Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL.

Summary:epidemiology and risk factors for IFI is important in identifying subsets of BMT recipients for clinical trials investigating the effects of novel preventive measures, as In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 well as clinical decision-making on the management of patients after allogeneic BMT. consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 wereIn most previous studies, the role of GVHD and especially the effects of regimens used for GVHD prophyretrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, laxis or treatment, have not been evaluated as risk factors for IFI. Due to the increasing age of BMT recipients, wider 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after use of unrelated donors, modifications in pre-and posttransplant immunosuppression and antifungal prophylaxis, BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the the incidence of fungal infections, as well as the spectrum of causative agents, may change. We therefore investigated pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = the incidence and risk factors for IFI and especially the effects of acute and chronic GVHD and their treatment with 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) steroids and antithymocyte globulin, on the risk of IFI in allogeneic BMT recipients transplanted between 1989 and were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors.1993. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. BetPatients and methods ter prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk Patients of IFI after allogeneic BMT.One hundred and forty-two adult patients received their first Keywords: invasive fungal infection; BMT; GVHD; risk allogeneic BMT (131 HLA-identical sibling donors, 11 factors; incidence unrelated donors) in the Department of Medicine, Helsinki University Central Hospital between 1989 and 1993. All patient charts were screened for relevant baseline data, Invasive fungal infections (IFI) mainly caused by Candida post-transplant course, occurrence and treatment of GVHD, and Aspergillus species constitute a major problem after as well as invasive fungal infections and their management. allogeneic BMT. Invasive Candida infections have beenThe patients had a median follow-up of 26 months postreported in 10-15% of patients, 1-4 and the incidence of BMT (range 1-82 months). The main pretransplant characAspergillus infections has varied between 3 and 7% in teristics are presented in Table 1. recent series. 2,[5][6][7] ...

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg m 72 ) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m 72 . Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction 450%. Twenty-eight patients received doxorubicin 5400 mg m 72 and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m 72 . Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction 450% in 10 patients (36%). Left ventricular ejection fraction decreased from 56+1.5% to 53.6+1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8+2.4% to 41.8+2.0% (P50.001) in patients with cardiotoxicity. For patients who developed cardiotoxicity, the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg m 72 was highly significant (left ventricular ejection fraction 49.7+1.8%, P=0.001 vs baseline). In receiver operator characteristic analysis, the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg m 72 for predicting cardiotoxicity in all patients was 0.858. The decrease in left ventricular ejection fraction of more than 4% units after a cumulative doxorubicin dose of 200 mg m 72 had a 90% sensitivity and 72% specificity for predicting later cardiotoxicity. Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early, already at low cumulative doxorubicin doses. This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity.

Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK-positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK-negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK-negative, ALCL-ALK-positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions.

Summary:Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD7local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m 2 ) (n ¼ 25) or intermediate-dose CY (ID-CY, 4 g/m 2 ) (n ¼ 32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 Â 10 6 /kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, Po0.001), lower frequency of fever (20 vs 73%, Po0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P ¼ 0.004) and days on parenteral antibiotics (0 vs 4 days, Po0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile. Bone Marrow Transplantation (2003) 31, 347-351. doi:10.1038/sj.bmt.1703840 Keywords: cyclophosphamide; progenitor cell mobilisation; efficiency; toxicity; multiple myeloma Patients with multiple myeloma (MM) have a median survival of 3-4 years with conventional chemotherapy. In a randomised trial, high-dose therapy supported by stem cell rescue was superior over conventional chemotherapy in terms of complete remission rate, progression-free survival and overall survival. 1 The superiority of single or tandem autotransplants over conventional therapy has also been suggested in some controlled studies. 2,3 More than 95% of autotransplants for MM are now performed with the support of blood progenitor cells. 4 High-dose (7 g/m 2 ) cyclophosphamide (CY) alone or combined with a growth factor was initially used for mobilisation of progenitor cells in myeloma patients. [5][6][7] Goldschmidt et al 8 found that CY 7 g/m 2 plus G-CSF was superior to CY 4 g/m 2 plus G-CSF in this regard. However, high-dose CY is associated with significant toxicity. 7,9 Recently, Fitoussi et al 9 showed that intermediate-dose CY (ID-CY) (4 g/m 2 ) plus growth factor was equally effective as high-dose CY in mobilising progenitor cells in myeloma patients but was less toxic.Mobilisation with CY 4 g/m 2 plus G-CSF is, however, also associated with significant toxicity and need for supportive care. We hypothesised whether low-dose CY (LD-CY) (up to 2 g/m 2 ) could be as effective and, less toxic mobilisation regimen in patients with newly diagnosed MM. Therefore, a retrospective analysis in myeloma patients previously...

Summary:To investigate diagnostic aspects of invasive aspergillosis (IA) in allogeneic BMT recipients, the charts of 22 consecutive patients with IA transplanted in 1989-1995 were reviewed. IA was diagnosed 69-466 days (median 131 days) post BMT. In 16 patients (73%), a definite or probable diagnosis of IA was made during life. Respiratory symptoms were the presenting feature in half of the patients followed by neurological symptoms (27%). Chest X-ray revealed single or multiple nodular lesions in 10 patients; cavitation was observed in five patients. Tissue biopsy was the most common method of diagnosis (nine patients: lungs 6, liver 1, subcutaneous tissue 1, brain 1). Five IA cases were detected by nine guided fine needle lung biopsies in eight patients and without complications. Bronchoalveolar lavage was performed in 14 patients with findings suggestive of invasive pulmonary aspergillosis in eight cases. Lungs were the most common organ affected (90%) followed by central nervous system (41%). The diagnosis of IA is still difficult, and a large number of patients have advanced infection at diagnosis. Methods for early diagnosis are needed. Patients with a clinical suspicion of IA should be treated vigorously with antifungal agents during the diagnostic work-up. Bone Marrow Transplantation (2000) 25, 867-871. Keywords: Aspergillus infection; allogeneic BMT; diagnosis; radiology; biopsy; bronchoalveolar lavage Invasive aspergillosis (IA) is an important clinical problem in allogeneic BMT recipients. In previous studies, the incidence of IA has ranged from 4 to 10% 1-5 and may be increasing. 6 Aspergillus infections have been considered difficult to diagnose. 7-9 They often present with non-specific symptoms and signs. In the allogeneic setting other opportunistic infections may make the diagnosis of IA even more difficult. Due to frequent colonization of the upper respiratory tract with Aspergillus sp, tissue biopsy is needed for definitive diagnosis. Knowledge of the spectrum of clinical presentation of IA is essential both for raising clinical suspicion and for guiding diagnostic attempts. Furthermore, information on the yield of different diagnostic methods is needed in choosing rational diagnostic strategies. We have therefore analyzed our experience on the diagnostic aspects of IA in a recent cohort of allogeneic BMT recipients. Patients and methods

The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis.

Aims:  To evaluate the biological roles and prognostic significance of the epithelial–mesenchymal transition (EMT)‐mediating transcription factors (TFs) Twist, ZEB1 and Slug in patients with diffuse large B‐cell lymphoma (DLBCL). EMT has been shown to enhance solid tumour metastasis, invasion, and proliferation. Methods and results:  Expression of Twist, ZEB1 and Slug was evaluated immunohistochemically in eight samples from reactive lymphoid tissues and in diagnostic samples from 102 DLBCL patients treated with curative intent with R‐CHOP‐type chemotherapy. ZEB1 and Slug expression correlated with adverse disease presentation. However, cytoplasmic Slug expression was linked to a favourable disease outcome, whereas nuclear expression of ZEB1 indicated an adverse outcome. Conclusions:  This study shows that an EMT‐like process occurs in lymphomas. Of the TFs investigated, ZEB1 seems to be the main one associated with adverse clinical presentation and clinical outcome. Surprisingly, Slug expression in cytoplasm was linked to a favourable prognosis. Further studies are needed to evaluate whether inhibition of ZEB1 could serve as a therapeutic target.