Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer.

Chemotherapy-induced myelosuppression is an acute, dose-limiting toxicity of chemotherapy regimens used in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low-frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all-cause hospitalisations, all-cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5. MAHE and its individual components were assessed in three randomised, double-blind, placebo-controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan-containing chemotherapy regimen for ES-SCLC and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared to placebo. In the pooled analysis, the cumulative incidences of all-cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after Week 5 were significantly reduced with trilaciclib vs placebo; however, no significant difference was observed in rates of all-cause hospitalisations. Additionally, compared to placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES-SCLC.

Hematologic Manifestations of Nutritional Deficiencies: Early Recognition is Essential to Prevent Serious Complications.

Nutritional deficiencies, including deficiencies of vitamin B12, copper, and vitamin C, may result in cytopenias and hematologic symptoms. Early recognition of these deficiencies is imperative for prompt treatment and improvement in hematologic and other manifestations. We describe 5 cases which illustrate the hematologic manifestations of nutritional deficiencies and challenges to initial diagnosis and management. Supplementation of the deficient vitamin or micronutrient in all of these cases resulted in rapid resolution of cytopenias, hemorrhage, and other associated hematologic symptoms. We also review other nutritional deficiencies that manifest with hematologic symptoms and compile recommendations on treatment and expected time to response.

Use of Cardioprotective Dexrazoxane Is Associated with Increased Myelotoxicity in Anthracycline-Treated Soft-Tissue Sarcoma Patients.

BACKGROUND: Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. METHODS: We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 received off-label DEX concurrently with the AI treatment. The differences between incidence of any of the explored outcomes were assessed according to the Fisher exact test. RESULTS: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of grade 3/4 hematological toxicities: leukopenia (56.5 vs. 28.7%; p = 0.0014), neutropenia (69.6 vs. 24.1%; p = 0.0001), febrile neutropenia (52.2 vs. 20.7%; p = 0.0004), anemia (41.3 vs. 28.7%; p = 0.1758), and thrombocytopenia (54.3 vs. 32.1%; p = 0.0159). Similarly, in the DEX group dose reductions were more frequent compared to the non-DEX group (39.1 vs. 19.5%; p = 0.0221). CONCLUSION: Adding DEX to AI in STS patients leads to higher rates of bone marrow suppression in all blood components, as well as to more frequent events of febrile neutropenia and dose reductions.

Effectiveness of adjuvant carboplatin-based chemotherapy compared to cisplatin in non-small cell lung cancer.

BACKGROUND: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early non-small cell lung cancer. However, few validated alternatives exist when cisplatin is not indicated or tolerated. Carboplatin is frequently used in this setting. We evaluated the 5-year overall survival, progression-free survival and toxicity in patients treated for stage IB to IIIB resected non-small cell lung cancer receiving adjuvant carboplatin-based chemotherapy compared to cisplatin in association with vinorelbine. METHODS: Single-center retrospective study of patients having received adjuvant chemotherapy between January 2004 and December 2013 at the oncology clinic at Institut Universitaire de Cardiologie et de Pneumologie de Québec (Canada). Three sub-groups, cisplatin/vinorelbine, carboplatin/vinorelbine and the substitution of cisplatin/vinorelbine for carboplatin/vinorelbine (cisplatin/vinorelbine/carboplatin/vinorelbine), were studied during treatment. RESULTS: One hundred twenty-seven patients were included in this study. The median PFS was not significantly different, with 50.4 months for cisplatin/vinorelbine, 57.3 months for cisplatin/vinorelbine/carboplatin/vinorelbine and not yet achieved for the carboplatin/vinorelbine group ( p = 0.80). Overall survival also did not differ significantly between the three groups. The 5-year overall survival rates were 66% in cisplatin/vinorelbine group, 55% in carboplatin/vinorelbine group and 70% in cisplatin/vinorelbine/carboplatin/vinorelbine group ( p = 0, 95). No differences were noted between groups concerning high-grade hematologic toxicity. CONCLUSIONS: Although the effectiveness and hematologic toxicity are comparable between cisplat in and carboplatin in the adjuvant treatment of resected non-small cell lung cancer, the results obtained corroborate the practice used at our oncology clinic. Nevertheless, more prospective studies would be needed to confirm these results.

[Systemic coagulopathic distress syndrome in surgery: concept, pathogenesis, prophylaxis]. / Ponyatie sistemnogo koagulopaticheskogo distress-sindroma v khirurgii, ego patogenez i printsipy profilaktiki.

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

The aspirin story - from willow to wonder drug.

The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century.

Understanding, treating and avoiding hematological disease: better medicine through mathematics?

This paper traces the experimental, clinical and mathematical modeling efforts to understand a periodic hematological disease-cyclical neutropenia. It is primarily a highly personal account by two scientists from quite different backgrounds of their interactions over almost 40 years and their attempts to understand this intriguing disease. It's also a story of their efforts to offer effective treatments for the patients who suffer from cyclic neutropenia and other conditions causing neutropenia and infections.

Antitoxic Activity of Extract from Salix Viminalis Leaves under Conditions of 5-Fluorouracil Treatment.

Injection of 5-fluorouracil to animals caused a pronounced toxic effect. Therapeutic and preventive treatment with Salix viminalis leaf extract significantly reduced the negative effects of the antitumor drug: promoted recovery of the bone marrow, peripheral blood, and visceral parameters and prevented ulceration. Combined use of the cytostatic and Salix viminalis extract increased the efficiency of antitumor therapy.

[Fundamental and applied aspects of preventing the adverse effects of aviation noise].

In the article, aviation noise is discussed as a harmful physical factor with ecological, hygienic, clinical and social implications. Noise contributes to development of general and occupational pathologies, chronic diseases, and reduction of professional longevity. The present-day knowledge of aviation noise sources and dynamics, and effects on environment, population, and aviation personnel is overviewed, as well as strategies to prevent noise consequences, muffling techniques being the key ones.

Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.

BACKGROUND: Methotrexate (MTX) is a disease modifying antirheumatic drug (DMARD) used as a first line agent for treating rheumatoid arthritis (RA). Pharmacologically, it is classified as an antimetabolite due to its antagonistic effect on folic acid metabolism. Many patients treated with MTX experience mucosal, gastrointestinal, hepatic or haematologic side effects. Supplementation with folic or folinic acid during treatment with MTX may ameliorate these side effects. OBJECTIVES: To identify trials of supplementation with folic acid or folinic acid during MTX therapy for rheumatoid arthritis and to assess the benefits and harms of folic acid and folinic acid (a) in reducing the mucosal, gastrointestinal (GI), hepatic and haematologic side effects of MTX, and (b) whether or not folic or folinic acid supplementation has any effect on MTX benefit. SEARCH METHODS: We originally performed MEDLINE searches, from January 1966 to June 1999. During the update of this review, we searched additional databases and used a sensitive search strategy designed to retrieve all trials on folic acid or folinic acid for rheumatoid arthritis from 1999 up to 2 March 2012. SELECTION CRITERIA: We selected all double-blind, randomised, placebo-controlled clinical trials (RCTs) in which adult patients with rheumatoid arthritis were treated with MTX (at a dose equal to or less than 25 mg/week) concurrently with folate supplementation. In this update of the review we only included trials using 'low dose' folic or folinic acid (a starting dose of ≤ 7 mg weekly). DATA COLLECTION AND ANALYSIS: Data were extracted from the trials, and the trials were independently assessed for risk of bias using a predetermined set of criteria. MAIN RESULTS: Six trials with 624 patients were eligible for inclusion. Most studies had low or unclear risk of bias for key domains. The quality of the evidence was rated as 'moderate' for each outcome as assessed by GRADE, with the exception of haematologic side effects which were rated as 'low'. There was no significant heterogeneity between trials, including where folic acid and folinic acid studies were pooled.For patients supplemented with any form of exogenous folate (either folic or folinic acid) whilst on MTX therapy for rheumatoid arthritis, a 26% relative (9% absolute) risk reduction was seen for the incidence of GI side effects such as nausea, vomiting or abdominal pain (RR 0.74, 95% CI 0.59 to 0.92; P = 0.008). Folic and folinic acid also appear to be protective against abnormal serum transaminase elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction (RR 0.23, 95% CI 0.15 to 0.34; P < 0.00001), as well as reducing patient withdrawal from MTX for any reason (60.8% relative (15.2% absolute) risk reduction, RR 0.39, 95% CI 0.28 to 0.53; P < 0.00001).We analysed the effect of folic or folinic acid on the incidence of stomatitis / mouth sores, and whilst showing a trend towards reduction in risk, the results were not statistically significant (RR 0.72, 95% CI 0.49 to 1.06)It was not possible to draw meaningful conclusions on the effect of folic or folinic acid on haematologic side effects of methotrexate due to small numbers of events and poor reporting of this outcome in included trials.It does not appear that supplementation with either folic or folinic acid has a statistically significant effect on the efficacy of MTX in treating RA (as measured by RA disease activity parameters such as tender and swollen joint counts, or physician's global assessment scores). AUTHORS' CONCLUSIONS: The results support a protective effect of supplementation with either folic or folinic acid for patients with rheumatoid arthritis during treatment with MTX.There was a significant reduction shown in the incidence of GI side effects, hepatic dysfunction (asmeasured by elevated serum transaminase levels) as well as a significant reduction in discontinuation of MTX treatment for any reason. A trend towards a reduction in stomatitis was demonstrated however this did not reach statistical significance.This updated review with its focus on lower doses of folic acid and folinic acid and updated assessment of risk of bias aimed to give a more precise and more clinically relevant estimate of the benefit of folate supplementation for patients with rheumatoid arthritis receiving methotrexate.

Postoperative hematological changes after spleen-preserving distal pancreatectomy with preservation of the splenic artery and vein.

BACKGROUND: The aim of this study was to determine the early postoperative hematological changes after spleen-preserving distal pancreatectomy (SpDP) with preservation of the splenic artery and vein (PSAV). METHODS: We reviewed 53 patients who underwent SpDP with PSAV (n = 21) or distal pancreatectomy with splenectomy (DPS; n = 32) for benign or low-grade malignant lesions between July 1998 and June 2010. Red and white blood cell (WBC) count, platelet count, serum hemoglobin, hematocrit, C-reactive protein, albumin level, and clinical factors were compared between the SpDP with PSAV and DPS. RESULTS: There were no significant differences in the patient characteristics between the two groups. Platelet count on postoperative day (POD) 5 and WBC count on POD 3 were significantly higher in the DPS group, and these differences continued to be significant until the 3rd month after surgery. Serum hemoglobin and hematocrit in the 1st month after surgery were also significantly higher in the SpDP with PSAV group. CONCLUSION: The hematological benefits of SpDP with PSAV include reduction of postoperative hematological abnormalities in the early postoperative phase and recovery of the serum hemoglobin and hematocrit levels in the early postoperative phase.

A prospective, controlled study of the botanical compound mixture LCS101 for chemotherapy-induced hematological complications in breast cancer.

BACKGROUND: This prospective, controlled study evaluated the safety, tolerability, and efficacy of the mixture of botanical compounds known as LCS101 in preventing chemotherapy-induced hematological toxicity in breast cancer patients. METHODS: Female patients diagnosed with localized breast cancer were randomly allocated to receive treatment with either LCS101 or placebo capsules, in addition to conventional chemotherapy. The study intervention was initiated 2 weeks prior to the initiation of chemotherapy and continued until chemotherapy was completed, with participants receiving 2 g of LCS101 capsules thrice daily. Subjects were assessed for the development of hematological and nonhematological toxicities, as well as the tolerability and safety of the study intervention. RESULTS: Sixty-five breast cancer patients were recruited, with 34 allocated to LCS101 and 31 allocated to placebo treatment. Patients in the treatment group developed significantly less severe (grades 2-4) anemia (p < .01) and leukopenia (p < .03) when comparing grades 0-1 with grades 2-4, with significantly less neutropenia (p < .04) when comparing grades 0-2 with grades 3-4. This effect was more significant among patients undergoing a dose-dense regimen. No statistically significant effect was found with respect to nonhematological toxicities, and side effect rates were not significantly different between the groups, with no severe or life-threatening events observed in either group. CONCLUSION: The addition of LCS101 to anthracycline- and taxane-based chemotherapy is safe and well tolerated, and may significantly prevent some chemotherapy-induced hematological toxicities in early breast cancer patients. These results should encourage further larger and more extensive clinical trials.

The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

Protective effects of zinc and selenium against benzene toxicity in rats.

The presented study investigates the protective role of zinc (Zn) and selenium (Se) in attenuating benzene-induced toxicity in rats. Male Sprague-Dawley rats were injected with benzene (0.5 mL/kg body weight ip) and received a diet supplement containing Zn and Se. Several hematological and biochemical parameters (representing antioxidant status) were estimated. Histopathological examinations were performed. Results showed that food intake and body weight gain of benzene-injected rats were significantly lower than that of the control rats. Benzene-injected rats showed increased plasma malondialdehyde (MDA) and decreased activity of: glutathione peroxidase (GSH-Px), catalase, superoxide dismutase (SOD) enzymes, as well as reduced glutathione (GSH) when compared to the control group. Histopathological investigations revealed structural changes in benzene-injected rats' liver. Supplementation with Zn and Se resulted in a significant decrease in MDA, elevation in GSH, GSH-Px, SOD and catalase levels. This study shows that Zn and Se supplementation can improve the activity of antioxidant enzymes in rats and decrease the histological anomalies induced by benzene toxicity as well.

[Hematological disorders in celiac disease].

Gluten-sensitive celiac disease (GSCD) belongs to systemic diseases one of manifestations of which may be various hematological disorders. Some patients with GSCD have blood changes, anemia in particular, which precede clinical symptoms of celiac disease. Anemia can arise as a result of disorders in iron, folic acid and/or vitamin B12 absorption. Celiac disease can be associated with thrombocytosis, thrombocytopenia, leucopenia, vein thrombosis, hyposplenism, immunoglobulin A deficiency. Patients with celiac disease have a high risk of lymphoma, especially of T-cell lymphoma associated with enteropathy, B-cell non-Hodgkin's lymphoma. Aglutenic diet, recovery of structure and function of the small intestine eliminate or attenuate hematological disorders associated with GSCD.

Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.

Quantitative Systems Toxicology (QST) models, recapitulating pharmacokinetics and mechanism of action together with the organic response at multiple levels of biological organization, can provide predictions on the magnitude of injury and recovery dynamics to support study design and decision-making during drug development. Here, we highlight the application of QST models to predict toxicities of cancer treatments, such as cytopenia(s) and gastrointestinal adverse effects, where narrow therapeutic indexes need to be actively managed. The importance of bifurcation analysis is demonstrated in QST models of hematologic toxicity to understand how different regions of the parameter space generate different behaviors following cancer treatment, which results in asymptotically stable predictions, yet highly irregular for specific schedules, or oscillating predictions of blood cell levels. In addition, an agent-based model of the intestinal crypt was used to simulate how the spatial location of the injury within the crypt affects the villus disruption severity. We discuss the value of QST modeling approaches to support drug development and how they align with technological advances impacting trial design including patient selection, dose/regimen selection, and ultimately patient safety.

Double umbilical cord blood transplantation for children and adolescents.

Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.

[Growth dynamics of transplantable murine tumors in the course of dicarbamin-protected chemotherapy].

Dicarbamin-assisted mono- and combination chemotherapy (cyclophosphamide + carboplatin + cisplatin) for transplantable tumors born by linear or hybrid mice of both sexes was investigated. It was shown that long-term oral administration contributed to the effect of a range of cytostatic therapeutic dosage rather than adversely affected it. Our findings were used to make a case for clinical studies of dicarbamin for its potential of lowering hematological toxicity of antitumor therapy.