Bone marrow (BM) examination is the gold standard test in discriminating between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia. However, this procedure is invasive. Mean platelet volume (MPV) is simple and may be used as an alternative diagnostic test in distinguishing these two types of thrombocytopenia. All thrombocytopenic patients (platelet count: <150.0 x 10(9)/l), except those with congestive splenomegaly, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy, were enrolled into the study prospectively. The mean MPV of normal Thais (7.9 fl) was tested as a cutoff value. Any thrombocytopenic patient with MPV of >7.9 fl would be presumptively diagnosed as hyperdestructive thrombocytopenia, whereas one with MPV of
2064 OBJECTIVE: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in Thailand. The objective of the study was to evaluate clinical features, histopathology, treatment outcomes and prognostic factors in Thai adult patients with NHL. METHODS: Using web-based registry system, we prospectively collected clinical information of newly diagnosed NHL patients from eleven major medical centers situated in various geographic regions of Thailand. All histopathological diagnoses were reviewed by consensus meeting of panels of 6 expert hematopathologists and classified according to the 2008 WHO classification of the lymphoid neoplasms. Clinical features and treatment outcomes were analyzed using STATA program. RESULTS: Between January 2007 and May 2009, there were a total of 939 NHL patients whose clinical information including follow-up data and tissue samples were readily available for analysis. The median age was 58 years (range, 15–99). Forty six percent of the patients were ≥60 years of age. Male:female was 1.18:1. The six leading subtypes were diffuse large B-cell lymphoma (67%), extranodal marginal zone lymphoma of MALT type (7%), follicular lymphoma (6%), mantle cell lymphoma (4%), peripheral T-cell lymphoma, not otherwise specified (NOS) (3%) and extranodal NK/T-cell lymphoma, nasal type (3%). T-cell lymphoma constituted 10% of all NHL. The three most common subtypes in T-cell lymphomas were peripheral T-cell lymphoma, NOS (26%), extranodal NK/T-cell lymphoma, nasal type (25%) and angioimmunoblastic T-cell lymphoma (15%). Fifty-eight percent of all patients had advanced disease (stage III, IV), 42% had B symptoms and 54% had elevated serum LDH. The IPI risk groups were 23% low, 30% low-intermediate, 30% high-intermediate and 17% high-risk. HIV-associated NHL was seen in 4.4% of the patients. Of the 801 patients who received chemotherapy, 90% were treated with anthracycline-containing regimen. Twenty-five percent of the patients received rituximab. Of the 663 evaluable patients, the rate of objective tumor response was 75% (CR+CRu, 59%). At a median follow-up time of 13 months, the 4-year projected overall survival (OS) was 73% (95% CI 69–77%). The OS of patients with T-cell lymphoma was inferior to B-cell lymphoma (58% vs. 74%, p = 0.04). With multivariate analysis, the independent adverse prognostic factors for OS in B-cell lymphoma were poor performance status (HR 2.4, 95% CI 1.7–3.5), elevated serum LDH (HR 2.1, 95% CI 1.4–3.1), stage III/IV (HR 1.6, 95% CI 1.1–2.3), WHO subtype (HR 1.1, 95% CI 1.0–1.2), no chemotherapy (HR 3.1, 95% CI 1.9–5.1) and no rituximab treatment (HR 1.7, 95% CI 1.1–2.6). The independent adverse factors for OS in T-cell lymphoma were elevated serum LDH (HR 3.7, 95% CI 1.2–11.1) and male sex (HR 3.4, 95% CI 1.3–8.8). CONCLUSIONS: This study confirmed the characteristic features of NHL among Thai population, i.e., a preponderance of diffuse large B-cell lymphoma and a low incidence of follicular lymphoma within B-cell lymphoma; a relatively high incidence of nasal NK/T-cell lymphoma within T-cell lymphoma. The IPI risk-groups and survival outcomes were comparable to most previously published reports. Disclosures: Bunworasate: Novartis Pharmaceutical: Research Funding. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. Chuncharunee:Novartis: Research Funding.
Introduction In pre-rituximab era, the IPI has been developed and widely used to predict the prognosis of aggressive lymphoma while Miller's stage modified IPI1 was reported as a better prognostic model for limited stage DLBCL. Recently, NCCN-IPI2 was stated to be a better predictor of prognosis for DLBCL in rituximab era. We aim to compare the prognostic significance between IPI, Miller's stage modified IPI, NCCN-IPI and the new proposed stage adjusted IPI (St-IPI) in limited stage DLBCL patients treated with rituximab based regimens. Methods From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were a total of 2,399 patients with DLBCL. We included patients with limited stage DLBCL receiving R-CHOP or R-CHOP-liked chemotherapy. The clinical outcomes were analyzed according to IPI, Miller's stage modified IPI, NCCN-IPI and St-IPI. To generate the St-IPI, we used 3 predictors from IPI namely, age > 60, elevated LDH and ECOG ≥ 2, classified patients into 3 risk cohorts, i.e., the low (score 0), intermediate (score 1-2), and high risk (score 3) group. Results A total of 274 patients with a median age of 58 years (range, 15-91) were included. Seventy-four percent of the cohort had stage II disease, 44% and 32% of them had elevated LDH and ECOG ≥ 2, respectively. According to St-IPI, 77, 183 and 14 patients were categorized as low (score 0), intermediate (score 1-2) and high risk groups (score 3), respectively. Most of the patients (96%) received R-CHOP regimen and one fifth of them underwent consolidation radiotherapy, contributing to a complete response rate of 76%. With a median follow up of 52 months, the 5-year progression free survival (PFS) according to St-IPI among low, intermediate and high risk groups were 79%, 66% and 22%, respectively (HR 2.48, 95%CI: 1.55-3.86). The corresponding figures for 5-year overall survival (OS) were 84%, 73% and 49%, respectively (HR 2.95, 95%CI: 1.54-4.37). The 5-year PFS and OS according to IPI, NCCN-IPI and Miller's stage modified IPI were described in Table 1. When comparing between risk models, St-IPI was able to discriminate more accurately low risk PFS than IPI, distinguished more precisely high risk PFS than NCCN-IPI and Miller's stage modified IPI (Figure 1). All risk models had no differences in predicting OS at 5 years, nevertheless, there was a trend of inferior survivals after 5 years among limited stage DLBCL patients with high risk St-IPI (Figure 2). Conclusion St-IPI is a simple and better model in predicting PFS for limited stage DLBCL treated with R-CHOP. The model is able to predict the lower risk disease more discriminately than the IPI which would suggest the tailor therapy approach to avoid unnecessary treatment related toxicities. Moreover, the St-IPI is better in predicting patients with high risk of relapses in whom more aggressive treatment is warranted to improve the cure rate of the patients. 1 Miller, et al. N Engl J Med 1998; 339: 21-6 2 Zhou, et al. Blood. 2014;123: 837-842 Table 1. 5-year PFS and OS according to risk groups categorized by St-IPI, IPI, NCCN-IPI and Miller's stage modified IPI Risk model 5-year PFS (%) HR (95%CI) P -value 5-year OS (%) HR (95%CI) P -value St-IPI (Age > 60, elevated serum LDH, ECOG ≥ 2) 2.48 (1.55-3.86) <0.001 2.95 (1.54-4.37) <0.001 Low (score 0, n= 77) 79 84 Intermediate (score 1-2, n=183) 66 73 High (score 3, n=14) 22 49 IPI (Age > 60, elevated LDH, ECOG ≥ 2, Stage ≥ III, extranodal involvement >1) 1.99 (1.43-2.78) <0.001 2.03 (1.40-2.97) <0.001 Low (score 0-1, n =203) 73 79 Low-intermediate (score 2, n=57) 61 69 High-intermediate (score 3, n=14) 22 49 High (score 4-5, n=0) - - NCCN-IPI (Age ≤40, >40-60, 60-75, >75; elevated serum LDH 1-3X, > 3X; ECOG ≥ 2, Stage ≥ III, extranodal disease in bone marrow, liver/GI tract or lung) 1.83 (1.30-2.57) <0.001 2.13 (1.45-3.13) <0.001 Low (score 0-1, n=82) 79 86 L-I (score 2-3, n=152) 67 74 H-I (score 4-5, n=40) 44 54 High (score ≥ 6, n=0) - - Miller's stage modified IPI (Age > 60, elevated serum LDH, ECOG ≥ 2, Stage II) 1.71 (1.28-2.28) <0.001 1.69 (1.22-2.35) 0.02 Low (score 0-1, n=107) 78 84 Intermediate (score 2, n=109) 65 73 High (score 3-4, n=58) 51 49 Figure 1. PFS according to risk groups categorized by St-IPI (Figure 1A), IPI (Figure 1B), NCCN-IPI (Figure 1C) and Miller's stage modified IPI (Figure 1D) Figure 1. PFS according to risk groups categorized by St-IPI (Figure 1A), IPI (Figure 1B), NCCN-IPI (Figure 1C) and Miller's stage modified IPI (Figure 1D) Figure 2. OS according to risk groups categorized by St-IPI (Figure 2A), IPI (Figure 2B), NCCN-IPI (Figure 2C) and Miller's stage modified IPI (Figure 2D) Figure 2. OS according to risk groups categorized by St-IPI (Figure 2A), IPI (Figure 2B), NCCN-IPI (Figure 2C) and Miller's stage modified IPI (Figure 2D) Disclosures Khuhapinant: Roche: Honoraria.
Introduction: Despite improved treatment outcome of DLBCL in the immunochemotherapy era, secondary CNS relapse remains a serious and fatal complication. Several prognostic models were reported in order to define high-risk patients for CNS relapse and provide proper prophylactic strategies. There is no standard approach for CNS prophylaxis in DLBCL with more data suggesting lack of efficacy of intrathecal chemoprophylaxis. In 2013, the DSHNHL introduced a prognostic model including each international prognostic index (IPI) factor (age, lactate dehydrogenase (LDH), stage, performance status (PS), extranodal involvement (EN) and kidney/adrenal involvement) to stratify patients into 3 groups. Herein, we applied and validated DSHNHL model to DLBCL patients treated at nationwide University hospitals in Thailand including analyzing an impact of rituximab and intrathecal chemoprophylaxis on CNS relapse. Method: From the nationwide multicenter registry of 4,371 newly diagnosed lymphoma patients in Thailand between 2007 and 2014, there were a total of 2,399 DLBCL patients. We looked at the incidence and clinical predictors of CNS relapse, the effect of immunotherapy and intrathecal chemoprophylaxis on CNS relapse in DLBCL who were treated with at least one cycle of CHOP-like or intensive chemotherapy regimens. Result: After excluding patients with CNS/ocular involvement at diagnosis, 2,034 DLBCL patients were included in the analysis. Table 1 summarizes baseline characteristics of DLBCL patients. The median follow up time for living patients was 51 months (interquartile range, 22-75 months). A total of 565 patients (27.8%) progressed or relapsed after first-line induction therapy and 61 patients (3.0%) developed CNS relapse. Median time to CNS relapse was relatively shorter than non-CNS relapse (8.4 vs 10.5 months, P=0.07). A total of 729 (35.8%), 1,024 (50.3%) and 281 (13.8%) patients were classified as low-, intermediate- and high-risk groups based on DSHNHL risk model for CNS relapse. Of high DSHNHL risk group, 45 patients (16%) received intrathecal chemotherapy for CNS prophylaxis along with induction treatments. Using the competing risk regression analysis, 2-year cumulative incidence of CNS relapse was 2.7% (1.5%, 3.1%, and 4.6% for low-, intermediate- and high-risk DSHNHL group respectively). Univariate analysis showed elevated LDH, poor PS, stage III/IV, presence of B symptoms, higher risk IPI and DSHNHL risk group as risk factors of CNS relapse (Table 2). Presence of concurrent EN involvement more than one site and elevated LDH was a significant predictor of CNS relapse (Hazard Ratio [HR] 2.39, P =0.004). Kidney/adrenal gland and gonadal involvement were not associated with higher risk of CNS relapse whereas breast involvement showed a trend toward higher incidence of CNS relapse (HR 2.46, P=0.07). Either immunochemotherapy or intrathecal chemoprophylaxis was not associated with lower risk of CNS relapse; in fact patients who received intrathecal chemotherapy had more CNS relapse though this could be due to selection bias. Median survival of patients with CNS relapse was 13.2 months which was significantly worse than patients without CNS relapse (81.8 months, P<0.001). Conclusion: The 2-year cumulative incidence of CNS relapse in DLBCL in this analysis was 2.7% which was comparable to other series. Using the DSHNHL prognostic model was able to define DLBCL patients into low, intermediate and high risk for CNS relapse. The high-risk group in our series had lower incidence of CNS relapse compared to German and recently reported British Columbia cohorts. Our study confirms poor survival outcome of DLBCL patients with CNS relapse and no protective effect of immunochemotherapy or intrathecal chemoprophylaxis on the incidence of CNS relapse. Novel risk-adapted CNS prophylaxis strategies are warranted to be further investigated in prospective studies. Figure 1. Baseline characteristics of DLBCL patients based on pattern of CNS relapse IQR: Interquartile Range Figure 1. Baseline characteristics of DLBCL patients based on pattern of CNS relapse. / IQR: Interquartile Range Figure 2. Univariate analysis for factors associated with risk of CNS relapse DSHNHL: The German High Grade Non-Hodgkin's Lymphoma Study Group, R:Rituximab Figure 2. Univariate analysis for factors associated with risk of CNS relapse. / DSHNHL: The German High Grade Non-Hodgkin's Lymphoma Study Group, R:Rituximab Figure 3. 1A shows cumulative incidence (CI) of CNS relapse. 1B shows CI of CNS relapse stratified by the presence of > 1 extranodal involvement and elevated LDH. 1C shows CI of CNS relapse stratified by DSHNHL risk group. 1D shows overall survival based on relapse status. Figure 3. 1A shows cumulative incidence (CI) of CNS relapse. 1B shows CI of CNS relapse stratified by the presence of > 1 extranodal involvement and elevated LDH. 1C shows CI of CNS relapse stratified by DSHNHL risk group. 1D shows overall survival based on relapse status. Disclosures Khuhapinant: Roche: Honoraria.
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