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Background : In myeloproliferative neoplasms, especially essential thrombocythemia (ET), platelet (Plt) counts and von Willebrand factor (vWF):Ristocetin cofactor (RCo) levels have been reported to be inversely correlated. However, there have been no reports of the comparison of high vs. low values of JAK2 allele burden and necessary of Plt counts reduction to achieve vWF:RCo levels ≥50%, which is required for major surgery. We investigated the correlation between vWF level and Plt counts for JAK2V617F mutation positive (JAK2V617F+) polycythemia vera (PV) and ET (allele burdens ≥50% and Method: We recruited patients with PV and ET who were diagnosed per the 2008 World Health Organization criteria at 3 hospitals since 2011 to 2018. All patients were analyzed at Juntendo University for JAK2 (V617F, exson12), CALR, and MPL mutations. We collected data of JAK2V617F+ or CALR+ patients. Triple-negative mutations of ET were excluded in this study because it is difficult to differentiate between ET and secondary thrombocytosis. We analyzed the correlation between Plt counts and vWF:RCo levels for three mutation groups mutations (JAK2V617F allele burden ≥50%, Results: We collected 146 PV and ET patients. Among 54 PV patients, 50 had JAK2V617F+, 3 had JAK2 exon 12, and 1 had a triple-negative mutation(s) in PV patients. Among 92 ET patients, 53 had JAK2V617F+, 35 had CALR+ (22 del52, 12 ins5 and 1 del34), and 4 had MPL mutations in ET patients. vWF:RCo levels were weakly inversely correlated with Plt counts in patients with JAK2V617F+ PV and ET from whom blood samples were obtained for the first time after enrolling in this study (Ps=-0.531 and Ps=-0.439, respectively). In contrast, vWF:RCo levels and Plt counts in patients with CALR+ ET showed a strong inverse correlation (Ps=-0.762). Interestingly, 3/50 PV and 4/53 ET patients with JAK2V617F mutations showed vWF:RCo levels >150% (normal vWF:RCo levels range: 50-150%). Furthermore, 3/50 PV and 1/53 ET patients with Plt counts 150% or During the entire observation period, 8/50 and 7/53 patients with JAK2V617F+ PV and ET, respectively, and 1/35 patients with CALR+ ET had vWF:RCo levels >150%. One case of JAK2V617F+ ET (allele burden When Plt counts were controlled to 30%. However, 13/86 patients did not achieve 50%, which is the standard for safely performing the major surgical procedures prescribed in most guidelines. In patients whose Plt counts controlled to Conclusion: For patients with CALR+ ET, we propose that vWF:RCo levels can be predicted based on Plt counts; however, it is difficult to predict vWF:RCo levels by Plt counts in JAK2V617F+ PV and ET patients because the inverse correlation between vWF:RCo levels and Plt counts was weak. Overactivation of vWF:RCo levels was often observed in JAK2+ PV and ET. Moreover, in 1 case, the patient exhibited only age as the risk factor for the complication of thrombosis. Because of these findings, overactivation of vWF:RCo levels may be one of the reasons for thrombotic events in JAK2V617F+ PV and ET. In addition, it was also found that cases of JAK2V617F+ allele burden ≥50% in PV and ET should be careful for hemorrhage in major surgery, even if Plt counts were controlled Disclosures No relevant conflicts of interest to declare.

Background Recent studies have shown that the concurrent expression of MYC and BCL2 protein evaluated by immunohistochemistry (IHC) in patients with de novo diffuse large B-cell lymphoma (DLBCL) is associated with worse survival when treated with standard R-CHOP, but the effect of intensive chemotherapies for such patients is unknown. Thus, we evaluated the impact of the co-expression of MYC and BCL2 protein among patients with advanced DLBCL, who were treated with a dose-intensive immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). Patients and Methods This is a retrospective analysis of patients with de novo DLBCL, who were categorized into high/high-intermediate risk by the age-adjusted International Prognostic Index (aaIPI). They were consecutively treated with the R-Double-CHOP regimen, consisting of rituximab (375 mg/m2, day -2), cyclophosphamide (750 mg/m2, day 1, 2), doxorubicin (50 mg/m2, day 1, 2), vincristine (1.4 mg/m2 [maximum 2.0 mg/body], day 1) and prednisolone (50 mg/m2, day 1-5) followed by consolidative high-dose chemotherapies at our institution from 2001 to 2013. MYC and BCL2 protein were measured by IHC assay using formalin-fixed paraffin-embedded tissue specimens for all available cases. Cut-off values of positivity for MYC and BCL2 protein were set as 40% and 50% of stained tumor cell, respectively. Lymphomas showing concurrent positivity for MYC and BCL2 protein were defined as "Double expressor lymphoma (DEL)". Results A total of 40 patients with a median 53-years (range 19-68) of age were analyzed. Twenty-one patients were at high risk and the other 19 patients were at high-intermediate risk by aaIPI. Cell of origin (COO) subtypes classified by Hans algorithm consisted of 14 germinal center B-cell (GCB) type and 26 non-GCB type. Totally, 10 (25%) patients were categorized into DEL. The overall response (OR) and the complete response (CR) rates to R-Double-CHOP for all patients were 93% and 83%, respectively. The OR and the CR rates were not significantly different between the DEL group and the non-DEL group (100% vs 90%, and 80% vs 83%, respectively). The proportion of patients proceeding to ASCT was not significantly different among these groups (50% vs 60%). With a median 52 months (range 3-155) of follow-up, the 3-year progression-free survival (PFS) and the overall survival (OS) rates for all patients were 55% and 72%, respectively (Figure a, b). Both the PFS and the OS were significantly worse in the DEL group than in the non-DEL group (Figure c, d). As for aaIPI and COO subtyping, either high/high-intermediate risk or GCB/non-GCB subtype were not significantly associated with the outcome of PFS or OS. Conclusion The concurrent expression of MYC/BCL2 protein in advanced DLBCL was associated with shorter remission duration and worse survival despite similar susceptibility to the treatment when a dose-intensive immunochemotherapy was applied. Our findings suggest that patients with advanced DEL may not benefit from dose-intensified therapies, and therefore need highly discrete strategies. Disclosures Miura: Astellas Pharma Inc.: Honoraria; Celgene K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; Meiji Seika Pharma: Honoraria; Janssen Pharmaceutical K.K.: Honoraria. Hatta:Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Celgene K.K.: Honoraria. Iriyama:Brystol-Myers K.K.: Honoraria. Takei:Kyowa Hakko Kirin CO., Ltd, Japan: Research Funding; Bristol-Myers K.K.: Research Funding; Nippon Kayaku Co.: Research Funding; Shionogi & Co.: Research Funding; Meiji Seika Pharma: Research Funding; Astellas Pharma Inc.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; TEIJIN PHARMA LIMITED: Research Funding; CSL Behring K.K: Research Funding; Japan Blood Products Organization: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; TORII, PHAMACEUTICAL CO: Research Funding; Alexion Pharmaceuticals: Research Funding; YAKULT HONSHA CO., Ltd.: Research Funding; Taisho Toyama Pharmaceutical Co., Ltd.: Research Funding; TAIHO PHARMACEUTICAL CO., Ltd.: Research Funding; CHUGAI PHARMACEUTICAL CO. LTD: Research Funding.

Abstract 3121 Background We evaluated the safety and efficacy of the CEM regimen containing ranimustine (MCNU) with autologous peripheral blood stem cell transplantation (PBSCT) in adult patients with relapsed or high-risk de novo DLBCL or DLBCL associated with follicular lymphoma (FL/DLBCL) in our institution. Patients and methods We retrospectively analyzed 55 consecutive patients who underwent autologous PBSCT following the CEM regimen between March 1999 and June 2011 for the treatment of relapsed or high-risk DLBCL and FL/DLBCL. High-risk DLBCL was defined as partial or no response to initial treatment or high-intermediate/high risk disease according to international prognostic index (IPI) at initial diagnosis. Age-adjusted IPI was used for patients under 60. The CEM regimen consisted of CY (60 mg/kg on days -7 and -6), etoposide (500 mg/m2 on days -6 to -4) and MCNU (250 mg/m2on day -3 and -2), followed by PBSCT. Results Median age at transplant was 51 years (range, 23–66), and median time from diagnosis to transplant was 5 months (range, 3–241). Of them, 7 patients received radiation therapy before transplant, and 11 had no history of rituximab use before transplant. The 36 patients in CR1 at transplant were with high or high-intermediate risk according to international prognostic index at diagnosis. Other 15 patients in CR2, and 4 patients who were not in CR1/2 at transplant were included. CY dose was reduced in five patients by physicians choice. The median number of infused CD34-positive cells was 3.98 × 106/kg (range, 1.36–26.87). The median post-transplant days of neutrophil recovery and platelet were 11 days (range, 9–20) and 12 days (range, 7–53), respectively. Common grade 3/4 non-hematological treatment-related toxicities within the first 100 days after transplant were nausea (24%), vomit (4%), stomatitis (15%), and diarrhea (9%). Infections included febrile neutropenia (85%), sepsis (15%) which contained catheter-related bacteremia (n=4) and pneumonia (n=2). Other less common severe toxicities were acute renal impairment (n=3), and pleural effusion (n=1). No sever cardiac, neurologic toxicity, or veno-occlusive disease of the liver was observed in any of the patients. Late-onset adverse effects during follow-up period includes chronic renal impairment (n= 5), therapy-related myelodysplastic syndrome (refractory anemia) (n=1, 120 months), and prostate cancer (n=1, 83 months). Serious late cardiac or pulmonary impairment was not diagnosed in this cohort. Median follow-up duration of 42 patients surviving at the time of the analysis was 52 months (range, 1–159). Relapse or disease progression after PBSCT was documented in 21 cases (range, 0–81 months after PBSCT). No therapy related mortality (TRM) associated with PBSCT was observed, and all the 13 deaths were due to disease relapse/progression. The 5-year estimated overall survival (OS) and progression-free survival (PFS) were 70.6% (95% CI, 54.0–82.1)% and 57.0% (95% CI, 39.5–71.2)% for all patients, respectively. In a univariate analysis for factors affecting OS and PFS, no significant factors associated with unfavorable OS and PFS was found including age at transplant, gender, history of rituximab use, histology, disease status at transplant, and previous BM involvement. Conclusion We conclude that the CEM regimen using MCNU would be a tolerable, effective conditioning regimen of autologous PBSCT for high-risk or relapsed de novo DLBCL or FL/DLBCL. Although no TRM was observed, relapse was the major cause of treatment failure. Late-onset complications in long-term survivors can occur, and should be carefully monitored. Disclosures: No relevant conflicts of interest to declare.

Abstract 1039 Background: The association between increase in body mass index (BMI) and development of acute promyelocytic leukemia (APL) has been reported. Interaction of APL cells with bone marrow adipocytes in vitro induces phosphorylation of STAT3 and MAPK, resulting in an anti-apoptotic effect in APL cells. However, the influence of obesity on the prognosis of APL is not well understood. Materials and Methods: To evaluate the effect of obesity on the prognosis of adult APL, we retrospectively analyzed 62 patients under the age of 65 with newly diagnosed APL. Patients who could not be administered intensified chemotherapy, because of either poor performance status or adverse events of chemotherapy, were excluded. Results: Median age of patients was 40 years (range, 14–63). Twenty-five were male and 37 were female. Median follow-up period was 646 days (range, 3–12,558). Median BMI was 22.7 (range, 16.0–33.0). Twenty-six patients diagnosed with APL between 1970 and 1992 had been treated with chemotherapy alone (chemotherapy group), and 36 patients diagnosed between 1995 and 2010 had been treated with all-trans retinoic acid (ATRA) ± chemotherapy (ATRA group). In both groups, the outcome was compared between high-BMI (BMI ≥ 24) and low-BMI (BMI < 24) patients. Eight out of 26 in the chemotherapy group and 16 out of 36 in the ATRA group were high-BMI patients. In the chemotherapy group, complete remission (CR) was obtained in 13 out of 18 (72.2%) low-BMI patients and in only 3 out of 8 (37.5%) high-BMI patients. By day 498, all 3 CR patients with high BMI had relapsed, whereas only 6 out of 13 (46.2%) low-BMI CR patients had relapsed. The 2-year relapse-free survival (RFS) rate, event-free survival (EFS) rate, and overall survival (OS) rate in high-BMI versus low-BMI patients were 0% v 50.5%, 0% v 61.1%, and 12.5% v 42.8%, respectively. Although the relapsed patients were salvaged with ATRA, arsenic trioxide, or allogeneic bone marrow transplantation, OS was significantly worse in high-BMI patients. On the contrary, in the ATRA group, prognosis between high-BMI and low-BMI patients was not statistically different. Rates of CR, relapse, 2-year RFS, EFS, and OS in high-BMI versus low-BMI patients were 87.5% v 94.7%, 35.7% v 38.9%, 73.3% v 46.2%, 55.0% v 52.5%, and 87.5% v 81.1%, respectively. The initial white blood cell (WBC) and platelet counts have been previously reported to be prognostic factors in APL; however, they were not associated with BMI in our study. A WBC count of >10 × 109/L and a platelet count of ≤40 × 109/L were observed in 4 (10.5%) and 28 (73.8%) out of 38 low-BMI, and 4 (16.5%) and 19 (79.2%) out of 24 high-BMI patients, respectively. Conclusions: Our results demonstrate that obesity at diagnosis is a poor prognostic factor in APL, especially in patients not administered ATRA. ATRA overcomes the anti-apoptotic effect of adipocytes for APL cells. Disclosures: No relevant conflicts of interest to declare.