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65 Publications visible to you, out of a total of 65
Modelling chemotherapy effects on granulopoiesis.
GLA - German Lymphoma Alliance, Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Although the growth-factor G-CSF is widely used to prevent granulotoxic side effects of cytotoxic chemotherapies, its optimal use is still unknown since treatment outcome depends on many … parameters such as dosing and timing of chemotherapies, pharmaceutical derivative of G-CSF used and individual risk factors. We showed in the past that a pharmacokinetic and -dynamic model of G-CSF and human granulopoiesis can be used to predict the performance of yet untested G-CSF schedules. However, only a single chemotherapy was considered so far. RESULTS: Model assumptions proved to be feasible in explaining granulotoxicity of 10 different chemotherapeutic drugs or drug-combinations applied in 33 different schedules with and without G-CSF. Risk groups of granulotoxicity were traced back to differences in toxicity parameters. CONCLUSION: We established a comprehensive model of combined G-CSF and chemotherapy action in humans which allows us to predict and compare the outcome of alternative G-CSF schedules. We aim to apply the model in different clinical contexts to optimize and individualize G-CSF treatment.

Authors: S. Schirm, C. Engel, M. Loeffler, M. Scholz

Date Published: 24th Dec 2014

Publication Type: Not specified

Human Diseases: leukopenia

Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: In the SMARTE-R-CHOP-14 … trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6xR-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6xR-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. RESULTS: The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. CONCLUSION: Extended rituximab exposure compared with eight 2-week applications in combination with 6xR-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6xR-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.

Authors: M. Pfreundschuh, V. Poeschel, S. Zeynalova, M. Hanel, G. Held, N. Schmitz, A. Viardot, M. H. Dreyling, M. Hallek, C. Mueller, M. H. Wiesen, M. Witzens-Harig, L. Truemper, U. Keller, T. Rixecker, C. Zwick, N. Murawski

Date Published: 20th Dec 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To investigate the impact and mechanisms of vitamin D deficiency (VDD) on the outcome of elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Three hundred … fifty-nine pretreatment 25-hydroxyvitamin D3 (25[OH]D3) serum levels from the RICOVER-60 study (Six Versus Eight Cycles of Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive CD20+ B-Cell Lymphomas) and 63 from the RICOVER-noRTh study (an amendment to the RICOVER-60 study in which patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone administered at an interval of 2 weeks plus two cycles of rituximab [R-CHOP-14], but without radiotherapy) were determined by chemoluminescent immunoassay. Rituximab-mediated cellular cytotoxicity (RMCC) was assessed by lactate dehydrogenase release assay of CD20+ Daudi cells. RESULTS: RICOVER-60 patients with VDD (</= 8 ng/mL) and vitamin D levels more than 8 ng/mL treated with rituximab had 3-year event-free survival (EFS) of 59% and 79% and 3-year overall survival (OS) of 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for International Prognostic Index risk factors with a hazard ratio (HR) of 2.1 (P = .008) for EFS and 1.9 (P = .040) for OS. EFS was not significantly different in patients with vitamin D levels </= 8 or more than 8 ng/mL (HR, 1.2; P = .388) treated without rituximab. This was confirmed in an independent validation set of 63 RICOVER-noRTh patients. RMCC increased significantly (P < .001) in seven of seven individuals with VDD after substitution and normalization of their vitamin D levels. CONCLUSION: VDD is a risk factor for elderly patients with DLBCL treated with R-CHOP. That VDD impairs RMCC and substitution improves RMCC strongly suggests that vitamin D substitution enhances rituximab efficacy, which must be confirmed in appropriately designed prospective trials addressing VDD and substitution not only in DLBCL, but also in malignancies treated with other antibodies, of which the major mechanism of action is antibody-dependent cellular cytotoxicity (eg, trastuzumab in breast cancer and cetuximab in colorectal cancer).

Authors: J. T. Bittenbring, F. Neumann, B. Altmann, M. Achenbach, J. Reichrath, M. Ziepert, J. Geisel, E. Regitz, G. Held, M. Pfreundschuh

Date Published: 10th Oct 2014

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin … Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with ECFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study.

Authors: N. Murawski, G. Held, M. Ziepert, B. Kempf, A. Viardot, M. Hanel, M. Witzens-Harig, R. Mahlberg, C. Rube, J. Fleckenstein, C. Zwick, B. Glass, N. Schmitz, S. Zeynalova, M. Pfreundschuh

Date Published: 31st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens.
GLA - German Lymphoma Alliance

Abstract

Not specified

Authors: K. Hohloch, S. Zeynalova, G. Held, M. Ziepert, M. Loeffler, G. Wulf, N. Schmitz, M. Pfreundschuh, L. Trumper

Date Published: 10th Jul 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Elevated serum free light chains do not predict outcome of elderly patients with aggressive CD20(+) B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract

Not specified

Authors: M. Achenbach, J. T. Bittenbring, M. Ziepert, E. Regitz, G. Ott, A. Rosenwald, M. Pfreundschuh, B. Altmann, G. Held

Date Published: 1st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSE-R-CHOP-14 trial of the DSHNHL.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial. PATIENTS AND METHODS: Rituximab (375 … mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS: One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.

Authors: N. Murawski, M. Pfreundschuh, S. Zeynalova, V. Poeschel, M. Hanel, G. Held, N. Schmitz, A. Viardot, C. Schmidt, M. Hallek, M. Witzens-Harig, L. Trumper, T. Rixecker, C. Zwick

Date Published: 15th Jun 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

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