The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004–0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s 2 ; 0.74 ± 0.16%/s 2 ), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s 2 ; 0.82 ± 0.24%/s 2 , all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s 2 ; 0.43 ± 0.14%/s 2 , all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s 2 ; 0.73 ± 0.18%/s 2 , all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.

ObjectivesPregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE.MethodsIn this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women’s and Children’s Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors.Results and conclusionsFrom 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

Aggressive T and NK/T-cell lymphoma are known to have a high risk of relapse and poor long-term prognosis. Hematopoietic stem cell transplantation has been performed as part of consolidation or salvage treatment. We retrospectively studied the outcomes of autologous (A) and allogeneic (allo) hematopoietic stem cell transplantation (SCT) in aggressive T and NK/T-cell lymphoma at our center between 2010 to 2020. Patients with nodal peripheral T-cell lymphoma (PTCL) that were younger than 65 years old who did not receive upfront autologous SCT (ASCT) at first complete remission were selected from our registry data for further comparison. Thirty-six patients underwent ASCT, and 16 patients underwent alloSCT. In the ASCT cohort, 18 patients with nodal PTCL who underwent upfront ASCT at first complete remission (upfront ASCT) were compared with 15 patients with nodal PTCL who were in first complete remission after single-line induction but did not receive ASCT. The twoyear progression-free survival (PFS) and overall survival (OS) rates for the ASCT cohort were 58% and 73%, respectively. The two-year PFS and OS for the alloSCT cohort were 47% (P=0.35, P=0.02, respectively). Twenty-four patients who received SCT at first remission (21 ASCT and three alloSCT) had a two-year PFS and OS of 75% and 89%, respectively. In comparison, 28 patients who received SCT at relapse/refractory (15 ASCT and 13 alloSCT) had a two-year PFS and OS of 40% and 50%, respectively (P=0.047, P=0.024, respectively). Patients in complete remission prior to transplantation (n=42) had a two-year PFS and OS of 59% and 73%, respectively. In contrast, patients in partial remission prior to transplantation (n=10) had a two-year PFS and OS of 40% and 48%, respectively (p>0.05). Non-relapse mortality occurred in 6% and 43% of ASCT and AlloSCT, respectively. Multivariate analysis revealed that EBV-positivity at diagnosis indicated poorer PFS. EBV-positivity at diagnosis and more than two prior lines of treatment at transplant were associated with poorer OS. For nodal PTCL, the two-year PFS and OS were 79% and 100% for the upfront ASCT cohort and 78% and 92% for the non-upfront ASCT cohort, respectively (p>0.05). Hematopoietic SCT is a feasible treatment option for aggressive T and NK/T-cell lymphoma. Patients who underwent SCT at first remission had better survival rates than those who underwent SCT at relapse/refractory. Nevertheless, due to the limited sample size of the current study, the role of upfront ASCT in patients with nodal PTCL who achieved first complete remission remains unclear.

Introduction Patients with relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL) whom are transplant-ineligible have limited treatment options. To address this specific treatment challenge, we undertook a clinical trial combining lenalidomide and rituximab (R2) with an established salvage regimen for DLBCL in gemcitabine, dexamethasone, cisplatin (GDP). Methods This was a single-center, open-label, phase I/II dose-escalation study of lenalidomide in combination with R-GDP for treatment of transplant-ineligible R/R DLBCL. The study was divided into a phase I dose-escalation study employing a '3+3' design followed by an expansion (phase II) portion with the recommended phase 2 dosing (RP2D), and a maintenance phase using 10 mg daily for 21 out of a 28-day cycle, for up to 1 year. The primary objective was to determine the maximum tolerated dose (MTD) of lenalidomide when combined with RGDP while secondary objectives was to analyze progression-free (PFS) and overall (OS) survival. Dose-escalation included 4 dose levels (DL) of 10 mg, 15 mg, 20 mg, 25 mg, starting at DL1. Lenalidomide was given for 6 cycles during induction therapy on days 1-21 every 28 days for a total of 6 cycles. The expansion phase used lenalidomide at the RP2D. Based on interim PET-CT assessment after cycle 2 (PET-2), patients in CR completed 2 more cycles of R2-GDP followed by two cycles of R2 and then stopped treatment without lenalidomide maintenance; patients with stable disease (SD) or partial remission (PR) completed 2 more cycles of R2-GDP and repeated PET-CT assessment after cycle 4 (PET-4). Based on PET-4, all responding patients (CR or PR) completed a further 2 cycles followed by maintenance with lenalidomide 10mg/day. Patients who failed to achieve at least PR at the point of PET-4 assessment were deemed treatment failure and stopped study treatment. Results The first patient was enrolled in February 2017. At data cut-off (July 20, 2020), 10 patients were enrolled into the dose-escalation study and a further 9 patients in the phase II part using lenalidomide at the RP2D of 15 mg/day (DL2). The MTD of lenalidomide of 15 mg/day was established after 2 of 3 patients at 20 mg/day (DL3) suffered neutropenic sepsis. The median age was 57.5 years (range, 40-76). Seven patients had primary refractory disease after R-CHOP while 13 had relapsed disease. Median time from first diagnosis to trial enrolment was 11.87 months. Median number of prior treatments were 2, including 4 patients who had previously undergone autologous transplant. After a median follow-up of 23.6 months in surviving patients, overall response rate was 68% (CR, N=7; PR, N=6). Median number of lenalidomide cycles completed in the induction phase was 4. Four patients completed less than 3 lenalidomide cycles due to progressive disease (PD). Nine patients died while on follow-up, 7 from PD and 2 infective deaths related to study treatment. The most common grade 3/4 treatment-emergent adverse events were neutropenia and thrombocytopenia with 4 and 11 patients experiencing at least one episode of grade 3 and 4 neutropenia and thrombocytopaenia, respectively. Out of these patients, 2 had neutropenic sepsis. Six patients went on to receive maintenance lenalidomide, completing a median of 5 cycles. Only one patient completed the planned 12 months of lenalidomide maintenance; 2 patients discontinued due to infective complications, one due to neutropenia, one due to patient's decision to stop without any adverse events documented, and one due to PD. For the entire cohort, median PFS and OS were 4.7 months and 26 months, respectively. Patients with primary refractory disease (N=7) had a median PFS of only 2 months. When these patients were excluded, the remaining (N=13) had a median PFS of 21 months. Conclusion In our cohort of transplant ineligible R/R DLBCL patients R2-GDP resulted in an ORR of 68%. Patients with primary refractory disease did not benefit from study treatment. However, for the remaining patients, the median PFS of 21 months compares favorably with other salvage regimens in this population. Lenalidomide at 15 mg/day may safely augment RGDP responses in chemotherapy-sensitive relapsed DLBCL. Disclosures No relevant conflicts of interest to declare.