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1.
Bone Marrow Transplant ; 52(10): 1406-1415, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28737775

ABSTRACT

Fertility preservation is an urgent challenge in the transplant setting. A panel of transplanters and fertility specialists within the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the International BFM Study Group provides specific guidelines. Patients and families should be informed of possible gender- and age-specific cryopreservation strategies that should be tailored according to the underlying disease, clinical condition and previous exposure to chemotherapy. Semen collection should be routinely offered to all postpubertal boys at the diagnosis of any disease requiring therapy that could potentially impair fertility. Testicular tissue collection might be offered to postpubertal boys; nevertheless, its use has been unsuccessful to date. Oocyte collection after hormonal hyperstimulation should be offered to postpubertal girls facing gonadotoxic therapies that could be delayed for the 2 weeks required for the procedure. Ovarian tissue collection could be offered to pre-/post-pubertal girls. Pregnancies have been reported after postpubertal ovarian tissue reimplantation; however, to date, no pregnancy has been reported after the reimplantation of prepubertal ovarian tissue or in vitro maturation of pre-/post-pubertal ovarian tissue. Possible future advances in reproductive medicine could change this scenario. Health authorities should prioritize fertility preservation projects in pediatric transplantation to improve patient care and quality of life.


Subject(s)
Antineoplastic Agents/adverse effects , Consensus , Cryopreservation/methods , Fertility Preservation/methods , Hematopoietic Stem Cell Transplantation , Ovary , Testis , Adolescent , Allografts , Antineoplastic Agents/therapeutic use , Child , Female , Humans , Male , Practice Guidelines as Topic
2.
Bone Marrow Transplant ; 52(2): 201-208, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27643863

ABSTRACT

Therapy for post-transplant relapse of paediatric ALL is limited. Standardised curative approaches are not available. We hereby describe our local procedure in this life-threatening situation. A total of 101 ALL patients received their first allogeneic stem cell transplantation (SCT) in our institution. After relapse, our primary therapeutic goal was to cure the patient with high-dose chemotherapy or specific immunotherapy (HDCHT/SIT) followed by a second SCT from a haploidentical donor (transplant approach). If this was not feasible, low-dose chemotherapy and donor lymphocyte infusions (LDCHT+DLI) were offered (non-transplant approach). A total of 23 patients suffered a post-transplant relapse. Eight patients received HDCHT/SIT, followed by haploidentical SCT in 7/8. Ten received LDCHT+DLI. The eight patients treated with a second transplant and the ten treated with the non-transplant approach had a 4-year overall survival of 56% and 40%, respectively (P=0.232). Prerequisites for successful treatment of post-transplant relapse by either a second transplant or experimental non-transplant approaches are good clinical condition and the capacity to achieve haematological remission by the induction treatment element.


Subject(s)
Immunotherapy , Lymphocyte Transfusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Stem Cell Transplantation , Tissue Donors , Adolescent , Allografts , Child , Child, Preschool , Female , Germany , Humans , Infant , Male , Recurrence , Retrospective Studies
3.
Early Hum Dev ; 98: 49-55, 2016 07.
Article in English | MEDLINE | ID: mdl-27351353

ABSTRACT

BACKGROUND: Maternal CD4+ cell microchimerism may be greater after caesarean section compared to spontaneous vaginal delivery and could cause mother-to-child transmission (MTCT) in HIV-exposed newborns. AIMS: To evaluate maternal CD4+ cell microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. STUDY DESIGN AND SUBJECTS: In this prospective single-centre study, neonates whose mothers were infected with HIV and had normal MTCT risk according to the German Austrian Guidelines were considered for study enrolment. Maternal CD4+ cell microchimerism in the newborns' umbilical cord blood was measured and compared by mode of delivery. RESULTS: Thirty-seven HIV-infected mothers and their 39 newborns were included in the study. None of the 17 (0.0%) newborns delivered vaginally had quantifiable maternal CD4+ cells (95% confidence interval (CI): 0.00-0.00) in their circulation at birth compared with four of 16 (25.0%) newborns delivered via planned caesarean section, who showed 0.01-0.66% maternal cells (95% CI: -0.06-0.16; P=0.02) in their circulation. The intention to treat analysis, which included six additional newborns delivered by unplanned caesarean section, showed quantifiable maternal CD4+ cells in one (0.05%; 95% CI: -0.02-0.04) of 23 (4.3%) newborn at birth compared to four of 16 (25.0%) born via planned caesarean section (95% CI: -0.06-0.16; P=0.04). There was no MTCT in any of the newborns. CONCLUSION: In this small cohort, spontaneous vaginal delivery in HIV-infected women with normal MTCT risk was associated with lower maternal CD4+ cell transfer to newborns compared to planned caesarean section.


Subject(s)
CD4-Positive T-Lymphocytes/virology , Cesarean Section/adverse effects , HIV Infections/blood , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/blood , Adult , DNA, Viral/genetics , Female , HIV Infections/transmission , Humans , Infant, Newborn , Male , Pregnancy
4.
Exp Clin Endocrinol Diabetes ; 120(8): 441-4, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22576256

ABSTRACT

OBJECTIVE: To examine the impact of rapidly changing environmental factors on the incidence of type 1 diabetes mellitus (T1D). METHOD: We compared the frequency of T1D in children before and after the reunification of Germany by means of the registries of the German Democratic Republic (GDR, 1960-1989) and of Baden-Wuerttemberg (BW, 1987-2006). The number of cases of diabetes onset in East Germany after the reunification was predicted by a mathematical model. The observed incidence rate in the Eastern part of Germany after the reunification was taken from the literature 1. RESULTS: In Germany, the incidence rate of T1D in children aged 0-14 was 7.2/100 000/year (95%-CI 6.9-7.5, GDR, 1980-1987), and 10.4/100 000/year (95%-CI 9.5-11.4, BW, 1987-1994). For the whole observation period (1960-2006), the observed incidence rates y could be described by the square of a linear function [GDR: y=(1.86 + 0.040 * (year - 1960))²; r²=0.85; BW: y=(3.03 + 0.085 * (year - 1987))², r²=0.89]. The mean rise in incidence before the reunification was less than half the mean rise after the reunification (mean slope: BW 0.085, 95%-CI 0.080-0.090 vs. GDR 0.040, 95% CI 0.036-0.044). The observed incidence for East Germany after 1989 was higher than the prediction on the basis of the GDR -registry (GDR 12.3/100 000/year vs. Saxony 15.7/100 000/year, 95%-CI 14.2-17.3, n=412; 1999-2003). CONCLUSION: We conclude that the basis for the disease progress is a genetic predisposition. Environmental factors may modify changes in incidence of type 1 diabetes but do not determine the overall risk.


Subject(s)
Child Development , Diabetes Mellitus, Type 1/epidemiology , Social Change , Adolescent , Child , Child, Preschool , Communism , Democracy , Diabetes Mellitus, Type 1/genetics , Female , Genetic Predisposition to Disease , Germany/epidemiology , Germany, East/epidemiology , Humans , Incidence , Infant , Male , Models, Biological , Registries
5.
Leukemia ; 23(8): 1472-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19322206

ABSTRACT

A standardized, sensitive and universal method for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) is still pending. Although hyperexpression of Wilms' tumor (WT1) gene transcript has been frequently proposed as an MRD marker in AML, wide comparability of the various methods used for evaluating WT1 expression has not been given. We established and standardized a multicenter approach for quantifying WT1 expression by quantitative reverse transcriptase PCR (qRT-PCR), on the basis of a primer/probe set combination at exons 6 and 7. In a series of quality-control rounds, we analyzed 69 childhood AML samples and 47 normal bone marrow (BM) samples from 4 participating centers. Differences in the individual WT1 expressions levels ranged within <0.5 log of the mean in 82% of the cases. In AML samples, the median WT1/1E+04 Abelson (ABL) expression was 3.5E+03 compared with that of 2.3E+01 in healthy BM samples. As 11.5% of childhood AML samples in this cohort harbored WT1 mutations in exon 7, the effect of mutations on WT1 expression has been investigated, showing that mutated cases expressed significantly higher WT1 levels than wild-type cases. Hence, our approach showed high reproducibility and applicability, even in patients with WT1 mutations; therefore, it can be widely used for the quantitation of WT1 expression in future clinical trials.


Subject(s)
Bone Marrow Examination/standards , Genes, Wilms Tumor , Leukemia, Myeloid/pathology , RNA, Messenger/analysis , RNA, Neoplasm/analysis , Reverse Transcriptase Polymerase Chain Reaction/standards , Acute Disease , Adolescent , Adult , Bone Marrow Examination/methods , Child , Child, Preschool , Cohort Studies , DNA Primers , Exons/genetics , Female , Gene Expression Regulation, Leukemic , Humans , Infant , Leukemia, Myeloid/diagnosis , Leukemia, Myeloid/genetics , Male , Middle Aged , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasm, Residual , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Sensitivity and Specificity , WT1 Proteins/biosynthesis , Young Adult
6.
Diabet Med ; 25(6): 755-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18544113

ABSTRACT

AIMS: To assess the incidence and the trend in incidence of Type 1 diabetes (T1DM) in children and adolescents < 15 years of age in Baden-Württemberg (BW), Germany. METHODS: BW is Germany's third largest federal state. All 31 paediatric departments in BW and one diabetes centre participated in the study. Case registration was done according to the EURODIAB criteria. The degree of ascertainment was 97.2%. RESULTS: From 1987 to 2003, the age- and sex-standardized incidence rate was 14.1/100,000 per year [95% confidence interval (CI) 13.7, 14.6, n = 4017]. The estimated annual increase in incidence was 3.8% (95% CI 1.1, 6.6). Compared with the first years of our registry, the current mean number of new cases of T1DM has doubled (1987-1989, n = 153; 2000-2003, n = 302). Generally, the highest rise in incidence occurred in the youngest age group of 0-4-year-old patients (5.8%; 95% CI 2.5, 9.3), followed by the age groups 5-9 (3.4%; 95% CI 0.8, 6.0) and 10-14 (2.7%; 95% CI 0.3, 5.1). CONCLUSIONS: In Germany, the number of children and adolescents with new-onset T1DM has been rising at a faster pace than expected. A distinct shift to younger age at onset has been observed in Germany.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Registries/statistics & numerical data , Adolescent , Age Distribution , Age of Onset , Child , Child, Preschool , Female , Germany/epidemiology , Humans , Incidence , Male
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