1/12. 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 = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
2/12. 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 = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
3/12. 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 = 2.1559287314083keywords = myelodysplastic (Clic here for more details about this article) |
4/12. Effective graft-versus-leukaemia effect after allogeneic stem cell transplantation using reduced-intensity preparative regimens in Fanconi anaemia patients with myelodysplastic syndrome or acute myeloid leukaemia.Allogeneic transplantation is the only curative treatment for Fanconi anaemia (FA) patients who develop myeloid malignancies. Dose-intensive preparative regimens, to decrease disease recurrence, lead to unacceptable transplant-related toxicity in FA. We report the outcome of three FA patients with such malignancies who underwent transplantation with reduced-intensity preparative regimens. This approach was well tolerated, even as second transplantations, and resulted in complete leukaemic remissions. However, the graft-versus-leukaemia effect was associated with fatal graft-versus-host disease. Even after transplantation, myeloid malignancies remain associated with a poor outcome in FA, and this argues in favour of early intervention when suitable donors are available.- - - - - - - - - - ranking = 4keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
5/12. delayed diagnosis and complications of Fanconi anaemia at advanced age--a paradigm.Fanconi anaemia (FA) is a rare recessive dna repair disorder clinically characterised by congenital malformations, progressive bone marrow failure and a high propensity for developing malignancies at an early age, predominantly acute myeloid leukaemia (AML) and squamous cell carcinoma. It is conceivable that a number of patients with hypomorphic mutations are not diagnosed as FA until severe complications in the treatment of a malignancy occur. Here, we report on a patient with FA-A, diagnosed only at the age of 49 years due to persistent pancytopenia and myelodysplastic syndrome/AML induced by a first cycle of chemotherapy for bilateral metachronic breast cancer. This exceptional case clearly demonstrates that, in instances of long-lasting mild pancytopenia or development of malignancies, especially at an unusually young age, FA should be ruled out, irrespective of the patient's age and features, especially before inflicting severe genotoxic stress.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
6/12. Myelodysplastic syndrome with trisomy 8 in an adolescent with Fanconi anaemia and selective iga deficiency.We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY, 8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective iga deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
7/12. Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.Two sisters in whom a diagnosis of Fanconi's anemia was made at ages 12 and 18 subsequently developed acute nonlymphocytic leukemia (ANLL). A third sibling had previously died at age 11 of apparent sepsis. Both sisters had cytogenetic studies that showed increased chromosomal breakage and a 46,XX karyotype, but subsequently developed ANLL after, or coincident with, the emergence of monosomy 7. These observations suggest that, in addition to myelodysplastic syndromes and defective neutrophil chemotaxis, monosomy 7 may be associated with the emergence of leukemia in this disorder.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
8/12. Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following fanconi anemia.We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB) which developed following fanconi anemia. The patient received BMT from an HLA-identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment was successful. The patient has maintained normal trilineage hematopoiesis with > 90% Karnofsky score for 30 months with disappearance of a clonal chromosomal abnormality (47,XY, i(lq)) which was detected before BMT.- - - - - - - - - - ranking = 2.4372858209389keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
9/12. fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.We have identified a new recurrent reciprocal translocation between chromosome 3 and 12 with breakpoints at bands 3q26 and 12p13, t(3;12)(q26;p13) in the malignant cells from five patients with acute transformation of myelodysplastic syndrome or blast crisis of chronic myelogenous leukemia. t(3;12)(q26;p13) appears as a rare but nonrandom event present in various myeloid leukemia subtypes, which is frequently associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and a very poor prognosis. Here, we report the molecular cytogenetic analysis of the t(3;12). fluorescence in situ hybridization results indicate that the 3q26 breakpoints are quite heterogeneous and occur 5' of MDS1, 3' of EVI1, or between MDS1 and EVI1. Our results are very similar to those observed in other 3q26 rearrangements in which breakpoints were shown to occur over considerable distances 5' and 3' of EVI1. fluorescence in situ hybridization investigations proved that, in three myelodysplastic syndrome cases with t(3;12)(q26;p13), the 12p 13 breakpoint occurred within the TEL gene.- - - - - - - - - - ranking = 6keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
10/12. Intermediate-dose busulfan and cyclophosphamide as a conditioning regimen for bone marrow transplantation in a case of fanconi anemia in myelodysplastic transformation.We report an 11-year old female with myelodysplastic (refractory anemia with excess of blasts) presentation of fanconi anemia. After failure of initial chemotherapy with low doses of 6-mercaptopurine and prednisolone she underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched sibling. busulfan 8 mg/kg and cyclophosphamide 40 mg/kg were used as conditioning. The post-transplant course was uneventful with fast trilineage engraftment and mild cutaneous acute GVHD. She is alive 17 months after BMT with full hematological reconstitution without evidence of MDS.- - - - - - - - - - ranking = 1.7966072761736keywords = myelodysplastic (Clic here for more details about this article) |
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