Biomedical subjects

Norbert Frickhofen

Publications and source records attributed to Norbert Frickhofen.

7 recordsLinked to original sources

PubMed2006

High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma.

PURPOSE: To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. PATIENTS AND METHODS: Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. RESULTS: Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). CONCLUSION: Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

Adult↗

PubMed2005

Aplastic anemia.

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Anemia, Aplastic↗

PubMed2004

Complete molecular remission of chronic eosinophilic leukemia complicated by CNS disease after targeted therapy with imatinib.

Many cases of hypereosinophilia, formerly classified as hypereosinophilic syndrome, can now be characterized as chronic eosinophilic leukemia (CEL) based on the demonstration of characteristic genetic markers indicating clonality of hematopoiesis. Here we report on a 33-year-old male patient with central nervous system manifestations of CEL and an excellent response to low-dose imatinib (Glivec). Molecular analysis demonstrated a constitutive activation of the platelet-derived growth factor receptor-alpha (PDGFR-A) as the mechanism of responsiveness to imatinib.

Adult↗

PubMed2003

6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

PURPOSE: To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance. RESULTS: A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). CONCLUSION: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

Adolescent↗

PubMed2002

Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia.

Immunosuppression with antithymocyte globulin, (methyl)prednisolone, and cyclosporin A is considered the treatment of choice for the patient with aplastic anemia without a donor for standard-risk stem cell transplantation. This consensus is supported by the results of several series, including a randomized German trial. Here we report 11-year results of the latter trial. With stringent response criteria and 4 months as the time to evaluate responses, this analysis confirms the superiority of the cyclosporine regimen regarding the response rate in all patients treated (70% vs 41%, with or without cyclosporine; P =.015) and in patients with severe aplastic anemia (65% vs 31%; P =.011). Patients responded more rapidly after treatment with cyclosporine (median, 60 vs 82 days; P =.019). Most patients treated with cyclosporine needed only one course of immunosuppression, whereas many patients treated without cyclosporine required repeated immunosuppressive treatment. Because of the efficacy of salvage treatment, overall survival was not different between the 2 treatment groups. However, failure-free survival favored the cyclosporine regimen (39% vs 24%; P =.04). The relapse rate, projected at 38% after 11.3 years, was similar between the 2 treatment groups. Remissions were cyclosporine dependent in 26% of the patients responding to a regimen that included cyclosporine. Clonal or malignant diseases developed in 25% of the patients. These data demonstrate that antithymocyte globulin, methylprednisolone, and cyclosporin A are an effective regimen for the treatment of aplastic anemia. However, remissions are unstable, and secondary diseases are common. In contrast to the results of stem cell transplantation, most patients are not cured.

Anemia, Aplastic↗

PubMed2002

Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression.

BACKGROUND: Aplastic anemia may develop during pregnancy and sometimes improves spontaneously after delivery. The effects of pregnancy on aplastic anemia after immunosuppressive treatment and of aplastic anemia on the outcome of pregnancy have not been described. OBJECTIVE: To determine the outcome of pregnancy and the disease course among women with aplastic anemia who received immunosuppressive therapy. DESIGN: Retrospective multicenter study. SETTING: Twelve centers participating in the European Group for Blood and Marrow Transplantation. PATIENTS: 36 women who received immunosuppressive therapy to treat aplastic anemia. MEASUREMENTS: Outcomes of pregnancy and aplastic anemia and blood counts before, during, and after delivery. RESULTS: The 36 pregnancies resulted in 34 live births (one set of twins), 2 elective abortions, and 1 spontaneous abortion. Of the 36 pregnancies, 22 were uncomplicated and 14 involved medical complications. Seven pregnancies (19%) were complicated by relapse of aplastic anemia, and 5 patients without relapse (14%) needed transfusions during delivery. After delivery, 3 of the 7 patients who had relapse recovered spontaneously and 3 recovered after retreatment. One patient who did not respond to treatment died of aplastic anemia. A woman with aplastic anemia and paroxysmal nocturnal hemoglobinuria had a fatal cerebral thrombosis after delivery. Women with uneventful pregnancies had better prepregnancy remission status (8 complete and 11 partial remissions) and a higher median platelet count (146 x 10(9) cells/L) than did women with complicated pregnancies (2 complete remissions, 8 partial remissions, and 4 cases of paroxysmal nocturnal hemoglobinuria; median platelet count, 92 x 10(9) cells/L). CONCLUSIONS: Successful pregnancy with normal outcome is possible in women with aplastic anemia previously treated with immunosuppression. Complications appear to be more likely in patients with low platelet counts and paroxysmal nocturnal hemoglobinuria-associated aplastic anemia.

Adult↗

PubMed2002

Acute myeloid leukemia: treatment over 60.

Undertreatment of older patients with acute myeloid leukemia (AML) can explain, in part, their inferior outcome when compared to that of younger patients. In agreement with the benefit seen by patients under age 60 from high-dose cytosine arabinoside (Ara-C), there are dose effects in the over 60s, in particular for daunorubicin, in induction treatment and for the duration of postremission treatment. The use of these effects can partly overcome the mostly unfavorable disease biology in older age AML, as expressed by the absence of favorable and the over-representation of adverse chromosomal abnormalities as well as the expression of drug resistance. We recommend an adequate dosage of 60 mg/m2 daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, and followed by a prolonged monthly maintenance chemotherapy for at least 1 year's duration. Further improvements in supportive care may help to deliver additional antileukemic cytotoxicity. As a novel approach, nonmyeloablative preparative regimens may open up the possibility of allogeneic transplantation for older patients with AML. Other new options like multidrug resistance modulators, antibody targeted therapies and molecular targeting are under clinical investigation. A questionnaire study in patients with AML showed that, according to patients' self-assessment, intensive and prolonged treatment did not result in a diminished quality of life. This finding did not vary by age, under or over 60 years. As the median age in this disease is more than 60 years, the adequate management of AML in older patients remains the major challenge.

Acute Disease↗