Selective engraftment of the granulocyte compartment after allogeneic bone marrow transplantation in a patient with severe aplastic anemia.

PURPOSE: We present a patient with severe aplastic anemia who had partial engraftment with full chimerism after allogeneic bone marrow transplantation from an HLA identical sibling. PATIENTS AND METHODS: A 3-year-old girl with severe aplastic anemia (SAA) received a bone marrow transplantation (BMT) from an HLA identical brother 9 months after her diagnosis. Before BMT she was red blood cell tranfusion dependent, had an absolute neutrophil count (ANC) of 1,000-1,500 x 10(9)/1 and a platelet count of 15-19,000 x 10(9)/1. She was conditioned with 800 cGy total body irradiation (TBI) and cyclophosphamide and received 3X10(8) nucleated cells/kg. RESULTS: She reached an ANC of 1500 x 10(9)/1 on day +35 but her reticulocyte and platelet counts did not recover. A bone marrow aspirate and biopsy post BMT showed hypoplasia with marked decrease in megakaryocyte and red blood cell precursors. The granulocyte compartment showed a left shift with predominance of promyelocytes and myelocytes. The karyotype showed full chimerism (46,XY) with no 46,XX metaphases. CONCLUSION: This case illustrates the possibility of a bone marrow microenvironment defect as the cause of SAA.

Discordant clinical presentation and outcome in infant twins sharing a common clonal leukaemia.

We report the different presentation features and clinical outcome between two identical infant twins with acute lymphoblastic leukaemia with a shared clonal disease and MLL gene rearrangement. One twin relapsed and died, but the other is in complete remission > 4 years after diagnosis. These data, and similar observations on other twin infants with leukaemia, suggest that despite a common clonal in utero, post-natally these leukaemias can evolve independently, at different rates, in the twinned individuals, and that the usually fatal leukaemia associated with t(4;11) MLL gene rearrangement can be effectively treated when the leukaemic burden is small.

[Cytogenetic studies of Chilean children with acute lymphoblastic leukemia]. / Estudios citogenéticos en niños chilenos con leucemia linfoblástica aguda.

Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer. The leukemic cells of ALL patients show several well defined numeric and structural chromosomal abnormalities which are universally known for its prognostic implications. We studied a group of 44 children with ALL, to investigate the incidence of chromosome aberrations in ALL, its lymphocyte lineage and some clinical feature associations, and the finding of non previously described aberrations. A high proportion of patients (79.5%) showed chromosomal abnormalities. Most of them had a pseudodiploid karyotype (46 chromosomes), characterized mainly by a translocation. In relation to chromosome number, 27% of them were hyperdiploid with more than 50; 9% hyperdiploid between 47-50 and 7% hypodiploid (less than 46). Among structural aberrations found, were the following recurrent translocations: t (1; 19), t (4; 11), t (9; 22) in 6.8%, 9.1% and 2.3% of cases respectively, all related to an early B immunophenotype. Other translocations found, compromised regions 7q22, 9p21 - 24. Two new translocations in ALL were found: t (1; 5)(q23; q33), apparently balanced, and t (13; 21)(q14; q22), unbalanced. Other recurrent structural changes found were: deletion (6q), (7q), (9p), (11q), (12p), inversion (3q), isochromosome (7q), maker chromosomes and double minutes. The distribution of chromosome abnormalities in this group of patients was in agreement with previous reports from other investigators.

[Chronic myeloid leukemia: cytogenetic and molecular study and its relationship with the disease course]. / Leucemia mieloide crónica: estudio citogenético y molecular y su relación con la evolución de la enfermedad.

The aim of this study was to perform a cytogenetic and molecular study in patients with chronic myelogenous leukemia and to seek a possible relation between bcr gene break points and the clinical evolution of the disease. The cytogenetic study allowed to establish the presence of Ph chromosome and the molecular study localized the break point in bcr region of chromosome 22 using the Southern technique, hybridizing with bcr fragment derived probes bcr1 and bcr2. Forty eight patients were studied, 27 male (aged 46.5 years) and 21 female (aged 56). Forty seven patients were Ph +. A rearrangement in 3' bcr region was found in 25 patients and in 5' region in 23. During the follow up period 20 patients developed a blast crisis or accelerated phase. In 11 of these the rearrangement was in region'3 and their chronic phase lasted a mean of 33.1 months; in 9 the rearrangement was in region 5' and their chronic phase lasted 44.1 months. There were no differences in event-free survival between those with rearrangement in region 3' or 5', however these was a tendency towards a longer chronic phase duration in those with 5' breaks. The lack of correlation between the location of break points and the evolution of the disease may be due to a selection of patients with a better evolution and the exclusion of those with a rapid progression to blast crisis or accelerated phase.

[Cytogenetic studies in myelodysplasias]. / Estudios citogeneticos en mielodisplasias.

Cytogenetic studies were performed in 29 patients with myelodysplasia, 12 males and 17 females with a mean age of 61 years. The distribution of patients according to FAB groups were as follows: refractory anemia (RA) 7, sideroblastic refractory anemia SRA) 6, refractory anemia with excess blasts (RAEB) 12 and refractory anemia with transformation excess blasts (RAEB-t) 4. Cytogenetic anomalies were found in 48% over all, 78% in patients with RAEB and RAEB-t forms and only 23% in patients with simpler forms of myelodysplasia. Multiple and complex chromosomal alterations were found in 50% of abnormal studies, only in patients with complex forms. In general, structural rearrangements and deletions were less frequent than numeric defects, with a slight preponderance of chromosomal losses. Alterations of chromosomes 5, 7, 28, 21, 22, 8, 11 and 15 were the most commonly observed. Survival was decreased from 60 months in patients with normal karyotype to 6 months in those with chromosomal alterations. Thus, chromosomal abnormalities are related to excess blasts and to survival in patients with myelodysplasia.