Josef Birkmann

Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent. With a median follow-up of 24.9 months, median overall and progression-free survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with rituximab and DHAP proved to be feasible and effective in this patient population.

EFFECTS OF RECOMBINANT HUMAN THROMBOPOIETIN ALONE AND IN COMBINATION WITH ERYTHROPOIETIN AND EARLY-ACTING CYTOKINES ON HUMAN MOBILIZED PURIFIED CD34+ PROGENITOR CELLS CULTURED IN SERUM-DEPLETED MEDIUM

The effects of recombinant thrombopoietin (TPO) alone and in combination with erythropoietin (EPO) and early‐acting cytokines such as interleukin 3 (IL‐3), stem cell factor (SCF) and GM‐CSF on highly purified mobilized human CD34+ progenitor cells were studied in a serum‐depleted culture system. Eight leukapheresis samples were cultured for seven days and analyzed; aliquots were replated and re‐evaluated on day 12. Three‐color flow cytometry was used together with morphologic analysis to determine proliferation and megakaryocytic or erythroid maturation.

Progressive Multifocal Leukoencephalopathy in Patients with a Hematological Malignancy: Review of Therapeutic Options

In the context of 2 patients with hematological malignancy who developed progressive multifocal leukoencephalopathy (PML), we review the current therapeutic options for this serious complication. Both patients had lymphoma and had been pretreated with the antibody rituximab. Diagnosis of PML was obtained upon the detection of the JC virus. The outcome was fatal in both cases. So far, no standard therapeutic approach for JC virus infection has been established in HIV-negative patients with hematological malignancies and the outcome is usually fatal. Serotonin receptor antagonists might have a beneficial effect by blocking the virus from entering the cells. Although hopes for the efficacy of mefloquine were disappointed by the results of 1 study, several case reports describe improvements in neurological impairment when this drug is administered. Taking the desperate situation of this patient group into consideration, the combination of mirtazapine and mefloquine might be worthy of an attempt.

The use of CD34^+-selected PBPC after high-dose chemotherapy in breast cancer patients is associated with prolonged recovery time and increased infectious complications

High-dose chemotherapy with autologous stem cell rescue can result in autotransplantation of tumor cells. A possible approach to reduce tumor cell contamination is the positive selection of CD34+ PBPC, but this might be associated with a prolonged recovery time as well as an increased risk of infectious complications because of the loss of committed progenitor cells. To investigate this aspect, we compared two sequentially treated cohorts of high-risk breast cancer patients. Both groups received the same high-dose chemotherapy regimen followed by autologous peripheral stem cell transplantation. Group I received CD34+-selected blood progenitor cells, and group II received nonselected blood progenitor cells. We compared these two identically treated groups with regard to recovery time, need for blood products, infectious complications, need for antibiotic treatment, and length of the transplantation-related hospital stay. We found a prolonged recovery time for neutrophils up to 0.5 x 10(9)/L (14 days in the selected group/10 days in the nonselected group) and platelets up to 30 x 10(9)/L (29/12 days), associated with an increased requirement for RBC transfusions (5/3 U) and platelet transfusions (10/2 U). The rate of severe infectious complications (2/0), the need for nonprophylactic antibiotic treatment (15/10), and the length of the hospital stay (25/21 days) in group I were also increased. We conclude that positive selection of PBPC should not be used routinely until randomized studies show a clear long-term benefit of using CD34+-selected stem cell products in breast cancer patients.

Refractory plasmablastic lymphoma—a review of treatment options beyond standard therapy

Plasmablastic lymphoma (PBL) is a rare distinct subtype of aggressive diffuse large B-cell lymphoma and a notoriously hard to treat entity with a dismal prognosis in both HIV-negative and HIV-positive patients. Clinicians often face the question of second or third line treatment. As the treatment options with novel agents in lymphomas are rapidly evolving, more and more options beyond standard chemotherapy are available. In connection with a review of treatment options with novel lymphoma agents, we present a case report of a patient with a complete remission after the administration of brentuximab vedotin and lenalidomide.

Reduction of HLA-DR+ lymphocytes after treatment with enzastaurin in patients with metastatic thyroid cancer.

Background: Cytotoxic anti-tumor agents like methotrexate or cyclophosphamide have been used in the treatment of autoimmune diseases although the exact mechanism of their immunomodulatory function is unclear. By contrast, molecularly targeted anti-tumor agents, such as the serine/threonine kinase inhibitor enzastaurin, have not been evaluated for treatments other than cancer. Methods: Blood was sampled from patients with metastatic thyroid cancer treated with enzastaurin followed by the combination treatment of enzastaurin and the anti-folate pemetrexed. During this sequential treatment, blood was drawn every 14 days to monitor changes in the lymphocyte population. Results: We observed that enzastaurin monotherapy reduced the number of HLA-DR-expressing lymphocytes. No signs of infection were observed in any patient. Conclusion: Our findings suggest an immunomodulatory effect of enzastaurin in addition to the anti-tumor effect.

Addressing Unmet Information Needs: Results of a Clinician-Led Consultation Service About Complementary and Alternative Medicine for Cancer Patients and Their Relatives

Purpose. To report on a telephone consultation service with cancer patients and their relatives about complementary and alternative medicine (CAM) between 1999 and 2011. Methods. We offered a Germany-wide, free-of-charge telephone consultation service about CAM led by oncology clinicians from a comprehensive cancer center. The consultations followed a patient-centered approach with the aim to provide guidance and evidence-based information. Sociodemographic, disease-related data as well as information about the consultations’ content were collected in a standardized manner, and feedback questionnaires were sent out immediately after the consultations. Results. Overall, 5269 callers from all over Germany used the service (57% patients, 43% relatives). The “big 4” cancer types (breast, gastrointestinal, prostate, and lung) accounted for 55% of all calls. In 67% of calls, patients had just received the diagnosis or commenced anticancer therapy; 69% of patients had advanced or metastatic diseases. More than half of the callers (55%) had vague concerns like “what else can I do?” rather than specific questions related to CAM. The consultations covered a broad spectrum of issues from CAM therapies to cancer treatment and measures supportive of health, nutrition, and psychosocial support. Callers highly valued the service. Conclusions. Consulting about CAM addresses important unmet needs from cancer patients and their relatives. It provides clinicians with the opportunity to engage in open and supportive dialogues about evidence-based CAM to help with symptom management, psychological support, and individual self-care. Consulting about CAM cannot be separated from consulting about conventional care and should be provided from the beginning of the cancer journey.

Severe Drug-Induced Liver Injury as an Adverse Drug Event of Antibiotics: A Case Report and Review of the Literature

Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.