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The aim of this study was to investigate the effect of low-dose ruxolitinib (daily dose ≤ 10 mg) for the treatment of myelofibrosis (MF). A retrospective analysis was performed on a total of 88 patients with myeloproliferative neoplasm-associated MF (MPN-MF) who were diagnosed and treated in West China Hospital, Sichuan University, China. A total of 44 MPN-MF patients received a low dose of ruxolitinib (daily dose ≤ 10 mg), while another 44 patients received 10-25 mg twice daily. Low-dose ruxolitinib treatment resulted in slow, but gradual spleen response. Compared with baseline, the mean changes in palpable spleen length in the low- and high-dose groups were -26.9 and -49.0% after 12 weeks of treatment, respectively, and -46.7 and -64.1% after 48 weeks of treatment, respectively. In the low dose group, the median myeloproliferative neoplasm symptom assessment form (MPN-SAF) total symptom score (TSS) decreased by 37.8 and 35.9% at the 12 weeks and 48 weeks after treatment, respectively. No statistical difference was observed in MPN-SAF TSS among different dose groups. After 48 weeks of treatment, bone marrow (BM) fibrosis improved in 43.3% (13/30) of evaluated patients and was stable in 56.7% (17/30) patients. In the low-dose treated group, BM fibrosis improved in 50% patients and was stable in remaining 50%. Low-dose ruxolitinib is effective in treating MF.

Early molecular response is associated with improved probability of deep molecular response and superior survival in patients with CML-CP. However, ~1 in 3 patients on first-line imatinib do not achieve this threshold. The phase 2b DASCERN trial (NCT01593254) assessed the outcome of early switch to dasatinib in patients with suboptimal response to first-line imatinib. Adult patients with CML-CP were randomized (2:1) to receive 100 mg dasatinib (n = 174) or continue imatinib at ≥400 mg (n = 86). The primary endpoint was the rate of major molecular response (MMR) at 12 months, which was 29% (dasatinib) and 13% (imatinib; P = 0.005). After ≥2 years of follow-up, 45 patients (52%) randomized to continue imatinib had crossed over to dasatinib. Considering treatment crossover, the 2-year cumulative MMR rate was 64% with dasatinib and 41% with imatinib (66% and 67%, respectively by intent-to-treat). Adverse events were consistent with the established safety profiles of both drugs. The results of this first prospective study support early monitoring of patients treated with first-line imatinib, and suggest that switching to dasatinib in cases of suboptimal response may offer clinical benefit. Further follow-up is needed to assess the long-term clinical benefit of early switching.

Mental health problems in the general population have been reported during the SARS-CoV-2 pandemic; however, there were rare data in persons with chronic myeloid leukemia (CML). Therefore, we performed a cross-sectional study on mental health evaluated using the 9-item Patient Health Questionnaire (PHQ-9; depression), the 7-item Generalized Anxiety Disorder (GAD-7; anxiety), and the 22-item Impact of Event Scale—Revised (IES-R; distress), including subscales of avoidance, intrusion, and hyper-arousal in persons with CML, non-cancer persons, and immediate family members of persons with cancer as controls (≥16 years) by an online survey. Data from 3,197 persons with CML and 7,256 controls were collected. In multivariate analyses, CML was significantly associated with moderate to severe depression (OR = 1.6; 95% Confidence Interval [CI], 1.4, 1.9; p < 0.001), anxiety (OR = 1.4 [1.1, 1.7]; p = 0.001), distress (OR = 1.3 [1.1, 1.5]; p < 0.001), and hyper-arousal (OR = 1.5 [1.3, 1.6]; p < 0.001). Moreover, delay in regular monitoring was significantly associated with depression (OR 1.3 [1.0, 1.7]; p = 0.024), anxiety (OR = 1.3 [1.0, 1.8]; p = 0.044), avoidance (OR = 1.2 [1.0, 1.4]; p = 0.017), and intrusion (OR = 1.2 [1.0, 1.4]; p = 0.057); tyrosine kinase-inhibitor dose reduction or discontinuation, depression (OR = 1.9 [1.3, 2.8]; p = 0.001), distress (OR = 2.0 [1.4, 2.8]; p < 0.001), avoidance (OR = 1.6 [1.2, 2.1]; p = 0.004), intrusion (OR = 1.6 [1.1, 2.1]; p = 0.006), and hyper-arousal (OR = 1.3 [1.0, 1.8]; p = 0.088). We concluded that persons with CML during the SARS-CoV-2 pandemic have worse mental health including depression, anxiety, and distress symptoms. Decreasing or stopping monitoring or dose resulted in adverse mental health consequences.

Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups. Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Müller, p. 3

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

Background: The prognosis of nasal type advanced-stage or relapsed extranodal NK/T cell lymphoma (ENKTL) is poor even with intensive multi-agent chemotherapy. It is therefore critical to develop more effective treatment strategies to improve outcomes and prognosis of ENKTL patients. Methods: We conducted a multi-center, prospective study to evaluate the efficacy and safety of a new treatment strategy: induction chemotherapy with gemcitabine, L-asparaginase or PEG-asparaginase, ifosfamide, dexamethasone and etoposide (GLIDE) followed by upfront autologous hematopoietic stem cell transplantation (ASCT) conditioning with either carmustine, etoposide, cytarabine, and melphalan (BEAM) or chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Findings: A total of 64 eligible patients were enrolled. After a maximum of 6 cycles of GLIDE, 43 patients (70·5%) achieved complete response, including 31 (50·8%) who achieved complete response after 2 cycles. With median follow-up of 23.8 months, estimated 5-year progression-free survival and overall survival of the whole cohort was 54·0% and 68.9% respectively. Among 50 chemo-sensitive patients (patients in complete or partial remission) , 27 underwent upfront ASCT, and they showed a significantly higher rate of 5-year progression-free survival than chemosensitive patients who did not receive upfront ASCT (78·8% vs. 36·0%, p=0·0004) as well as a significantly higher rate of 5-year overall survival (87·2% vs. 55·4%, p=0·0035). Interpretation: GLIDE chemotherapy showed a high efficacy in disease control for the patients with advance-staged or relapsed ENTKL, and in whom achieved partial or complete response, GLIDE followed by upfront ASCT may be a more effective treatment strategy than GLIDE alone. Trial Registration Information: The study was registered at the Chinese Clinical Trial Registry (Chictr.org.cn, Chicrt-TNC-10000782). Funding Statement: This work was supported by a grant from Science and Technology Fund of Sichuan Province, China, NO.18ZDYF2063. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital, Sichuan University. Written informed consent was obtained from all patients.

We report the clinical results of sustainedly integrating imatinib and interferon-α into maintenance therapy in the patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Maintenance therapy lasted for 5 years with imatinib 400 mg daily, interferon-α 3 million units, 2∼3 doses per week, and chemotherapy including vindesine and dexamethasone scheduled monthly in first year, once every 2 months in second year, and once every 3 months in third year. The chemotherapy was discontinued after 3 years and the imatinib and interferon-α continued for another 2 years. For 41 patients without allo-HSCT with a median follow-up of 32 months, the 3-year DFS and OS were 42.7 ± 8.6% and 57.9 ± 8.4%, respectively. Our study suggests that sustaining maintenance with low-dose chemotherapy, imatinib and interferon-α improved survival of adult Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients ineligible for allo-HSCT, and even provided an opportunity for cure. BCR/ABL persistent negativity at 6 and 9 months may have benefit to choose suitable patients for the imatinib/interferon-α maintenance strategy.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

In the tyrosine kinase inhibitor (TKI) era, imatinib is the first-line therapy for patients with chronic myeloid leukemia (CML) in chronic or accelerated phase. Although second-generation TKIs (TKI2), including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 (n = 33) and allo-HSCT (n = 60) groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 (36.7%), 35 (58.3%), and 3 (10%) patients underwent allo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients (100%) achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate (42.9% vs. 86.4%, P = 0.002), 5-year event-free survival rate (14.3% vs. 76.1%, P < 0.001), and 5-year progression-free survival (28.6% vs. 78.1%, P < 0.001) than those in the allo-HSCT group. Multivariate analysis showed that male sex and TKI2 therapy were predictors of poor overall survival, whereas hemoglobin < 100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patients with CML in accelerated phase.

Background: Ruxolitinib, a potent JAK1/JAK2 inhibitor, has been proved to improved splenomegaly and debilitating myelofibrosis-related symptoms in several clinical trials. However, not much is known about the efficacy of ruxolitinib, especially low-dose ruxolitinib, in real world patients in China. Here we assess the efficacy of ruxolitinib in treatment of patients with myeloproliferative neoplasms associated myelofibrosis (MPN-MF) in real world and to analyze factors affect the treatment efficacy. Methods and Results: From July 2017 to June 2019, data of MPN-MF patients treated with ruxolitinib in West China hospital, Sichuan University, China, were retrospectively collected and analyzed. Logistic regression was used for univariate and multivariate analysis of binary variables. Simple linear regression was used in univariate analysis of continuous variables, and multiple linear regression was used in multivariate analysis of continuous variables. Dose of ruxolitinib were decided according to platelet count and financial condition of patients. Of 72 MPN-MF patients, 1 patient was treated with ruxolitinib in an initial dose of 5mg qd, 37 patients with 5mg bid, 15 patients with 10mg bid, 2 patients with 25mg bid. At week 12, 89.3% of patients achieved reduction from baseline in palpable spleen length, of which 44.6% patients achieved ≥50% reduction (Figure 1) ; 95.6% patients achieved reduction from baseline in Total Symptom Score (TSS), of which 44.6% patients achieved ≥50% reduction(Figure 2). At week 48, all 25 patients with bone marrow biopsies achieved improved or stable bone marrow fibrosis grading from baseline, of which 44.0% improved (Figure 3). Both univariate analysis and multivariate analyses showed higher dose of ruxolitinib (>5mg bid VS ≤5mg bid and>10mg bid VS ≤10mg bid) was the major factor associated with better spleen response(P10mg VS ≤10mg) was the only factor associated with better TSS improvement(P Conclusion These data indicated that ruxolitinib treatment provided reduction in spleen, improvement in symptoms and stable or improve bone marrow fibrosis in Chinese MPN-MF patients. Although some MPN-MF patients derived benefit at low-dose ruxolitinib, higher dose were associated with better spleen and symptom responses. Legends to figures Figure 1: Percent change from baseline in palpable spleen length at week 12 for individual patients. Only patients with palpable spleen length measurements at baseline and week 12 (n=56) were included. qd: once daily, bid: twice daily Figure 2: Percent change from baseline in TSS at week 12 for individual patients. Only patients with TSS measurements at baseline and week 12 (n=68) were included. qd: once daily, bid: twice daily Figure 3: Change in marrow histomorphologic features in 25 patients at week 48. Green: fibrosis improved, Yellow: fibrosis stable, Red: fibrosis progress Disclosures No relevant conflicts of interest to declare.

This multicenter, randomized, open-label phase III study compared the efficacy and safety of micafungin and itraconazole in prophylaxis of invasive fungal infections in neutropenic patients undergoing hematopoietic stem cell transplants in China. Micafungin (50 mg/day i.v.) or itraconazole (5 mg/kg/day p.o.) was administered for ≤42 days. The primary endpoint, treatment success, was defined as no proven, probable, or suspected invasive fungal infection through therapy and the absence of proven or probable invasive fungal infection through the end of 4 weeks after therapy. Noninferiority of micafungin against itraconazole was established if the lower boundary of the 95% confidence interval (CI) was >10%. Of 287 patients, 283 were evaluable for efficacy (136 for micafungin, 147 for itraconazole, intent-to-treat population). Treatment success was documented in 92.6% (126 of 136) of micafungin-treated patients and 94.6% (139 of 147) of itraconazole-treated patients (95% CI, −7.562% to 3.482%; P = .48), indicating noninferiority of micafungin against itraconazole. Results were similar for patients treated per protocol. Whereas the rates of proven or probable invasive fungal infection were numerically higher with micafungin than itraconazole at 4.4% (6 of 136) and 1.4% (2 of 147), rates of suspected invasive fungal infection were similar at 5.9% (8 of 136) and 7.5% (11 of 147), respectively. More patients treated with micafungin than itraconazole completed the study (82.9% versus 67.3%, respectively). Significant differences in incidence of withdrawal due to an adverse event (4.4% versus 21.1%) and drug-related adverse events (8% versus 26.5%) were shown between micafungin and itraconazole (P = .00, chi-square test). Micafungin was as effective as itraconazole in preventing invasive fungal infections in patients with neutropenia. In comparison to itraconazole, treatment tolerance was much better with micafungin.

Natural killer (NK) cell neoplasms are unusual disorders. In this study we compared results of flow cytometric immunophenotype (FCI) with cytomorphology, histopathology and clinical findings in a series of patients with NK cell neoplasms with peripheral blood and/or bone marrow involvement, and the FCI of neoplastic and normal NK cells were compared. Retrospective data and specimens (bone marrow aspiration or peripheral blood) from 71 cases of NK cell neoplasms were obtained. All patients have been demonstrated laboratory and clinical features consistent with NK cell neoplasms, and the subtypes were determined by integrated clinical estimation. Routine 4-color flow cytometry (FCM) using a NK/T cell related antibody panels was performed. NK cell neoplasms were divided into two major subtypes by FCI, namely malignant NK cell lymphoma, including extranodal nasal type NK cell lymphoma (ENKL, 11 cases) and aggressive NK cell lymphoma/leukemia (ANKL, 43 cases), and relative indolent chronic lymphoproliferative disorder of NK cell (CLPD-NK, 17 cases). The former exhibited stronger CD56-expressing, larger forward scatter (FSC) and more usually CD7- and CD16-missing. FCI of CLPD-NK was similar to normal NK cells, but CD56-expressing was abnormal, which was negative in five cases and partially or dimly expressed in eight cases. Cytomorphologic abnormal cells were found on bone marrow slides of 4 cases of ENKL and 30 cases of ANKL. Eight cases of ENKL were positive in bone marrow biopsies, and other three cases were negative. In 32 cases of ANKL which bone marrow biopsies were applied, 21 cases were positive in the first biopsies. Lymphocytosis was found only in six cases of CLPD-NK by cytomorphology, and biopsy pathology was not much useful for diagnosing CLPD-NK. These results suggest that FCM analysis of bone marrow and peripheral blood was superior to cytomorphology, bone marrow biopsy, and immunohistochemistry in sensitivity and early diagnosis for ANKL, stage III/IV ENKL and CLPD-NK. FCI could not only define abnormal NK cells but also determine the malignant classification. It is beneficial for clinical management and further study of NK cell neoplasms.

Introduction: Treatment with dasatinib, a second-generation tyrosine kinase inhibitor (TKI), has resulted in high rates of cytogenetic and molecular responses for pts with CML-CP, both as initial therapy and after failure of other therapies. A reduction in BCR-ABL1 transcript levels to ≤ 10% on the International Scale (IS) at 3 mo is associated with an improved probability of deep molecular responses and superior progression-free and overall survival (PFS and OS). In DASISION, considerably more pts treated with dasatinib achieved BCR-ABL1 ≤ 10% IS compared to imatinib. BCR-ABL1 ≤ 10% IS at 3 mo is considered an optimal response by international guidelines; however, approximately one-third of pts with CML-CP on first-line (1L) imatinib will not achieve this threshold. Clinical studies exploring the potential benefit of early switching to dasatinib in pts with less than optimal responses on initial imatinib treatment have not been reported. Methods: DASCERN (NCT01593254) is a randomized, open-label, international phase 2b trial in adult pts with CML-CP who had achieved complete hematologic response (CHR) but who had BCR-ABL1 > 10% IS at 3 mo after initial treatment with 400 mg imatinib once daily (QD). Imatinib must have been started within 6 mo of the initial CML-CP diagnosis. Pts were randomized 2:1 to receive 100 mg dasatinib QD or continue imatinib at ≥ 400 mg daily with the option for dose escalation. Pts initially randomized in the imatinib cohort who met European LeukemiaNet 2013 failure criteria after randomization and without dasatinib-resistant mutations were crossed over to the dasatinib arm. The primary endpoint in DASCERN is the rate of MMR (BCR-ABL1 < 0.1% IS) at 12 mo after day 1 initiation of 1L imatinib (9 mo after randomization). Secondary endpoints include time to MMR, OS, and PFS (progression was defined as transformation to accelerated/blast phase or death). Tertiary endpoints include safety and tolerability profile of both treatment arms and cytogenetic response over time. Results: All 260 randomized pts (dasatinib: n = 174; imatinib: n = 86) had a minimum follow-up of ≥ 12 mo from the last pts 1st visit (Sokal scores: 28% low, 30% intermediate, 24% high, 18% unknown; median age 37 y [range 18-82, 95% were < 65 y]; 78% male; 73% Asian). All pts had e13a2 or e14a2 transcript types. At the time of analysis, 84% of pts were continuing in the study. Median daily dose was 100 mg QD (range 26-142) for dasatinib and 400 mg QD (range 129-825) for imatinib. Median treatment duration was 111 wk (774 d) in the dasatinib arm and 68 wk (477 d) in the imatinib arm; 42 (49%) imatinib-randomized pts crossed over to dasatinib. Rate of MMR at 12 mo in the intent-to-treat population was 29% (95% confidence interval [CI] 22, 36) for dasatinib and 13% (95% CI 7, 22) for imatinib (P = 0.005); median time to MMR was 14 mo (range 12-18) for dasatinib vs 20 mo (range 14-26) for imatinib (P = 0.053). No differences in the rate of progression or OS were observed between treatment arms. No new safety signals were observed for either treatment arm and the early switch to dasatinib did not increase the toxicity rate. Treatment-emergent pleural effusion (PE; any grade) occurred in 11 (6%) pts randomized to dasatinib and 3 (7%) imatinib-randomized pts who crossed over to dasatinib; treatment-emergent PE grade 3/4 occurred in 1 (1%) pt randomized to dasatinib and 2 (5%) pts randomized to imatinib who crossed over to dasatinib. Hematologic toxicity was similar between treatment arms: neutropenia grade 3/4 occurred in 18 (11%) pts randomized to dasatinib and 12 (29%) pts randomized to imatinib who crossed over to dasatinib; thrombocytopenia grade 3/4 occurred in 18 (11%) pts randomized to dasatinib and in 7 (17%) pts randomized to imatinib who crossed over to dasatinib. Two dasatinib-treated pts discontinued due to hematologic toxicity (1 neutropenia, 1 thrombocytopenia). Conclusions: Early results from DASCERN show that pts with suboptimal responses to imatinib at 3 mo who switched to dasatinib had a significantly increased rate of MMR at 12 mo compared to pts who remained on imatinib. Longer follow-up is required to assess the impact of early switching on PFS and OS, and achievement of deep molecular responses. Disclosures Cortes: Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding. Hochhaus:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Takeda: Research Funding. Kim:BMS: Research Funding; Ilyang: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Savona:Boehringer Ingelheim: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Martin Regueira:Bristol-Myers Squibb: Employment, Equity Ownership. Sy:Bristol-Myers Squibb: Employment. Gurnani:Bristol-Myers Squibb: Employment.

Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently the standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). In this study, we present results of the ENESTchina (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-China) that was conducted to investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a Chinese population. ENESTchina met its primary end point with a statistically significant higher rate of major molecular response (MMR; BCR-ABL1 ≤0.1% on the International Scale) at 12 months in the nilotinib arm vs the imatinib arm (52.2% vs 27.8%; P < .0001), and MMR rates remained higher with nilotinib vs imatinib throughout the follow-up period. Rates of complete cytogenetic response (0% Philadelphia chromosome-positive [Ph+] metaphases by standard cytogenetics) were comparable and ≥80% by 24 months in both arms. The estimated rate of freedom from progression to accelerated phase/blast crisis at 24 months was 95.4% in each arm. The safety profiles of both drugs were similar to those from previous studies. In conclusion, rates of MMR at 12 months were superior with nilotinib vs imatinib in Chinese patients with newly diagnosed Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01275196.

In an attempt to establish the advantages of fluorescence in situ hybridization (FISH) studies over conventional cytogenetic (CC) analysis, a total of 2302 de novo MDS patients from 31 Chinese institutions were prospectively selected in the present study for both CC and standardized FISH analysis for +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities. CC analysis was successful in 94.0% of the patients; of these patients, 35.9% of the cases were abnormal. FISH analysis was successful in all 2302 patients and detected at least one type of common cytogenetic abnormality in 42.7% of the cases. The incidences of +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities by FISH were 4.1% to 8.7% higher than those by CC. FISH identified abnormalities in 23.6% of the patients exhibiting normal CC results and revealed that 20.7% of the patients with adequate normal metaphases (≥20) had abnormal clones. FISH identified cytogenetic abnormalities in 50.4% of the patients with failed CC analysis. In summary, our multicenter studies emphasised and confirmed the importance of applying standardized FISH testing based on an appropriate panel of probes to detect common cytogenetic abnormalities in Chinese de novo MDS patients, particularly those with normal or failed CC results.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell clinical disease, which has been reported associated with T cell monoclonal expansion and plasma cell dyscrasias. There we reported a case with a 20-year clinical history of PNH. Lately diagnosis of Waldenström macroglobulinemia with the offered evidences of bone marrow examination, flow cytometry and immunofixation electrophoresis. T cell monoclonal expansion was established by polymerase chain reaction. Meanwhile the decreased expression of CD55 and CD59 on neutrophils and erythrocyte were obvious observed. Here we describe the diagnostic evaluation of this patient and provide a brief review of such clonal disorder.

Objective. Hemophagocytic lymphohistiocytosis (HLH), also known as Hemophagocytic Syndrome (HPS), is an increasingly recognized clinical syndrome that is characterized by extreme immune activation. HLH was first described as an inherited immune disorder in pediatrics, but it may also arise in adults as the result of persistent antigen stimulation due to infections, autoimmune disorders or malignancies. Early recognition of HLH and appropriate treatment are critically important. For the pediatric patients, the Histiocyte Society Study Group for HLH has developed the HLH-94 and HLH-2004 treatment protocols, but there is no such guideline or consensus for adult HLH. Although there were increasing amount of clinical studies in adult HLH, the majority of them just described the etiologies and clinical profiles, and failed to analyze the treatment effects on outcomes. Therefore, there is an urgent need for more clinical data focusing on treatment in adult HLH patients, in order to clarify optimal therapeutic regimens. Our study retrospectively analyzed the causes, treatment strategies, and relevant outcomes in 104 adult HLH patients in our institution, and with the goal of identifying more appropriate therapeutic strategies for adult HLH patients. Methods. After the approval of our protocol by local institutional Ethics Committee, the medical records of 104 consecutive patients with adult onset HLH in West China Hospital from June 2008 to February 2016 were reviewed. The diagnosis was re-confirmed according to HLH-04 criteria, and demographic data, clinical profiles, treatments and outcomes were collected and analyzed. The latest follow-up visit occurred on 1st July 2016. The different therapeutic effects on prognosis were discussed based on the endpoints which were defined as short-term (30 days) and long-term (last follow-up date) survival rates. Statistical analysis was performed on SAS 9.4 software, and was involved in Log-rank test in univariate analysis and Cox proportional hazard regression model in multivariate analysis. All p values were two-sided and p Results. All of 104 consecutive patients with adult HLH were enrolled in this study. The male/female ratio was 1.6:1 with the median age of 35 (range 16-77). In etiological classification, 75 cases were lymphoma-associated HLH, 13 cases were infection-associated HLH, 2 cases were with autoimmune disorders, and for the remaining 14 cases, the underlying diseases could not be identified. In treatment analysis, corticosteroids were used in 91 cases (87.5%), the median initiation time was 0 day (range 0-26 days) after HLH diagnosis, the median four-week accumulating dosage was 236.57mg dexamethasone. Etoposide was employed in 55 cases (52.9%), the median initiation time was 3.5 days (range 0-62 days), the median four-week accumulating dosage was 590.00mg. Cyclosporine A (CSA) was used in 42 cases (40.4%), the median initiation time was 2 days (range 0-51 days), the median four-week accumulating dosage was 7100.00mg. The median survival time for all patients was 46 days (1-2529 days). On the 30th day after admission, 27 patients (26.0%) had died, and 77 patients (74.0%) had survived. At the last follow-up visit, 74 patients (71.2%) had died, 17 patients (16.2%) were still alive, and 13 patients had been lost to follow-up. Statistical analysis indicated that patients in etoposide-treated group was associated with superior short-term survival rate, compared with non-etoposide-treated group (p=0.0471), but there was no difference in long-term survival rate between the two groups. CSA-treated group was associated with inferior long-term survival rate (p=0.0214), compared with non-CSA-treated group. In patients with lymphoma-associated HLH, those who received antineoplastic chemotherapy had a higher long-term survival rate than those who did not receive it (HAZARD=0.07, p Conclusion. The major underlying diseases of adult onset HLH are malignant lymphomas. Etoposide might only improve the short-term survival, but fail to change the long-term survival. Immunosuppressor CSA seems to be associated with negative effects on long-term survival rate. For patients with lymphoma-associated HLH, antineoplastic chemotherapy might improve the long-term outcome. More clinical prospective studies should be initiated for adult acquired HLH. Disclosures No relevant conflicts of interest to declare.

Recent data indicates that nucleoside/nucleotide analogue (NUC) is effective in preventing and controlling hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the ideal antiviral agent and optimal application protocol still needs to be determined. Meanwhile, it is uncertain whether those with past HBV infection require antiviral prophylaxis during chemotherapy. This report retrospectively analyzed non-Hodgkin’s lymphoma (NHL) patients seen from January, 2004 to June, 2009 in West China Hospital. We found that the prevalence of chronic HBV infection in our NHL patients was 20.7 % while that of past HBV infection was 21.05 %. Compared with the high rate (25.6 %) of HBV reactivation in patients with chronic HBV infection, none of those with past HBV infection in fact had occult HBV infection thus none experienced reactivation. Of the 82 patients with chronic HBV infection who received chemotherapy, antiviral prophylaxis could significantly reduce the incidence of HBV reactivation (5.0 vs. 45.2 % in the control group) and the incidence of liver function damage (32.5 vs. 73.8 % in the control group). The results of the current study confirmed previous reports that prophylactic NUCs administration can effectively prevent HBV reactivation and significantly reduce the incidence of HBV reactivation especially for patients receiving rituximab-containing regimens. Due to the fact that none of individuals who had past HBV infection developed HBV reactivation reported in our study, antiviral prophylaxis may not be required for patients with past HBV infection. Close observation of alanine aminotransferase and HBV–DNA contributes to early diagnosis and timely treatment of HBV reactivation.

Background In China, the incidence of aplastic anemia (AA) is about 0.74/105, with 0.14/105 of severe aplastic anemia (SAA). Most of these SAA patients are treated in big medical centers or traditional Chinese medicine (TCM) hospitals, which could stand for the current practices in China. Despite the China Aplastic Anemia Consensus, published in 2010, recommended that the immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) were the standard treatment for SAA, very severe aplastic anemia (VSAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA), the current treatment options for patients with these diseases are diverse, including antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) + cyclosporin A (CsA), CSA + androgen, CSA or androgen alone, only supportive care, TCM, etc. This national disease registry study aimed to describe the current clinical practice and treatment patterns for SAA, VSAA and TD-NSAA patients in China and understand their IST patterns as well as the supportive care measures. Methods In this prospective, multi-center, observational study, adult or pediatric patients diagnosed as acquired aplastic anemia within 3 months and met the guideline criteria of SAA, VSAA or TD-NSAA were enrolled from October 2012 to April 2014. All enrolled patients will be followed at least for one year. Each subject will be visited every 3 months in the first year and every 6 months from the second year until the patients withdraw the ICF or study close. The main evaluation criteria is the treatment patterns of SAA, VSAA and TD-NSAA which will be specified as: IST (ATG + CsA, CsA + androgen, CsA and others), HSCT, TCM, androgen, supportive care and others. The response of SAA/VSAA and TD-NSAA after each treatment, and serious adverse events, will also be evaluated by the investigators. An interim analysis is planned when all patients have been enrolled (target N=350) and will focus on their baseline characteristics and first treatment choice. This study was sponsored by Sanofi. Results A total of 352 patients were enrolled at 29 sites in China (SAA 221 pts; VSAA 84 pts; TD-NSAA 47 pts). The median age was 21 years (range, 0-84) and 65.1% were adults. 51.7% were male and 71.6% had ECOG PS Conclusions Chinese AA patients received diverse treatments in real life clinical practice. Based on this interim analysis, 74.1% of the SAA, VSAA and TD-NSAA patients in China received IST. But only 26.4% of them received the standard ATG + CsA therapy. TCM therapy still played a role in the treatment, especially for SAA and VSAA patients in China. Final results including efficacy and safety profiles will be reported later. Disclosures Off Label Use: Anti-thymocyte globulin-Fresenius is used as an immunosuppressive therapy for the treatment of aplastic anemia.

Abstract 3714 Background: The non-GCB subtype of diffuse large B-cell lymphoma(DLBCL) has inferior response to rituximab based chemothrapy. Recent reports show a constitutional expression of NF-κB pathway in non-GCB subtype of DLBCL. Bortezomib, as proteasome inhibitor, has been shown a promising new agent for the treatment of DLBCL. As how the efficacy, doses and protocol of Bortezomib need to be clarified. Objective: This trial is a pilot multicenter clinical study to evaluate the efficacy and safety of an escalated dose of bortezomib based chemotherapy for the treatment of patients with relapsed or refractory non-GCB subtype of DLBCL. Patients and Materials: A total 24 pts with DLBCL were enrolled in 4 different medical centers. According to Hans' Tissue Microarray (TMA) Classification, 23 pts were diagnosed as non-GCB subtype, and 1 patient have not done the test. 16 pts had relapsed or refractory disease, while 8 pts had fail response to the first line treatment. All the patients had received Rituximab based chemotherapy previously. There were 16 male and 8 female. The patient age ranged from 19 to 73, of which the median age was 55. Methods: All patients were given bortezomib 2.0mg/m2, day 1, I.V. (intravenous injection 12 hours before chemotherapy), 5 pts were given additional dose of 0.7 mg/m2, I.V., at day 8. The combination protocols include: Bortezomib(V)+ICE(G) 13 pts; Bortezomib(V)+HyperCVAD 7 pts; Bortezomib(V)+EPOCH 3 pts; Bortezomib(V)+DHAP 1 pts. The patients were given 1 to 5.courses differently. Results: The follow-up time were 2 to18 months, with a median time of 8 months. Of 24 pts, 21 evaluable pts received more than 2 courses of therapy: 7 pts achieved complete remission (CR 33.3%), 9 pts achieved partial remission (PR 42.8%), 5 pts had no response (NR 23.8%), The overall response rate (ORR) was 76.1%. Of 16 responsive pts, the PFS were 2 to 18 months; the average PFS was 7.6 months and median PFS was 7.5 months. Up to now, 13 pts were still alive, and 7 pts were dead, and 1 pts lost follow-up. Of 7 death, 5 were caused by disease progression with 4 pts of central nervous infiltrates, 2 were caused by severe infections. The one year overall survival rate (OS) was 65%. Of all the 24 pts, 10 pts had 3 to 4 grade of myelosuppression; 1 case with severe pulmonary infection;1 case with septicemia; 1 case with skin and soft tissue infection; 1 case with fungus infection; 3 cases with herpes zoster infection; 2 cases with skin rashes; 2 cases with hypotension, 1 case with hepatic dysfunction; 1 case with neuralgia. Conclusion: Our study showed that the escalated dose of bortezomib based chemotherapy had promising response for the treatment of relapsed or refractory non-GCB originated DLBCL. Bortezomib at a single dose of 2.0mg/m2 was safe and tolerable. No acute toxicity or vital adverse events were observed. The relapse of disease in central nervous system as well as infections were relatively common and might need further study. Disclosures: No relevant conflicts of interest to declare.

Abstract 4243 [Background] Imatinib combined with intensive chemotherapy protocol markedly has markedly improved the prognosis of patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ALL), and has become the standard therapy for this disease. Based on experience from patients with chronic myelogenous leukemia in blast crisis or accelerated phase, this highly specific tyrosine kinase inhibitor was given 600mg or 800mg daily in most clinical trials. However, some pilot study and case report implied that either lower dose of imatinib or less intensive chemotherapy could also achieve a satisfying remission rate. We carried out this pilot study to testify whether a lower dose of imatinib and less intensive chemotherapy could generate similar outcome, especially for patient who are unwilling to or unsuitable for allogeneic hematopoietic stem cell transplantation. [Method] Thirty six patients with de novo Ph+ALL were enrolled between Dec-2008 and Dec-2010. All patients received imatinib 400mg daily, vindesine 4 mg weekly and dexamethasone 10 mg/m2/day for 4 days per week as induction therapy. After complete remission, these patients received 3 courses chemotherapy of protocols adapted from China Acute Lymphocytic Leukemia Group (CALLG) as intensification. Those who were unwilling to receive or unsuitable for allo-HSCT received maintenance therapy with imatinib 400mg daily with chemotherapy by vindesine 4 mg on D1 and D11, dexamethasone 10mg/m2/day on D1-5 and D11-15 with or without interferon-α 3 million unit every other day. Patients over 55 year old skipped the intensification therapy. The maintenance chemotherapy was given once a month in the first year, once per 2 months in the second year, and once per 3 months in the third year. Sixteen cycles of intrathecal chemotherapy with cytarabine and dexamethasone +/− methotrexate was scheduled for central nervous system leukemia (CNSL) prophylaxis. [Result] Thirty six patients were enrolled, and the median age of this group of patients was 33.5 years (shown in table 1). All but one patients (97.2%) achieved complete remission after 4 weeks of induction therapy. One patient was loss of follow-up and one patient quit from this study because of severe hepatic dysfunction thought to be caused by imatinib. Three patients (8.3%) died of infections (pneumonia or sepsis) within intensification cycles. Three (8.3%) patients received allo-HSCT either from a sibling or an unrelated donor at CR1 after 3–4 courses of intensification therapy. The median time of follow-up was 8 months. The median overall survival was were 22.1 (shown in figure 1A.). For patients who received imatinib and chemotherapy only, the median overall survival was 20.4 months (shown in figure 1B). Although there was no evidence for CNSL at diagnosis in all patient, four (11.1%) patients had CNS relapse and three died despite of regular CNSL prophylaxis. [Conclusion] In this pilot study, our data showed that imatinib combined with less intensive chemotherapy could also achieve a over 90% remission rate in patients with de novo Ph+ALL. With the short time of follow-up, the long term effect of this strategy on survival and relapse can not determined yet, and a prospective randomized study is warranted. With reduced chemotherapy intensity, a more intensive protocol for CNS prophylaxis or new generation of TKI (e.g. dasatinib) with higher blood-brain barrier permeability may be considered. Disclosures: No relevant conflicts of interest to declare.

294 Background: From 2000 to 2008, the incidence of bladder urothelial cancer in the young adults was diagnosed at an increasing trend at the Tongji Hospital, China. To investigate whether bladder urothelial cancer in patients under the age of 40 years behaves significantly differently from the bladder urothelial cancer in elder patients. Methods: From 1994 to 2008, the records of 4,568 patients with pathological diagnosis of bladder urothelial cancer presented to the Tongji Hospital were retrospectively reviewed. 82 patients were younger than 40 at the time of diagnosis. The clinicopathologic parameters were compared between this group and a serial of 164 older patients during the same time period. The Kaplan-Meier and Cox regression analyses were performed for the survival analysis. Results: 2.05% of patients with pathological diagnosis of bladder urothelial cancer presented to the Tongji Hospital were younger than 40 years (median age 32.93). Compared to the older group, young adults group had a lower sex ratio (male-to-female ratio, 3.4:1vs.6.5:1, p Conclusions: Despite an increasing trend of diagnosis, both the pathologic features and clinical outcomes were significantly better in the young patients with bladder urothelial cancer when compared to their elderly counterparts. These findings suggested that more consevertive management approaches may be warranted for this group of patients even under the circumstances of extensive bladder involvement. No significant financial relationships to disclose.

108 Background: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as P21, P27, P53, Bcl-2, Bax, and c-myc, and clinicopathological features and their prognostic value. Methods: From January 1996 to December 2007, 4,426 patients had undergone gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of P21, P27, P53, Bcl-2, Bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. Results: There were 339 males and 162 females (2.09:1) with a mean age of 57. The percentages of positive expression of P21, P27, P53, Bcl-2, Bax, and c-myc were 73%, 25%, 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between P21, P53, Bax, and c-myc expression (p = 0.00). There was significant association between P27, Bcl-2, and Bax expression (p < 0.05). The P21 expression correlated with male (p = 0.00), histological grade (p = 0.00), Borrmann type (p = 0.02), tumor location (p = 0.01); the P53 expression with histological grade (p = 0.01); Bcl-2 expression with pathological stage (p = 0.01); Bax expression with male (p = 0.02), histological grade (p = 0.01), Borrmann type (p = 0.01), tumor location (p = 0.00), lymph node metastasis (p = 0.03), pathological stage (p = 0.01); c-myc expression with Borrmann type (p = 0.00). Bcl-2 expression was related with good survival in univariate analysis (p = 0.01). Multivariate analysis showed that Bcl-2 expression and pathological stage were defined as independent prognostic factors for gastric cancers. There was significant differences of overall 5-year survival rates according to Bcl-2 expression or not in stage III (p = 0.00). Conclusions: The expressionof Bcl-2 was an independent prognostic factor for Chinese patients with gastric cancer; it might be a candidate for the gastric cancer staging system. No significant financial relationships to disclose.

Abstract 1117 Poster Board I-139 Objective The human organic cation transporter-1(hOCT-1) is the major active influx protein responsible for the transport of imatinib into cells. The functional activity of the hOCT-1 protein using 14-C detected by others demonstrated a link between CML molecular response and hOCT-1 activity. However, 14-C labeled detection is not convenient in routine clinical practice. Hence, we use flow cytometry to detect hOCT-1 protein expression level in CML patient and try to find some relation between hOCT-1 expression and imatinib response. Subjects and methods In this study, 64 CML CP patients and 31 healthy donors were enrolled. Totally, there are 78 patient' peripheral blood (PB) or bone marrow (BM) samples and 31 donor PB samples were measured. The hOCT-1 protein expression levels were detected by indirect immunofluorescent flow cytometry. The hOCT-1 levels were expressed as mean fluorescent intensity (MFI). In avoided to systematic error, lymphocytes which had little hOCT-1 expression were used as internal negative control. Results ‡@ Assessing PB hOCT-1 expressing in patients with donors, hOCT-1 level is higher in healthy donors than in CML patient (mean±standard deviation 9.11±6.04,5.60±3.74,P=0.005). ‡AThe hOCT-1 level was compared with molecular response in patients. Of 39 patients achieved optimal molecular response, the hOCT-1 level was 6.49±3.83, versus 3.86±2.91 in 20 patients with non-optimal response(P=0.009). Comparing 39 optimal responders with 16 sub-optimal responders, hOCT-1 level were 6.49±3.83, versus 3.98±1.23(P=0.025. ‡B Assessing CML stages with hOCT-1 expression, there is no significant difference in chronic stage and advanced stage(5.93±3.87, 3.49±1.64, P=0.085). Conclusions hOCT-1 expression level measured by flow cytometry is very convenient and clinically available. The hOCT-1 expression level can be an important predictor in CML patients treated with imatinib mesylate. Disclosures No relevant conflicts of interest to declare.

Objective: To evaluate effect of human organic cation transporter 1((hOCT1) polymorphism on Imatinib Mesylate (IM) in Chinese CML patients. Material and Methods: Totally 76 patients were enrolled(53 CML, 23 non-CML patients). The 53 CML patients were categorized as optimal-, suboptimal-and failure ones, according to their clinical response. 2 Tibetan nationality Chinese patients were described separately. In this study, amplification refractory mutation system (ARMS)-polymerase chain reaction was used to amplify the polymorphism gene segment of hOCT1- P283L, R287G, M408V. Results: In the 74 Chinese Han subjects: ‡@ The frequencies of CC ACT ATT genotype in hOCT1- P283L were 35.14%,50.00%,14.86%; the allele C AT frequencies were 60.14% and 39.86%, respectively; ‡A The frequencies of CC ACG AGG genotype in hOCT1- R287G were 51.35%,39.19%,9.46% Gthe allele C AG frequencies were 70.95% and 29.05%, respectively G‡B The frequencies of AA AAG AGG genotype in hOCT1- M408V were 28.37%,52.70%,18.92% Gthe allele A AG frequencies were 54.73% and 45.27%, respectively. The genotypes of hOCT1- P283L, R287G, M408V in 2 Tibetan nationality Chinese were CC ACC AAG and CC ACG AAG, respectively. In the CML patients with suboptimal response (group IIa), the frequency of hOCT1-283T allele was predominant, which was 55.56%, compared with that of 30.77% in the optimal response group(group I). The difference in the frequency distribution of hOCT1-P283L allele between two groups was statistically significance(X2=5.406,P=0.020). The frequencies of CC ACG AGG genotype of hOCT1-R287G in patients with suboptimal response group(group IIa) were 38.89%,61.11%,0 Gcompared with that of 57.69%,30.77%,11.54% in patients with optimal group (group I). A significant difference was found in the frequency distribution of hOCT1-R287G genotype between two groups(X2=6.149,P=0.046). In group IIa, the CG genotype was more common than group I, but no GG genotype. Non-significant difference was found in the frequency distribution of hOCT1-P283L, R287G, M408V genotype and allele between patients with failure response group (group IIb) and group IIa. Non-significant difference was found in the frequency distribution of hOCT1- M408V genotype and allele among the 3 groups: I AIIa and IIb (X2 =0.268,P=0.874 GX2a =0.988,Pa=0.610 GX2b =2.819, Pb=0.244). Conclusion Three coding single nucleotide polymorphisms (cSNP) --- hOCT1- P283L, R287G, M408V, were found in the human Organic Cation Transporter 1 gene from 74 Chinese Han individuals. The frequency distributions of their genotype and allele were different from that reported by others. The polymorphisms of hOCT1-R287G, M408V were found in 2 Tibetan nationality Chinese subjects. In this current study, hOCT1 gene polymorphism was associated with the long-term molecular response of CML patients administered with IM, the CG genotype of hOCT1-R287G and T allele of hOCT1- P283L in the suboptimal response group are prevalent; there is no specific association between hOCT1-M408V and patients’ response. This indicated that the polymorphism of hOCT1- P283L, R287G might be a valuable factor in predicting patients’ response. In our study, there was no specific correlation between the polymorphism of hOCT1- P283L, R287G, M408V and CML patients resistant to IM secondarily.

Purpose: The objective of this study was to evaluate the efficacy and potential toxicity of the Hyper-CVAD/MTX-Ara-C regimen,a dose-intensive regimen, in the patients with acute lymphocytic leukemia (ALL) and highly aggressive non-Hodgkin lymphoma (NHL) in China. PATIENTS AND METHODS: Between June 2004 and June 2007, fifty-six patients with ALL or highly aggressive lymphoma were treated with the Hyper-CVAD/MTX-Ara-C regimen at our institution. Median age was 26 years (range 13 to 60 years), and 35 patients (62.50%) were male. All patients were comprised of 32 previously untreated cases and 24 refractory/relapsed ones. Among the 41 patients with ALL, B-cell disease was present in 82.93%, T-cell disease in 17.07%, and Ph-positive ALL was present in 14.63%, refractory/relapsed disease in 43.90%. Among the 15 patients with highly aggressive NHL, lymphoblastic lymphoma was present in 46.67%, Burkitt’s lymphoma was in 53.33% and refractory/relapsed disease in 40.00%. CNS involvement was present in 8% at diagnosis. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and aggressive supportive care with granulocyte colony-stimulating factor (G-CSF), transfusion and antibiotic prophylaxis therapy. Maintenance therapy based on cytogenetics and immunophenotypes in most of patients contained 2-year treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: The median follow-up time was 7 months (range 1+ to 37+ months). Of the previously untreated 31 patients, twenty-nine patients (93.55%) achieved complete remission (CR) and no patients died during induction therapy. Of the refractory /relapsed 24 patients, fourteen cases (58.33%) achieved CR. Remarkably, the CR rate of the patients with Burkitt’s lymphoma was 75.00% (6/8). The median courses finished during the dose-intensive phase were 4 (range 1 to 8), and the median time to delivery of all eight courses was 10 months. The estimated 3-year overall survival (OS) for the untreated and refractory/relapsed patients with ALL was 46.80% and 28.60%, respectively. Meanwhile, the estimated 2-year OS for the aggressive NHL patients was 84.00%. Compared with the patients with ALL who did not receive CR and get less than four courses of this regimen, the patients who did receive CR and get more than four courses of this dose-intensive regimen showed much better OS (p CONCLUSION: The present outcome from our single center in China demonstrated that Hyper-CVAD/MTX-Ara-C, a dose-intensive regimen with much higher CR was superior to our previous regimens, even in patients with highly aggressive lymphoma such as lymphoblastic and Burkitt’s lymphoma, and in refractory/relapsed ALL/lymphoma ones. Our study also showed that this regimen was less toxic and well tolerated in most of treated patients in China. Long-term treatment benefits and severe side effects needed further investigation in a well-designed, multiple-center study in China with more eligible patients entering onto the study.

BACKGROUND: Although the safety and efficacy of the Hyper-CVAD/MTX-Ara-C regimen in hematologic malignancies has been well established by the large clinical trials developed at the University of Texas M. D. Anderson Cancer Center, the outcome with this regimen in patients in China has not been determined. The objective of this study was to evaluate the efficacy and potential toxicity of this regimen in acute lymphocytic leukemia (ALL) and highly aggressive non-Hodgkin lymphoma (NHL) in a single center in China. PATIENTS AND METHODS: Between September 2004 and July 2006,36 patients with ALL or highly aggressive lymphoma were treated with the Hyper-CVAD/MTX-Ara-C regimen at our institution. Median age was 35 years (range 14 to 60 years), and 23 patients (64%) were male. All patients are comprised of 19 previously untreated cases and 17 refractory/relapsed ones. Among the 28 patients with ALL, B-cell disease was present in 82%, T-cell disease in 18%, and Ph-positive ALL was present in 18%, refractory/relapsed disease in 46%. Among the 8 patients with highly aggressive NHL, lymphoblastic lymphoma was present in 63%, Burkitt’s lymphoma was in 37% and refractory/relapsed disease in 50%. CNS involvement was present in 8% at diagnosis. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and aggressive supportive care with granulocyte colony-stimulating factor, transfusion and antibiotic prophylaxis therapy. Maintenance therapy according to cytogenetics and immunophenotype in partial patients included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: The median follow-up was 7 months (range 1+ to 23+ months). Of the previously untreated 19 patients, seventeen patients (89.47%) achieved complete remission (CR) and no patients died during induction therapy. Of the refractory/relapsed 17 patients, seven cases (41.48%) achieved CR. Remarkably, the CR rate of the patients with Ph-positive ALL was 60.00%(3/5), and Burkitt’s lymphoma 66.67%(2/3). The median finished courses during the dose-intensive phase were 5 (range 1 to 8), and the median time to delivery of all eight courses was 10 months. The estimated 5-year survival and 5-year CR rates were not concluded so far. The incidence of CNS relapse was low (5%). Myelosuppression-associated complications including documented infections, fever of unknown origin, hemorrhage were the more frequent side effects. Other significant side effects included neurotoxicity, renal and hepatic toxicities, fatigue, mucositis, nausea, vomiting, diarrhea, skin rashes, and G-CSF therapy-associated bone aches. CONCLUSION: The preliminary experience from our single center in China demonstrated that Hyper-CVAD/MTX-Ara-C, a dose-intensive regimen with much higher CR is superior to our previous regimens, even in poor-risk Ph-positive ALL, and highly aggressive lymphomas such as lymphoblastic and Burkitt’s lymphoma, and refractory/relapsed ALL/lymphoma. Our data also showed that this regimen is less toxic and well tolerated in patients. Due to the aggressive supportive care, the expense with this regimen is more expensive than conventional chemotherapy. Long-term treatment benefits, such as disease-free survival rates and severe side effects need further investigation in a well-designed, multiple-center study in China with more eligible patients entering onto the study.

Background Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. Methods We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis. Results Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p