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Biomedical subjects

K Höffken

Publications and source records attributed to K Höffken.

At least 19 recordsLinked to original sources
PubMed2006

ATRA can enhance apoptosis that is induced by Flt3 tyrosine kinase inhibition in Flt3-ITD positive cells.

Among activating Flt3 mutations that have been shown in 25-30% of acute myeloid leukaemia (AML) Flt3-internal tandem duplication (ITD) mutations are predominant. We investigated the influence of all-trans-retinoic acid (ATRA) and granulocyte colony stimulating factor (G-CSF) for their effects on differentiation and apoptosis in human cell lines with different Flt3 variants (THP-1 versus MV4-11 and MOLM13) dependent on the inhibition of Flt3 tyrosine kinase by the bis(lH-2-indolyl)methanone D-65476. While myeloid differentiation was not observed in both Flt3-ITD cell lines (MV4-11 and MOLM13), we demonstrate an enhanced proapoptotic effect of D-65476 in the presence of ATRA that was restricted to the Flt3-ITD expressing cells. The combined treatment with ATRA and D-65476 also led to a pronounced down-regulation of surviv in on mRNA and protein level in Flt3-ITD but not in Flt3 wildtype expressing cells (THP-1). Surprisingly, there was no differential expression of important proteins like Bcl-X(L), Bcl-2 or Bax that might explain enhanced apoptosis. Furthermore, Akt phosphorylation after stimulation with Flt3 ligand dependent on D-65476 was not affected by pretreatment with ATRA. We suggest that regulation of inhibitors of apoptosis might play a crucial role how ATRA can increase the proapoptotic effect of Flt3 inhibitors in myeloid leukemia cells expressing Flt3-ITD. This effect can potentially be exploited for the treatment of Flt3-ITD positive acute myeloid leukemia.

Apoptosis↗
PubMed2006

Differential interaction of magnetic nanoparticles with tumor cells and peripheral blood cells.

PURPOSE: The separation of tumor cells from healthy cells is a vital problem in oncology and hematology, especially from peripheral blood. Magnetic assisted cell sorting (MACS) is a possibility to fulfill these needs. METHODS: Tumor cell lines and leukocytes from peripheral blood were incubated with carboxymethyl dextran-coated magnetic nanoparticles under various conditions and separated by MACS. RESULTS: We studied the interaction of magnetic nanoparticles devoid of antibodies with healthy and tumor cells. The magnetic nanoparticles interact with tumor cells and leukocytes and are located predominantly within the cell cytoplasm. Incubation of cell culture cells with magnetic nanoparticles led to a labeling of these cells without reduced biological properties for at least 14 days. The interaction of the magnetic nanoparticles with cells depends on several factors. The ionic strength (osmolality) of the solvent plays an important role. We could show that an increase in osmolality led to a dramatic reduction of labeled leukocytes. Tumor cells, however, are mildly affected. This could be detected not only in pure cultures of tumor cells or leukocytes but also in mixed cell populations. CONCLUSION: This observation gives us the opportunity to selectively label and separate tumor cells but not leukocytes from the peripheral blood.

Blood Cells↗
PubMed2006

Flt3-ITD mutations can generate leukaemia specific neoepitopes: potential role for immunotherapeutic approaches.

Flt3 internal tandem duplications (Flt3-ITD) can be detected in 25 - 30% of acute myeloid leukaemia (AML) and differ in length and sequence. We sequenced patient specific Flt3-ITD mutations in 2 Flt3-ITD positive AML cell lines and 13 Flt3-ITD harbouring AML patients. We addressed the question whether Flt3-ITD mutations can harbour HLA class I specific neoepitopes potentially able to induce a leukaemia and Flt3-ITD specific immune response. Here, we demonstrate that all but 1 Flt3-ITD mutations were unique. Interestingly, the peptide sequence of several Flt3-ITD fusion regions harbour 9 mer neoepitopes that potentially bind to HLA class I molecules in a HLA restricted manner (e.g. A1, A2, B27). The specific binding of Flt3-ITD derived neoepitopes to HLA-A2 is demonstrated. Peptide affinity of HLA-A2-restricted putative neoepitopes can be significantly improved by construction of mimotope candidates. We suggest that Flt3-ITD mutations can form new immunogenic and HLA class I-restricted peptide epitopes.

Acute Disease↗
PubMed2006

Chronomodulated chemotherapy with oxaliplatin, 5-FU and sodium folinate in metastatic gastrointestinal cancer patients: original analysis of non-hematological toxicity and patient characteristics in a pilot investigation.

OBJECTIVE: Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate. METHODS: Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity. CONCLUSION: The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.

Adult↗
PubMed2006

Pharmacokinetics of oxaliplatin and non-hematological toxicity in metastatic gastrointestinal cancer patients treated with chronomodulated oxaliplatin, 5-FU and sodium folinate in a pilot investigation.

OBJECTIVE: To analyze in a pilot study the association between the pharmacokinetics of chronomodulated administered oxaliplatin and non-hematological toxicity in patients with metastatic gastrointestinal cancer. METHODS: 16 patients received a 4-day chemotherapeutic regimen consisting of a 12-h chronomodulated infusion of oxaliplatin (25 mg/m2) followed by a 12-h chronomodulated infusion of 5-fluorouracil (750 mg/m2) and sodium folinate (150 mg/m2) daily. Plasma pharmacokinetics of oxaliplatin, measured as ultrafiltrable platinum, were determined. RESULTS: Pharmacokinetics and non-hematological adverse events could be assessed in all patients included in the study. Pharmacokinetic parameters showed moderate interpatient variability. The occurrence of nausea and vomiting, but not diarrhea, was significantly associated with the pharmacokinetics of ultrafiltrable platinum. Thus, increased AUC values were observed in patients who experienced nausea or vomiting. No differences in pharmacokinetic parameters were found between patients with and without oxaliplatin-induced neurotoxicity or the other selected non-hematological toxicities. CONCLUSION: The preliminary results in this pilot study suggest an association between pharmacokinetics of ultrafiltrable platinum and non-hematological toxicity such as nausea and vomiting. Furthermore, although the sample size is limited, systemic exposure to ultrafiltrable platinum appears to predict the risk of non-hematological toxicity in patients treated with chronomodulated oxaliplatin combined with 5-FU and FS.

Adult↗
PubMed2005

Impact of early NK cell recovery on development of GvHD and CMV reactivation in dose-reduced regimen prior to allogeneic PBSCT.

Dose-reduced allogeneic peripheral blood stem cell transplantation (PBSCT) is a therapeutic approach for patients with haematological malignancies who are not eligible for conventional allogeneic PBSCT. We analysed early development of lymphocyte subpopulations and the occurrence of cytomegalovirus (CMV) reactivation and acute graft-versus-host reaction (GvHD) in patients undergoing the protocol according to Slavin vs conventionally treated patients. Lymphocyte status prior to conditioning and at day +30 after allogeneic PBSCT was determined in 24 out of 51 patients who received conventional allogeneic PBSCT (eg cyclophosphamide plus total body irradiation) and compared with 27 patients being treated according to the Slavin protocol (fludarabine, busulphan and ATG). There is a significant delay in CD4 (T helper) cell development and consecutive lower CD4/CD8 ratios and a better reconstitution of CD8 (T cytotoxic) and NK (natural killer) cells after the Slavin protocol. Patients undergoing this protocol and no, or only grade I, acute GvHD show an even better NK cell reconstitution compared to patients with grade II-IV GvHD. A low CD4/CD8 ratio represents a CMV risk factor only in conventionally treated patients with grade 0-I GvHD, while after preparative regimen according to the Slavin protocol, the NK/CD8 ratio might be a marker for the prediction of CMV reactivation in addition to CMV risk status.

Adult↗
PubMed2004

[Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction].

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.

Adult↗
PubMed2004

Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial.

This prospective, parallel-group, dose-escalation study evaluated the cardiac safety of trastuzumab (Herceptin) plus epirubicin/cyclophosphamide (EC) in women with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) and determined an epirubicin dose for further evaluation. HER2-positive patients received standard-dose trastuzumab plus epirubicin (60 or 90 mg/m(2))/cyclophosphamide (600 mg/m(2)) 3-weekly (EC60+H, n=26; EC90+H, n=25), for four to six cycles; 23 HER2-negative patients received EC alone (90/600 mg/m(2)) 3-weekly for six cycles (EC90). All patients underwent thorough cardiac evaluation. Two EC90+H-treated patients experienced symptomatic congestive heart failure 4.5 and 6 months after the end of chemotherapy. One EC60+H-treated patient experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) to <50% 6 months after the end of chemotherapy. No such events occurred in control patients. Asymptomatic LVEF decreases of >10% points were detected in 12 (48%), 14 (56%) and 5 (24%) patients treated with EC60+H, EC90+H, and EC90. Objective response rates with EC60+H and EC90+H were >60%, and 26% for EC90 alone. These results indicate that trastuzumab may be combined with EC with manageable cardiotoxicity and promising efficacy.

Adult↗
PubMed2004

Combined standard graft-versus-host disease (GvHD) prophylaxis with mycophenolate mofetil (MMF) in allogeneic peripheral blood stem cell transplantation from unrelated donors.

In this open single-centre phase II study, MMF was added on day +10 after allogeneic transplantation to standard immunosuppressive prophylaxis consisting of cyclosporine and methotrexate to decrease the incidence of GvHD. In all, 30 patients aged 20-59 years with advanced haematological malignancies received an unmanipulated blood-stem-cell graft (median of 8.5 x 10(6) CD34(+) and 349 x 10(6) CD3(+) cells per bodyweight) from matched unrelated (n=26), or mismatched donors (n=4). Prior to transplantation, 13 patients underwent fractionated total body irradiation and cyclophosphamide, one patient additional etoposide. In all, 16 patients received reduced conditioning of fludarabin, busulfan, and antithymocyte globulin. All patients engrafted in a median of 12 days, and 19 developed acute GvHD>/=II, including two patients with GvHD III and three with GvHD IV. Subsequently, nine patients developed limited and two patients extensive chronic GvHD. With a median follow-up of 28 months, the overall survival is 53.3% and disease-free survival 50%, respectively. Only two deaths were due to GvHD IV. Out of 13 patients, 10 being CMV IgG positive became positive for pp65. In conclusion, this MMF schedule seems to be safe and feasible in the prophylaxis of severe acute GvHD for high-risk patients, restricted by an increased risk for reactivating CMV in seropositive patients.

Adult↗
PubMed2003

Antimicrobial therapy of unexplained fever in neutropenic patients--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society).

Cytostatic chemotherapy of hematological malignancies is often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/microl. Frequently, fever is the first, and in most patients the only, sign of an infection. Unexplained fever is defined as follows: temperature of >/=38.3 degrees C or >/=38.0 degrees C for at least 1 h, or measured twice within 12 h, if the neutrophil count is <500/microl or <1000/microl with predicted decline to 500/microl. Different risk categories can be identified according to the duration of neutropenia: low risk </=5 days, intermediate risk 6-9 days, high risk >/=10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with tazobactam or a carbapenem. In duotherapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 h of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbapenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), itraconazole, voriconazole or caspofungin should be started. After defervescence to <38 degrees C, treatment should be continued for 7 days if the neutrophil count is <1000/microl, and for 2 days if the neutrophil count is >1000/microl.

Anti-Bacterial Agents↗
PubMed2003

[Hormone therapy, chemotherapy and immunotherapy in breast carcinoma. The best strategy for your patient].

Modern treatment of cancer of the breast is based on established prognostic factors (patient age, receptor status, tumor size, lymph node involvement, tumor grading), and thus takes the patient's individual risk profile into account. In addition to the antiestrogen, tamoxifen, new hormonal preparations, such as the aromatase inhibitors, hold out promise of improved results from adjuvant treatment in elderly women. In premenopausal women, additional hormone blockade by means of GnRH analogs is of advantage. Neoadjuvant (preoperative) chemotherapy protocols will enable rapid evaluation of new therapeutic options. When metastases have developed, treatment with hormonal drugs is indicated in the case of slowly progressing disease (low risk), while clinically progressive metastasization (high risk) requires cytostatic chemotherapy. Here, studies involving more recent substances with improved tolerability, and tumor-specific antibodies, confirm an improvement in the prognosis. The concentration of drug treatment in interdisciplinary centers is a necessary element of quality assurance and therapeutic optimization.

Adult↗
PubMed2003

Pneumocystis carinii pneumonia as a complication of bendamustine monotherapy in a patient with advanced progressive breast cancer.

BACKGROUND: Bendamustine is an alkylator with anticipated antimetabolic activity. It has shown activity in malignant lymphoma, multiple myeloma, and breast cancer. Recognized side-effects are relatively mild with myelosuppression as the dose-limiting toxicity. The CD4/CD8 ratio may be reduced. To what extent the alteration of lymphocytes, especially CD4(+) lymphocytes, correlates with an increase in opportunistic infections cannot be definitively answered. CASE REPORT: The patient, female, aged 48 years, was suffering from an advanced progressive breast cancer. After initial treatment with several chemotherapies, a cytotoxic therapy was initiated, with bendamustine (150 mg/m(2)) administered on two consecutive days and repeated every 4 weeks. After five courses, the patient developed Pneumocystis carinii pneumonia (PCP), disclosed in the bronchoalveolar lavage. While receiving bendamustine therapy, the CD4(+) and CD8(+) lymphocyte counts in the peripheral blood were determined by flow cytometry. The next-to-normal CD4/CD8 ratio before therapy (0,82) had decreased to 0,05 during the therapy mainly due to a decline of CD4(+) lymphocyte. The patient was seronegative for human immunodeficiency virus. In spite of high-dose intravenous trimethoprim/sulfamethoxazole and methylprednisolone application, the patient died of a respiratory failure 3 days after PCP was diagnosed. CONCLUSION: Bendamustine is capable of inducing a reduction in CD4(+) lymphocyte counts causing a severe T-lymphocyte-mediated immunosuppression. Measuring CD4(+) lymphocyte counts may be helpful in determining the risk of PCP in patients treated with bendamustine.

Antineoplastic Agents↗
PubMed2003

[Oncologic pharmacotherapy of elderly patients].

Age is the major risk factor for the development of cancer. Difficulties in medical treatment of elderly patients with cancer may be due to age dependent changes in physiological organ function, which result in pharmacokinetical and pharmacodynamical changes. They also may be due to co-morbidities with the need of pharmacological therapy. The choice of adequate treatment protocols has to consider this age dependent changes in pharmacokinetics and the presence of co-morbidities. Most of the data reporting results of medical oncological treatment in patients with cancer are collected in younger patients. Therefore, the present knowledge concerning medical oncological treatment of elderly patients with cancer is still limited.

Aged↗
PubMed2003

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P<or=0.001). Death occurred because of relapse in 29 patients (25.6%), infection in 12 patients (10.6%), acute graft-versus-host disease in eight patients (7.0%) and organ toxicity in nine patients (7.9%). In multivariate analysis, higher number of blasts in the marrow, alternative donors and low Karnofsky performance score were independent adverse prognostic factors for EFS.

Adolescent↗
PubMed2002

Phase I clinical and pharmacokinetic study of combination chemotherapy with topotecan and ifosfamide in patients with progressive or relapsed solid tumors.

PURPOSE: Topotecan and ifosfamide are effective in the treatment of various solid tumors. Up to the time of this study, the two drugs have been combined just once (Smith et al. 1998). Due to its hematotoxicity, topotecan has been used predominantly within monochemotherapy protocols. However, the combination of topotecan and alkylating agents is supra-additive in many preclinical models. This phase-I trial was primarily performed to evaluate the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of a combination chemotherapy with topotecan and ifosfamide using a 5-day schedule. A secondary goal was to estimate the response rate in a group of heavily pretreated patients with advanced solid tumors. METHODS: The pharmacokinetics of topotecan were preliminarily determined in some of the patients. A total of 12 patients (three female/nine male), median age 49 years (range 19-69), 11 with prior chemotherapy, received a total of 24 courses of chemotherapy at three dose-levels of topotecan. Ifosfamide was administered by intravenous infusion over 3 h immediately followed by a 30-min infusion of topotecan. Mesna (3 x 300 mg x m(2) x day) was given routinely during chemotherapy as a uroprotector. G-CSF (filgrastim) was permitted only in cases of febrile neutropenia (FN). RESULTS: The major toxicity was non-hematologic; severe liver and renal toxicity were observed in three out of 11 patients. Two treatment-related deaths occurred. No clinical remissions occurred in 11 evaluable patients. The pharmacokinetics of topotecan were relatively similar in our patients and supported findings in recent literature. The MTD of this combination was defined at dose-level 2 (1.0 mg/m(2) of topotecan and 750 mg/m(2) of ifosfamide). CONCLUSIONS: Further trials should not exceed this dose. The pharmacological causes for the pronounced toxicity have to be clarified.

Adult↗
PubMed2002

[Paraneoplastic pityriasis rubra pilaris in metastatic adenocarcinoma without diagnosable primary].

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman, without a history of severe illness, developed an erythematosquamous skin disease on hands and forearms. After continued spreading of these cutaneous lesions, she was admitted to hospital, presenting with a generalised desquamating erythrodermia and marked pruritus. INVESTIGATIONS: Skin biopsy showed cornocutaneous signs with alternating ortho- and parakeratosis, typical for pityriasis rubra pilaris. Laboratory findings showed a chronic to acute inflammation with leukocytosis, granulocytosis in the differential blood count, raised C-reactive protein in a range from 54.7 to a maximum of 157.2 mg/l and a protein electrophoresis with elevated alpha1- and alpha2-fraction. TREATMENT AND COURSE: The erythrodermia only temporarily receded under systemic therapy with acitretin and prednisolone. The patient developed intermittent septic fever accompanied by reduction or loss of consciousness. The general condition of the patient worsened considerably. Out of a rapidly progressing pleural effusion malignant cells similar to adenocarcinoma were isolated. Because CA15-3 was elevated we conducted an extended search especially for a breast carcinoma, but found only pathologically enlarged axillary, mediastinal and abdominal lymph nodes in conventional X-ray, CT, ultrasound and endoscopic procedures. The patient died from paraneoplastic pulmonary embolism. At autopsy, the widespread metastatic dissemination from poorly differentiated adenocarcinoma was confirmed. A necrosis in the right breast containing tumour cell remnants could probably be regarded as the primary neoplasm. Immunohistochemically no definite proof of breast nor gastro-intestinal carcinoma could be found. CONCLUSIONS: This case presents a rare paraneoplastic cutaneous manifestation as pityriasis rubra pilaris triggered by a poorly differentiated adenocarcinoma. The primary neoplasm could not definitely be identified, neither pre nor post mortem.

Acitretin↗
PubMed2002

Hepatic veno-occlusive disease (VOD) with complete occlusion of liver venules after tandem autologous stem cell transplantation-- successful treatment with high-dose methylprednisolone and defibrotide.

Veno-occlusive disease (VOD) is a life-threatening complication following allogeneic or autologous stem cell transplantation. We report on a patient with a high grade B-cell lymphoma who presented 28 days after the second autologous stem cell transplantation with weight gain, ascites, hyperbilirubinemia, and liver venules occlusion as demonstrated by sonography. Starting with high-dose methylprednisolone treatment followed by defibrotide maintenance therapy the patient showed dramatic complete response of VOD, resulting in a normal sonography of the liver and normalization of laboratory values. The response of the occlusion of nearly all liver venules underlines the value of anti-inflammatory treatment combined with new thrombolytic medication such as defibrotide for the treatment of severe VOD.

Adult↗