CD40L-transfected myeloma cells transfer prolonged immunity in vivo.

BACKGROUND: In a large number of patients with multiple myeloma, chemotherapy is the only therapeutic option. During recent years, major effort has been put into immunotherapeutic approaches for this malignancy. MATERIALS AND METHODS: In this study, wild-type (wt) myeloma cells (5x10(5)) were injected subcutaneously into Balb/c mice. CD40L-transfected myeloma cells (5x10(5)) were subsequently injected intratumorally into the established (>100 mm(3)) wt tumor nodules. Overall survival and tumor growth were measured. RESULTS: Out of eight animals receiving wt tumor cells, one died prior to the formation of a solid tumor nodule. Following the CD40L-transfected myeloma cell injection, stable complete remission at day 60 with all the animals surviving resulted. On day 60, a re-challenge was performed with wt myeloma cells. No tumor growth was observed after 120 days out of seven remaining animals, one died. CONCLUSION: Intratumoral injection of CD40L-transfected myeloma cells induces complete tumor remission and long lasting immunity against tumor recurrence.

Prevention of lethal tumor growth and generation of long-lasting immunity in vivo using CD137L and interleukin-12 gene transfer.

In a wide range of solid tumors, overexpression of CD137L has been shown to induce tumor immunity partly due to the stimulation of CD8+ CTL, which was even increased when immunotherapy with interleukin-12 (IL12) was additionally employed. However, little in known regarding hematologic neoplasias in this respect. Of the 8 animals receiving IL12-secreting tumor cells, 2 died. Animals treated with CD137L-expressing tumor cells and the combination group, all animals survived. Interestingly, re-challenge with wild-type tumor cells was rejected by all animals in the CD137L group and all remaining animals in the IL12 group, while these in the control group died. IL12- and CD137L-transfected plasmocytoma cells prevented tumor growth and induced long-lasting immunity. Our results warrant follow-up for future clinical use in patients with myeloma.

DHAP in combination with rituximab vs DHAP alone as salvage treatment for patients with relapsed or refractory diffuse large B-cell lymphoma: a matched-pair analysis.

The addition of rituximab to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) has been shown to improve outcome in first-line therapy. However, in patients with relapsed or refractory disease, the value of adding rituximab to salvage chemotherapy is less clearly defined. This study performed a matched-pair analysis of patients with relapsed or refractory DLBCL by comparing the combination of dexamethasone, high-dose cytarabine and cisplatin (DHAP) with rituximab to DHAP alone. Sixty-seven patients with relapsed or refractory DLBCL were collected from two prospective phase II trials from Germany and Italy. Twenty-three patient pairs treated with either DHAP in combination with rituximab or DHAP alone could be analysed after matching for important prognostic factors. The addition of rituximab to the DHAP regimen led to higher complete and similar overall remission rates. However, differences with regard to complete remission rates failed to reach statistical significance, thereby necessitating further evaluation of the role of combined immunochemotherapy in this patient population.

Standard of care of patients with Chronic Myeloid Leukemia (CML) treated in community based oncology group practices between 2001-2015 in Rhineland- Palatinate (Germany)

Background: The aim of this study was to assess retrospectively treatment and outcome of CML-patients in community based oncology practices in Germany and whether European LeukemiaNET (ELN) recommendations were followed. Method: All Ph+, BCR-ABL1+ CML-patients who were treated between 11/2001 and 12/2015 in nine oncology group practices were analyzed retrospectively. Results: Two hundred sixty patients with a median age of 60 (18­90) were analyzed. 254 (98%) were in chronic phase, 5 (2%) in accelerated and 1 (0.4%) in blast crisis. 248 patients (95%) received some form of TKI-therapy. 1st line TKI was imatinib in 197 patients (79%), 51 (21%) received a second generation TKI. 75% of TKI-therapies were monitored by PCR. Overall survival after 10 years according to Charlson comorbidity index (CCI) was: CCI 2: 100%; CCI 3­4: 83%; CCI 5­6: 52%; CCI ≥7: 39%. More patients died from comorbidities (8%) than from CML (5%). Whether patients died was strongly correlated to CCI at diagnosis: CCI 2: 3% of patients died, CCI 3­4: 16% of patients died, CCI 5­6: 38% of patients died, CCI ≥ 7: 42% of patients died. Conclusion: CML-patients treated in oncology group practices receive standard of care as recommended by ELN. Overall survival in routine care is comparable to international studies. Molecular monitoring should be improved (AU)

High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma.

BACKGROUND: High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) plays an important role in the treatment of aggressive non-Hodgkin's lymphoma (NHL). We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. METHODS: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL). Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. RESULTS: A complete remission (CR) was achieved in 14 of 25 patients (56%). Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS) in multivariate analysis. CONCLUSIONS: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

Pegfilgrastim as hematopoietic support for dose-dense chemoimmunotherapy with R-CHOP-14 as first-line therapy in elderly patients with diffuse large B cell lymphoma.

GOALS OF WORK: Recently, 6 cycles of R-CHOP-14 have been recommended as the reference standard regimen for the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim has been shown to facilitate dose-dense chemotherapy schedules with a single administration per chemotherapy cycle. The aims of this study were to evaluate the use of pegfilgrastim in combination with the R-CHOP-14 regimen in a homogenous group of previously untreated elderly patients with DLBCL and to assess the pharmacokinetics of pegfilgrastim within this patient population. MATERIALS AND METHODS: Ten patients with DLBCL between 60 and 80 years of age received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after administration of R-CHOP chemoimmunotherapy, which was repeated for 6 to 8 cycles in two-weekly intervals. A total of 348 blood samples were collected. Pegfilgrastim plasma levels and absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles. MAIN RESULTS: Sixty-three of 72 cycles (87.5%) could be delivered on time and at the planned dose. Median absolute neutrophil nadir was 0.32 g/l on day 9. Grade 3/4 granulocytopenia occurred in all patients. Febrile neutropenia occurred in two patients. Plasma levels of pegfilgrastim remained elevated during the neutropenic phase. At the start of hematologic recovery, plasma concentrations of pegfilgrastim decreased rapidly to baseline levels. Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application. CONCLUSIONS: A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to allow two-weekly drug administration in previously untreated elderly patients with DLBCL. However, close monitoring for infectious complications is mandatory in this patient population.

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.