Extranodal NK/T-cell lymphoma, nasal type: Clinical features, outcome, and prognostic factors in 101 cases.

OBJECTIVES: We aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T-cell lymphoma (ENKTL) patients in Taiwan. METHODS: We retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015. RESULTS: The median age of 101 patients was 52 years old (range 22-85); 76.2% of patients were Ann Arbor stage I/II disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV-DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline-containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5-year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease-free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733-8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312-26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses. CONCLUSIONS: Age ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early-stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline-containing regimen but with a high relapse rate and short disease-free survival. Anthracycline-containing regimen in advanced stage had poor response and dismal outcome.

A noninterventional observational registry of patients with multiple myeloma treated with lenalidomide in Taiwan.

BACKGROUND/PURPOSE: The incidence of multiple myeloma in Asia has risen in the past 30 years. Lenalidomide, an IMiD immunomodulatory agent, has improved the overall survival in patients with relapsed/refractory multiple myeloma (RRMM) when used with dexamethasone versus dexamethasone alone. This observational registry (T-CC-MM-009; NCT01752075) assessed the safety and efficacy of lenalidomide plus dexamethasone in a large Chinese population of patients with RRMM. METHODS: This registry followed the first 100 patients treated with lenalidomide plus dexamethasone in Taiwan. Patients were ≥18 years old and had ≥1 prior treatment. The recommended starting dose for the first four 28-day cycles was 25 mg lenalidomide on days 1-21 and 40 mg dexamethasone on days 1-4, 9-12, and 17-20. Thereafter, dexamethasone was given on days 1-4 only. The primary objective was safety; secondary objectives were efficacy, lenalidomide dosage, and reasons for discontinuation. RESULTS: The median duration of treatment was 34.6 weeks, and 75.5% completed ≥3 cycles. Most patients (82.7%) experienced ≥1 treatment-related adverse event; the most commonly reported were neutropenia (23.5%), thrombocytopenia (19.4%), anemia (16.3%), fatigue (16.3%), and hypoesthesia (15.3%). Bleeding events (25.5% of patients) were mostly grade 1/2 (80%). Three patients (3%) had venous thromboembolic events. Two invasive second primary malignancies were reported; however, time to onset was <1 year, suggesting they may not be related to lenalidomide. The overall response rate was 34.7%; median time to disease progression was 20.5 months. CONCLUSION: These data confirm the safety and efficacy of lenalidomide plus dexamethasone for patients with RRMM in Taiwan.

Clinical features of testicular lymphoma.

Testicular lymphoma is a rare condition, so large scale prospective studies are difficult to conduct. Consensus regarding standard treatment is lacking. This study retrospectively reviewed 22 patients with testicular lymphoma. One patient with diffuse large B-cell lymphoma (DLBCL) was lost to follow-up after diagnosis. Two patients with Burkitt's lymphoma had poor outcomes regardless of treatment. Thus, we analyzed the clinical features, treatments, and outcomes of 19 patients with DLBCL. The median progression-free and overall survival was 28.3 and 36.3 months, respectively. A good response to treatment was a favorable prognostic factor. Because of the high relapse rate, the outcome is poor for testicular lymphoma. Therefore, long-term follow-up is strongly recommended.

Acute promyelocytic leukemia-associated thrombosis.

Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. The bleeding complications are well known. In contrast, APL-associated thrombosis is relatively underappreciated. We aimed to explore the issue of APL-associated thrombosis events. In the past 20 years, 127 cases with APL were found in our hospital database. We collected their coagulation laboratory profiles, including leukemia burdens, white blood cell and platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen levels, and disseminated intravascular coagulation scores. Data were compared between patients with or without thrombosis. Clinical outcomes and potential risk factors were obtained for analysis. Ten cases with APL-associated thrombosis were found. The incidence of thrombosis was 7.9% in our cohort. Five patients had cerebral infarction, 5 had catheter-related thrombosis and 1 had acute myocardial infarction. No laboratory data were associated with clinical thrombosis. Three patients died during the induction phase but thrombosis was not the direct cause of death for any of them. We conclude that patients with APL are susceptible to thrombosis in addition to bleeding. Laboratory coagulation parameters did not predict thrombosis in our series. Ischemic stroke and catheter-related thrombosis were the most common events in our Taiwanese cohort. Such a thrombosis pattern is unique and worth further investigation.

Clinical and laboratory significance of defective P2Y(12) pathway function in patients with myeloproliferative neoplasms: a pilot study.

BACKGROUND: Patients with myeloproliferative neoplasms (MPN) have an increased risk for thrombosis and bleeding and show a defect in adenosine diphosphate (ADP)-induced platelet aggregation. This risk of thrombosis is further increased in MPN patients bearing the JAK2V617F mutation. Two ADP receptors, P2Y1 and P2Y12, are present on platelets. Although the pattern of defective ADP-induced platelet aggregation in MPN suggests an abnormality in the P2Y12 pathway, no previous studies have specifically evaluated P2Y12 function in MPN or the relationship between P2Y12 function and the JAK2V617F mutation. METHODS: Forty-one MPN patients were enrolled, including 24 with essential thrombocythemia (ET), 16 with polycythemia vera (PV) and 1 with primary myelofibrosis. Platelet P2Y12 function in MPN was evaluated by flow-cytometric measurement of the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Clinical data were collected by review of medical records. JAK2V617F mutation was detected by allele-specific polymerase chain reaction. JAK2V617F allele burden was measured by the pyrosequencing method. RESULTS: In patients with MPN, platelet P2Y12 function determined by VASP platelet reactivity index (PRI) was inversely correlated with platelet and white blood cell (WBC) counts. In subgroup analysis, PRI was inversely correlated with platelet and WBC counts in PV. PRI was also inversely correlated with platelet counts in ET, but the correlation of PRI and WBC counts did not reach statistical significance. Eight of the 41 patients had a history of thrombosis and only 2 had a bleeding history. Neither thrombosis nor bleeding patients were found to have significantly different PRIs. JAK2V617F mutation data were available in 35 cases. PRI was not different between JAK2V617F mutation and wild-type patients but PRI had a trend towards an inverse correlation with JAK2V617F allele burden for patients with mutations. CONCLUSIONS: The present study provides the first explicit demonstration of a defect in the P2Y12 pathway in platelets of patients with MPN. Furthermore, platelet P2Y12 function, assayed by VASP, is inversely correlated with platelet and WBC counts in patients with MPN. Platelet P2Y12 function also appears to be inversely correlated with JAK2V617F allele burden. This compromised P2Y12 function may be a novel mechanism for the bleeding tendency associated with extreme thrombocytosis in MPN.

The impact of age, Charlson comorbidity index, and performance status on treatment of elderly patients with diffuse large B cell lymphoma.

Treatment intensity will affect outcome in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 333 DLBCL patients aged over 60 years who were diagnosed between January 2003 and December 2010 to evaluate the difference between different treatment regimens. The median age was 73 years; 56.8 % of patients received treatment with rituximab-containing regimens. In univariate analysis, patients with younger age, better performance status, early Ann Arbor stage, lower International Prognostic Index (IPI), normal serum lactate dehydrogenase, normal serum albumin, or normal serum beta-2 microglobulin received more intensive treatment regimens. In multivariate analysis, patients with younger age (p < 0.001) or better performance status (p = 0.027) received treatment of more intensive regimens. The treatment regimens were not different between patients with lower and higher Charlson comorbidity index (CCI). Female gender, normal serum beta-2 microglobulin, lower CCI, lower IPI, and treatment with more intensive regimens predicted better progression-free survival and overall survival in multivariate analysis. Patients treated with rituximab-containing regimens had better progression-free survival (median 22.2 vs. 9.9 months, p = 0.005) and better overall survival (median 34.9 vs. 21.8 months, p = 0.042) as compared to those treated without rituximab. In conclusion, our results showed that patients with younger age or better performance status received more intensive treatment. The treatment regimen was not different between patients with lower and higher CCI. Rituximab-containing regimens improved the outcome of elderly patients with DLBCL.

Value of surveillance computed tomography in the follow-up of diffuse large B-cell and follicular lymphomas.

Computed tomography (CT) as a routine follow-up has been a standard practice for patients with non-Hodgkin lymphoma although it is not recommended in most guidelines. We aimed to describe the value of surveillance CT in detection of disease relapse in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma grade 3 (FL3) and to evaluate whether relapse detected by different methods influenced outcome. In this retrospective review of consecutive 341 patients with DLBCL or FL3 diagnosed between 2003 and 2009 in complete response (CR) or unconfirmed CR, 113 patients experienced relapses. We found that routine surveillance CT detected asymptomatic relapse in 25 patients (22.1%; group 1), including 22 of 100 patients with DLBCL and three of 13 with FL3. The first presentation of relapse of the other 88 patients (group 2) included patient-reported symptoms (60.2%), physical examination (13.3%), or abnormal laboratory data (4.4%). For 72 patients received chemotherapy after relapse, the overall survival after relapse was not different between groups 1 and 2 (p = 0.569). The results of our study suggested that routine surveillance CT only has a limited role in the early detection of relapse and the relapse detected by surveillance CT or not has no impact on survival after relapse for patients with DLBCL or FL3.

Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia.

BACKGROUND: Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. DESIGN AND METHODS: For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. RESULTS: Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per µL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non-bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all-trans retinoic acid (ATRA). CONCLUSIONS: Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.

Primary bone marrow diffuse large B cell lymphoma: a case series and review.

Diffuse large cell lymphoma involving bone marrow is not uncommon, but primary, de novo, bone marrow diffuse large B cell lymphoma (DLBCL) is rare. To understand the clinical features and outcomes of this distinct entity, we collected 12 cases in 5 years from a single-center database. They accounted for 1.16% of lymphoma, or 2.65% of diffuse large B cell lymphoma. Nine cases presented with fever of unknown origin. Lactate dehydrogenase levels were elevated in all but one case. Nine cases belonged to the high-risk group according to their international prognosis indexes (score 4 or 5). Four patients received no chemotherapy, all of whom died within 1 month. Four patients received cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP)-like chemotherapy, and their median survival was 13 months. Finally, four patients received rituximab 375 mg/m(2) in addition to CHOP-like chemotherapy. All of them had complete remission and three are still alive without relapse. We concluded that primary bone marrow DLBCL is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.

Primary colonic lymphoma: an analysis of 74 cases with localized large-cell lymphoma.

BACKGROUND: Surgical resection is considered a crucial treatment in patients with primary colonic lymphoma, but combining surgery with chemotherapy has provided additional therapeutic benefits in some studies. To further explore the optimal therapeutic approach in different clinical scenarios, we reviewed cases with localized large-cell lymphoma and analyzed the factors related to the outcomes. PATIENTS AND METHODS: The 74 cases diagnosed between February 1979 and October 2010 were retrospectively reviewed for clinical features, laboratory findings, and pathological diagnosis. The outcomes were correlated with their demographics and different treatment modalities. RESULTS: Of the 74 cases, only the patients who had complete tumor resection had significantly improved progression-free survival (PFS). The patients treated with resection and chemotherapy had better overall survival (OS) and PFS than those treated with resection alone. The OS and PFS of the patients who were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy without surgery were similar to those of patients treated with CHOP and resection, but the patients treated with resection followed by cyclophosphamide, vincristine, and prednisone (COP) chemotherapy had significantly better OS and PFS than the patients treated with COP chemotherapy alone. For patients with diffuse large B-cell lymphoma (DLBCL), rituximab-based chemotherapy with or without resection had similar OS and PFS. CONCLUSIONS: We conclude that chemotherapy alone provides similar therapeutic effect compared with surgery and chemotherapy and that surgical resection can be spared if an endoscopic diagnosis could be made.

Classical hairy cell leukemia and its variant: a 17-year retrospective survey in Taiwan Chinese.

BACKGROUND: Classical hairy cell leukemia (HCL-C) and its variant (HCL-V) are rare chronic B-cell lymphoproliferative disorders. Only a few reports in Chinese patients are available. METHODS: We retrospectively reviewed 16 patients with HCL-C and HCL-V in Taiwan over a 17-year period. RESULTS: Eight were HCL-C and 8 were HCL-V. All HCL accounted for 0.7% of all adult leukemias. Compared to HCL-V, HCL-C was characterized by profound leukopenia, monocytopenia, thrombocytopenia and fewer circulating hairy cells. One HCL-C and 2 HCL-V patients had second malignancies. Seven HCL-C patients achieved hematological remission after splenectomy (n = 1) or 2-chlorodeoxyadenosine (n = 6). Of the 8 HCL-V patients, 6 received splenic irradiation. Only one achieved complete remission and another had partial remission; relapse or disease progression was noted 13.4 or 25.7 months later, respectively. Two of three HCL-V patients who underwent splenectomy had stable disease. All patients with HCL-C were alive while 3 with HCL-V expired. Compared to HCL-C, HCL-V had a significantly shorter leukemia-free survival. CONCLUSION: A relatively higher proportion of HCL-V in all HCL comparing to Westerners is observed. Second malignancies are common. With an inferior outcome and dismal response to most treatment, enrollment in a clinical trial should be considered for HCL-V.

Heterogeneous patterns of CEBPalpha mutation status in the progression of myelodysplastic syndrome and chronic myelomonocytic leukemia to acute myelogenous leukemia.

PURPOSE: We aimed to assess the role of CEBPalpha mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations. EXPERIMENTAL DESIGN: Mutational analysis of CEBPalpha with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution. RESULTS: CEBPalpha mutations were identified in four patients at diagnosis of MDS, including one with refractory anemia with excess blasts and three with chronic myelomonocytic leukemia. At AML transformation, three patients retained the identical mutant clones as their initial diagnosis, three acquired the mutations, and one lost CEBPalpha mutation when she gained FLT3/ITD mutation. Together, seven patients had CEBPalpha mutations throughout the disease course; four patients had NH(2)-terminal mutations resulting in a frameshift and truncation of the protein, three of them had two different mutations either on the same alleles or on different alleles, two had missense mutations, and one had a deletion in the basic region leucine zipper domain. Except for one with coexistence of N-ras mutation, no sample harbored cooperating mutations with FLT3 or N-ras genes. CEBPalpha mutations had no influence on the time to AML progression or overall survival. CONCLUSIONS: Our results show that CEBPalpha mutations play a role in a subset of patients with MDS, especially in chronic myelomonocytic leukemia. The mutation status was heterogeneous, exhibiting identical clone, clonal change, or clonal evolution during the progression to AML.

Clinical features, outcome and prognostic factors of 87 patients with angioimmunoblastic T cell lymphoma in Taiwan.

We retrospectively analyzed 87 patients with angioimmunoblastic T cell lymphoma (AITL) in Taiwan. The median age was 68 (range 18-89) years. Of these patients, 74 % was at an advanced stage. The most common extra-nodal site involved was bone marrow (36 %). Of these patients, 77 % were International Prognostic Index (IPI) >1 and 79 % had a prognostic index for peripheral T-cell lymphoma (PIT) >1. Of 75 patients who received systemic chemotherapy, the complete remission rate was 60 %, the relapse rate was 47 %, and the 2-year progression-free survival rate was 37.4 %. The 2-year overall survival (OS) rate for all patients was 51.9 %. By multivariate analysis, bone marrow involvement (P < 0.001) and ECOG >1 (P = 0.007) were independent adverse factors for OS. A simplified prognostic index efficiently stratified patients into the following three groups: 2-year OS rates 79.8 % (0 factor), 28.3 % (1 factor), and 10.2 % (2 factors) by using bone marrow involvement and ECOG >1 (P < 0.001). In conclusion, AITL patients were older and had poorer prognosis in Taiwan. Bone marrow involvement, EOCG >1, IPI >1 and PIT >1 had adverse impact on OS. The usefulness of this simplified prognostic index needs further validation.

Heterogeneous patterns of FLT3 Asp(835) mutations in relapsed de novo acute myeloid leukemia: a comparative analysis of 120 paired diagnostic and relapse bone marrow samples.

PURPOSE: We analyzed Asp(835) mutations of FLT3 on paired marrow samples at diagnosis and relapse from 120 adult patients with de novo acute myeloid leukemia (AML) to determine the role of FLT3 Asp(835) mutation in the relapse of AML. EXPERIMENTAL DESIGN: Asp(835) mutation was analyzed by DNA PCR amplification of exon 20 of FLT3 gene followed by EcoRV digestion. All of the mutations were confirmed by sequence analysis. Mutant to wild-type allelic ratio was determined by Genescan analysis. The Expand Long Template PCR System was used to determine the allelic location of internal tandem duplication of FLT3 (FLT3/ITD) and Asp(835) mutations. RESULTS: Thirteen patients had Asp(835) mutations at diagnosis, of them 8 lost the mutations at relapse, and the remaining 5 patients carrying Asp(835) mutations at diagnosis relapsed with the identical mutation types. Another 6 patients acquired Asp(835) mutations at relapse. Five samples harbored both FLT3/ITD and Asp(835) mutations that were found on different alleles by cloning analysis in the 3 patients studied. There were no differences in WBC count, French-American-British subtype, percentage of marrow blasts, or circulating blasts between patients with and without Asp(835) mutations, whereas the difference in the prevalence of Asp(835) mutations among cytogenetic/molecular subgroups was statistically significant (P = 0.025). CONCLUSIONS: The present study showed that patients with AML had heterogeneous patterns of FLT3 Asp(835) mutations, either acquisition or loss of the mutations at relapse. Asp(835) mutant clone may develop as a secondary event in a subset of patients with AML.

High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Age over 60 years is one of the five parameters of the International Prognostic Index (IPI), which is the most important clinical prognostic predictor in DLBCL. A previous study on German DLBCL patients over 60 years of age showed that immunoblastic morphology, but not germinal center B cell-like (GCB)/non-GCB subtype, correlated with short survival. We collected 174 DLBCL cases over 60 years of age in Taiwan and performed immunophenotyping and detection of Epstein-Barr virus (EBV)-encoded RNA (EBER) by in situ hybridization. Of the cases, 5.2 % were positive for CD5 and 5.7 % positive for EBER. Neither immunoblastic morphology nor GCB/non-GCB subtype correlated with survival. In univariate analysis, adverse prognostic factors included IPI ≥ 3 (P < 0.000001), B symptoms (P = 0.000075), bone marrow/peripheral blood involvement (P = 0.017), EBER positivity (P = 0.0013), and CD5 positivity (P = 0.016). In multivariate analysis, CD5 positivity was the only independent adverse prognostic factor (HR = 3.16; 95 % CI = 1.34-7.47; P = 0.0087) in addition to IPI ≥ 3 (HR = 3.07; 95 % CI = 1.84-5.11; P = 0.000018). Surprisingly, despite an overall 5.2 % incidence of central nervous system (CNS) relapse in our patients, none of the CD5+ cases experienced CNS relapse (P = 1.00). This is in stark contrast to the more frequent CNS relapse in Japanese CD5+ DLBCL patients. EBER positivity was associated with IPI ≥ 3 (P = 0.010), stage III-IV (P = 0.0082), and B symptoms (P = 0.011). In multivariate analysis, EBER positivity was not an independent adverse prognostic factor (P = 0.81), its effect being due likely to accompanying adverse clinical parameters.

Primary breast lymphoma: a single-institute experience in Taiwan.

BACKGROUND: Breast is an uncommon location of lymphoma involvement. The most common type of primary breast lymphoma (PBL) is diffuse large B-cell lymphoma (DLBCL). Rituximab is the widely used monoclonal antibody against CD20+ B-cell lymphoma, especially DLBCL. We aimed to analyze the clinical features, prognostic factors, and treatment outcome with or without rituximab in primary breast DLBCL. METHODS: We retrospectively analyzed patients diagnosed with PBL from October 1987 to March 2012 in our hospital, excluding metastasis by whole-body computed tomography and bone marrow study. RESULTS: Twenty-three patients were diagnosed with PBL. All were females. Eighteen patients were stage IE and five were stage IIE according to the Ann Arbor staging system. Two patients had lymphoma other than DLBCL. The median age of primary breast DLBCL patients was 48 years (range 27-79). Two were excluded from the analysis due to refusal or ineligibility for chemotherapy. No significant prognostic factor was found. Patients receiving chemotherapy with (RC) or without (C) rituximab were not significantly different in the 5-year overall survival (RC: 57.1%; C: 58.3%; p = 0.457) or progression-free survival (RC: 57.1%; C: 50.0%; p = 0.456). A high incidence of relapse in the central nervous system (CNS) (17.6%) was observed. CONCLUSIONS: In accordance with prior literature reports, our Taiwanese cohort of primary breast DLBCL seemed younger than those reported in Japan, Korea, and Western societies. Relapse in the CNS was not uncommon. The benefit of rituximab in addition to chemotherapy was not statistically significant. Treatment modality remained to be defined by further large-scale studies.

Chronic lymphocytic leukemia presenting with ascites diagnosed by clonality analysis via gene rearrangement assay: A case report.

The diagnosis of chronic lymphocytic leukemia (CLL) presenting with ascites is predominantly based on the morphological and immunophenotypic characteristics, which are comparable to peripheral blood and bone marrow cells. However, it is relatively difficult to diagnose CLL due to the pleomorphism of the lymphocytes in ascites. The current study presents an 80-year-old male with a prior diagnosis of CLL who developed large ascites. Predominant T lymphocytes rendered morphological and immunophenotypic diagnosis difficult. Clonality analysis of immunoglobulin (Ig) gene rearrangements was performed on the lymphocytes from the ascites to diagnose the involvement of CLL, a laparotomy and biopsy from the peritoneal node confirmed the involvement of small lymphocytic lymphoma/CLL. The clonality analysis of Ig gene rearrangements may provide a powerful and accurate method for diagnosing CLL presenting with ascites.

Retinoic acid syndrome in patients following the treatment of acute promyelocytic leukemia with all-trans retinoic acid.

BACKGROUND: Retinoic acid syndrome (RAS) is a potentially lethal complication during all-trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL). The incidence and risk factors have been shown to vary in different series. In this study we want to establish the incidence of RAS in our hospital and try to elucidate factors that increase its risk. METHODS: We retrospectively analyzed 102 patients diagnosed with APL between August 1993 and December 2007 at Chang Gung Memorial Hospital, Taiwan. All patients received ATRA as an induction regimen with or without conventional chemotherapy. RESULTS: Eight of the 102 patients (7.8%) experienced RAS which developed after a median of 9 days (range: 2 to 23 days) of ATRA treatment. Respiratory distress and fever were the most common presentations, occurring in 7 of 8 patients (87.5%). Age, gender, morphological or molecular subtypes, an initial white blood cell (WBC) count of more than 10 x 10(9)/L and concurrent chemotherapy did not statistically attribute to the occurrence of RAS. One patient developed RAS manifesting with pulmonary hemorrhage but experienced a complete recovery after administration of high-dose dexamethasone. The RAS-related mortality was 12.5% (1 out of 8 patients). CONCLUSION: The incidence of RAS in this study was similar to those of other series with ATRA and concurrent chemotherapy. Age, gender, morphological or molecular subtypes, an initial leukocyte count of more than 10 x 10(9)/L or the presence of concurrent chemotherapy is not significantly associated with the occurrence of the RAS.

Primary gastric diffuse large B-cell lymphoma.

BACKGROUND: The optimal treatment of primary gastric large-cell non-Hodgkin's lymphoma (PGL) has not been defined. Recent studies have suggested that organ-preserving treatment produces the same results as surgical treatment. METHODS: We retrospectively reviewed the data of 88 patients diagnosed with PGL between 1995 and 2003 at Chang Gung Memorial Hospital. Sixty-two patients received chemotherapy (CT), three received CT followed by radiotherapy (CT+RT), three received surgery (ST), 14 received surgery followed by CT (ST+ adjuvant CT), one patient received ST followed by radiotherapy (ST+RT), one patient received radiotherapy (RT) alone, one received eradication therapy for Helicobacter pylori only and 3 patients received no further therapy after diagnosis. RESULTS: Of the 81 patients who received endoscopic biopsy of gastric lesions, the diagnosis of PGL could be made in all but one. Seven patients were diagnosed by pathology after ST without preoperative pathologic diagnosis. The complete remission rate was 77.3%. The 5-year overall survival (OS) and disease-free survival (DFS) were 50.0% and 81.6%, respectively. There was no difference in OS (p = 0.4051) and DFS (p = 0.8519) between patients receiving mainly CT (CT or CT+RT) and those receiving primary surgery (ST, ST+ adjuvant CT or ST+RT). We found that poor performance status (p < 0.0001), elevated beta2-microglobulin level (p = 0.0082) and no CT (p = 0.0002) had adverse effects on OS. CONCLUSION: The present data show that CT should be the primary treatment for patients with PGL if the diagnosis can be made with endoscopic biopsy.