Cord blood banking and transplantation at the Mexican Institute of Social Security: the first 5 years.

BACKGROUND: In January 2005, the Cord Blood Bank (CBB) at the Mexican Institute of Social Security initiated activities. Herein, we describe the experience generated during this period (January 1, 2005-December 31, 2009). STUDY DESIGN AND METHODS: Good manufacturing practices and standard operating procedures were used to address donor selection, as well as umbilical cord blood (UCB) collection, processing, and cryopreservation. Based mainly on HLA and nucleated cell content, specific UCB units were thawed, processed, and released for transplantation. RESULTS: A total of 589 UCB units were stored, representing 54% of the total number of units collected. Forty-eight units (8.14% of the stored units) were released for transplantation of 36 patients. Twenty-six patients (72% of cases) corresponded to patients with acute leukemia, five (14%) to patients with marrow failure, and the rest (five; 14%) to patients with hemoglobinopathies and other syndromes. The median number of nucleated cells infused per patient was 6.71 × 10(7) /kg and the median number of CD34+ cells was 4.8 × 10(5) /kg. Current engraftment data indicate that engraftment occurred in 56%, and no engraftment in 44%, of cases. Engraftment was more frequent (59%) in patients that received more than 3 × 10(7) total nucleated cells (TNCs)/kg body weight, than in those receiving fewer than 3 × 10(7) TNCs/kg (40%). Myeloid engraftment was observed 7 to 54 days posttransplant (median, 23 days), whereas platelet engraftment was detected on Days 12 to 87 posttransplant (median, 38 days). To date, the disease-free survival rate was 41% and the overall survival was 47%, with survival periods of 126 to 1654 days. CONCLUSION: Although the experience presented herein is still limited and the period of analysis is still short, the results obtained during these 5 years are encouraging.

Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment.

By application of morphological and ultrastructural methods for identification of apoptosis, we analyzed the incidence of morphologically evident apoptosis in the bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone marrow of 12 healthy individuals. According to FAB classification, out of 30 patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia with ringed sideroblasts, 14 (46.6%) had refractory anemia with excess of blasts and two (6.8%) had refractory anemia with excess of blasts in transformation. Three patients (10%) had chronic myelomonocytic leukemia. Cells in apoptosis were examined on semithin slides and expressed as the apoptotic index (AI) (percent counted on at least 1000 cells). An overall increase in apoptosis in patients with MDS was found (median AI in patients vs controls, 3.13% vs 1.05%, P < 0.01 by Mann-Whitney U test). Also, negative correlation between AI and white blood cell count was found (linear r= -0.53, or Spearman rank R= -0.52, both P < 0.01). In patients with evident karyotype changes AI was not higher than in patients with normal karyotype. This suggests that discrete alterations in apoptosis are present even in karyotypically 'normal' clones. Our results strongly support the hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a mechanism responsible for the paradox of hypercellular bone marrow and peripheral blood pancytopenia in MDS.

Assessment and characterization of hemopoietic stem cells.

The adequate production of blood cells is sustained by pluripotent hemopoietic progenitors whose behavior is influenced by a permissive hemopoietic microenvironment. Hemopoietic progenitors have in common the expression of CD34 surface molecules, but are heterogeneous with respect to other properties. It is commonly accepted that primitive progenitors, considered to be candidates for marrow repopulating cells, are HLA-DR-, without expressing lineage-specific determinants. They are usually quiescent with respect to their cell cycle status. In addition to CD34, they may display adhesion molecules on their surface and express receptors for ligands such as c-kit, FLT2/FLK3 and various other cytokines. Some of these are expressed constitutively, while others emerge as the cells progress through their regular maturation program. This process appears to include a gradual reduction of their proliferative capabilities as demonstrated by a progressive loss of the length of their telomeric structures.