1/67. Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family.Four Fanconi anaemia group A (FAA) patients within two related consanguineous families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns). Assignment of the patients to FAA was based on the functional complementation analysis by somatic cell hybridization and confirmed by mutation screening showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gene to be present in all four patients. The newborn patients had been diagnosed prenatally by dna analysis. In spite of identical molecular pathology and close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcephaly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical molecular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic value for the haematological course of the disease.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
2/67. Delayed engraftment and mixed chimerism after HLA-identical sibling donor BMT in Fanconi anaemia.A 12-year-old girl with Fanconi anaemia (FA) received a bone marrow transplant from her HLA-identical brother following conditioning with cyclophosphamide (20 mg/kg), thoraco-abdominal radiation (TAI) (4 Gy) and equine anti-thymocyte globulin (ATG) (90 mg/kg). Engraftment was delayed and initially tenuous, and was followed by mixed chimerism (MC) over a follow-up period of 2 years. dna analysis of engraftment was performed on whole peripheral blood and on separated granulocytes, B and T lymphocytes using PCR detection of CA tandem repeat polymorphisms. At 10 weeks post BMT, granulocytes were predominantly donor, but B and T lymphocytes recipient, in origin. Over the subsequent 90 weeks, granulocytes and B lymphocytes were donor-derived, whilst T cells showed persistent MC but with an increasing donor component. Marrow haemopoietic function (Hb, ANC and platelet count) improved gradually in parallel with a rise in the proportion of donor lymphocyte engraftment. We postulate that a population of recipient lymphocytes survived conditioning and in turn delayed the development of full donor chimerism. Although transient MC has been described after allogeneic BMT in FA, its association with delayed engraftment, and persistence for more than 1 year post BMT, has not been documented clearly.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
3/67. Failure of allogeneic bone marrow transplantation to correct diamond-Blackfan anaemia despite haemopoietic stem cell engraftment.We report the case of a 10-year-old boy with congenital pure red cell aplasia (diamond-Blackfan anaemia) who received an allogeneic bone marrow transplant (BMT) from his HLA-identical sister. The transplant was complicated by moderate veno-occlusive disease (VOD). Despite cytogenetic evidence of complete donor haemopoietic stem cell engraftment there was selective failure of red cell engraftment and he remains red cell transfusion-dependent. This is the first case of a stem cell transplant failing to correct the defect in this condition despite engraftment.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
4/67. pregnancy in bone marrow failure syndromes: diamond-Blackfan anaemia and Shwachman-diamond syndrome.pregnancy in bone marrow failure syndromes has risk to mother and fetus. There are fewer than 30 reports of cases with diamond-Blackfan anaemia (DBA), and none with Shwachman-diamond syndrome (SD). We report two DBA and one SD cases. One DBA mother received transfusions intra-partum, and the other only post-partum. Both required caesarean sections (C-sections) for failure of labour to progress and severe pre-eclampsia respectively. Both subsequently resumed pre-pregnancy steroid-induced control of anaemia. approximately 40% of DBA pregnancies required maternal transfusions; 25% delivered by C-section. The SD patient also had Ehlers-Danlos (ED) syndrome and urticaria pigmentosa (UP). Her blood counts were adequate until week 38, when the platelet count dropped and a C-section was performed. pregnancy management in marrow failure disorders requires obstetricians with expertise in high-risk pregnancies, and haematologists with experience with marrow failure syndromes.- - - - - - - - - - ranking = 1.2keywords = anaemia (Clic here for more details about this article) |
5/67. Congenital hypoplastic anaemia in a patient with a new multiple congenital anomalies-mental retardation syndrome.We report on a girl with congenital hypoplastic anaemia, "coarse" face, generalized hypertrichosis with scalp hypotrichosis, short fifth finger, hypoplastic toenails, and mental retardation. A sister of the proposita, who died at the age of 1 year, had severe congenital anaemia, hypoplastic fingernails, low birth weight, failure to thrive, and repeated upper respiratory tract infections. Based on family history, we suspect that hypoplastic anaemia and the same multiple congenital anomalies-mental retardation syndrome (MCA/MR) were also present in this sister. To the best of our knowledge, this patient represents the first report of congenital hypoplastic anaemia and such a complex MCA/MR syndrome, probably inherited as an autosomal recessive trait.- - - - - - - - - - ranking = 1.6keywords = anaemia (Clic here for more details about this article) |
6/67. A microdeletion in 19q13.2 associated with mental retardation, skeletal malformations, and diamond-Blackfan anaemia suggests a novel contiguous gene syndrome.diamond-Blackfan anaemia (DBA) is a constitutional red blood cell hypoplasia which may be associated with a variety of developmental abnormalities. A gene for DBA was recently mapped to chromosome 19q13.2 and subsequently cloned. Analysis of 19q marker alleles in dna of sporadic DBA cases showed de novo microdeletions in three patients also presenting with mental retardation. We have studied one of these patients and characterised the deletion by fluorescence in situ hybridisation (FISH) to extended dna fibres. The deletion was shown to be continuous over a 3.2 Mb region and the fibre-FISH analysis showed both chromosomal breakpoints. In combination, the clinical and molecular findings suggest a contiguous gene syndrome with a gene locus for mental retardation and, probably, skeletal malformations included in the deletion.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
7/67. growth hormone deficiency in one of two siblings with Fanconi's anaemia complementation group FA-D.Fanconi's anaemia (FA) shows great variability in phenotypic symptoms. We report on two FA siblings of German ancestry with the very rare form of the complementation group FA-D. Both presented with a similar phenotype and mild disease severity but with different growth. In the sister, growth velocity was normal, puberty and menarche occurred spontaneously. Her final height was within her parental target height. The younger brother had a reduced growth velocity, height SDS values below -5.5 SDS, a markedly retarded bone age, and delayed puberty. At the age of 12.9 years, growth hormone deficiency (GHD) was diagnosed and treatment with growth hormone was initiated. Our cases emphasize the heterogeneity of symptoms in FA even in siblings with the same genotype. In FA-children with severe growth retardation, GHD must also be considered.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
8/67. Follow-up by cytogenetic and fluorescence in situ hybridization analysis of allogeneic bone marrow transplantation in two children with Fanconi's anaemia in transformation.Results of bone marrow transplantation (BMT) in patients with Fanconi's anaemia (FA) in transformation are very poor and only a few cases with favourable outcome have been reported. We present the follow-up of two FA-myelodysplastic syndrome (MDS) patients with monosomy 7 and complex karyotype implicating chromosome 1. Both relapsed with acute myeloid leukaemia (AML) following an allogeneic BMT from an HLA-identical brother. The patients showed clonal cytogenetic evolution coinciding with the leukaemic transformation. In one patient, fluorescence in situ hybridization using X and y chromosome probes detected an increase of host cells before clinical relapse. Both patients received a successful second allogeneic BMT from the same donor using a more intensive treatment regimen and remain in clinical and cytogenetic remission more than 3 years later.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
9/67. stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts.We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34( ) E-rosette(-) (CD34( )E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34( )E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.- - - - - - - - - - ranking = 1.4keywords = anaemia (Clic here for more details about this article) |
10/67. Fludarabine-based stem cell transplantation protocol for Fanconi's anaemia in myelodysplastic transformation.Allogeneic stem cell transplantation (SCT) represents the treatment of choice for severe bone marrow (BM) failure in patients with Fanconi's anaemia (FA). However, for FA patients developing leukaemic or myelodysplastic transformation, the results of SCT are much less encouraging. We present a 17-year-old girl with myelodysplastic transformation of FA (refractory anaemia with excess blasts) and oculocutaneous albinism, who was treated by sibling SCT using conditioning with fludarabine, cyclophosphamide (CY) and anti-lymphocyte globulin (ALG). She had rapid engraftment with no toxicity and no graft-versus-host disease (GVHD). Twenty-two months after SCT, she had 100% donor chimaerism on Southern blot analysis.- - - - - - - - - - ranking = 1.2keywords = anaemia (Clic here for more details about this article) |
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