Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma.

The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study.

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Post-Treatment Neutrophil and Lymphocyte Counts Predict Progression-Free Survival Following First-Line Chemotherapy in Hodgkin's Lymphoma.

Hodgkin's lymphoma carries an excellent prognosis with modern chemotherapy, but a significant proportion of patients remain refractory to or relapse after first-line treatment. Immunological changes post-treatment, such as chemotherapy-induced neutropenia (CIN) or lymphopenia, have shown prognostic significance in multiple tumor types. Our study aims to investigate the prognostic value of immunologic changes in Hodgkin's lymphoma by examining the post-treatment lymphocyte count (pALC), neutrophil count (pANC) and the neutrophil-lymphocyte ratio (pNLR). Patients treated for classical Hodgkin's lymphoma at the National Cancer Centre Singapore using ABVD-based regimens were retrospectively analyzed. An optimal cut-off value for high pANC, low pALC and high pNLR in predicting progression-free survival was determined by receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional models. Overall OS and PFS were excellent, with a 5-year OS of 99.2% and a 5-year PFS of 88.2%. Poorer PFS was associated with high pANC (HR 2.99, p = 0.0392), low pALC (HR 3.95, p = 0.0038) and high pNLR (p = 0.0078). In conclusion, high pANC, low pALC and high pNLR confer a poorer prognosis for Hodgkin's lymphoma. Future studies should evaluate the potential of improving treatment outcomes by the adjustment of chemotherapy dose intensity based on post-treatment blood counts.

Burkitt lymphoma - no impact of HIV status on outcomes with rituximab-based chemoimmunotherapy.

We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era.

A genomic-augmented multivariate prognostic model for the survival of natural-killer/T-cell lymphoma patients from an international cohort.

With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E). Cox-proportional hazard multivariate regression also showed that the new GPM is independent and significant for both progression-free survival (PFS, HR: 3.73, 95% CI 2.07-6.73; p < .001) and overall survival (OS, HR: 5.23, 95% CI 2.57-10.65; p = .001) with known risk-features of these indices. When we assign an additional risk-score to samples, which are mutant for the GPM, the Harrell's C-indices of GPM-augmented IPI, PINK, and PINK-E improved significantly (p < .001, χ2 test) for both PFS and OS. Thus, we report on how genomic mutational information could steer toward better prognostication of NKTCL patients.

Treatment outcomes of T and natural-killer/T-cell lymphoma with ifosfamide, carboplatin and etoposide chemotherapy.

BACKGROUND: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. AIMS: We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. METHODS AND RESULTS: Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively. CONCLUSION: In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.

A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma.

Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profiles­low, medium, and high­achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.

Prognostication of diffuse large B-cell lymphoma patients with Deauville score of 3 or 4 at end-of-treatment PET evaluation: a comparison of the Deauville 5-point scale and the ΔSUVmax method.

Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI) <3 selects for patients with extremely low risk of disease progression (HR 0.06, 95% CI 0.01 to 0.62, p 0.018) compared to DS 4 and IPI ≥3.

Treatment Outcomes and Survival Patterns of Asian Patients With Relapsed/Refractory Mantle Cell Lymphoma.

Background: Mantle cell lymphoma (MCL) is widely considered an incurable malignancy even with current therapies and relapsed/refractory (R/R) disease to primary treatment remains common. With improved treatment guidelines and the advent of novel agents, patients are increasingly being treated with more lines of regimens. However, outcomes after each line of treatment remain poorly characterized, especially in the Asian population. In this paper, we described the survival outcomes in a group of R/R MCL patients. Methods: We retrospectively studied 35 patients with R/R MCL between 1998 and 2020 at the National Cancer Centre Singapore. Patients were followed longitudinally throughout their disease course. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method. Results: The median OS and PFS from diagnosis were 105 and 40 months, respectively. After first relapse, the median OS and PFS were 52 and 19 months, post-second relapse 32 and 8 months, and post-third relapse 12 and 6 months, respectively. Patients older than 65 years at first relapse had shorter survival (median OS: 22 vs. 55 months, P = 0.0417; median PFS: 9 vs. 29 months, P = 0.001). Early treatment failure after first line therapy was also associated with worse survival outcomes (median OS: 13 vs. 55 months, P < 0.001; median PFS: 9 vs. 26 months, P < 0.001). Conclusion: With each relapse, survival outcomes for patients with MCL are worse. Novel treatment and contemporary outcomes of R/R MCL are encouraging and support the need for continued research in this area.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

STUDY OBJECTIVE: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. DESIGN: Prospective, single-arm study. SETTING: National Cancer Centre, Singapore. PATIENTS: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. INTERVENTION: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. MEASUREMENTS: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. MAIN RESULTS: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. CONCLUSIONS: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.

Clinical Features of Plasmablastic Lymphoma: Case Series From an Asian Tertiary Cancer Center and Literature Review.

BACKGROUND: Plasmablastic lymphoma (PBL) is an aggressive subtype of mature B-cell non-Hodgkin lymphoma. Given its rarity, there remains a lack of clinicopathological data to guide its management, particularly on Asian patients. METHODS: We conducted a retrospective chart review of 10 patients diagnosed with PBL at the National Cancer Centre Singapore and performed a literature review of similar studies on Asian cohorts. RESULTS: Most patients were male (n = 9), with median age at diagnosis of 55 years (range, 33 - 91 years). Seven (70%) patients were considered to be immunocompromised. In the overall cohort, the median overall survival (OS) was 19.4 months with 5-year survival estimates given at 60% and 36% for OS and progression-free survival (PFS), respectively. At diagnosis, patients with HIV/AIDS (n = 5) were younger compared to others (median, 43 vs. 61 years; P = 0.0278), had greater number of nodal site involvement (median, 6 vs. 0; P = 0.0333), and higher international prognostic index (IPI) scores (P = 0.034 for trend). Amongst different chemotherapy used, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH)-based regimens (n = 6) elicited prominent complete response rates (83%) and led to durable responses even in the setting of advanced stage, high-risk IPI score and immunodeficiency. CONCLUSIONS: In conclusion, our study describes the features of PBL in an Asian cohort and highlights disease features unique to HIV-associated PBL.

A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in Asian patients treated in the Rituximab Era.

Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is uncommonly found on lymph node biopsy and represents a rare haematological malignancy. We aim to examine clinico-pathological features of patients with FL/DLBCL and investigate predictors of survival outcome. We included in our retrospective study patients with histologically-proven FL/DLBCL at diagnosis (n = 106) and who were subsequently treated with rituximab-based chemoimmunotherapy from 2002-2017 at the National Cancer Centre. The cohort consisted of 34 women and 72 men with a median age of 59 years (range, 24-82). In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, advanced stage (p = 0.0136), presence of MYC and/or BCL6 rearrangement (p = 0.0376) and presence of B symptoms (p = 0.0405) were independently prognostic for worse overall survival (OS). The only remaining independent prognostic variables for worse OS after including first-line treatment data in the model were use of chemotherapy regimens other than R-CHOP (p = 0.0360) and lack of complete response to chemotherapy (p < 0.0001) besides the presence of B symptoms (p = 0.0022). We generated a Clinico-Genotypic Index by point-wise addition of all five adverse parameters (score of 0-1, 2, 3, 4-5) which revealed four prognostic risk groups with a predicted 5-year OS of 100%, 62%, 40% and 0% (p < 0.0001) accounting for 50.0%, 24.5%, 18.9% and 6.6% of the cohort respectively. We propose that R-CHOP should be the recommended first-line regimen for composite FL/DLBCL.

A clinicohaematological prognostic model for nasal-type natural killer/T-cell lymphoma: A multicenter study.

Extranodal NK/T-cell lymphoma, nasal type (NKTL) is an aggressive type of non-Hodgkin lymphoma closely associated with Epstein-Barr virus and characterized by varying degrees of systemic inflammation. We aim to examine the prognostic significance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTL. Therefore, we conducted a retrospective review of 178 patients with biopsy-proven NKTL from the National Cancer Centre Singapore and Samsung Medical Center, South Korea. Using receiver operating curve analysis, an optimal cut-off for high NLR (>3.5) in predicting overall survival (OS) was derived. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. In patients with high NLR, estimated 5-year OS was 25% compared to 53% in those with low NLR. In multivariable analysis, high NLR, in addition to age ≥60 years, presence of B-symptoms and stage III/IV at diagnosis, was independently correlated with worse OS (HR 2.08; 95% CI 1.36 to 3.18; p = 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p = 0.0128). A new prognostic index (NABS score) derived from these factors stratified patients into low (0), low-intermediate (1), high-intermediate (2) and high (3-4) risk subgroups, which were associated with 5-year OS of 76.5%, 55.7%, 29.2% and 0% respectively. In conclusion, high NLR is an independent prognostic marker and the NABS model can be used to risk-stratify NKTL patients.

Successful therapeutic rechallenge after a severe episode of high dose methotrexate-induced choreoathetosis: A case report.

Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy.

Real world experience of R-CHOP with or without consolidative radiotherapy vs DA-EPOCH-R in the first-line treatment of primary mediastinal B-cell lymphoma.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinico-pathological subtype of diffuse large B-cell lymphoma with unclear prognostic factors and limited clinical data. Optimal treatment and role for radiotherapy is not fully defined. We performed a multicenter retrospective review of 124 patients with newly diagnosed PMBCL between 2001 and 2016. Treatment regimens were R-CHOP (n = 41), R-CHOP + RT (n = 37), and DA-EPOCH-R (n = 46). 6% (n = 3) in the DA-EPOCH-R group received RT. With a median follow up of 45 months, the overall 5-year OS and PFS was 89.4% and 82.4%, respectively. The type of chemo-radiotherapy regimen, B symptoms and Ann-Arbor staging showed a significant association with OS on univariate analysis but only B symptoms remained prognostic (P = 0.012) after multivariate analysis. The chemo-radiotherapy regimen, Japanese IPI and Ann-Arbor stage was significantly associated with PFS in univariate analysis, but only chemo-radiotherapy regimen remained significant (P = 0.02) after multivariate analysis. Patients who received R-CHOP + RT or DA-EPOCH-R had better PFS than those receiving R-CHOP alone, with 5-year PFS of 90% vs 88.5% vs 56%, respectively (P = 0.02). In the subgroup analysis of patients with bulk (n = 71), R-CHOP alone (n = 21) had inferior 5-year PFS 56.6% compared to those who received R-CHOP + RT (n = 23) 91.3% or DA-EPOCH-R (n = 27) 92.6% (P = 0.007). In contrast, in patients without bulk (n = 42), there was no impact of treatment regimen on PFS (P = 0.25). In conclusion, R-CHOP + RT and DA-EPOCH-R provide excellent outcomes in patients with PMBCL. In patients with bulky disease, the use of DA-EPOCH-R may be preferable as it allows omission of RT without reduction in efficacy.

Management of hepatitis B reactivation in lymphoma patients on rituximab with past hepatitis B exposure: An observational study.

BACKGROUND: Currently, a standardized approach to prevent and manage hepatitis B reactivation in lymphoma patients with past hepatitis exposure receiving rituximab in Singapore is lacking. This study is designed to report the current management approach and outcomes associated with hepatitis B reactivation. OBJECTIVES: The primary objective was to report 6-, 12-, 24-month cumulative hepatitis B reactivation-related outcomes. Secondary objectives were to report monitoring frequencies of hepatitis B DNA and liver function tests performed in lymphoma patients with resolved hepatitis B receiving rituximab, and anti-viral prophylaxis use. METHODOLOGY: This was a single centre, retrospective observational study. Patients with resolved hepatitis B initiated on rituximab from January 2011 to December 2015 were identified and reviewed over a two-year period starting from the date of rituximab initiation. Relevant parameters were obtained from electronic medical records. Hepatitis B reactivation was defined by hepatitis B DNA levels 20 IU/ml (1.30 log/ml) and above. Data were analysed using descriptive statistics. RESULTS: Seventy-five patients were retrospectively reviewed over a two-year period. Hepatitis B reactivation was defined as hepatitis B DNA levels ≥20 IU/ml (1.30 log/ml). The 24-month cumulative hepatitis B reactivation rate was 4.0%. The median (interquartile range) number of hepatitis B DNA tests performed during treatment, initial six-month follow-up, and subsequent follow-up were 1.0 (0.0-2.6), 1.0 (0.0-2.0), and 1.0 (0.0-3.1), respectively. CONCLUSION: Large variations in hepatitis B reactivation monitoring and management strategies were observed. Further studies are required to develop and determine a standardised protocol that could contribute to safer and more cost-effective care for lymphoma patients with resolved hepatitis B on rituximab.