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17α­hydroxylase/17,20­lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to high production of adrenocorticotropic hormone (ACTH). Although affected patients have absolute cortisol deficiency, they do not show clinical signs of cortisol deficiency or hyperpigmentation. These patients most commonly present with delayed puberty and amenorrhea at late pubertal age. Impaired production of sex steroids leads to ambiguous or female external genitalia in affected 46, XY individuals. In this report, we describe a patient with 17OHD who presented with hyperpigmentation and hypergonodotropic hypogonadism while receiving chemotherapy.

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We examined SCC development of 24 FA patients, who received HSCT from HLA-matched relatives. In our BMT center, we applied low-dose CY + LFI + ATG (n:13) as conditioning regimen for FA patients between 1992 and 1999, and CY + BU + ATG (n:11) between 1999 and 2002. The aim of this study was to investigate SCC development after HSCT and examine features of the follow-up patients. The 10-year overall survival (OS) of the group with LFI + regimen was 43%, whereas the group without LFI regimen was 60%. There was a statistically significant relationship between infections (viral/bacterial) and overall survival (Fisher's Exact test P < .001). Five out of 13 long-term (>1 year) surviving patients developed SCC in the HNSCC (n:4) and esophagus (n:2) region (a patient with oral SCC developed a second primary esophageal SCC). The SCC rate in our FA patients was 38%, four of the SCC patients were transplanted with irradiation used conditioning regimens, three of them had acuteGvHD (Grade II-III), only one developed chronic GvHD. The interval between HSCT and SCC diagnosis was median 13 (range 6-18) years, the age for the development of cancer was median 21 (range 15-32) years. Survival after SCC was low, median 6 months (range 6-12), due to delayed SCC diagnosis, tumor progression under therapy and treatment-related toxicities of the usually reduced RT and/or CT.

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Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive lethal condition characterized by fever, cytopenia, hepatosplenomegaly and hemophagocytosis. The hallmark of FHL is defect apoptosis triggering and lymphocyte cellular cytotoxicity. Thus far three disease-causing genes (PRF1, UNC13D, STX11) have been identified. We performed a genotype-phenotype study in a large, multi-ethnic cohort of 76 FHL patients originating from 65 unrelated families. Biallelic mutations in PRF1, UNC13D and STX11 were demonstrated in 13/74 (18%), 6/61 (10%) and 14/70 (20%) patients, respectively. In 27/60 (45%) patients analyzed for all three genes, no molecular diagnosis was established. STX11 mutations were most common in Turkish families (7/28, 25%), whereas in Middle East families, PRF1 mutations were most frequent (6/13, 46%). No biallelic mutation was identified in most families of Nordic origin (13/14, 93%). Patients carrying PRF1 mutations had higher risk of early onset (age <6 months) compared to patients carrying STX11 mutations [adjusted odds ratio 8.23 (95% confidence interval [CI] = 1.20-56.40), P = 0.032]. Moreover, patients without identified mutations had increased risk of pathological cerebrospinal fluid (CSF) at diagnosis compared to patients with STX11 mutations [adjusted odds ratio 26.37 (CI = 1.90-366.82), P = 0.015]. These results indicate that the disease-causing mutations in FHL have different phenotypes with regard to ethnic origin, age at onset, and pathological CSF at diagnosis.

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Trichosporon spp. are emerging as opportunistic agents that cause systemic diseases in immunocompromised hosts. Trichosporonosis carries a poor prognosis in neutropenic patients. Trichosporon japonicum was isolated from the air and named by Sugita et al. Here we present the first case of T. japonicum isolated from a clinical specimen. Two cases of acute myeloid leukemia who had Trichosporon isolates are discussed because of their rarity and growing importance. T. asahii was isolated from the throat, feces and urine of the first patient. T. japonicum was isolated from the sputum of the second patient. Both cases produced high MICs to itraconazole, and low MICs to fluconazole and voriconazole. In virulance factor investigations there was (++) biofilm formation in T. japonicum but not in T. asahii. Conventional mycological studies were not adequate for the identification of the isolate at the species level. In our second case as in the first one, the isolate was identified as T. asahii with 99.9% accuracy by API 20C AUX. Although two T. asahii isolates from the same patient yielded identical typing profiles by arbitrary primed-PCR, the isolates of the two different patients showed different arbitrary primed-PCR typing profiles. However, the genetic identification of the other patient's strain gave the result of T. japonicum.

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Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n=16), osteopetrosis (n=2), MDS (n=1), amegakaryocytic thrombocytopenia (n=1), and aplastic anemia (n=1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 x 10(6) G-CSF-mobilized peripheral CD34(+) progenitor cells and a median of 4.19 x 10(4) T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B- SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation.

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Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder of immune regulation. Mutations in the gene encoding perforin were previously identified in a subset of FHL patients. The present analysis of two novel candidate genes, granzyme B and granulysin, by direct sequencing in a total of 16 FHL families, disclosed several sequence variations. However, none of these sequence variations were associated with the manifestations of FHL. These data do not support the notion that granulysin and granzyme B are candidate genes for FHL.

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We report a positive association between HLA-DRB1*15 (p= 0.0002) in Turkish patients with pediatric severe aplastic anemia (SAA) and a paradoxically favorable influence of the susceptibility marker on the clinical response to immunosuppressive therapy. These findings point to an immune mechanism mediated by DRB1*15 in SAA which confers responsiveness to treatment.

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Previous studies reported significant HLA-DR associations with various leukemias one of which is with HLA-DRB4 (DR53) family in male patients with childhood ALL. We have HLA-DR-typed 212 high-risk or relapsed patients with childhood (n=114) and adult (n=98) ALL and a total of 250 healthy controls (118 children, 132 adult) by PCR-SSP analysis. The members of the HLA-DRB3 (DR52) family were underrepresented in patients most significantly for HLA-DRB1*12 (P=0.0007) and HLA-DRB1*13 (P=0.0001). In childhood ALL, the protective effect of DRB3 was evident in homozygous form (P=0.001). The DRB4 marker frequency was increased in males with childhood ALL (67.4%) compared to age- and sex-matched controls (42.1%, P=0.003) and female patients (35.7%, P=0.004). Besides being a general marker for increased susceptibility to childhood ALL in males, HLA-DRB4 is over-represented in high-risk patients. These results further suggest that the HLA system is one of the components of genetic susceptibility to leukemia but mainly in childhood and in boys only.

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