Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

[Palliative chemotherapy for colorectal cancer--current state, significance, trends]. / Palliative Chemotherapie beim kolorektalen Karzinom--Stand, Wertigkeit, Tendenzen.

BACKGROUND: There are a number of effective substances available for palliative treatment of colorectal cancer, contributing to a considerable extension of the median survival time either purely medically or by increasing the chance of secondary resectability through improved effectiveness of the administered drugs. PATIENTS / MATERIAL: Defining treatment depending on predominant patient characteristics remains crucial for any therapeutic success. This requires interdisciplinary co-ordination within tumour boards. METHODS: In aggressive tumours a therapeutic approach inducing high response rates is favoured, usually including a triple or quadruple combination incl. antibodies. In cases of slow tumour progress and limited patient profile, a sequence of chemotherapy is chosen. Implementing and integrating locally ablative modes of therapy into the treatment strategy can increase the effectiveness additionally. In a best case scenario additional systemic side effects can be avoided resulting in a not insignificant benefit in quality of life. RESULTS: Further genotyping beyond the K-RAS state is necessary to make predictive and prognostic statements concerning the drugs applied and to avoid ineffectiveness. CONCLUSION: Considerable progress has been achieved in the medical therapy for metastasised colorectal cancer. The targeted application of already available as well as recently developed substances requires further evaluation by appropriate studies.

Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission.

Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype.

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: I. A randomized dose escalation and feasibility study with bi- and tri-weekly regimens.

BACKGROUND: To determine the maximum tolerated dose of a bi- and tri-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone plus etoposide (CHOEP) regimen without stem-cell support. PATIENTS AND METHODS: Randomized phase I/II multicenter four-level (cyclophosphamide: 1000-1200-1400-1600 mg/m2; doxorubicin: 55-60-65-70 mg/m2; etoposide: 375-450-525-600 mg/m2) dose escalation study with CHOEP-14 and CHOEP-21 in young patients (18-60 years) with newly diagnosed aggressive non-Hodgkin's lymphoma. Dose-limiting toxicity was defined as thrombocytopenia <80,000/mm3 and leukocytopenia <2500/mm3 on days 16 (CHOEP-14) and 23 (CHOEP-21) or prolonged (>4 days) leukocytopenia (<1000/mm3) or thrombocytopenia (<20,000/mm3). RESULTS: One hundred and thirty-nine patients (high-CHOEP-14: 47, high-CHOEP-21: 92) were randomly allocated to the study. Maximal tolerated dose was level 2 for CHOEP-14 and level 4 for CHOEP-21. With a less favorable profile of patients in CHOEP-14, 4-year event-free survival was 47.9% after high-CHOEP-14 and 66.2% after high-CHOEP-21, 4-year overall survival 62.1% after high-CHOEP-14 and 73.4% after high-CHOEP-21, respectively. CONCLUSION: Significant dose escalations of CHOEP are possible with granulocyte colony-stimulating factor support, with different chemotherapy models favoring the maximally escalated bi- or tri-weekly regimen, respectively. Because a higher total dose can be achieved with six cycles of the tri-weekly compared with the biweekly regimen, CHOEP-21 at dose escalation level 3 was chosen for a nationwide randomized comparison with baseline CHOEP-21 in a subsequent phase III trial.

Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

Increased risk of venous thromboembolism in patients with acute leukaemia.

Patients with malignancies have an increased risk for venous thromboembolisms (VTE), but data on patients with acute leukaemia are very limited so far. We found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in association with central venous catheters, with equal risk of ALL and AML.

Long-term remission in a patient with carcinoma of unknown primary site.

BACKGROUND: Cancer of unknown primary site also designated as CUP syndrome usually presents as metastatic disease with a poor prognosis and low remission as well as survival rates. CASE: We report a 46-year-old male with para-aortal and left-sided cervical lymph node metastases. Histological examination of a cervical lymph node revealed papillary carcinoma. Despite thorough investigation, no primary tumor was found. The patient was empirically treated with six courses of the FACP regimen (5-fluorouracil, Adriamycin, cyclophosphamide and cisplatin) combined with radiotherapy (40 Gy) and has remained in complete remission for 124 months. CONCLUSION: This case indicates that treatment of a patient with cancer of unknown primary site may be rewarded by a benign course. However, complete cure remains a very rare event in CUP. Remission can be achieved with a platinum-containing regimen combined with radiotherapy.

Increased risk of thromboembolism in patients with malignant lymphoma: a single-centre analysis.

An increased risk for thromboembolism in cancer patients has been observed in patients with solid tumours, whereas little data exist on malignant lymphoma. We found an overall thromboembolic event incidence of 7.7% in 1038 lymphoma patients treated in our institution, with a statistically significantly higher incidence in high-grade than in low-grade lymphoma.

[Diagnosis of the antiphospholipid syndrome in anticoagulated patients]. / Diagnose des Antiphospholipid-Syndrom beim antikoagulierten Patient: Was gibt es zu beachten?

The antiphospholipid syndrome is characterized by thromboembolic events and/or recurrent miscarriages in the presence of anticardiolipin antibodies and/or a lupus anticoagulant. Anticardiolipin antibodies are detected by ELISA whereas lupus anticoagulant detection includes a variety of coagulometric tests. However, a large number of patients with suspected antiphospholipid syndrome are anticoagulated with either heparin or coumadin when evaluated for the presence of a lupus anticoagulant and false positive test results may ensue, thus making coagulometric testing unreliable in this situation. Modifications of standard coagulometric tests have been suggested in order to circumvent this problem and studies of several patient cohorts have shown that the majority of patients with the antiphospholipid syndrome are anticardiolipin positive. However diagnosis in patients receiving anticoagulation remains a difficult task.

High-dose treosulfan in patients with relapsed or refractory high-grade lymphoma receiving tandem autologous blood stem cell transplantation.

This phase I/II study evaluated high-dose treosulfan in patients with high-grade lymphoma. In all, 21 patients (median age 51, 25-60 years) with primary refractory disease (n=3) or early (n=11) or late (n=7) relapse received DexaBEAM and one course etoposide for cytoreduction and PBPC mobilization. Subsequently, 16 patients received 30 g/m2 treosulfan and 140 mg/m2 melphalan, followed by autologous transplantation. Nine patients received a 2nd high-dose treatment (HDT) with 30 g/m2 treosulfan and 750 mg/m2 thiotepa. Recovery time to >1/nl leukocytes and >25/nl thrombocytes was 8.9 (range 8-11) and 11.9 (8-16) days after 1st and 9.6 (7-13) and 13 (9-19) days after 2nd HDT. Reversible grade 3 or 4 nonhematologic toxicities included mucositis (n=7), infection (n=7) and one episode of re-entry tachycardia. Two treatment-related deaths occurred after 2nd HDT. Since three dose-limiting toxicities occurred among nine patients receiving tandem HDT, 30 g/m2 of treosulfan was considered MTD in this setting. Patients with late compared to early relapse or refractory disease had a higher probability of CR (6/7 vs 3/14 patients, P=0.017) and overall survival (71 vs 21%, P<0.05, 24-49 months follow-up). In conclusion, high-dose treosulfan as major therapy component induces sustained complete remissions in relapsed high-grade lymphoma with acceptable toxicity.

Takayasu's arteritis secondary to myelodysplasia as a predictor of poor outcome: two case reports.

We present two patients with myelodysplasia in association with Takayasu's arteritis (TA). In both patients intensive immunosuppressive treatment could not control the vascular inflammation. Subsequently both patients developed myelodysplasia, rapidly progressing to secondary acute myelogenous leukaemia. One patient had a peripheral blood stem cell transplant from a compatible sibling donor, but died of refractory leukaemia 5 months later. The other patient died of fungal sepsis. These are the first two patients reported to have TA associated with myelodysplasia/secondary leukaemia.

Magnetic resonance imaging guided corticosteroid injection of the sacroiliac joints in patients with therapy resistant spondyloarthropathy: a pilot study.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) guided corticosteroid injections of inflamed sacroiliac (SI) joints in patients with spondyloarthropathy with therapy resistant sacroiliitis. METHODS: We performed 16 injections in 9 patients on an outpatient basis (6 men, 3 women, mean age at onset 24.7 +/- 7.5 yrs). All patients had MRI guided injection of 40 mg triamcinolone acetonide into SI joints using an open 0.2 Tesla unit. Before and 3 months after corticosteroid injection they underwent an MRI examination with a closed 1.5 Tesla unit. RESULTS: Seven of 9 patients reported subjective improvement that lasted at least a mean of 10.8 +/- 5.6 months. Subchondral bone marrow edema on fat suppressed images resolved in 8 patients after corticosteroid injection. CONCLUSION: MRI guided corticosteroid injection of SI joints appears to be an effective and safe procedure without exposure to radiation. It is a useful therapeutic modality, especially in young patients with severe isolated sacroiliitis.

[Interferon-alpha-associated polyarthritis. Possible induction of seropositive rheumatoid arthritis by interferon-alpha: two case reports and review of the literature]. / Interferon-alpha-assoziierte Polyarthritis. Mögliche Induktion einer seropositiven rheumatoiden Arthritis durch Interferon-alpha: zwei Fallbeispiele und Literaturübersicht.

We describe a patient with chronic myelogenous leukemia (CML) and a patient with hairy cell leukemia being effectively treated with alpha-interferon who developed a seropositive chronic polyarthritis formally fulfilling the ACR criteria for rheumatoid arthritis. Because of its efficacy, interferon was not discontinued, and the arthritis treated with low-dose prednisolone or NSAIDS. These are the 19th and 20th case of symmetrical polyarthritis during alpha-interferon therapy fulfilling the criteria for RA. The possible mechanisms of the relatively frequent appearance of autoimmune diseases during interferon therapy are discussed.

Lower limb pitting edema in systemic lupus erythematosus.

We report two patients with lower limb pitting edema and systemic lupus erythematosus (SLE) who showed immediate response to systemic steroids. In one of the patients, the edema had been present for about 6 months and was the first manifestation of her SLE. In the second patient with a long history of SLE and antiphospholipid syndrome, a thrombosis was suspected, but not confirmed. Only after therapy with steroids did the edema disappear completely. Pitting edema of the lower limb could be a rare manifestation of SLE.

Articular involvement in patients with relapsing polychondritis.

Our objective was to study joint symptoms in patients with relapsing polychondritis (RP) and their relationship to other clinical manifestations and laboratory findings. Fourteen patients who met the diagnostic criteria proposed by Michet et al. for RP were studied. Clinical symptoms were recorded and a detailed laboratory analysis with HLA-DR typing was carried out. In 2 patients arthritis was the first manifestation. During the follow-up, 10 patients developed arthritis. It was polyarticular in 6, and oligoarticular in 4 cases. The development of arthritis was unrelated to the appearance of chondritis at other sites. HLA class II typing was determined in 7 patients. Six of them were positive for HLA-DR4. Arthritis in RP is a frequent manifestation occurring in approximately 70% of patients with an asymmetric articular involvement. There is no correlation between articular involvement and any particular clinical or laboratory feature. Susceptibility to RP is significantly related to the presence of HLA-DR4.

[Effect of preparation and preservation modality on thrombocyte quality]. / Einfluss von Präparation und Lagerungsmodalität auf die Thrombozytenqualität.

In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.