Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients.

PURPOSE: We aimed to explore the clinical outcomes and prognostic factors for PTCL-NOS patients in the real world. METHODS: Clinical data were retrospectively collected from adult patients with PTCL-NOS treated at a single center in Taiwan. RESULTS: 104 PTCL-NOS patients with a median age of 53.0 years were enrolled. Patients with the International Prognostic Index (IPI) or prognostic index for peripheral T-cell lymphoma (PIT) scores of zero had a longer overall survival (OS) and progression free survival (PFS), while patients with IPI or PIT scores ≥1 did poorly. For patients who are eligible for transplantation, the use of pralatrexate as salvage chemotherapy has shown better OS (2-year OS 83.3% vs. 24.4%, P = 0.011) compared to patients who did not. By multivariate analysis, age >60 years, male, B symptoms, ECOG >1, lung involvement, and thrombocytopenia were independent adverse factors for OS. Incorporating factors in multivariate analysis, we established a novel predictive index for PTCL-NOS which efficiently stratifies patients into low (0-1 factor), intermediate-1 (2 factors), intermediate-2 (3 factors), and high risk (4-6 factors) groups with 2-year OS rates of 81.5%, 32.9%, 8.8%, and 0%, respectively (P < 0.001). CONCLUSION: PTCL-NOS patients have a dismal prognosis in Taiwan. Novel agents may improve the outcomes of PTCL-NOS patients. The usefulness of the novel prognostic index for PTCL-NOS needs further validation.

Primary breast diffuse large B-cell lymphoma characterized by CNS relapse and successful hematopoietic stem cell transplantation salvage therapy.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is rare, with a high incidence of central nervous system (CNS) relapse. This study aims to investigate clinical characteristics, prognostic factors, and outcomes in Taiwanese PB-DLBCL patients and review the literature on PB-DLBCL. METHODS: Thirty-one PB-DLBCL patients diagnosed between 2000 and 2021 were retrospectively enrolled for analysis. RESULTS: The median age was 49 (range 26-79) years. The complete remission (CR) rate was 90.3%. Nine (90%) of the ten patients who experienced relapse had CNS involvement at the time of relapse. The one-year, two-year, and five-year progression-free survival (PFS) rates were 86.6% (95% confidence interval [CI] 75.2-99.8), 75.8% (95% CI 61.6-93.2), and 45.1% (95% CI 29.5-68.9), respectively. The five-year overall survival (OS) rate was 64.1% (95 % CI 48.4-85.0). A stage-modified International Prognostic Index (mIPI) less than two (five-year PFS rate 52.5% vs. 17.1%, P = 0.02) and the achievement of CR after first-line treatment (two-year PFS rate 80.3% vs. 33.3%, P < 0.001) were significant favorable prognostic factors for PFS. Hematopoietic stem cell transplantation (HSCT) after the first relapse was associated with significantly improved post-relapse OS (five-year OS rate 85.7% vs. 20.0%, P = 0.02) and PFS (five-year PFS rate 85.7% vs. 20.0%, P = 0.02). CONCLUSION: Patients with low-risk mIPI scores, CR after first-line treatment, and those who underwent HSCT after the first relapse had significantly better survival. Intrathecal chemotherapy conferred no benefit in preventing CNS relapse. Further research is needed to assess frontline HSCT's effectiveness in improving outcomes and preventing CNS relapses in PB-DLBCL patients.

Children with chronic myeloid leukaemia treated with front-line imatinib have a slower molecular response and comparable survival compared with adults: a multicenter experience in Taiwan.

BACKGROUND: The direct comparison of molecular responses of front-line imatinib (IM) monitored at the same laboratory between children and adults with chronic phase (CP) of chronic myeloid leukaemia (CML) had not been reported. In this multicenter study, we compared the landmark molecular responses and outcomes of paediatric and adult CML-CP cohorts treated with front-line IM in whom the BCR::ABL1 transcript levels were monitored at the same accredited laboratory in Taiwan. METHODS: Between June 2004 and July 2020, 55 newly diagnosed paediatric and 782 adult CML-CP patients, with molecular diagnosis and monitoring at the same reference laboratory in Taiwan, were enrolled. The criteria of 2020 European LeukemiaNet were applied to evaluate the molecular responses. RESULTS: By year 5, the cumulative incidences of IS <1%, MMR, MR4.0 and MR4.5 of paediatric patients were all significantly lower than those of adult patients (58 vs 75%, 48 vs 66%, 25 vs 44%, 16 vs 34%, respectively). The 10-year progression-free survival (PFS) (90%) and overall survival (OS) (94%) of paediatric patients did not differ from those (92%) of adult patients. CONCLUSIONS: We demonstrated the paediatric cohort had slower molecular responses to front-line IM and similar outcomes in 10-year PFS and OS in real-world practice.

Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia.

Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.

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

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

Application of comprehensive geriatric assessment in predicting early mortality among elder patients with B-cell lymphoma receiving immunochemotherapy.

OBJECTIVES: Early mortality, defined as death within 120 days after initiated antitumor therapy, is an important issue especially for elder patients with B-cell lymphoma. This study aimed to evaluate the clinical value of comprehensive geriatric assessment (CGA) in early mortality prediction in elderly patients with B-cell lymphoma receiving immunochemotherapy. METHODS: Seventy-six consecutive patients with newly diagnosed B-cell lymphoma receiving immunochemotherapy from a medical center in Taiwan were prospectively enrolled. Patients were divided into fit (n = 49) and frail (n = 27) groups per pretreatment CGA for early mortality comparison. RESULTS: The early mortality rate in our patient cohort was 16% (n = 12): from 6% in patients with no CGA domain impairment to 43% in patients with ≥4 CGA domain impairment. The early mortality rate was 6% and 33% in fit and frail patients (odds ratio, 7.67; 95% CI, 1.86-31.6; P = .005), respectively. Frailty was the significant predictor for early mortality in univariate and multivariate analysis. CONCLUSION: In this study, the number of geriatric domain impairment is positively associated with the early mortality risk in elderly patients with B-cell lymphoma. Therefore, CGA can help clinicians to identify the risk of early mortality in elderly patients and provide alternative treatment.

Impact of Platelet Counts, Surgical Methods, and Preoperative Platelet Transfusion on the Outcome of Splenectomy for Immune Thrombocytopenia.

INTRODUCTION: Splenectomy is an important and potentially curative treatment for immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has replaced open splenectomy (OS) as the standard approach. The prognostic role of platelet count and the clinical indication of preoperative platelet transfusion are not entirely clear. METHODS: We designed a study to explore the prognostic impact of surgical methods, platelet count, and platelet transfusion in a large, single-institute, long-term cohort of ITP patients. RESULT: In 118 ITP patients, there was no difference between OS and LS in response and surgical complications. The overall response rate was 77% and the complete response (CR) rate was 70%. Patients with a CR had a trend towards a higher baseline platelet count. A stable platelet count 14-28 days after splenectomy was associated with a sustained long-term response. Patients requiring preoperative platelet transfusion had a lower preoperative platelet count and were more likely to need postoperative transfusion of red blood cells and platelets. They also had a lower postoperative platelet count than the nontransfusion group. Relapse-free survival did not differ. CONCLUSIONS: Baseline and postoperative platelet counts are apparently associated with the treatment response to splenectomy but the difference did not reach statistical significance. Preoperative platelet transfusion did not overcome the disadvantage of thrombocytopenia and was not recommended when other preparative measures are available.

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3-23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4-39 and were exclusively associated with un-mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un-mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3-23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity-dependent association in Taiwanese CLL patients.

Pharmacokinetic study of bortezomib administered intravenously in Taiwanese patients with multiple myeloma.

This phase 4, single-arm, non-randomized, open-label, post approval commitment study evaluated the pharmacokinetics and safety of bortezomib in Taiwanese patients with multiple myeloma. Patients (≥20 years) with measurable secretory multiple myeloma (serum monoclonal IgG ≥10, IgA/IgE ≥5, IgD ≥0.5 g/L, IgM present [regardless of level], and urine M protein of ≥200 mg/24 h) received intravenous bortezomib 1.3 mg/m2 , twice weekly for 2 weeks, followed by a 10-day resting phase (days 12 to 21). Pharmacokinetics and safety were assessed at pre-specified time points. All enrolled patients (n = 18, men: 11; women: 7) completed the study. Mean (SD) Cmax (maximum observed plasma concentration) on day 11 was 266 (77.5) ng/mL, approximately 60% higher compared with non-Asian patients receiving a similar bortezomib regimen but with overlapping ranges. Because of the protracted terminal phase, half-life (t1/2 ), area under the plasma concentration-time curve from time 0 to infinity (AUC∞ ), volume of distribution (Vz ), and systemic clearance were not assessable. All patients experienced treatment-emergent adverse events (TEAEs); 78% were drug-related. Most commonly reported TEAEs were thrombocytopenia (n = 11 [61%]), neutropenia (n = 9 [50%]), leukopenia (n = 6 [33%]), and diarrhoea (n = 6 [33%]); the most common serious adverse event was pneumonia (n = 2 [11%]). One patient had a dose reduction due to a TEAE of thrombocytopenia. Overall, bortezomib exposure (AUC) in Taiwanese patients (AUClast [SD]: 230 [147] ng·h/mL) with twice weekly intravenous administration was comparable with non-Asian population (AUClast [SD]: 241 [82] ng·h/mL). Bortezomib treatment was associated with manageable toxicity profile and did not limit the continuity of therapy.

Immune thrombocytopenia: Effectiveness of frontline steroids and comparison of azathioprine, splenectomy, and rituximab as second-line treatment.

OBJECTIVE: For immune thrombocytopenia (ITP), efficacy of frontline steroids is well established. However, clinical data comparing various treatment options for refractory or relapsed ITP are limited. We aimed to investigate the outcome of frontline steroid treatment for ITP patients and compare common second-line modalities in a single institute in Taiwan. METHODS: We collected the complete outpatient list over a 6-month period. Patients were identified from the list, and medical records were reviewed to capture the data retrospectively. The diagnosis of ITP was made by excluding other etiologies. RESULTS: Among 665 patients with thrombocytopenia, the diagnosis of ITP was made in 375. Two hundred and fifty-seven patients (51 males, median age 45.5) received treatment. Response to steroids was evaluable for 184 patients. Complete response (CR) was achieved in 120 (65.2%) and partial response in 43 (23.3%). In 21 (11.4%) patients, ITP was refractory to steroids. Among those with CR, 76 (63%) patients relapsed in a median of 9.5 months. After relapse or steroid failure, 57 (49%) received azathioprine treatment and 38 (32%) underwent splenectomy. Response rate was 71.4% (38.1% CR) for azathioprine and 91.4% (77.1% CR) for splenectomy. Rituximab was effective in 8 of 10 patients. CONCLUSION: Steroids are effective frontline treatment for ITP, but relapse is common. Both azathioprine and splenectomy are effective treatment after steroid failure. Rituximab appears to a reasonable second-line treatment option in our limited experience.

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.

Pneumocystis jirovecii pneumonia in patients with acute myeloid leukaemia.

The association of Pneumocystis jirovecii pneumonia (PJP) and acute myeloid leukaemia (AML) is not clearly defined. In our experience of 291 patients with AML, 20 (14 males and 6 females, median age 56) developed PJP (incidence 6.8%). Thirteen patients (65%) survived until discharge from hospital. We conclude that PJP is not uncommon among patients with AML. In clinical care of AML, awareness of PJP should be heightened and prophylaxis should be considered.

Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.

Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone.

Clinical Features and Recurrence Pattern of Perianal Abscess in Patients with Acute Myeloid Leukemia.

INTRODUCTION: Perianal abscess may develop during neutropenia periods in patients with acute myeloid leukemia (AML). The standard of care for perianal abscess in AML is unclear. METHODS: We retrospectively collected patient data in our institute from 2009 to 2012. RESULTS: Two hundred ninety-two patients with AML were analyzed. In total, 1,051 chemotherapy sessions were administered. Twenty-three patients experienced perianal abscess. Patients with perianal abscess were younger than those without (44 vs. 60 years, p < 0.0001). Perianal abscess developed in various phases of treatment and in the stem cell transplantation period. Twelve recurrences developed in 6 patients. Patients with a prior perianal abscess have a 10-fold risk of developing a subsequent abscess following further chemotherapy. The microbiology profile revealed that most pathogens were derived from the intestinal tracts, which was similar to the findings of previous studies. The 28-day mortality was 14.3% and the direct cause of death was not perianal abscess in any case. Surgical interventions had no impact on recurrence or survival. CONCLUSION: In patients with AML, perianal abscess results from gastrointestinal tract pathogens. Many patients do not require surgical interventions. The mortality is low but recurrence is common following subsequent chemotherapies. Therefore, awareness of recurrence is important for the timely management of perianal abscess in AML.

Concordance of two approaches in monitoring of minimal residual disease in B-precursor acute lymphoblastic leukemia: Fusion transcripts and leukemia-associated immunophenotypes.

BACKGROUND/PURPOSE: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry. RESULTS: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively. CONCLUSION: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.

Cyclophosphamide plus granulocyte-colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma.

We retrospectively reviewed the results of cyclophosphamide (3 g/m(2) ), doxorubicin and dexamethasone plus granulocyte-colony stimulating factor (G-CSF) (ID-CY/DOX group), low-dose cyclophosphamide (2 g/m(2) ) plus G-CSF (LD-CY group) and G-CSF alone (G-CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10(9) /L for ID-CY/DOX and LD-CY groups and after eight doses of G-CSF (5 µg/kg twice daily) for G-CSF group. For five mobilizations in ID-CY/DOX group, the rate of successful mobilization (≥4.0 × 10(6) /kg CD34+ cells) was 80%. For 78 mobilizations in LD-CY group, the successful rate was 80.8%. For 10 mobilizations in the G-CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID-CY/DOX and LD-CY groups as compared with that in G-CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID-CY/DOX and LD-CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID-CY/DOX and LD-CY plus G-CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G-CSF alone and their engraftment time were similar. Total WBC count >10 × 10(9) /L can be used as a guide to start apheresis in CY-based stem cell mobilization. J. Clin. Apheresis 31:423-428, 2016. © 2015 Wiley Periodicals, Inc.

Clonal leukemic evolution in myelodysplastic syndromes with TET2 and IDH1/2 mutations.

Somatic mutations of TET2, IDH1, and IDH2 have been described in myelodysplastic syndrome. The impact of these mutations on outcome of myelodysplastic syndrome and their progression to secondary acute myeloid leukemia remains unclear. Mutation status of TET2, IDH1 and IDH2 was investigated in a cohort of 46 paired myelodysplastic syndrome/acute myeloid leukemia samples and 122 non-paired cases with de novo myelodysplastic syndrome, to clarify their roles in the evolution of myelodysplastic syndrome to acute myeloid leukemia. Among the 168 de novo myelodysplastic syndrome patients, the frequency of TET2, IDH1, and IDH2 mutations was 18.5%, 4.2% and 6.0%, respectively. TET2/IDH mutations had no impact on survivals, while TET2 mutations were significantly associated with rapid progression to acute myeloid leukemia. Seventeen of the 46 paired myelodysplastic syndrome/secondary acute myeloid leukemia samples harbored TET2/IDH mutations; none acquired these mutations in acute myeloid leukemia phase. Progression to acute myeloid leukemia was accompanied by evolution of a novel clone or expansion of a minor pre-existing subclone of one or more distinct mutations in 12 of the 17 cases with TET2/IDH mutations. A minor subclone in 3 cases with biallelic TET2 inactivation subsequently expanded, indicating biallelic TET2 mutations play a role in acute myeloid leukemia progression. Twelve patients acquired other genetic lesions, and/or showed increased relative mutant allelic burden of FLT3-ITD, N/K-RAS, CEBPA or RUNX1 during acute myeloid leukemia progression. Our findings provide a novel insight into the role of TET2/IDH mutation in the pathogenesis of myelodysplastic syndrome and subsequent progression to acute myeloid leukemia.

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.

Major impact of prognosis by age and sex in patients with primary mediastinal large B­cell lymphoma.

The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients.