The significance of upfront autologous stem cell transplantation for high-intermediate/high-risk stage IV diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common (30%-35%) type of B-cell lymphoma. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated with x6 R-CHOP. High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve as an option to improve a prognosis in these patients. AIMS: This trial aimed to improve prognosis in DLBCL by upfront auto-HSCT. METHODS AND RESULTS: A group of 105 patients: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 R-CHOP/DA-EPOCH-R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia was retrospectively analyzed. The HSCT group included patients with upfront HDCT followed by auto-HSCT (n = 35). The control group included patients with non-invasive follow-up after induction (n = 70). Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate and relapse rate. The 3-year OS (p = .013) and 3-year PFS (p = .033) were significantly higher in the HSCT group. The 3-year OS was decreased by the occurrence of relapse (p ≤ .001) and weight loss (B-symptom) (p = .04). DEL was the negative prognostic factor for 3-year PFS in all patients (p = .001) and control group (p = .001). DA-EPOCH-R significantly increased the 3-year PFS (p = .041). CONCLUSION: Upfront HDCT followed by auto-HSCT can increase 3-year OS and PFS and improve prognosis in DLBCL NOS, age 18-65, stage IV, IPI ≥2 patients.

Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants.

Gemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60-89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB.

Enchancement of Toremifene Anti-Tumor Action by Metformin and Unusual Side Effect of Toremifene in Male Transgenic Mice with HER2-Positive Breast Tumor.

HER2-positive breast tumors are found in 25-30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm3 and 1309 ± 120 mm3, respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene.