A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined treatments, and should be increasingly integrated in multimodal combination therapy regimens. The goal of this manuscript is to provide better understanding and key considerations for developing new combined nanomedicines and nanotheranostics. We will clarify the potential of combined nanomedicine strategies that are designed to target different steps of the cancer growth as well as its microenvironment and immunity interactions. Moreover, we will describe relevant experiments in animal models and discuss issues raised by translation in the human setting.

Modified DCF (Docetaxel, Cisplatin and 5-fluorouracil) chemotherapy is effective for the treatment of advanced rectal squamous cell carcinoma.

Background: Advanced rectal squamous cell carcinoma (rSCC) is a very rare and aggressive entity, and the best initial management is crucial for long survival as well as organ preservation and quality of life. Whereas local diseases are treated with chemo-radiotherapy and salvage surgery, data are scarce on how to treat more advanced diseases, and the role of induction chemotherapy is unknown. Methods: We retrospectively analyzed all consecutive patients with advanced rSCC and treated with modified DCF (docetaxel, cisplatin, 5-fluorouracil; mDCF) regimen, from January 2014 and December 2021 in two French centers. Exploratory endpoints were efficacy (overall survival, recurrence-free survival, response rate, organ preservation rate) and safety. Results: Nine patients with locally advanced or metastatic diseases received a mDCF regimen and were included for analysis. The median age was 62.0 years, 7 patients (77.8%) were women, and all eight available tumors were positive for HPV, mostly (85.7%) to genotype 16. With a median follow-up of 33.1 months, 77.8% of patients were still alive and disease-free, and the median overall survival was not reached at six years. The objective response rate was 87.5% after mDCF, and the complete response rate was 25.0% after mDCF and was increased to 75.0% after chemoradiotherapy. Only one patient underwent surgery on the primary tumor, with a complete pathological response. The median mDCF cycle was eight over eight scheduled, and all patients received the complete dose of radiotherapy without interruptions. Conclusions: Induction mDCF chemotherapy followed by chemoradiotherapy is safe and highly effective in patients with advanced rSCC, and should be considered as an option in metastatic stage or locally advanced disease with an organ-preservation strategy.

Primary tumor resection in patients with unresectable colorectal cancer with synchronous metastases could improve the activity of poly-chemotherapy: A trial-level meta-analysis.

INTRODUCTION: Primary tumor resection (PTR) in patients with metastatic unresectable colorectal cancer is less and less used to prevent local complications. Although its therapeutic effect is debated, poor data are available about the activity of chemotherapy (CHT) after PTR. The study aims to evaluate trials that compared PTR followed by CHT vs. CHT alone. METHODS: After a literature search on two databases by predefined criteria, studies published from 2011 to 2021 were selected. All studies evaluating the progression-free survival (PFS) of patients receiving CHT after PTR or not were included in a meta-analysis. Finally, 18 possible moderating variables were extracted from each study and examined. RESULTS: Eleven trials reported a reduced risk of progression after first-line CHT among patients receiving PTR (HR 0.72, CI 0.66-0.79). The heterogeneity was moderate (Q = 17.52; p-value = 0.093) and the grade of inconsistence intermediate (I2 = 37.21%). Among moderating variables, female sex and low percentage of patients with liver metastases were related with a stronger effect size of PTR on PFS, whereas a longer OS and a trend to better PFS was evident after poly-chemotherapy regimens. CONCLUSION: PTR could improve the results of first-line CHT in patients with unresectable colorectal cancer with low tumor burden only in the subgroup receiving more aggressive chemotherapy.

Correlation between Structural Transformations in Mesenteric Lymph Nodes and the Levels MicroRNA during Polychemotherapy of Breast Cancer.

We studied interrelationships between the cytoarchitectonics of the mesenteric lymph node and the levels of microRNA-21, microRNA-221/222, and microRNA-429 in the lymph, blood serum, and breast tissues in female Wistar rats with chemically induced breast cancer. After polychemotherapy, significant correlations were found between miRNA-221 and the number of lymphoblasts in the germinal centers and between miRNA-222 and the number of lymphoblasts in the germinal centers and macrophages in the medullary cords of the mesenteric lymph nodes.

[Predictors of severe lesions of the central nervous system in the treatment of blood system diseases]. / Prediktory tyazhelykh porazhenii tsentral'noi nervnoi sistemy pri lechenii zabolevanii sistemy krovi.

OBJECTIVE: To determine the types, frequency and key symptoms of severe lesions of the central nervous system (SLCNS) that occurred in patients with hematological malignancies (HM). MATERIALS AND METHODS: The authors conducted a retrospective exploratory study by analyzing the data of 3.620 patients with HM during the period from 01.01.18 to 31.12.19. Thirty-four patients (14 men and 20 women, median age 39 years), who developed SLCNS during treatment, were selected. For comparison with the main group of patients and exclusion of predictors associated with the development of SLCNS, a comparison group was added (by Kernel matching method). A comparison group consisted of 137 patients (59 men and 78 women, median age - 36 years) and was similar to the main group by clinical and laboratory characteristics. A neurological complication was marked as SLCNS if it was an indication for transfer to the intensive care unit (ICU). Statistical analysis included multivariate analysis - multiple binary logistic regression with stepwise inclusion of variables (that were found in the preliminary contingency table analysis) in the model, with control false results (by the false discovery rate method) and estimating the odds ratio, OR (95% CI). RESULTS: SLCNS in patients with HM developed in 0.94% of cases. The main SLCNS in patients with HM were: epileptic seizure (50.0%, n=17), ischemic stroke (20.6%, n=7), hemorrhagic stroke (17.6%, n=6) and meningoencephalitis (11.8%, n=4). The following independent significant (Wald test p≤0.05) predictors associated with the development of SLCNS in patients with HM during inpatient treatment were identified: antibiotic therapy (when more than 5 drugs are prescribed), OR=2.9 (1.2-7, four); polychemotherapy (if more than 4 drugs are prescribed), OR=2.9 (1.1-7.8); thrombocytopenia (with a platelet count less than 50·109 g/l), OR=2.3 (1.0-5.2) and delirium, OR=3.7 (1.3-10.8), and also the presence of neurological disorders in the patient's history, OR=2.6 (1.1-6.3). CONCLUSION: The main types of SLCNS in patients with HM were: epileptic seizure, ischemic and hemorrhagic strokes, and meningoencephalitis. Four predictors associated with the development of SLCNS in the course of HM treatment were identified: massive antibacterial (with more than 5 drugs) and chemotherapeutic (with more than 4 drugs) effects, thrombocytopenia and manifestation of delirium, as well as one risk factor: a history of neurological disorder. These factors need to be considered and monitored during treatment, because each of them increases the risk of developing SLCNS.

Caracterización clínica y marcadores de estrés oxidativo en pacientes con cáncer de pulmón tratados con poliquimioterapia / Clinical description and oxidative stress markers in patients with lung cancer treated with polychemotherapy

Introducción: Los tratamientos oncológicos aplicados en el cáncer de pulmón, en especial la poliquimioterapia, promueven en su mecanismo de acción citotoxicidad y liberación de ciertas especies reactivas del oxígeno. Objetivo: Caracterizar a pacientes con cáncer de pulmón según los marcadores de estrés oxidativo y de defensa antioxidante en el momento del diagnóstico y después de concluido el tratamiento con poliquimioterapia. Métodos: Se realizó un estudio analítico, prospectivo, en 86 casos divididos en dos grupos: casos diagnosticados con cáncer de pulmón (n= 52) y sanos (n= 34) en Hospital Neumológico Benéfico Jurídico en el período comprendido desde mayo de 2016 a mayo de 2018. Resultados: Predominó el sexo masculino (63,5 por ciento) y el 55,8 por ciento con más de 60 años. El tipo histológico más frecuente fue el adenocarcinoma (57,7 por ciento) y el 61,5 por ciento emplearon la modalidad de quimioterapia cisplatino y etopósido. Los pacientes con cáncer de pulmón mostraron un mayor daño oxidativo endógeno a lípidos y a proteínas (40,4 por ciento y 28,8 por ciento) respectivamente, mientras que el 63,5 por ciento mantienen la normalidad de concentraciones plasmáticas de peróxidos totales. En el 40,4 por ciento de los pacientes se incrementaron las actividades de defensa enzimáticas de la superóxido dismutasa, la catalasa y glutation peroxidasa, las cuales tuvieron una tendencia a la normalidad (63,5 por ciento y 48,0 por ciento) respectivamente. El 76,9 por ciento alcanzó niveles normales de glutation s-transferasa concluido el tratamiento oncoespecífico. Conclusiones: La quimioterapia se relaciona con una exacerbación del estrés oxidativo y una disminución del sistema de defensa antioxidante(AU)

Introduction: Oncological treatments used in lung cancer, particularly polychemotherapy, promote cytotoxicity and the release of certain reactive oxygen species in their mechanism of action. Objective: To describe patients with lung cancer according to oxidative stress and antioxidant defense markers at the time of diagnosis and after the end of treatment with polychemotherapy. Methods: An analytical, prospective study was carried out in 86 cases. They were distributed into two groups: subjects diagnosed with lung cancer (n= 52) and healthy subjects (n= 34) at the Pneumological Hospital from May 2016 to May 2018. Results: The male subjects predominated (63.5 percent) and 55.8 percent were over 60 years old. The most frequent histological type was adenocarcinoma (57.7 percent) and 61.5 percent used the cisplatin and etoposide chemotherapy modality. Lung cancer patients showed higher endogenous oxidative damage to lipids and proteins (40.4 percent and 28.8 percent) respectively, while 63.5 percent kept normal plasma concentrations of total peroxides. In 40.4 percent of the patients, the enzymatic defense activities of superoxide dismutase, catalase and glutathione peroxidase increased, which tended to normal (63.5 percent and 48.0 percent respectively. 76.9 percent reached normal levels of glutathione s-transferase after oncospecific treatment. Conclusions: Chemotherapy is related to exacerbation of oxidative stress and a decrease in the antioxidant defense system(AU)

Primary non-Hodgkin diffuse large B-cell lymphoma of the lacrimal sac: a rare case of aggressive tumor and literature review.

Primary malignant lymphomas of the lacrimal sac are rare neoplasms. They are mainly B-cell lymphoma with nonspecific and atypical symptoms, which can lead to misdiagnosis and a delay in the appropriate cure. Early diagnosis made by biopsy and the right choice of treatments can increase the chance of survival. We report a case of a non-Hodgkin diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac, involving also the drainage system, in a 77-year-old female. She presented with an epiphora, swelling and a heavy visual impairment at the left eye successfully treated with cycles of polychemotherapy and radiotherapy.

Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome.

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1-141) in non-study patients and 51 months (1-105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0-21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0-45)/21 months (95% CI 18-25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

PERIODONTAL RESPONSE TO CYTOSTATIC DRUGS IN CHILDREN.

OBJECTIVE: The aim: To study the effect of different types of cytostatic drugs on the periodontium in children with malignant tumors. PATIENTS AND METHODS: Material and methods: The material for generalization was based at the results of examination of 44 patients with malignant tumors of the abdominal cavity who underwent preoperative treatment in the oncohematology department of Poltava Children's City Clinical Hospital. RESULTS: Results: In the absence of proper dental care in patients of this group, under the influence of chemotherapeutic drugs, significantly worsens the level of oral hygiene and the condition of periodontal tissues. There are also changes in the process of differentiation of the epithelial structures of the gingival margin, which is accompanied by an increase in smears - reprints of the number of inflammatory cells of the peripheral blood, both with preserved structure and destructive forms. CONCLUSION: Conclusions: In children with malignant tumors, during antitumor therapy, there is a decrease in the level of hygiene of the oral cavity, accompanied by morphological destructive changes in the integumentary epithelial layer of the gingival margin. The severity of these disorders depends on the type and dose of cytostatic drugs, which should be considered in the formation of treatment and prevention measures for them.

[Systemic treatment of bladder cancer]. / Blasenkarzinomsystemtherapie.

Cisplatin-based chemotherapy regimens represent the standard of care in patients with locally advanced or metastatic urothelial carcinoma of the bladder. However, many patients are ineligible for cisplatin due to comorbidities or performance status. Immunotherapy with checkpoint inhibitors (CPI) has become a well-established treatment alternative in metastatic bladder cancer. The following review discusses current literature and guideline recommendations based on two case studies, in order to provide practical know-how about therapy sequences and treatment processes.

Cytokines of the Lymph and Blood Serum as Markers of Oncogenesis and Efficiency of Therapy in Chemically Induced Breast Cancer in Wistar Rats.

We studied the levels of serum and lymph cytokines involved in the pathogenesis of BC. BC was induced by injection of N-methyl-N-nitrosourea to Wistar rats. The animals underwent surgery, or received polychemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil), or surgical treatment was combined with polychemotherapy; in a special group, Panagen (fragmented DNA) was added to polychemotherapy. Cytokine concentration in the lymph was measured using Bio-Plex Pro Rat Cytokoness 24-Plex Assay test system (Bio-Rad). In rats with BC, the content of most studied cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, MIP-1α, MIP-3α, RANTES, TNFα, and MCP-1) in the lymph and blood was significantly higher, while the content of IL-10 and GRO/KC was lower than in intact animals. Surgical resection of the tumor led to a significant decrease in the content of both pro- and anti-inflammatory cytokines in the lymph. Polychemotherapy led to a significant decrease in the content of IL-1ß, IL-4, IL-6, IL-7, MIP-1α, MIP-3α, and RANTES in the serum and lymph. Comparison of the cytokine content in the serum and lymph of operated animals after polychemotherapy with and without Panagen showed that the content of most cytokines (IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A , IL-18, GRO/KC, IFNγ, and MIP-3α) was higher after Panagen administration.

Mola invasiva en adolescente de 13 años. Aspectos fundamentales del diagnóstico y tratamiento / Invasive mola in 13-year-old girl. Fundamental aspects in diagnosis and treatment

Resumen ANTECEDENTES: La neoplasia gestacional trofoblástica es un tumor raro, derivado de la gestación que procede de un desarrollo anormal del tejido trofoblástico. Incluye cuatro variedades, entre las que se encuentra la mola invasiva y el coriocarcinoma. Puede tener diferentes grados de proliferación; el diagnóstico diferencial es decisivo porque influye directamente en el tratamiento. Las molas premalignas suelen tratarse con legrado uterino, las malignas requieren tratamiento sistémico con mono o poliquimioterapia. CASO CLÍNICO: Paciente de 13 años, hospitalizada debido a un cuadro de vómitos y dolor abdominal. Durante el internamiento se le practicaron estudios complementarios: determinación de la fracción β de la gonadotropina coriónica humana (β-hCG) y tomografía axial computada para plantear el diagnóstico diferencial. El diagnóstico definitivo lo aportó la biopsia obtenida mediante legrado. El tratamiento se basó en la poliquimioterapia. En la actualidad está en remisión completa de la enfermedad. CONCLUSIONES: Resulta imprescindible detectar lo más temprano posible la gestación anómala, entender perfectamente su evolución e importancia de la anticoncepción mientras se trata y la enfermedad desaparece y minimizar la cantidad de pacientes que deben recibir quimioterapia.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is a rare tumor that originates from pregnancy and it develop from anormal proliferation of trophoblastic tissue. It includes four varieties, including invasive mole and choriocarcinoma. They can present different degrees of proliferation, being essential differential diagnosis since it directly influences the treatment. Premalignant moles are usually treated by suction curettage while malignant forms require systemic therapy with mono or polychemotherapy. OBJECTIVE: Report the case, paying special attention to the differential diagnosis and treatment used, analyzing the reasons why polychemotherapy is established and describing the different possible options, based on current scientific evidence. CLINICAL CASE: We present the case of an invasive mola in a 13-year-old patient hospitalized by vomiting and abdominal pain. During this period, complementary techniques such as the determination of the β fraction of the human chorionic gonadotropin (β-hCG) or computed tomography (CT) are required to establish the differential diagnosis. Finally, the definitive diagnosis is provided by the biopsy obtained by curettage. Treatment is instituted with the pattern of polychemotherapy being, currently, with complete remission of the disease. CONCLUSIONS: Thus, it is essential to detect anomalous gestation early, to understand perfectly the evolution of this entity, the importance of contraception during its resolution, and to minimize patients susceptible to chemotherapy.

Abdominal Lymphocyte-Depleted Hodgkin Lymphoma: A Rare Presentation.

BACKGROUND: Hodgkin lymphoma (HL) is a type of lymphoma that arises from the B lymphocytes. The four main subtypes of HL are the nodular sclerosing, mixed cellularity, lymphocyte rich and the lymphocyte depleted. Nodular sclerosis subtype accounts for majority of all classical HL, whereas lymphocytic depletion type accounts for less than 1%. The main objective of reporting this case is to share with the medical fraternity a rare presentation of abdominal lymphocyte-depleted classical Hodgkin lymphoma.A 47-year-old gentleman of Malay ethnicity with no known pre-morbidities, presented to the haematology unit with a 2-month history of night fever, loss of weight, malaise, anorexia and abdominal swelling. Abdominal examination revealed a periumbilical and lower epigastric swelling measuring 6x6 cms. The swelling was non-tender, firm in consistency and smooth on palpation. The Contrast Enhanced Computed Tomography (CECT) imaging revealed an enlarged mesenteric mass measuring 5.8x6.9x5.7 cm and multiple enlarged aorta-caval lymph nodes. The mesenteric tumour histology and immunohistochemistry were consistent with lymphocyte depleted HL. He completed six cycles of intravenous ABVD polychemotherapy consisting of doxorubicin (Adriamycin) 25mg/m2, Bleomycin 10mg/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2. The Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET /CT) imaging post 2 cycles and 6 cycles of ABVD polychemotherapy showed complete metabolic response to chemotherapy. CONCLUSION: Lymphocyte-depleted classical Hodgkin lymphoma (LDcHL) is a rare entity and is mostly diagnosed at a later stage rendering it a disease with poor prognostic outcomes. Early detection and prompt institution of therapy is crucial in the management of this disease.

Correction of Damaging Effects of Cisplatin-Containing Polychemotherapy on the Intestinal Epithelium with Tussilago farfara L. Polysaccharides.

A possibility for correction of damaging effects of polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides was studied on C57Bl/6 mice with Lewis lung carcinoma. The polysaccharides had protective and/or stimulating effects on the intestinal epithelium during polychemotherapy and promoted reparative regeneration in the intestine.

Impact of polychemotherapy on the oral soft tissues in children with malignant abdominal tumors.

OBJECTIVE: Introduction: According to modern standards of treatment of malignant neoplasms conducting polychemotherapy requires up to 90% of cancer patients. However, in addition to the expected cytotoxic effects, it is accompanied by disorders in dental health in the vast majority of patients. The aim: To study the effect of cytostatics on soft tissues of the oral cavity in children with malignant tumors of the abdominal cavity. PATIENTS AND METHODS: Materials and methods: Material for writing this scientific work served as a synthesis of results for 25 people aged 7 to 15 years with malignant tumors of the abdominal cavity, in which a comprehensive oral examination was performed to determine the manifestations of dental toxicity cytostatics. RESULTS: Results: At the end of the first course of chemotherapy, all patients had dry redness of the lips, 20 - (80,0%) with eruptions, in 18 - (20,0%) erosion. The Green-Vermillion, PMA, and PBI indices grew by 1,8; 7 and 3,3 times respectively. In cytograms with buccal epithelium an increase in the number of cells of polymorphic sizes and forms with signs of gidropic dystrophy was found. The nuclear-cytoplasmic ratio decreased by 1,4 times compared with the primary examination. CONCLUSION: Conclusions: This situation creates the preconditions for the development of inflammatory process in the tissues of the oral cavity and requires the use in this category of patients of a substantiated pathogenetic correction of existing disorders.

Management of recurrent nasopharyngeal carcinoma: current perspectives.

Nasopharyngeal carcinoma is a rare disease in Western countries. Nevertheless, its incidence in China, Singapore, and other Eastern countries reaches 20 cases per 100,000 people. Being an extremely chemo- and radiosensitive disease, upfront treatment often consists in the association of intensity-modulated radiation therapy and concurrent cisplatin. Unfortunately, about 20% of the patients suffer from a radioresistant disease which recurs after upfront therapy. For these patients, mainly available therapeutic options consist in systemic therapy, in particular poly-chemotherapy. In those showing a single locoregional recurrence, chemotherapy is not considered to be the preferred approach and other different strategies may be employed. Re-irradiation and surgery are strategies that are always used more often, albeit related to high risk of morbidity. Immunotherapy and targeted therapy, such as heavy ions-based re-irradiations, are experimental but very intriguing options.

Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group).

BACKGROUND: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. RESULTS: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

Protective Effect of Polysaccharides from Tussilago farfara L. on Bone Marrow Cells and Small Intestinal Epithelium Under Conditions of Polychemotherapy Evaluated by DNA Comet Assay.

Using DNA comet assay we found that polysaccharides from Tussilago farfara L. reduced the intensity of polychemotherapy-induced apoptosis and DNA damage in bone marrow cells and small intestinal epithelium of C57Bl/6 mice, which attested to genoprotective properties of these polysaccharides.

Modification of the Myelotoxic and Antitumor Effects of Polychemotherapy by Polysaccharides from Tussilago farfara L.

The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.