Jesinghaus ◽

Nicole Pfarr ◽

...

Keyword(s):

Gastric Cancer ◽

Surgical Resection ◽

Molecular Subtypes ◽

Strong Association ◽

Multivariable Analysis ◽

Tumor Localization ◽

Prognostic Impact ◽

P53 Expression ◽

Prognostic Effect ◽

Barr Virus

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.

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Prevalence of gastric cancer precursors in gastroscopy-screened adults by family history of gastric cancer and of cancers other than gastric

BMC Cancer ◽

10.1186/s12885-020-07612-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Rui Wu ◽

Cheng Yang ◽

Lin Ji ◽

Zhi-Ning Fan ◽

Yu-Wen Tao ◽

...

Keyword(s):

Gastric Cancer ◽

Family History ◽

High Risk ◽

Intraepithelial Neoplasia ◽

Cross Sectional Study ◽

Cross Sectional ◽

Younger Age ◽

Significant Difference ◽

History Of ◽

Cancer Precursors

Abstract Background People are at a high risk of gastric cancer if their first-degree relatives suffered from atrophic gastritis (AG), intestinal metaplasia (IM), intraepithelial neoplasia (IEN), dysplasia (DYS), or gastric cancer (GC). This study was performed to analyse the association between FDR-GC and GC precursors. Methods A cross-sectional study was performed to screen the prevalence of GC precursors from November 2016 to September 2019. A total of 1329 participants with FDR-GC, 193 participants with a family history of non-gastric cancer in FDRs (FDR-nGC), and 860 participants without a family history of cancer in FDRs (FDR-nC) were recruited in this study. The logistic regression model was used in this study. Results The prevalence of normal, Non-AG, AG/IM, IEN/DYS, and GC was 31.91, 44.21, 13.81, 8.73, and 1.34%, respectively. The prevalence of IEN/DYS was higher in people with FDR-GC and FDR-nGC (FDR-GC: odds ratio (OR) = 1.655; 95%CI, 1.153–2.376; FDR-nGC: OR = 1.984; 95%CI, 1.122–3.506) than those with FDR-nC. The younger the age at which FDRs were diagnosed with GC, the more likely the participants were to develop AG/IM (Ptrend = 0.019). The risk of precursors to GC was higher in participants whose FDR-GC was the mother than in those whose FDR-GC was the father or sibling (OR, non-AG: 1.312 vs. 1.007, 1.274; AG/IM: 1.430 vs. 1.296, 1.378; IEN/DYS: 1.988 vs. 1.573, 1.542). There was no statistically significant difference in non-AG (OR = 1.700; 95%CI, 0.940–3.074), AG/IM (OR = 1.291; 95%CI, 0.579–2.877), and IEN/DYS (OR = 1.265; 95%CI, 0.517–3.096) between participants with one or more FDR-GC. Conclusion People with FDR-GC and FDR-nGC are at a high risk of IEN/DYS. When an FDR was diagnosed at a younger age, the risk of AG/IM was higher. The risk of GC precursors was higher in people whose FDR-GC was the mother.

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Prognostic impact of lymphatic and/or blood vessel invasion in patients with node-negative advanced gastric cancer

Annals of Surgical Oncology ◽

10.1007/bf02573892 ◽

2002 ◽

Vol 9 (6) ◽

pp. 562-567 ◽

Cited By ~ 61

Author(s):

Woo Jin Hyung ◽

Jun Ho Lee ◽

Seung Ho Choi ◽

Jin Sik Min ◽

Sung Hoon Noh

Keyword(s):

Gastric Cancer ◽

Blood Vessel ◽

Advanced Gastric Cancer ◽

Blood Vessel Invasion ◽

Prognostic Impact ◽

Node Negative ◽

Vessel Invasion

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Prognostic impact of HER2, EGFR, and c-MET status on overall survival of advanced gastric cancer patients

Gastric Cancer ◽

10.1007/s10120-015-0471-6 ◽

2015 ◽

Vol 19 (1) ◽

pp. 183-191 ◽

Cited By ~ 53

Author(s):

Nozomu Fuse ◽

Yasutoshi Kuboki ◽

Takeshi Kuwata ◽

Tomohiro Nishina ◽

Shigenori Kadowaki ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Prognostic Impact ◽

Gastric Cancer Patients

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Long-term outcomes of omentum-preserving versus resecting gastrectomy for locally advanced gastric cancer with propensity score analysis

Scientific Reports ◽

10.1038/s41598-020-73367-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yusuke Sakimura ◽

Noriyuki Inaki ◽

Toshikatsu Tsuji ◽

Shinichi Kadoya ◽

Hiroyuki Bando

Keyword(s):

Gastric Cancer ◽

Propensity Score ◽

Advanced Gastric Cancer ◽

Missing Values ◽

Propensity Score Analysis ◽

Locally Advanced ◽

R0 Resection ◽

Significant Difference ◽

First Recurrence ◽

The Impact

Abstract Omentectomy is conducted for advanced gastric cancer (AGC) patients as radical surgery without an adequate discussion of the effect. This study was conducted to reveal the impact of omentum-preserving gastrectomy on postoperative outcomes. AGC patients with cT3 and 4 disease who underwent total or distal gastrectomy with R0 resection were identified retrospectively. They were divided into the omentum-preserved group (OPG) and the omentum-resected group (ORG) and matched with propensity score matching with multiple imputation for missing values. Three-year overall survival (OS) and 3-year relapse-free survival (RFS) were compared, and the first recurrence site and complications were analysed. The numbers of eligible patients were 94 in the OPG and 144 in the ORG, and after matching, the number was 73 in each group. No significant difference was found in the 3-year OS rate (OPG: 78.9 vs. ORG: 78.9, P = 0.54) or the 3-year RFS rate (OPG: 77.8 vs. ORG: 68.2, P = 0.24). The proportions of peritoneal carcinomatosis and peritoneal dissemination as the first recurrence site and the rate and severity of complications were similar in the two groups. Omentectomy is not required for radical gastrectomy for AGC.

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Analysis of 12 Genes in 268 Cases with CMML Identifies ASXL1 Mutations As the Most Important Genetic Alteration Associated with Adverse Outcome

Blood ◽

10.1182/blood.v120.21.3491.3491 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3491-3491

Author(s):

Susanne Schnittger ◽

Manja Meggendorfer ◽

Vera Grossmann ◽

Tamara Alpermann ◽

Christiane Eder ◽

...

Keyword(s):

Overall Survival ◽

Adverse Outcome ◽

Multivariable Analysis ◽

Melting Curve ◽

Gene Mutations ◽

Prognostic Impact ◽

Mutant Genotype ◽

Cox Regression Analysis ◽

Significant Difference ◽

Equity Ownership

Abstract Abstract 3491 Introduction: Chronic myeloid monocytic leukemia (CMML) has been associated with a high number of somatic mutations in diverse genes and various mutant genotype combinations were observed. The patterns of marker combinations and prognostic impact of single markers are poorly understood. Aims: Comprehensive analysis of the genetic marker profile in a large CMML cohort and evaluation of potential prognostic implications. Patients and Methods: In total, 268 cases with CMML (CMML-1 n=191, CMML-2 n=77) were included. The cohort comprised 186 males and 82 females with a median age of 73.0 yrs (range: 21.9 – 93.3 yrs). In 262 cases cytogenetic data was available: 185 cases (70.6%) had a normal karyotype and 77 (29.4%) showed aberrant karyotypes. Data on mutations were available in all patients for SRSF2, U2AF1, JAK2 V617F, and in subcohorts for: ASXL1 (n=255), CBL (n=267), EZH2 (n=205), KIT D816 (n=263), KRAS (n=260), NRAS (n=266), RUNX1 (n=267), SF3B1 (n=240), and TET2 (n=157). Mutations were analyzed by a combination of amplicon deep-sequencing (Roche 454, Branford, CT), direct Sanger sequencing, real time PCR or melting curve analyses. Analysis for overall survival was restricted to 185 cases with evaluable clinical data (median follow-up: 427 days, median OS: 51%). Results: In total 633 mutations were detected in 268 patients (median: 2 per patient, range 0–7). In CMML-1 the mean number of mutations was equal to CMML-2 (2.38 vs. 2.55, p=n.s.). In detail, the most frequent mutations were detected in TET2 (61.1%; 96/157), followed by SRSF2 (47.8%; 128/268), ASXL1 (44.7%; 144/255), RUNX1 (22.8%; 61/267), CBL (19.1%; 51/267), NRAS (15.4%; 41/266), KRAS (10.8%; 28/260), EZH2 (9.3%; 19/205), JAK2 (6.7%; 18/268), U2AF1 (5.2%; 14/268), SF3B1 (5.0%; 12/240), and KIT (4.2%; 11/263). Impact on survival was tested for all 12 gene mutations. A significant difference in overall survival (OS) was observed only for ASXL1 mut vs ASXL1 wt patients (median OS: 19.4 months vs not reached; p=0.003). None of the other gene mutations showed a significant impact on OS. In a next step mutations from the RAS pathway (NRAS, KRAS, CBL) were combined into one group (n=85) and were analyzed in comparison to all others (n=90). However, no impact on OS was detected. Next, patients with at least one mutation in a gene from the splicing machinery (U2AF1, SRSF2, SF3B1) (n=109) were combined and tested vs all other patients (n=57), however, no prognostic relevance was found. In addition, no difference in outcome was observed between CMML-1 and CMML-2 patients. Of note, the adverse impact of ASXL1 mut was restricted to the CMML-2 subcohort (25 mut, 31 wt, median OS: 17.3 months vs n.r.; p=0.001), whereas there was no effect in CMML-1 pts (59 mut and 54 wt). We also evaluated the cytogenetic risk score introduced by Such et al. (Haematologica 2011) and were not able to find differences in survival (neither pairwise between the respective subgroups, nor overall). However, we were able to show prognostic impact of ASXL1 mut within the cytogenetic risk groups suggested by Such: within the favorable subgroup ASXL1 mut patients (n=56) had worse outcome than ASXL1 wt (n=65) (median 19.4 months vs n.r.; p=0.027). This was true also for the adverse subgroup showing a trend to worse outcome for ASXL1 mut vs ASXL1 wt (n=16 vs n=9; median 17.3 months vs n.r.; p=0.057). No difference was seen between the 9 ASXL1 mut and 8 ASXL1 wt patients within the intermediate risk group. In the univariable cox regression analysis taking age, gender, type dysplastic vs proliferative, CMML-1 vs CMML-2, WBC, hemoglobin (Hb), Such score and ASXL1 mut into account, the following parameters were found to be relevant for outcome: age (p=0.001, HR 1.74 per decade), WBC (p=0.044, HR 1.08 per 10×109/L), Hb (p<0.001, HR 0.70, ASXL1 mut (p=0.004, HR 2.38). These parameters entered the multivariable analysis and age (p=0.005, HR: 1.61 per 10 yrs of increase), Hb (p<0.001 HR 0.704) and mutated ASXL1 status (p=0.009, HR 2.30) were independent prognostic parameters for OS. Conclusion: 1) CMML-1 as well as CMML-2 are genetically complex diseases each showing a high number of mutations. 2) One of the most frequently mutated genes in both subgroups is ASXL1. 3) ASXL1 is the only one out of 12 genes which is independently associated with adverse outcome. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Equity Ownership. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Grossmann:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

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