ALBERT

Description: Background: Rituximab (R) plus CHOP (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) and revised IPI were reported as prognostic indicators for DLBCL in 1993 and 2007, respectively. Although they are widely accepted, the performance status (PS) factor is sometimes ambiguous or subjective. Therefore, we developed a new prognostic index, the SIL, that includes only three objective prognostic factors: the clinical stage (S), a soluble interleukin-2 receptor level 〉2,500 U/mL (I), and an elevated lactate dehydrogenase level (L) (Cancer Sci. 2012). This study was conducted to confirm the value of the SIL index in a larger cohort and in each risk stratification of patients and to validate the SIL index in an independent patient cohort. Methods: Between 2003 and 2012, we registered and treated 781 consecutive patients with DLBCL, excluding those with mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, and primary effusion lymphoma. All the included patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Patients in whom the initial therapy dose was reduced by 〉20% were excluded. Finally, 572 of 781 patients were retrospectively analyzed. Patients with partial remission (PR) after the initial four cycles underwent eight R-CHOP cycles in total, whereas those who did not achieve PR after the initial four R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. If deemed necessary by the attending physician, additional local irradiation was performed in patients with PR or complete remission.Furthermore, we verified the value of the SIL index in an independent cohort of 89 DLBCL patients. Results: The median age at diagnosis was 63 years (range, 18-89 years). The median number of therapy cycles was 6 (range, 1-8), and 90% of patients received 〉6 cycles. Sixty-one patients (11%) received radiation therapy as primary treatment, which was often used to treat sites of residual masses at the end of chemotherapy. The median observation time for survivors was 55 months (range, 1-131 months). For 572 patients, the 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates were 70% and 81%, respectively. The 5-year PFS rate was significantly different as 86%, 73%, 63%, and 41% for 0, 1, 2, and 3 of SIL index, respectively (Fig 1; P 〈 0.0001). The 5-year OS rate was also significantly different as 92%, 87%, 78%, and 52% for 0, 1, 2, and 3 of SIL index, respectively (P 〈 0.0001). According to the SIL index, 367 (64%) and 205 patients (36%) were classified as having standard (SIL index: 0 or 1) and high (SIL index: 2 or 3) risks, respectively. In patients with a low/low-intermediate risk on the IPI, 84% were categorized as having standard risk according to the SIL index, whereas in patients with a high-intermediate/high risk on the IPI, 82% were categorized as having high risk according to the SIL index. Five-year PFS rates in the standard and high risk groups according to the SIL index were 79% and 53%, respectively (Fig 2; P 〈 0.0001). Five-year OS rates in the standard risk and high risk groups were 90% and 66%, respectively (P 〈 0.0001). Cox regression analysis of the SIL index, age (〉60 years), PS (2-4), sites of extranodal involvement (〉1), and sex showed that the SIL index (P 1), and sex, the SIL index was still a good prognostic indicator for PFS and OS in both groups. Lastly, when they were divided by the PS (0-1 and 2-4), the SIL index was effective in the good PS group. However, in the poor PS group, the SIL index showed a statistically significant difference in the OS, but not in the PFS. In the validation cohort analysis, 5-year PFS rates in the standard and high risk groups were 81% and 49%, respectively (Fig 3; P = 0.001). Five-year OS rates in the standard risk and high risk groups were 87% and 59%, respectively (P = 0.003). Conclusion: The SIL index is a simple and objective prognostic indicator for DLBCL patients treated with R-CHOP. Disclosures Fujita: Chugai Pharmaceutical CO.,LTD.: Honoraria.

Description: Abstract 3028 Introduction: We performed a multicenter retrospective study of the significance of the addition of cytarabine (CA) or thiotepa (TT) to the myeloablative standard regimen consisting of total body irradiation (TBI) and cyclophosphamide (CY). Methods: Among the patients who underwent allogeneic hematopoietic stem cell transplantation between 2,000 and 2,010 in the four institutions related to Yokohama City University Hematology Group, a total of 365 patients who used the TBI/CY-based regimen were included to the cohort. Conditioning regimens were distributed to three groups: TBI/CY group (TC, n=82), TBI/CY/CA group (TCC, n=90), and TBI/CY/TT group (TCT, n=193). A standard TBI and CY regimen consisted of 12 Gy of TBI with four fractions and 60 mg/kg of CY for two days. Two days of CA (2 g/m2/day) or TT (200 mg/m2/day) were added to the TBI/CY regimen. A minimum dose reduction was permitted according to an older age or poorer co-morbidity. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. Gray's test was employed for comparison of cumulative incidence curves for relapse and non-relapse mortality (NRM). NRM and relapse were competing events. Adjusted multivariate Cox regression models were employed for each disease stage. Results: The median age was 42 years old (16–62). Diagnoses were acute myeloid leukemia (AML, n=219), acute lymphoid leukemia (ALL, n=105), and myelodysplastic syndrome (MDS, n=41). Complete remission or refractory cytopenia with multilineage dysplasia was defined as the standard stage (n=211), while the others were advanced (n=154). The stem cell sources were related bone marrow (RBM, n=79), related peripheral blood (RPB, n=51), unrelated bone marrow (UBM, n=161), and unrelated cord blood (UCB, n=74). As for patient characteristics, there was a deviation in the transplant year (P

Description: Abstract 1620 Few randomized prospective studies have been conducted on patients with localized DLBCL in the rituximab era. The SWOG 0014 study examined DLBCL patients treated with 3 cycles of R-CHOP followed by involved-field radiotherapy. Each of the patients had at least 1 of the 4 risk factors (nonbulky stage II, over 60 years of age, WHO performance status [PS] of 2, or elevated LDH), but showed 4-year progression-free survival (PFS) and 4-year overall survival (OS) rates of 88% and 92%, respectively. However, long-term observations showed that the PFS and OS curves did not plateau (Persky DO, et al. J Clin Oncol 2008). We retrospectively analyzed a series of patients with localized DLBCL treated with R-CHOP therapy alone. This study included 190 consecutive, untreated patients with localized DLBCL seen between 2003 and 2009 in 1 of the 7 participating hospitals. All the patients were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP in 1 of the hospitals. Patients who required a dose reduction of more than 20% were excluded from the study, as were patients with special forms of DLBCL, such as intravascular lymphoma, primary mediastinal large B-cell lymphoma, and T-cell-rich B-cell lymphoma. Patients who achieved partial remission (PR) after the 4 initial cycles underwent a total of 8 R-CHOP cycles. Patients who did not achieve PR after the 4 initial cycles or those with disease progression at any time during the study underwent salvage therapy, and that time point was designated as the point at which the disease progression began. Additional local irradiation was allowed in patients with PR. Patients who received additional radiotherapy following CR in the decision of attending physicians were excluded from this study. Patients who achieved CR but who were initially at risk of central nervous system (CNS) involvement received 4 intrathecal doses of methotrexate (15 mg) and hydrocortisone (25 mg) for CNS prophylaxis. Central pathological reviews were not performed; only the individual institutional diagnoses were used. The study included 111 men and 79 women, with a median age at diagnosis of 63 years (range, 18–80 years). According to the IPI, 133 patients were classified as L; 49, as LI; 5, as HI; and 3, as H. Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. CNS prophylaxis was performed in 15 patients who had an initial CNS risk and achieved CR. The median observation period for the living patients was 52 months. The responses to therapy were 180 CR, 8 PR, and 2 progression of disease (PD). The 5-year PFS and 5-year OS rates were 84% and 90%, respectively, and both plateaued (Figure 1). None of the patients experienced PD after 4 years of observation. Multivariate analysis revealed that the presence of bulky mass, which was evident in 18 patients, was an independent risk factor for PFS (P = 0.007, relative risk [RR] 3.5) and OS (P = 0.003, RR 5.8), along with poor performance status. During the observation period, 29 patients experienced PD. The progression sites included the primary sites in 15 patients, outside the primary sites in 10, and undetermined in 4. There were 16 deaths, 14 of which were due to the lymphoma. In 149 patients with at least one of the 4 risk factors used in the SWOG 0014 study, the 5-year PFS and 5-year OS rates were 86% and 94%, respectively. Six cycles of R-CHOP therapy alone were observed to be highly effective in attaining good survival results with plateaus. These results suggest that the “standard” strategy of 3 cycles of R-CHOP followed by involved-field radiotherapy for localized DLBCL should be replaced by R-CHOP alone. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1561 Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma (NHL), with a highly variable natural history, ranging from an indolent disease to a rapidly progressive disease such as transformation to aggressive NHL. The MIB-1 labeling index, based on the Ki67 immunostaining, is widely used for evaluating the proliferation of tumor cells. We retrospectively evaluated the prognostic impact of the MIB-1 labeling index at diagnosis in patients with FL treated with rituximab plus cyclophosphamide, doxorubicine, vincristine, and prednisolone (R-CHOP) alone. Ninety-eight consecutive FL patients (48 men and 50 women; median age, 57 years [range, 34–85 years]) were enrolled in one of the 7 participating hospitals between 2001 and 2009. Since 2001, the Yokohama City University Hematology Group in Japan has uniformly treated FL patients with curative intent, except for those in stage 1 disease, with 6 cycles of standard R-CHOP therapy for 21 days. Patients who had partial response (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles, whereas patients who did not achieve PR after the 4 initial R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. Patients who had a bulky mass defined as any mass exceeding 10 cm in diameter in a horizontal plane or a mediastinal mass with a maximum diameter exceeding one-third of the maximum chest diameter, received additional irradiation following CR with 6–8 cycles of R-CHOP. Patients who required a dose reduction of more than 20% were excluded from this study. The pathological diagnosis and MIB-1 labeling index were reviewed by 3 hematological pathologists (S. S., N. Ts., and K.T.). The WHO pathological grading in patients was as follows: grade1 in 63 patients, grade 2 in 21 patients, grade 3a in 12 patients, and grade 3b in 2 patients. The median MIB-1 index was 12.9% (range, 0.8%-79.9%). The median observation period for living patients was 59 months. The estimated 5-years progression-free survival (PFS) and 5-years overall survival (OS) rates were 48% and 84%, respectively. Patients with a MIB-1 index above 10% (n = 60) showed inferior survival curves compared with patients with a MIB-1 index below 10% (n = 38) in PFS (5-year PFS of 35% versus 67%, P = 0.02; Figure 1) and OS (5-year OS of 77% versus 94%, P = 0.009), respectively. Pathological grading was not correlated with PFS and OS. The following variables were assessed for their impact on PFS: (1) gender, (2) age 〉 60 years, (3) elevated serum lactate dehydrogenase level, (4) advanced clinical stage, (5) pathological grade, and (6) a MIB-1 labeling index above 10%. A MIB-1 labeling index above 10% was independently associated with poor PFS (P = 0.01, RR = 2.6), as well as advanced clinical stage (P = 0.004, RR = 2.7). A MIB-1 labeling index of above 10% is a useful prognostic factor in FL treated by R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Description: Background The prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience relapses after achieving first complete remission (CR), leading to poor survival. Although a specific predictor of relapse of non-Hodgkin’s lymphoma has not been identified thus far, recently, the peripheral blood lymphocyte/monocyte ratio (LMR) at diagnosis, which reflects the host’s immune status, was reported to predict clinical outcomes in DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, the significance of LMR as a predictor of relapse in DLBCL patients in remission is not clear. The aim of this study was to assess whether LMR at 6 months after remission is a predictor of relapse after R-CHOP therapy in DLBCL patients. Methods From 2003 to 2009, 357 consecutive DLBCL patients were diagnosed, treated with R-CHOP, and followed up at 1 of the 7 participating hospitals in Japan. Of these, 315 DLBCL patients achieved CR after 6–8 cycles of R-CHOP therapy. Among the 315, those who were in remission for more than 6 months (n = 280) were enrolled in this study. The cumulative incidence of relapse was calculated from 6 months after CR to the first subsequent relapse or last follow-up. The effects of risk factors of relapse were assessed in univariate and multivariate Cox regression analyses. In multivariate analysis, risk factors tested at the time of diagnosis, confirmed remission and 6 months after remission included gender, International Prognostic Index at diagnosis (age 〉 60 years, elevated lactate dehydrogenase level, poor Eastern Cooperative Oncology Group performance status [ECOG PS], the presence of 2 or more extranodal involvement sites, and advanced clinical stage), and LMR ≤ 3.3. Results The study included 161 men and 119 women, with a median age of 64 years at diagnosis (range, 18–80 years). The median LMR at 6 months after remission was 3.7 (range, 0.5–18.0). The median observation period for surviving patients was 63 months. In all, 35 (12.5%) patients had confirmed relapse after achieving first CR, with a median time to relapse of 23 months (range, 6–61 months). The estimated 5-year cumulative incidence rate of relapse for the entire cohort was 14.7%. According to the LMR at 6 months after remission, the 5-year cumulative incidence rate for LMR ≤ 3.3 was 17.0% compared to 12.7% for LMR 〉 3.3 (P = 0.188). In the univariate analysis, advanced clinical stage at diagnosis (hazard ratio [HR] = 2.61, 95% confidence interval [CI], 1.33–5.13, P = 0.005) and poor ECOG PS at diagnosis (HR = 2.62, 95% CI, 1.19–5.77, P = 0.017) were associated with the occurrence of relapse. Multivariate analysis identified advanced clinical stage at diagnosis (HR = 2.42, 95% CI, 1.11–5.27, P = 0.026) and LMR ≤ 3.3 at 6 months after remission (HR = 2.10, 95% CI, 1.01–4.35, P = 0.047) as the risk factors for relapse. Conclusions The LMR at 6 months after remission is an independent predictor of relapse in first CR in DLBCL patients treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Description: Background: In lymphoma patients, it is believed that serum lactate dehydrogenase (LDH) reflects the tumor mass and that soluble interleukin-2 receptor (sIL-2R) is indicative of activated T-cell reaction. Although it is important to characterize the pattern of LDH and sIL-2R in each subtype of lymphoma, limited information is available on this topic. We investigated LDH and sIL-2R in patients with representative subtypes of lymphoma. Patients and Methods: In the Yokohama City University Hematology Group Lymphoma Database, 3,484 untreated patients were registered between 1996 and 2014. We extracted the data of 3,005 patients with the 8 following subtypes: follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALT), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), peripheral T-cell lymphoma (PTCL), and extranodal NK/T cell lymphoma (ENKL). In this retrospective study, we included 2,889 patients in whom both LDH and sIL-2R were recorded. We used the Kruskal-Wallis test to compare LDH and to compare sIL-2R in all 8 subtypes. Each subtype was compared using the Dwass, Steel, Critchlow-Fligner test (multiple comparison test). Results: The 2,889 patients consisted of 1,630 men and 1,259 women, with a median age of 65 years (range, 15-95 years). The median LDH was 1.0 x upper normal limit (N) (range, 0.1 N–53.9 N). The median sIL-2R was 1,150 U/ml (range, 53-142,000 U/ml). The distribution of lymphoma subtypes was as follows: 584 FL (20%), 219 MALT (8%), 82 MCL (3%), 1,579 DLBCL (54%), 39 BL (1%), 162 HL (6%), 162 PTCL (6%), and 62 ENKL (2%). Overall, LDH as well as sIL-2R showed significant difference in the 8 subtypes (P 〈 .0001 for both). The median values of LDH and sIL-2R in each subtype were as follows: 0.9 N and 1,114 U/ml in FL, 0.8 N and 467 U/ml in MALT, 1.15 N and 4,460 U/ml in MCL, 1.1 N and 1,230 U/ml in DLBCL, 2.4 N and 1,700 in BL, 1.0 N and 1,460 U/ml in HL, 1.2 N and 3,193 U/ml in PTCL, and 1.0 N and 679 U/ml in ENKL, respectively. In LDH analysis, BL showed higher value than any other subtypes and MALT showed lower value than any other subtypes. In sIL-2R analysis, MCL showed a higher value than any other B-cell lymphomas, except for BL, and MALT showed lower value than any other subtypes. In the comparison of the most frequent subtypes of FL and DLBCL, LDH was significantly higher in DLBCL (P 〈 .0001); however, sIL-2R was not significantly different (P = 0.31). The correlation between LDH and sIL-2R in each subtype was depicted in the Figure. The diameter of the circle indicated the number of patients. Conclusion: Our findings suggested that the tumor mass was greatest in BL and that T-cell reaction was greater in MCL. Furthermore, both tumor mass and T-cell reaction were lowest in MALT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background Peripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and Methods Serum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. Results The study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P〈 0.001), and ferritin levels ≥ 300 ng/ml (P〈 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels〈 300ng/ml (n = 57; 22% vs. 65%; P〈 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. Conclusion The serum ferritin level is a useful prognostic marker for PTCL. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Consistent with more direct measures of body fat, body mass index (BMI), defined as a personfs weight in kilograms divided by the square of his height in meters (kg/m2), is strongly correlated with various adverse health outcomes. Recent studies have reported the prognostic benefits of higher BMI at diagnosis in acute myeloid leukemia (AML). However, there are few reports on the prognostic impact of BMI classification and post-remission therapy, including hematopoietic stem cell transplantation (HSCT). Although some studies have reported worse outcomes related to lower BMI at transplant, there are no studies on the prognostic impact of the difference-BMI (d-BMI) between time of transplant and time of AML diagnosis. We hypothesized that lower BMI at transplant and reductions in BMI from diagnosis are associated with worse survival outcomes, including graft-versus-host disease-free survival, relapse-free survival (GRFS), which is currently defined as a novel composite endpoint in the first post-HSCT year. Patients and Methods: We identified 369 patients from January 2000 to March 2015 newly diagnosed with adult AML who had been administered daunorubicin or idarubicin in combination with cytarabine as induction chemotherapy (IC) at any of the seven Japanese hospitals that collaborate to form the Yokohama Cooperative Study Group for Hematology. Patients with acute promyelocytic leukemia, myeloid sarcoma, and aged 66 years or more were excluded from this study. For adjustment treatment intensification, patients who had over 20% reduction in actual dosage of IC were also excluded. In this study model, 184 patients were eligible for HSCT. According to the classification of obesity by the World Health Organization, underweight patients were characterized by BMI of 30 kg/m2. d-BMI was calculated as BMI at the time of transplant subtracted from BMI at the time of diagnosis, which reflects constructive changes in body structure due to intensive chemotherapy. Based on the ranges of d-BMI, patients were divided into three groups: under −2, between −2 and +2, and over +2. We analyzed overall survival (OS), disease-free survival (DFS), and GRFS in different BMI groups at transplant and in d-BMI groups. Results: This study included 115 males and 69 females, with median age of 43 years (range, 17-65 years) at diagnosis. In BMI classification at transplant, 29 patients were underweight, 116 were normal weight, 30 were overweight, and nine were obese. At transplant, median BMI was 22.1 kg/m2 (range, 14.8-33.2 kg/m2) and median d-BMI was −0.39 (range, −7.9-+10.0). There were no significant differences in basement characteristics of patients at transplant and in each BMI and d-BMI group. Survival outcomes were observed with a median follow-up period of 1081 days (range, 8-5230 days). At 1 year, OS was 67.9% (95% CI, 60.7-74.2), DFS was 64.1% (95% CI, 56.7-70.6), and GRFS was 40.2% (95% CI, 33.1-47.2). There was no significant association between BMI at transplant and survival outcomes. GRFS at 1 year for the d-BMI groups under −2, between −2 and +2, and over +2 was 16.1% (95% CI, 5.1-31.4), 45.4% (95% CI, 36.4-53.7), and 41.7% (95% CI, 22.2-60.1), respectively (P = 0.0067) (Figure 1). Multivariate analysis showed that a worse GRFS was associated with lower BMI at transplant than that at diagnosis (d-BMI 〈 −2) (HR 2.72, 95% CI, 1.47-5.03, P = 0.015) and the other prognostic factors of performance status (PS) and disease risk. Conclusions: Our results showed that among 184 AML patients who underwent HSCT for the first time, those with d-BMI 〈 −2 had worse GRFS. Figure GRFS of patients with newly diagnosed AML according to d-BMI. Figure. GRFS of patients with newly diagnosed AML according to d-BMI. Disclosures Fujita: Chugai Pharmaceutical Co.,LTD: Honoraria.

Description: Introduction Although chemotherapy induces complete remission (CR) in the majority of patients with newly diagnosed acute myeloid leukemia (AML), disease will recur in most. The pretreatment cytogenetic and molecular genetic findings are the most important predictors of outcome. However, there are some reports that post treatment parameter value are valuable for prediction of disease recurrence. Here, we examine clinical findings to assess risk of relapse in AML. Patients & Methods We performed a retrospective study involving 303 adult patients newly diagnosed with AML excepted acute promyelocytic leukemia between 2001 and 2012 and received either daunorubicin or idarubicin in combination with cytarabine as induction therapy. 230 patients (75.9%) obtained CR. Data was analyzed for cumulative incidence of relapse (CIR) and disease-free survival (DFS) in these 230 patients. Results The study included 140 males and 90 females, with median age at diagnosis of 48 years (range, 15-77 years). Pretreatment cytogenetics was determined in 228 (99%): 57 (25%) were categorized as favorable (t(8;21) or inv(16)/t(16;16) with or without other abnormalities), 23 (10%) had abnormalities of chromosome 7 and/or complex karyotype defined as Results: One hundred and seventy three PA-AML cases, reported in 88 papers, were analyzed. AML was reported in 120 cases (69%) and APL in 53 cases (31%). The French-American-British (FAB) AML categorization, available for 59 non-M3 AML cases, showed the distribution of AML subtypes similar to that reported in non-pregnant women (M1 - 3%, M2 - 12%, M4 - 30%, M5 - 27%, M6 - 5%, M7 - 1%). Median age at diagnosis was 28 years (range 15-45). Thirty seven women (22%) were diagnosed during 1st trimester, 85 (50%) in 2nd and 47 (28%) in 3rd trimester. The trimester was not reported in 4 cases. One hundred and twenty five women received chemotherapy during pregnancy: 18 in whom therapy was started in 1st trimester, 81- in 2nd and 26 - in 3rd trimester. In 46 patients, treatment was administered either after elective abortion (n = 26), or after delivery of a live baby (n =20). Data on therapy were unavailable in 2 cases. Delay in therapy beyond 1 week (range 2-20) from diagnosis (n = 21) did not affect the overall survival (OS) compared to that obtained in women treated promptly (median 11.5 vs 10.5 months, respectively; p=0.572). Among patients for whom remission data were available (n=151), 82 (73%) treated during pregnancy, and 27 (70%) treated after delivery, achieved CR. Within a median follow-up of 9 months (range 0-300), median OS for the entire cohort was 10.5 months (9 for AML vs 15.5 for APL; p=0.001). A multivariate analysis showed APL to be the only independent predictive factor for an improved OS (p=0.037), while maternal age and treatment delay had no statistically significant impact on OS (p= 0.83 and 0.889, respectively). Notably, the OS of women with PA-AML tended to improve over time (19 months for women treated over the last 30 years vs 8 months for those treated earlier; p = 0.09) (Figure 1); however, it is still less than the median OS of 3 years reported in age-matched non-pregnant women (http://seer.cancer.gov). One hundred and forty seven pregnancies were evaluable for the fetal outcome (excluding elective abortions); 117 (80%) pregnancies ended in delivery of a live baby. Six pregnancies where fetuses were exposed to chemotherapy during the 1st (n=1) or 2nd (n=5) trimester resulted in delivery of malformed newborns; 28 pregnancies ended in fetal death (5 stillbirths, 13 intrauterine fetal deaths, 4 post-delivery deaths, 5 unplanned abortions, 1 cause unavailable). Fetal outcome was unavailable for 2 babies. The median birth weight was 2.3 Kg for the 89 babies with reported weight (range 1.7-5 Kg). Among the 83 babies for whom data about birth weight and pregnancy week were available, 59% had a weight appropriate for the gestational age, 30% were small for gestational age and 11% were large for gestational age. In 89% of cases where information was available, the delivery was pre-term. No case of fetal leukemia was reported. Conclusions Based on our retrospective analysis, the outcome of women diagnosed with AML during pregnancy appears to be worse than that reported in age-matched non-pregnant women. The survival rate of the fetuses exposed to chemotherapy is encouraging. The incidence of malformations is low and the birth weight of most newborns is appropriate for the gestational age. Therapy delay could be considered in some of these patients, but large registry-based studies are warranted to establish treatment recommendations for the management of PA-AML. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1630 Background: In almost all cases, follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are CD20 positive. Since the introduction of rituximab (R), the outcome of the patients with FL or DLBCL has improved perceptively. Since 2001 and 2003, the Yokohama City University Hematology Group in Japan has uniformly treated FL and DLBCL patients, respectively, with 6 cycles of standard (21 days) R-CHOP therapy with curative intent, except in the case of stage 1 FL. Here, we report our experience. Patients and Methods: Five hundred and twenty-six untreated consecutive patients (158, FL; 368, DLBCL) between 2001 and 2009 were the subjects of this study. All the patients were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP in our 7 hospitals. Patients who had partial remission (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles. Patients who did not achieve PR after the 4 initial R-CHOP cycles or those with disease progression at any given time received salvage therapy, and that time point was designated as the point at which the disease had started progressing. Patients who required more than 20% dose reduction were excluded from the study. Those with special forms of DLBCL, such as intravascular lymphoma, primary mediastinal large B-cell lymphoma, and T-cell-rich B-cell lymphoma, were also excluded. Additional local irradiation was performed in patients with PR or complete remission (CR) if deemed necessary by the attending physician. No patients received maintenance therapy with R. DLBCL patients who achieved CR but were initially at risk of central nervous system (CNS) involvement received methotrexate (15 mg) and hydrocortisone (25 mg) 4 times intrrathecally for CNS prophylaxis. Central pathological reviews were not performed; only the individual institutional diagnoses were used. Results: In the cases of FL, the pathological grading was grade 1 for 65 patients, grade 2 for 61 patients, grade 3a for 20 patients, and grade 3b for 12 patients. There were 81 men and 77 women, and the median age at diagnosis was 57 years (range, 25–76). In accordance with the International Prognostic Index (IPI), 60 patients were at low risk (L); 60, at low-intermediate risk (LI); 26, at high-intermediate risk (HI); and 12, at high risk (H). According to the Follicular Lymphoma IPI, 43 patients were classified as L; 49, as being at intermediate risk; and 59, as H. For 7 patients, the risk was undetermined. Ten patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. None received CNS prophylaxis. Twelve deaths were observed among the FL patients, 10 of which were due to the lymphoma. In the DLBCL group, there were 209 men and 159 women, and the median age at diagnosis was 64 years (range, 18–80). According to the IPI, 158 patients were classified as L; 93, as LI; 57, as HI; and 60, as H. Thirty-seven patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. CNS prophylaxis was performed in 42 patients who had an initial CNS risk and achieved CR. In the observaton period, there were 58 deaths among the DLBCL patients, 50 of which were due to the lymphoma. The median observation period for the living patients with FL and DLBCL was 45 months and 43 months, respectively. For the FL group, the CR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) rates were 86%, 50%, and 92%, respectively. Between patients with grade 1–2 FL, and grade 3 FL, the PFS (P = 0.16) and OS (P = 0.17) were not significantly different. This was found to also be true when the PFS (P = 0.19) and OS (P = 0.32) of grade 1–3a and grade 3b FL patients were compared. For the DLBCL group, the CR, 5year PFS, and 5-year OS rates were 89%, 72%, and 80%, respectively. The PFS rate was significantly higher in the DLBCL group compared to the FL group (Fig 1(A), P = 0.001), but the OS was significantly greater in the FL group (Fig 1(B), P = 0.006). Conclusion: Standard R-CHOP therapy is effective for patients with FL and DLBCL, with the 5-year OS rate exceeding 80% for both. However, in the FL group, the PFS did not show a plateau, suggesting the incurability of this lymphoma with R-CHOP therapy. The good OS indicated the effectiveness of salvage therapy for FL patients. Since the OS and PFS in patients with grade 3 FL were similar to those in patients with grade 1–2 FL, all grades of FL should probably be categorized simply as “FL” with regard to R-CHOP therapy. Disclosures: No relevant conflicts of interest to declare.