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Biomedical subjects

C Hirt

Publications and source records attributed to C Hirt.

9 recordsLinked to original sources
PubMed2006

Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

BACKGROUND: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.

Adolescent↗
PubMed2006

The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.

Adolescent↗
PubMed2005

[Minimal residual disease in follicular and mantle cell lymphoma. Detection using quantitative molecular monitoring of circulating lymphoma cells].

BACKGROUND AND OBJECTIVE: In patients with follicular lymphoma and mantle cell lymphoma circulating lymphoma cells can be detected by quantitative real-time PCR with a high sensitivity and reproducibility. With this study we wanted to ascertain whether a continuous molecular remission achieved in patients with mantle cell lymphoma and follicular lymphoma has an impact on survival of these patients. PATIENT AND METHODS: We conducted these investigations in 32 patients (24 with follicular lymphoma and 8 with mantle cell lymphoma) who were treated in a randomized trial with chemotherapy plus/minus rituximab (MCP, R-MCP). A further ten patients had follicular lymphoma (stage I and II) in long-term complete remission after radiation therapy. RESULTS: Up to 18 years after initial diagnoses of a stage I or II follicular lymphoma circulating t(14;18) positive cells could be detected in the peripheral blood. In advanced stage follicular lymphoma patients molecular remissions could only be achieved when they were treated with combined chemo-immunotherapy (MCP+R). A significantly higher relapse-free survival correlates with sustained molecular remission. In contrast, the frustrating clinical results obtained from the treatment of patients with mantle cell lymphoma corresponded to an achievement of only short molecular remissions in very few patients. CONCLUSIONS: The consequent application of quantitative real-time PCR will further improve current treatment strategies in lymphoma patients. Especially, individual treatment options can be developed for patients who do not respond to a standard chemotherapy or progression of disease is recognized, if results of molecular monitoring will be confirmed in large prospective studies.

Humans↗
PubMed2000

Quantitative detection of t(14;18)-positive cells in patients with follicular lymphoma before and after autologous bone marrow transplantation.

The aim of this study was to evaluate whether a quantitative analysis of circulating t(14;18)-positive cells is of prognostic significance in patients with follicular lymphoma (FL) after myelo-ablative therapy supported by ABMT. We tested DNA from primary lymphoma tissue as well as PBMC before and after ABMT from 15 patients for the presence of the t(14;18) translocation. Nine patients showed a t(14;18) translocation, six patients were t(14;18)-negative. Circulating t(14;18)-positive cells of seven patients were quantitatively determined by limiting dilution assays combined with a two-step PCR and by real-time quantitative PCR. The results of both methods correlate very well. The number of circulating t(14;18)-positive cells decreased significantly in all patients after myeloablative therapy and ABMT, t(14;18)-negative blood samples were found in five of seven patients. In all patients circulating t(14;18)-positive cells reappeared within 2 years after ABMT showing two different patterns. During continuous CR the numbers of circulating t(14;18)-positive cells were found to be stable within one order of magnitude. In contrast, in one patient the relapse was accompanied by a logarithmic increase of t(14;18)-positive cells. In a second patient the enlargement of lymph nodes developing over a period of 12 months was accompanied by very slowly increasing numbers of t(14;18)-positive cells. In all cases where diagnostic lymph node tissue was available, the same t(14;18) translocation was found at first diagnosis and after ABMT as shown by nucleotide sequence analysis. We conclude that the quantitative detection of circulating t(14;18)-positive cells during follow-up of patients with FL after ABMT reflects the clinical course of the disease. Relapses are associated with increasing numbers of circulating t(14;18)-positive cells and continuous complete remissions with stable cell counts.

Adult↗
PubMed1996

BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases.

PURPOSE: To answer the question whether t(14;18)-positive cells can be detected by polymerase chain reaction (PCR) in the peripheral blood of healthy blood donors and patients with nonmalignant diseases. PATIENTS AND METHODS: Peripheral-blood mononuclear cells (PBMNC) from healthy donors (n = 36) and patients with nonmalignant diseases (n = 21) were examined by two-step PCR for the detection of t(14;18)-positive cells with a breakpoint within the major breakpoint region (MBR). Approximate numbers of t(14;18)-positive cells were determined using limiting dilution assays, as well as the stochastic multiple-tube approach. RESULTS: We were able to detect t(14;18)-positive cells in PBMNC of approximately 50% of healthy donors and patients with nonmalignant diseases if DNA amounts up to 10 microg were tested. Compared with 17 t(14;18)-positive patients being in complete remission after radiotherapy for low-stage malignant follicular lymphoma, the majority of 26 healthy donors were found to have significantly lower numbers of t(14;18)-positive cells circulating in the peripheral blood. In the case of six healthy donors, more than one t(14;18) DNA fragment based on size and nucleotide sequence analysis was detected. In one healthy individual, four different t(14;18)-positive cell clones were found in nine samples found over 5 years. CONCLUSION: The occurrence of the t(14;18) translocation is not restricted to follicular lymphoma cells. In healthy donors, long-lived t(14;18)-positive cells can be detected by PCR if the sensitivity is high enough. Based on nucleotide sequence analysis, the t(14;18) DNA fragments detected in healthy donors cannot be distinguished from those found in follicular lymphomas.

Adult↗
PubMed1994

Specific developmental profiles of lysosomal and brush border enzymuria in the human.

Various enzymatic urinary activities have been proposed to assess renal proximal tubule damage in children, including neonates. Nevertheless comprehensive knowledge on the developmental aspects of physiological enzymuria is limited, particularly with regard to lysosomal and brush border enzymuria. Urinary activities of two lysosomal enzymes, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and of two brush border enzymes, alanine aminopeptidase (AAG) and gamma-glutamyltransferase (GGT) were comparatively investigated in normal prematures (n = 28), term neonates (n = 52), infants aged less than 2 years (n = 19) and children (n = 33), and compared to urinary excretion of beta 2-microglobulin (B2M). Enzymatic activities were assayed using either spectrophotometrical (NAG, AAP, GGT) fluorimetrical (GAL) or radioimmunological (B2M) methods, and were related to urinary creatinine excretion. Developmental profiles of both the studied lysosomal enzymes and of B2M were similarly characterized with significantly decreasing values from prematures (NAG 9.29 +/- 1.44, GAL 2.26 +/- 0.26 IU/mmol creatinine, indicated as mean +/- SEM) to term neonates (6,94 +/- 0.58 and 1.76 +/- 0.15 IU/mmol creatinine, respectively) and older infants and children. Lysosomal enzymatic urinary activities correlated linearly with a coefficient of r = 0.75, (p < 0.05), while correlations between each lysosomal enzymatic activity and B2M urinary excretion were weaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗