IntroductionMature T-cell and natural killer (NK)-cell lymphomas are rare and heterogeneous diseases following an aggressive clinical course which necessitates immediate therapy. Outcome is generally believed poor although only 1 recent study 1 comprises all major T-cell lymphoma subtypes according to the World Health Organization classification 2,3 with spin-off studies reporting on clinical outcome and prognostic factors of various subtypes. [4][5][6] In contrast to the progress made in the treatment of aggressive B-cell lymphoma, 7-9 evidence for similar therapeutic improvements in T-and NK-cell lymphoma is largely absent. Therefore, we analyzed a large cohort of patients with T-cell lymphoma who have been treated on protocols of the German High-Grade Non-Hodgkin Lymphoma Study Group (Deutsche Studiengruppe Hochmaligne Non-Hodgkin Lymphome [DSHNHL]). We were particularly interested in the long-term results achieved with "standard" CHOP (cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone) and CHOP-like therapy and wanted to define prognostic factors which should influence the decision which patients should be treated on standard or experimental protocols in the future. Methods PatientsBetween October 1993 and May 2007, 343 patients with mature nodal or extranodal T-cell or NK-cell lymphoma 2 were treated on protocols of the DSHNHL. Mandatory reference pathology was performed in 1 of the 6 German Reference Centers for Malignant Lymphomas (Berlin, Frankfurt, Kiel, Lübeck, Ulm, and Würzburg) prior to therapy. Of 343 patients, 320 could be assigned to 1 of the following subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase-positive (ALKpositive); ALCL, ALK-negative; peripheral T-cell lymphoma unspecified (PTCLU); angioimmunoblastic T-cell lymphoma (AITL); NK/T-cell lymphoma; lymphoblastic lymphoma; enteropathy-type T-cell lymphoma; hepatosplenic ␥␦ T-cell lymphoma; or subcutaneous panniculitis-like T-cell lymphoma. In a subset of ALCL cases the ALK status had not been determined at the time of diagnosis, because antibodies were not available at that time. In these cases, the ALK status was defined retrospectively using the ALK1 antibody from DAKO (dilution 1:80, citrate buffer pH 6.0). The definition of ALK1-negative ALCL followed the current World Health Organization classification and required characteristic large cell morphology (indistinguishable from ALK-positive ALCL), strong and consistent expression of CD30 and negativity for ALK1. Moreover, most cases had expression of at least 1 cytotoxic molecule (Perforin, Granzyme B, or TIA). Twenty-three patients were excluded from the analysis because the ALK For personal use only. on May 12, 2018. by guest www.bloodjournal.org From status of some ALCL patients remained unknown (n ϭ 11) or the T-cell lymphoma subtype could not be confirmed for technical (n ϭ 3) or other reasons (n ϭ 9).All patients had thorough baseline and follow-up assessments (history, clinical evaluation, labor...

The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

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Background Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. Methods This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7•5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²), and vincristine (1•4 mg/m², with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m² of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of-5•5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421.

In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL.

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

Summary. Chronic myeloid leukaemia (CML) is believed to represent a stem cell disorder involving all three cell lineages. The typical chromosomal aberration, the Philadelphia chromosome, is the translocation (9;22)(q34;q11). Several studies with cytogenetics, fluorescence in situ hybridization (FISH), or polymerase chain reaction have investigated the presence of the t(9;22) in different cell compartments. However, questions still remain. In six cases of CML we combined the standard May-Grü nwald-Giemsa staining with FISH at the single-cell level and were able to demonstrate that not only all maturation stages of granulopoiesis, erythropoiesis, and megakaryocytes, but also plasma cells, eosinophils, basophils and monocytes carried the Philadelphia chromosome in 53-98% of samples. Using immunological identification of single cells we were able to demonstrate that the t(9;22) is detectable in 34% of CD3-positive T lymphocytes, in 32% of CD19-positive B lymphocytes, and in 82% of CD34-positive precursor cells. The results give new insight into the biology of CML and may have implications for future therapeutic strategies.

FL recurrence after autoSCT follows a biphasic pattern with continuing relapse during the first 6 years and only few events thereafter. The prognosis after relapse is relatively good and appears to be comparable to that of disease recurrence after standard treatment. The situation is less favorable for patients who relapse within the first posttransplant year.