Kooperativer Bibliotheksverbund

In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 24, No. 35 ( 2017-11-20)

Type of Medium: Online Resource

ISSN: 0929-8673

URL: Article

DOI: 10.2174/0929867324666170718110606

Language: English

Publisher: Bentham Science Publishers Ltd.

Publication Date: 2017

SSG: 15,3

In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2018 ( 2018), p. 1-14

Abstract: The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric Curcuma longa , has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.

Type of Medium: Online Resource

ISSN: 1942-0900 , 1942-0994

URL: Article

DOI: 10.1155/2018/9698258

Language: English

Publisher: Hindawi Limited

Publication Date: 2018

detail.hit.zdb_id: 2455981-7

In: Journal of Education, Health and Sport, Uniwersytet Mikolaja Kopernika/Nicolaus Copernicus University, Vol. 12, No. 9 ( 2022-09-05), p. 477-483

Abstract: Introduction Iodine is necessary for the proper production of triiodothyronine and thyroxine, which affect the development and proper functioning of the body. Thyroid hormones are involved in the transformation of proteins, fats, carbohydrates and vitamins, and also regulate the processes of cell growth and maturation. Iodine deficiency during pregnancy has many consequences for the fetus and newborn, some of them an increased risk of miscarriage, stillbirth, birth defects or abnormal mental development. Iodine deficiency through lack of supplementation or deficiency in the daily diet, as well as the consumption of an excess amount of this microelement, may be associated with serious and irreversible consequences affecting the development and further functioning of the fetus. Aim of the study  Presentation of the impact of iodine supplementation in reproductive age and pregnancy on fetal development and students' knowledge of the need for this supplementation. Materials and method A survey of 404 students. The results were compared with the current scientific literature. Statistical analysis was performed using Microsoft Excel.   Results  In the study group, almost every third student believed that current recommendations recommend that women planning pregnancy should take iodine preparations. Every tenth student gave the correct dose of recommended supplementation of the microelement in question.   Conclusions Research shows that more than half of students are not aware of the need to supplement iodine at the reproductive age. The data indicate that young people should be made aware of the need for iodine supplementation.

Type of Medium: Online Resource

ISSN: 2391-8306

URL: Article

DOI: 10.12775/JEHS.2022.12.09.055

Language: Unknown

Publisher: Uniwersytet Mikolaja Kopernika/Nicolaus Copernicus University

Publication Date: 2022

detail.hit.zdb_id: 2842726-9

In: Journal of Education, Health and Sport, Uniwersytet Mikolaja Kopernika/Nicolaus Copernicus University, Vol. 12, No. 9 ( 2022-09-05), p. 484-490

Abstract: Introduction Nowadays, it has become fashionable to use dietary supplements containing large doses of vitamin D available without a prescription. In the case of children, dietary supplementation with a properly selected dose of vitamin D is extremely important and brings many benefits, of which it is important to prevent rickets in the pediatric population, attention is also drawn to its toxicity and consequences in the event of an overdose of vitamin D preparations, to which infants and young children are most exposed, examples of risks are hypercalcemia, hypercalciuria and nephrocalcinosis. The aim of the study Showing the benefits and dangers of vitamin D supplementation. Material and methods The research was conducted using PubMed articles and on: vitamin D supplementation in children, vitamin D overdose, vitamin D deficiency. Description of the state of knowledge Vitamin D is the generic name for ergocalciferol and cholecalciferol that we can find in foods, however, food and supplementation are not its only sources, it should be borne in mind that it is possible to synthesize vitamin D in the skin after exposure to ultraviolet reproduction (UV-B). The concentration of 25(OH)D in childhood serum is influenced by the amount and frequency of vitamin D consumed, sun exposure, body weight and body fat levels. The main risk of vitamin D deficiency in children is rickets and defromation of the osteoarticular system and metabolic disorders, and long-term use of its high doses can lead to hypercalcemia and nephrocalcinosis. Summary It is very important to educate parents about the importance of vitamin D supplementation in a dose properly selected for the newborn along with an explanation of the possible consequences of deficiency, as well as overdose.

Type of Medium: Online Resource

ISSN: 2391-8306

URL: Article

DOI: 10.12775/JEHS.2022.12.09.056

Language: Unknown

Publisher: Uniwersytet Mikolaja Kopernika/Nicolaus Copernicus University

Publication Date: 2022

detail.hit.zdb_id: 2842726-9

In: Acta Agrobotanica, Polish Botanical Society, Vol. 76 ( 2023-03-23)

Abstract: Horticulture is now revolutionized by advancements in light-emitting diode (LED) lighting. New technologies enable knowledge expansion on how plants require different spectral illumination for optimal growth and development. The aim of this study was to evaluate the quality of cucumber ( Cucumis sativus  L. ‘Parys F1’) and tomato ( Solanum lycopersicum  L. ‘Poranek’) seedlings produced in indoor controlled conditions, using three different types of LED tubes emitting warm light (AP67, AP673L, and G2). The photosynthetic photon flux density was set at 50–65 µmol m −2  s −1 and a 16-hour light regime was used. The results were compared to the cool daylight-emitting fluorescent (FL) control (tube lamp TLD 36W/54). A detailed analysis of the biometrical parameters of the aboveground and underground parts of seedlings was performed. Moreover, the content of chlorophyll in the leaves was measured. No effect of light spectra on the underground part of cucumber was found. On the other hand, the type of lamp affected the number of leaves and chlorophyll content in this species. Lamps AP673L and FL can be recommended in the production of cucumber seedlings. The obtained seedling had characteristics desired for horticultural production, i.e., compact habit with a fair number of leaves and chlorophyll content. As for tomato, the FL lamp had the best effect on the development of seedlings. Due to the high share of far red light, the tested LEDs stimulated the elongated growth of flaccid plants, unsuitable for commercial producers. Our findings not only described the effect of various light spectra on plant development but can also be useful for producers of popular vegetable crops.

Type of Medium: Online Resource

ISSN: 2300-357X

URL: Article

DOI: 10.5586/aa.762

Language: English

Publisher: Polish Botanical Society

Publication Date: 2023

detail.hit.zdb_id: 2586014-8

In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5332-5332

Abstract: Background Preparative regimen consisting of high dose chemotherapy HDC/T and/or cranial irradiation (CI) in combination with prolonged steroid therapy may cause abnormal gonadal function. Objective Evaluate puberty disorders in children occurring after HSCT as single center experience. Material and methods The study group consisting of 21 patients (13 girls and 8 boys) age 10–20 years at grafting (median 14 years) was prospectively evaluated post grafting. The indications for HSCT were: ALL (5), AML (4), CML (5), MDS (2) and NHL, JMML, SAA, Blackfan Diamond anemia, RMS. According to donor availability 11 children had mached sib donors (MSD), 7 matched unrelated donors (MUD) and 3 patients HLA-mismatched related donors. The preparative regimens consisted of HDC/T usually BU/MEL (2pts); BU/CY/VP (5pts); BU/CY/ATG (4pts) and total body irradiation (TBI) received 3 patients with 12 Gy. CI prior to grafting was delivered to 5 children: 18 Gy (4) and 24 Gy (1). Prolonged high doses steroids (beyond day +28) received 7 children prior to- and 10 children after grafting. Endocrine function after allo-HSCT was evaluated from 10 to 42 (median 26 months). Analysis of LH, FSH, PRL, oestradiol and testosterone levels, fT3, fT4, aTPO, TRH test and LHRH test was performed in all study patients. Bone age according to Pyle-Grulich method was estimated. Results: Abnormal gonadal function was present in 12/21 children (9 girls, 3 boys) in average 28 months after HSCT Primary amenorrhea occurred in 3, secondary amenorrhea in 6 girls. Delayed bone age was documented in 2 children in average 30 mths post grafting. No significant correlation was found between children’s age during allo-HSCT and occurrence of puberty disorders. Gender of children had no effect on evalated variables. Time elapsing from HSCT did not influence the occurrence of abnormal gonadal function. No association was found between abnormal gonadal function and TBI, prolonged high doses steroids prior to- and after HSCT. Occurrence of puberty disorders was statistically significantly blunted by conditioning regimen containing Cyclophosphamide (p=0,019) and Busulfan (p=0,0179) while Melfalan did not turn out such a risk factor. PRL levels and thyroid function do not have any determination on occurrence of abnormal gonadal function after HSCT. Conclusion: Abnormal gonadal function as late effect frequently occure after HSCT. High-dose Cyclophoshamide and Busulphan tretaed children often had blunted puberty. Melfalan and TBI, however, did not cause such an effect reported by others. Endocrinological care for patients after HSCT is necessary in order to: - Discover the impaired endocrine function - Initiate correct hormonal substitution therapy - Significantly improve the quality of life after allo- HSCT and - Secondary prevent treatment related complications.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V108.11.5332.5332

Language: English

Publisher: American Society of Hematology

Publication Date: 2006

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 3-4

Abstract: Background: AML is the most common acute leukemia in adults. While most adults & lt; 60 years achieve complete remission (CR) with intensive induction chemotherapy, approximately one third have primary refractory disease and, overall, the majority of AML patients still relapse despite having attained initial remission (Dohner et al, Blood 2017). The combination of an anthracycline and cytarabine has been the mainstay of intensive AML induction for more than 50 years. Combined with cytarabine (AraC), high-dose daunorubicin (90 mg/m2) in induction (DA-90) resulted in a higher rate of CR (70.6% vs. 57.3%, P & lt;0.001) and improved overall survival (OS) (median 23.7 vs. 15.7 months; P = 0.003), without increased serious adverse events compared with DA-45 (Fernandez et al, NEJM, 2009). In two PALG randomized trials, the combination of cladribine with DA (DAC regimen) also resulted in significantly increased CR after a single induction course, compared with the standard two-drug induction (DA-60) (Holowiecki et al, Leukemia, 2004 and JCO 2012). Both regimens have a recommendation from the National Cancer Comprehensive Network (NCCN) for routine use. For patients with primary refractory disease, the commonly used FLAG-IDA (fludarabine, cytarabine, idarubicin, GCSF) regimen results in a CR rate of 52% (Pastore et al, Ann Hem, 2003). Two previous PALG studies confirmed that another standard regimen, CLAG-M (a combination of cladribine, Ara-C, G-CSF and mitoxantrone) is also effective with tolerable toxicity in refractory/relapsed AML patients (Robak et al Leuk Lymph, 2000; Wrzesień-Kuś et al, Eur J Haematol 2003; Wrzesień-Kuś et al, Ann Hematol, 2005; Wierzbowska et al, Eur J Haematol ,2008; Jaglal et al, Leuk Res, 2014). PALG-AML1/2016 aims to compare the safety and efficacy of two commonly used induction and salvage regimens in AML. This trial is also the first international randomized trial in AML induction to prospectively evaluate the impact of measurable residual disease (MRD) on overall survival, using multi-modality testing (flow-cytometry, next-generation sequencing, and PCR) of serial samples. The study is conducted in accordance with the principles of the "Declaration of Helsinki". Study Design and Methods: PALG-AML1/2016 is a multicenter, randomized, Phase III study which will include 582 patients with newly-diagnosed AML treated at multiple centers across Poland and at Weill Cornell Medicine and The New York Presbyterian Hospital in New York City. This will allow a 10% difference in CR rate between the DAC and DA-90 induction regimens to be confirmed with a power of 80% and level of significance 0.05. Eligible patients must be 18 to 60 years of age with untreated AML, Eastern Cooperative Oncology Group performance status 0-2 and HCT-CI Index of comorbidities, ≤ 3. As midostaurin treatment has become approved and available the study was amended with an exclusion of FLT3-mutated patients. The trial schema is shown in Figure 1. The trial was initiated in July 2017 and 279 patients have been enrolled to date and accrual is ongoing. Preliminary safety and efficacy data were reviewed by the data safety monitoring committee after 194 patients and the recommendation was to proceed without changes. Serial samples for MRD are being collected from all patients at multiple time points and analysis is ongoing. ClinicalTrials.gov Identifier: NCT03257241 Figure 1 Disclosures Wierzbowska: Janssen: Honoraria; Celgen/BMS: Honoraria; Novartis: Honoraria; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Research Funding. Pluta:Angelini: Research Funding; Celgene/BMS: Honoraria. Libura:Novartis: Honoraria. Wrobel:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau. Zaucha:Abbvie: Honoraria; Sandoz: Consultancy, Honoraria; Cellgene: Other: travel, accomodations, expenses; Novartis: Consultancy; BMS: Consultancy; Takeda: Consultancy, Honoraria, Other: travel, accomodations, expenses; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses. Robak:AstraZeneca: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; GSK: Research Funding; Bristol Meyers Squibb: Research Funding; Novartis: Honoraria, Research Funding; Morphosys: Research Funding; UCB: Honoraria, Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; UTX-TGR: Research Funding; BioGene: Honoraria, Research Funding; Acerta: Research Funding; Momenta: Consultancy; Pfizer: Research Funding; Sandoz: Consultancy, Honoraria; Octapharma: Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Medical University of Lodz: Current Employment; Takeda: Consultancy. Lee:BMS: Consultancy; Helsinn: Other: Member -DSMB; AstraZeneca: Consultancy; Jazz: Consultancy; Roche Molecular Systems: Consultancy. Ritchie:Novartis: Honoraria; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria, Research Funding; Jazz pharmaceuticals: Honoraria, Research Funding. Guzman:Cellectis: Research Funding; SeqRx: Honoraria. Roboz:Agios: Consultancy; Amphivena: Consultancy; Astex: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Array BioPharma: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Eisai: Consultancy; Jazz: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Actinium: Consultancy; Argenx: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; AstraZeneca: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Takeda: Consultancy; Trovagene: Consultancy; Cellectis: Research Funding; Jasper Therapeutics: Consultancy; Epizyme: Consultancy; Helsinn: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Novartis: Consultancy. OffLabel Disclosure: cladribine - in induction regimen in AML

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-140694

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1715-1715

Abstract: Abstract 1715 Poster Board I-741 Introduction Gene polymorphism coding for drug-metabolizing enzymes may cause individual differences in effectiveness and toxicity of many medications, including cytostatics. Although intensified treatment resulted recently in better prognosis of leukemia, many adverse effects are still observed during therapy resulting from nonspecific activity and narrow therapeutic index of anti-cancer drugs. The objectives of the study: 1. Determining the frequency of selected allele variants: CYP2C9, CYP2C19 in population of Polish children treated for acute leukemia. 2. Analysis of the role of CYP2C9 and CYP2C19 in cyclophosphamide metabolism. 3. Determininig the influence of carrying selected CYP2C9 and C19 polymorphism on cyclophosphamide metabolism in form of increased adverse reaction risk (according to WHO score), relapse and other infringements in treatment protocols and procedures following the use of standard doses of alkylating agents. Patients: 184 patients (106 boys, 78 girls) were examined, age between 1 and 18 (median age 7 years, average age 7.64 years, SD=5.3) treated for acute leukemia (ALL:167, AML:17) at various time points: on diagnosis, during cytostatic treatment and after therapy cessation. All patients were treated with current uniform treatment protocols and procedures. Adverse reactions in each child was recorded according to WHO toxicity scale, during the entire length of observation period and in particular stages (6 periods). Methods Either bone marrow or peripheral blood samples were used for the analyses. DNA isolation procedure was carried out with the use of standard tests. CYP2C9*2,*3 and CYP2C19*2 allelic variant determination was carried out with real-time PCR with double-marked probe hydrolysis with the use of Pre-Developed TaqMan Assay Reagents for Allelic Discrimination sets. PCR products fluorescence was carried out on 7900HT Fast Real-Time PCR device. Results 1. For CYP2C9, IM phenotype was present in 22.3% patients (n=41) and PM phenotype in 7.6% cases (n=14), the most frequently detected polymorphic variant being CYP2C9*2 (75.3%). In case of CYP2C19, IM phenotype occurred in 22.3% patients (n=41) and PM phenotype in 7.1% (n=13). 2. Toxicity risk analysis in patients with acute leukemia did not reveal statistically significant differences depending on CYP2C9 genotype. In patients with CYP2C19*2 allelic variant, statistically lower level of alkaline phosphatase (p=0.013) was observed during the entire treatment and in particular stages (I: p=0.0096; II: p=0.022; III: p=0.038; IV:p=0.0024; V:p=0.044). Lower alkaline phosphatase levels were observed only in patients with ALL (p=0.026). Lower transaminase levels after completion of intensive treatment phase were observed in patients with CYP2C19 mutations (GOT, p=0.044). In patients with CYP2C19 and CYP2C9 polymorphic variants no dependence of risk of adverse reactions with correlation to cyclophosphamide and its dose was observed. 3. In patients with CYP2C9 and CYP2C19 polymorphism no significant relation was discovered. 4. Death risk was not relevant to CYP2C9 or CYP2C19 genotype. Conclusions 1. Occurrence of slow metaboliser phenotype for CYP2C9 and CYP2C19 is more frequent in patients with acute leukemia than in the untreated population. 2. CYP2C9 and CYP2C19 cytochromes are involved in cyclophosphamide metabolism but do not play a major role in drug metabolism. 3. CYP2C9 and CYP2C19 single nucleotide polymorphism is correlated neither with an increased risk of adverse reactions or death during therapy, nor with a relapse of acute leukemia in children. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.1715.1715

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 1761-1761

Abstract: It was investigated whether in children demonstrating high risk of toxicity related to conventional preparative regimens (prep-reg) for allo-HSCT, the prep-reg based on Treosulfan (TREO) (Feit, Rastrup-Andersen, 1970) enables to avoid severe toxic complications without increased incidence of graft failure and/or relapse. From July 2000 to April 2005 the TREO-based prep-reg was used prior to allo-HSCT in 43 children with increased risk of severe Busulfan- and FTBI-based regimens related toxicity (RRT) and/or non-compliance. In 37 patients (pts) allo-HSCT was performed for, usually advanced, hematological malignancy, incl. 19 pts (1–17 yrs, med. 9) transplanted from MSD for ALL (n=8), AML (n=7), LCH (n=2), MDS (n=1) and NHL (n=1), and 18 pts (0.5–17 yrs, med. 9.5) from MUD for AML (n=7), ALL (n=4), CMML (n=3), NHL (n=2) and CML (n=2). Six pts (0.5–12 yrs, med. 6) underwent HSCT for congenital disorder, i.e. 5 from MSD for ALD (n=2), WAS (n=2) and B-DA (n=1), and one from MUD for osteopetrosis. Total of 24 pts were transplanted from MSD and 19 from MUD. TREO (3x10 g/m2, n=22; 3x12 g/m2, n=19; 3x14 g/m2, n=2) was given i.v. in various combination with FLUDA, CY, MEL or VP-16 acc. to diagnosis, risk factors of RRT and/or regimen used for previous HSCT. Prior MUD-HSCT and all pts with congenital disorders received ATG (n=18) or Campath (n=3). RRT was graded acc. to Bearman (1988). In 21 out of 43 pts (incl. all 6 with congenital diseases) no features of RRT occured, I° in 13, II° in 5, and III° in 4 (mucositis). Engraftment was achieved in all pts, except one transplanted from MUD for CML with low dose of CD34 cell (1.7x106/kg). Acute GvHD II–III° occurred in 9/24 pts after MSD-HSCT and in 10/19 after MUD-HSCT, chronic GvHD in 4/24 post MSD-HSCT and 1/19 after MUD-HSCT. Chimerism was evaluated in 22/24 pts after MSD-HSCT and in 18/19 post MUD-HSCT. Respectively, complete donor chimerism was observed in 17/22 and 16/18 pts, mixed in 5/22 and 1/18, and autologous recovery in 1/18 after MUD-HSCT. Non-relapse deaths occurred in 6 out of 37 pts with malignancy, incl. one 40 mo. post MSD-HSCT (pulmonary aspergillosis, cGvHD), and 5 after MUD-HSCT (abdominal aorta thrombosis day+59, LPD day+63, BKV infection day+66; intracranial bleeding day+138). The 1-year non-relapse mortality was 13,5%. Relapse was diagnosed in 8/19 pts post MSD-HSCT (4xAML, 4xALL) and in 1/18 after MUD-HSCT (sAML). Out of 24 pts transplanted from MSD, 15 are alive, i.e. 10/19 with malignant disease in CCR (med. 27, 16–50 mo.) and 5/5 with congenital disorder (med. 21, 6–58 mo.). After MUD-HSCT, 12/18 pts with malignancy are alive in CCR (med. 19, 7–42 mo.) and a child with osteopetrosis (4 mo.). At 3 years from HSCT in 19 pts with malignancy transplanted from MSD the progression-free survival (PFS) was 46% and overall survival (OS) 49%, while in 18 transplanted from MUD 82% and 68%. The PFS and OS estimated for 6 pts with congenital disorders at 4 years after HSCT was 67% and 100%. Conclusions: In children with high risk of conventional regimen related toxicity the prep-reg for allo-HSCT based on TREO given at the dose of 3 x 10–12 g/m2i.v. demonstrates almost exclusively mucosal toxicity, along with sufficient myeloablative and immunosuppressive effects. Its anti-leukemic effect is at least comparable with that one of Busulfan-based regimens.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V106.11.1761.1761

Language: English

Publisher: American Society of Hematology

Publication Date: 2005

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5390-5390

Abstract: The aim of the study was to analyze the correlation between the number of transplanted CD34+ cells and CD3+ cells and the incidence of severe Graft versus Host Disease (GvHD) in children undergoing allogeneic hematopoietic cell transplantation from HLA-matched or mismatched unrelated donors. 115 patients (median age 11.4, range 0.7 – 31.6; ALL n=41, AML n=22, CML n=21, MDS/JMML n=10, NHL/HD n=4, SAA/FA n=13, SCID/WAS n=4) underwent unmanipulated allogeneic BMT (n=34) or PBSCT (n=81) from unrelated donors between 1999 and 2005. There were 88 matched- and 27 mismatched donor-recipient pairs, respectively (acc. to ALL SZT - BFM 2003 protocol). Among 88 matched pairs, 51 were 10 out of 10 HLA-allele matched (High Resolution Class I and II typed), whereas in another 37 cases 9 out of 10 alleles were matched. In the mismatched group there were 22 pairs with a 8 out of 10 allele-match and 5 pairs with 7 out of 10 allele-match, respectively. No single DRB1* mismatch was accepted. A distinct correlation between the degree of HLA-match and the risk of grades III-IV aGvHD was found (p=0.05), which occurred in 11 out of 27 pts in the mismatched group (40.7%) and in 19 out of 88 pts in the matched group (21.6%). No difference between the 2 groups was observed with regard to the incidence of extensive cGvHD. No correlation was found between the number of transplanted CD34+ cells/kg or CD3+ cells/kg and the incidence of aGvHD grades III–IV or extensive cGvHD. Median numbers of transplanted CD34+ cells/kg and CD3+ cells/kg were 7.7 × 106 (10.9 × 106) and 2.6 × 108 (3.3 × 108) respectively in the group of patients with grades III–IV aGvHD (extensive cGvHD) and 9.3 × 106 (8.8 × 106) and 3.4 × 108 (3.1 × 108) respectively in the group without these complications. Pts in the mismatched group were given slightly higher numbers of CD3+ cells/kg (4.9 vs 3.0 × 108 in the matched group) and similar numbers of CD34+ cells/kg (median 8.1 vs 8.9 × 106 in the matched group). Despite a higher incidence of severe aGvHD in the mismatched group, probability of 5-year survival was in contrast slightly better in the mismatched group (pS = 0.59 vs pS = 0.48 in the matched group, p=NS). Seventeen from 27 pts in the mismatched group remain alive (62.9%). Median follow-up of all 63 surviving pts (55%) is 21 months (range 6 – 69). Neither degree of HLA match, nor the source of stem cells (PB vs BM), nor number of transplanted CD34 (less or more than 8 × 106/kg) or CD3 cells/kg had an impact on survival. In conclusion, there seems to be no correlation between the numbers of transplanted CD34+ cells/kg and/or CD3+ cells/kg and the incidence of severe GvHD in the unrelated donor setting in children. It is safe and feasible to perform allogeneic transplants from unrelated mismatched donors, provided a detailed selection of more than 1 HLA-allele-mismatched donors is performed. This conclusion remains in contrast with the ALL SZT-BFM 2003 protocol, which requires extensive T-cell depletion in case of mismatched donor-recipient pairs. High number of transplanted CD34+ cells seems to be a positive factor influencing engraftment and survival in this constellation. There seems to be not necessary to limit the number of transplanted CD34+ cells to 6 or 8 × 106/kg, which had been previously suggested by studies performed in Europe or USA in adults.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V108.11.5390.5390

Language: English

Publisher: American Society of Hematology

Publication Date: 2006

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detail.hit.zdb_id: 80069-7