Curricular course for medical students at a hematology and oncology specialty practice, 2010-2022.

Aim: For several years now, medical students have also been taught general practice at academic medical teaching practices. Specialty practices have not yet been included in the curricular education. Since 1998, we have conducted a block seminar in hematology twice per semester for eighth-semester medical students. This block seminar was offered from 1998-2001 to students at the Philipps University in Marburg and since 2001 to students at the Johannes Gutenberg University in Mainz. Since 2010 our block seminar has been part of the curriculum at the Johannes Gutenberg University. Method: Standardized course evaluation by students who had attended our block seminar between January 2010 and March 2022. Courses that were held virtually due to corona were not included in the analysis. The questionnaire used to evaluate courses in the medical degree program at the Johannes Gutenberg University served as the evaluation instrument. Results: Since 1998 more than 1,000 students have attended our seminar. The systematic evaluation of the course by 500 students who participated in the curricular, classroom-based seminar sessions since 2010 shows that the highest ratings possible are given for practical relevance, learning atmosphere, teaching and effectiveness. Conclusion: High quality in teaching curricular courses to medical students at a specialty practice is possible. Insights into the possibilities connected with working in the outpatient setting at a medical practice broadens students' experience. This teaching format facilitates external university instructors in terms of teaching and, at the same time, relieves the university in terms of staff and financial budget.

Survival improvement of patients with chronic lymphocytic leukemia (CLL) in routine care 1995-2017.

Seven hundred and twenty-four CLL-outpatients with a median age of 67 (35-92) were analyzed. Four hundred and twenty-seven (59%) were male, 297 (41%) female. At diagnosis 556 (77%) were in Binet stage A, 91 (13%) stage B and 36 (5%) stage C. Forty-six percent received treatment during the evaluation period. Treatment consisted of purine analogs in 38%, alkylating agents in 96%, chemoimmunotherapy with anti-CD20 monoclonal antibodies in 63%, ibrutinib in 9%, venetoclax in 1% and idelalisib in 3%. 3% received allogeneic hematopoietic stem cell transplantation. Overall survival (OS) according to Binet stage was: A 13.9 years (0.1-37.4), B 9.2 years (1.4-29.3) and C 7.9 years (0.5-19.4) respectively. Median OS from the start of therapy improved over time; 1995-2001: 5.8 years, 2002-2008: 6.1 years and 2009-2017: median not reached. Survival of patients with CLL has improved in routine care and was strongly related to active disease, disease stage, performance status and whether therapy included an anti-CD20 monoclonal antibody.

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. METHODS: Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33-81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days or to intravenous bendamustine (90 mg/m(2) per day) for the first 2 days of each cycle. Rituximab 375 mg/m(2) was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m(2) during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0-45·5) median progression-free survival was 41·7 months (95% CI 34·9-45·3) with bendamustine and rituximab and 55·2 months (95% CI not evaluable) with fludarabine, cyclophosphamide, and rituximab (HR 1·643, 90·4% CI 1·308-2·064). As the upper limit of the 90·4% CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected. Severe neutropenia and infections were more frequently observed with fludarabine, cyclophosphamide, and rituximab (235 [84%] of 279 vs 164 [59%] of 278, and 109 [39%] vs 69 [25%], respectively) during the study. The increased frequency of infectious complications with fludarabine, cyclophosphamide, and rituximab was more pronounced in patients older than 65 years. INTERPRETATION: The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and rituximab is associated with less toxic effects. FUNDING: Roche Pharma AG, Mundipharma, German Federal Ministry of Education and Research.

Adherence assessment of patients with metastatic solid tumors who are treated in an oncology group practice.

Due to the increase of oral agents nonadherence is an emerging challenge in cancer care. We evaluated how well different assessments match and how adherence could be measured in routine care. For this purpose patients suffering from metastatic solid tumors who were treated with oral anticancer drugs in an oncology group practice were surveyed. Attending oncologists answered a questionnaire, too, and a retrospective analysis of prescription data was conducted. Caregivers who were eligible for an interview were surveyed additionally. 128 patients (70 % female) with a median age of 69 years (36-88) took part, 95 % of all approached patients. 56 % suffered from metastatic breast cancer, 44 % from other metastatic solid tumors. 65 caregivers (60 % female) with a median age of 62 years (21-82) were interviewed as well. Patients were assessed in 84 % as very reliable in medication-taking by their oncologists. This high adherence rate was supported by patients, caregivers and prescription data. However, concordance between assessments of patients, caregivers and oncologists was not substantial. Our method of considering different perspectives to assess adherence has to be improved and validated but could help to evaluate adherence with oral cancer therapy in routine care.

Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014.

BACKGROUND: The aim of this study was to evaluate the treatment reality for outpatients with immune thrombocytopenia (ITP) managed by hematologists in routine care. PATIENTS AND METHODS: All patients with ITP diagnosed between 06/1995 and 12/2014 in a community-based oncology group practice in Germany were retrospectively analyzed. RESULTS: 422 patients with a median age of 55 years (range 7-91 years) were evaluated. 57% were female and 43% male. Only 198 (47%) patients needed therapy. First-line therapy (n = 198) consisted of steroids in 81%, intravenous immunoglobulins (IVIG) in 12%, and IVIG plus steroids in 6%. Patients received a median of 2 (range 1-10) lines of therapy. The most frequently used treatment modalities were steroids in 93%, IVIG in 55%, splenectomy in 21%, and other immunosuppressive agents (OISA) in 23% of patients. Rituximab and thrombopoietin receptor agonists (TRAs) were used in 10% and 6% only. 9 (2%) patients needed hospitalization due to bleeding complications. 72% of patients achieved a durable remission after their last line of therapy. 1 (0.2%) patient died due to bleeding complications. CONCLUSION: The treatment modalities most frequently used are steroids, immunoglobulins, splenectomy, and OISA. Rituximab and TRAs are only used infrequently. 72% of ITP patients achieve durable remissions. The rate of hospital admissions due to bleeding complications and the ITP-related mortality are low. The majority of ITP patients can be safely managed by hematologists on an outpatient basis.

Metastatic breast cancer: prolongation of survival in routine care is restricted to hormone-receptor- and Her2-positive tumors.

18,000 women die due to metastatic breast cancer in Germany per year. Median survival is 20-28 months after diagnosis. The question we wanted to answer was whether survival has improved in routine care? For this purpose we conducted a retrospective analysis of all patients with metastatic breast cancer who were treated between 06/1995-06/2013 in a community-based oncology group practice in Germany. 716 patients were analyzed with a median age of 61 (31-93). Localizations of metastases were distributed as follows: 47% visceral, 36% bone, 9% lymphatic, 4% CNS, 4% others. 79% were hormone-receptor-positive, 20% Her2-positive, 9% triple-negative. Median overall survival was 34 months (95% Confidence Interval: 31-37), median disease-specific survival 36.8 months and disease-specific survival after 5 years 34%. Survival was significantly correlated with localizations of metastases, number of metastasized organs, disease free survival since initial diagnosis, hormone-receptor status and age. Patients with hormone-receptor-positive tumors had a median overall survival of 37 months, Her2-positive patients of 34 months and triple-negative patients of 13 months. 86% of hormone-receptor-positive patients received antihormonal therapy. 81% of Her2-positive patients received anti-Her2 therapy. In summary, longer survival is strongly restricted to hormone receptor- and Her2-positive tumors most likely due to targeted therapies directed against the estrogen-receptor and Her2.

Breast cancer morbidity: questionnaire survey of patients on the long term effects of disease and adjuvant therapy.

BACKGROUND: Many women have symptoms of various kinds after being treated for breast cancer. It is unclear how frequently these different side effects of treatment arise. METHOD: All women who underwent surgery for breast cancer and subsequently received adjuvant systemic treatment in a single certified breast-cancer center from 2006 to 2010 were asked to fill out a standardized questionnaire. Medical data were retrieved from their charts and statistically analyzed together with the questionnaire responses. The questionnaire was also given to an age-adjusted control group. RESULTS: 734 questionnaires were filled out and returned (response rate, 70%). The mean interval from the diagnosis of breast cancer to the time of response to the questionnaire was 38 months. The median age at time of response to the questionnaire was 65 years (range, 30 to 91 years). The distribution of UICC stages at the time of initial diagnosis was as follows: I 46%, II 42%, III 12%. 78% of the patients underwent breat conserving surgery, 85% had radio - therapy, 85% had antihormonal treatment, and 49% had chemotherapy. 91% were satisfied or very satisfied with the outcome of surgery. 34% reported operation site pain; 35% reported limitations of shoulder or arm function. Younger patients suffered from emotional sequelae more than older ones did. 25% reported a change in their relationship with their spouse. Before being diagnosed with breast cancer, 9% had consulted a psychiatrist or psychotherapist; after the diagnosis, 19% did. 14% had taken psychoactive medication before the diagnosis, and 26% did afterward. CONCLUSION: Treatment for breast cancer has negative physical, emotional, and social effects on many patients. They suffer these effects to varying degrees depending on age, type of surgery, and systemic treatment.

Retreatment with bendamustine-containing regimens in patients with relapsed/refractory chronic lymphocytic leukemia and indolent B-cell lymphomas achieves high response rates and some long lasting remissions.

Bendamustine and bendamustine/rituximab combinations have shown high efficacy in relapsed/refractory chronic lymphocytic leukemia (CLL) and indolent B-cell malignancies (non-Hodgkin lymphoma, NHL). No data exist about bendamustine retreatment after relapse, concerning efficacy and toxicity in this patient population. Eighty-eight outpatients (57 patients with CLL, 31 patients with NHL) who had previously been treated with bendamustine were retreated with a bendamustine regimen. Treatment consisted of bendamustine (B) or bendamustine + mitoxantrone (BM) or bendamustine + rituximab (BR) or bendamustine + mitoxantrone + rituximab (BMR). Median age was 72 years (50-88). A reversible grade 3 or 4 leukocytopenia or thrombocytopenia was observed in 24% and 13%, respectively. The overall response rate (ORR) was 76% (7% complete remission [CR], 69% partial remission [PR]) with 77% (6% CR, 71% PR) in CLL and 71% (8% CR, 63% PR) in NHL. ORR according to regimen was as follows: B: 57% (14% CR, 43% PR), BM: 70% (4% CR, 66% PR), BR: 55% (10% CR, 45% PR), BMR: 84% (7% CR, 78% PR). Bendamustine retreatment is feasible and achieves high response rates and some long lasting remissions.

Bendamustine plus mitoxantrone for relapsed/refractory chronic lymphocytic leukaemia (CLL): results of a multicentre phase II study of the German CLL Study Group (GCLLSG).

The efficacy of bendamustine (50 mg/m², days 1-3) plus mitoxantrone (10 mg/m², day 1), every 28 days for up to four courses, was evaluated in a Phase II multicentre trial enrolling 59 patients with relapsed or refractory B-cell chronic lymphocytic leukaemia (CLL). Major toxicities were grade 3/4 leucopenia, thrombocytopenia and infections in 42%, 12% and 12% of patients, respectively. Complete and partial response was achieved in 5/59 and 25/29 patients, respectively (overall response rate, 51%). Median time to progression was 22 months (range 1-49 + ) and median survival 27 months (range 0-49 + ). The combination of bendamustine and mitoxantrone is an active regime in relapsed or refractory CLL.

Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: a retrospective medical records review.

AIMS: This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. MATERIALS AND METHODS: We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. RESULTS: Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). CONCLUSIONS: Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid.

Improved survival of patients with metastatic breast cancer in routine care: results of a retrospective study in a community-based oncology group practice 1995-2005.

BACKGROUND: Little is known about the treatment reality in metastatic breast cancer (MBC) outside clinical trials. We undertook this analysis to evaluate the actual treatment reality for unselected patients with MBC in routine care. PATIENTS AND METHODS: All patients with MBC, who were treated in our community-based group practice between 1995 and 2005, were analyzed retrospectively concerning prognostic factors, treatment, and survival. RESULTS: 403 consecutive patients were evaluated with a median age of 60 years (range 32-93). Aromatase inhibitor therapy was used in 87% of all patients. 83% received chemotherapy with the median number of lines being 3 (1-15). An anthracycline was given to 49%, a taxane was used in 55%, vinorelbine in 42%, capecitabine in 36%, gemcitabine in 28%, and a platinum compound in 9%. 94% of patients with bone metastasis received a bisphosphonate, and 63% of HER-2/neu-positive patients were treated with trastuzumab. Median survival since the start of palliative therapy was 30 months. Statistical analysis revealed as major prognostic factors hormone receptor status and prevalence of only bone metastasis. CONCLUSIONS: Treatment reality of MBC in routine care reveals a prolonged median survival of 30 months which is probably due to the sequential use of the most effective treatment modalities.

Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review.

PURPOSE: This retrospective study compared renal impairment rates in breast cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients treated with ibandronate or zoledronic acid. STUDY DESIGN: Medical records in two German oncology clinics from May 2001 to March 2006 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before bisphosphonate treatment) to last available measurement for each patient. The Cox proportional hazards model and the Andersen-Gill extension of the Cox model for multiple events analysis were used for multivariate analysis, which controlled for age, clinic site, primary cancer type, baseline SCr or GFR value, prior bisphosphonate use, concomitant use of drugs associated with acute renal failure, and renal-related comorbidities. RESULTS: Of 333 patients, 109 received ibandronate and 256 received zoledronic acid (32 patients had both drugs). Compared with ibandronate, the zoledronic acid group had a significantly better baseline renal function and fewer patients had a history of renal disease. Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by approximately 1.5-fold in all assessed patients (all tumors) compared with ibandronate. Multivariate analysis found significantly higher hazards ratios for zoledronic acid over ibandronate (two to sixfold), after adjusting for differences in characteristics between the two treatment groups. CONCLUSIONS: In this retrospective review, patients were significantly more likely to experience renal impairment with zoledronic acid than with ibandronate.

Bendamustine/mitoxantrone/rituximab: a short remission induction chemoimmunotherapy for elderly patients with relapsed or refractory chronic lymphocytic leukemia.

We have evaluated all outpatients with relapsed or refractory chronic lymphocytic leukemia (CLL) who were treated with bendamustine/mitoxantrone/rituximab (BMR) between May 1999 and December 2008. Treatment consisted of bendamustine 90 mg/m2 on day 1 + 2, Mitoxantrone 6 mg/m2 on day 1, and Rituximab 375 mg/m2 on day 8, 15, 22 + 29. Thirty-nine patients (19 males, 20 females) received BMR with a median age of 69 years (46­81). Nineteen patients (49%) were above 70 years and 13 patients (33%) were 75 years or above. Performance score ranged between 0 and 2. The median number of previous therapies was 2 (1­4). Therapy was tolerated well with two observed therapy-associated hospitalizations. A reversible grade 3 or 4 hematotoxicity was seen in 30 patients (77%). Other reversible grade 3 or 4 toxicities were seen in two patients (5%). The overall response rate was 92% (10% complete remission, 82% partial remission). Median time to next CLL-therapy was 13 months (0­69). We conclude that BMR is a short and effective outpatient chemoimmunotherapy for patients with relapsed or refractory CLL, which can be used safely in elderly patients.

Ovarian cancer treatment reality in northern Rheinland-Pfalz (Germany). Suboptimal surgical treatment as a possible cause for inferior survival.

BACKGROUND: With regard to incidence, ovarian cancer has the highest mortality of all gynecologic cancers. PATIENTS AND METHODS: The treatment of 139 consecutive patients with epithelial ovarian cancer who were treated in an oncology group practice in Koblenz, Germany between 1995 and 2003 was evaluated retrospectively. RESULTS: The median age of the patients was 61 years (18-84). FIGO stages were distributed as follows: stage I 15.8%, stage II 12.9%, stage III 53.2%, stage IV 16.5%. 49 patients (35.5%) received surgical treatment at a university hospital or a teaching hospital. 89 patients (64.5%) were operated on in a local or district hospital. A macroscopically complete resection was achieved in only 15 patients (10.8%). The residual tumor was <1 cm in 50 patients (36%), >1 cm in 24 patients (17.3%), and >2 cm in 49 patients (35.5%). 93.3% of the patients received postoperative, platinum-based chemotherapy. Median survival since first diagnosis was 42 months (1-346(+)). The 5-year survival rate of the whole cohort was only 28%. CONCLUSIONS: Overall survival in epithelial ovarian cancer was significantly inferior in this patient cohort compared to the results of the FIGO report from 2003. One possible cause may be the suboptimal surgical treatment, with 52.8% of the patients having a postoperative residual tumor larger than 1 cm.

High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG).

On the basis of a preceding phase I study, the current trial explored bendamustine in combination with mitoxantrone and rituximab (BMR) in patients with stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL) with or without prior rituximab containing chemo-immunotherapy (R-chemo) treatment. Therapy consisted of bendamustine 90 mg/m(2) days 1 + 2, mitoxantrone 10 mg/m(2) day 1, rituximab 375 mg/m(2) day 8. Treatment was repeated on day 29 for a total of four cycles. Between 3 April and 04 July, 57 patients were recruited from 24 participating institutions, 39% of whom had received prior R-chemo therapy. Median age was 66 years (40 - 83). Lymphoma subtypes were 29 follicular (FL), 18 MCL, and 10 other indolent lymphomas. The overall response rate (ORR) was 89% with 35% CR and 54% PR. ORR in R-chemo pretreated patients was 76% (38% CR, 38% PR). After a median observation time of 27 months (1 - 43), the estimated median progression free survival is 19 months. The 2 year overall survival is 60% for patients with FL and MCL. Treatment related toxicities of grade 3/4 comprised a reversible myelosuppression (10% anemia, 78% leukocytopenia, 46% granulocytopenia, 16% thrombocytopenia). However, unexpected hospitalisations were necessary after 4% of BMR-application only. BMR is a very effective new outpatient immuno-chemotherapy with low toxicity for patients with relapsed/refractory FL, MCL and other indolent lymphomas.

Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study.

We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m2 (80 mg/m2 in CLL) day 1 + 2, (M): 10 mg/m2 day 1 and (R): 375 mg/m2 day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 x BMR followed by 5 x BM. We have treated 54 patients with BMR. Median age was 68 years (36-82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1-7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3-60+). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.

Bendamustine plus mitoxantrone--a new effective treatment for advanced chronic lymphocytic leukaemia: results of a phase I/II study.

The toxicity arid efficacy of the combination bendamustine plus mitoxantrone (BM) was evaluated in 22 patients with advanced chronic lymphocytic leukaemia (CLL). Twenty out of twenty-two patients had received at least one prior regimen. Median age was 71 years (range 53-86). Six out of twenty-two patients were Binet stage B and 16/22 Binet stage C. Bendamustine was given in escalating doses from 80 up to 240 mg/m2 divided in two to three doses per course, mitoxantrone was given as short infusion with 8 up to 10 mg/m2 per course. The number of courses was limited to six and chemotherapy stopped when a complete remission (CR) or partial remission (PR) according to NCI-Criteria was achieved. Haematotoxicity and infection were dose limiting with 4/6 patients suffering from grade 3 infectious complication in the bendamustine level with 240 mg/m2. Six out of twenty-two patients achieved a CR and 13/22 patients a PR resulting in an overall response rate of 86% (19/22 patients). Median time to progression was 10 months (range 4-22) and median survival 39 months (range 6-50). For further studies we recommend a bendamustine dose of 150 mg/m2 combined with 10 mg/m2 mitoxantrone.

Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.

PURPOSE: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged

Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory indolent lymphoid malignancies.