Jaime García-Chávez

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a single center experience.

BACKGROUND Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.

Role of CD4+CD25+highFoxp3+CD62L+ regulatory T cells and invariant NKT cells in human allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for some hematological diseases; however, graft-versus-host disease (GVHD) is still one of the most important and deleterious complications. Regulatory T cells and iNKT cells can decrease the incidence and severity of GVHD, while preserving the graft-versus-tumor response. In order to analyze the relationship between the transfused dose of these cells, the presence of GVHD and survival, 15 normal donors and 15 patients with hematological diseases who underwent allogeneic HSCT from HLA-identical siblings were studied. The mobilization and infused doses of valpha24-vbeta11(iNKT cells) lymphocytes and CD4+CD25+FoxP3+, CD4+CD25+FoxP3+CD62L+, regulatory T cells were analyzed. All patients were conditioned with busulfan and cyclophosphamide and received cyclosporine and methotrexate as GVHD prophylaxis. iNKT and FoxP3 cells were mobilized after G-CSF administration. Acute GVHD was present in 9 of 15 (60%) and cGVHD in 7 of 13 (54%) patients. Patients who received a dose <0.6 x 10(6)/kg of iNKT cells and >4 x 10(6)/kg of FoxP3 had better disease-free survival and overall survival. Individuals transfused with >1.1 x 10(6)/kg of FoxP3+ CD62L+ Treg cells had better overall survival. In conclusion, iNKT and Treg cells are mobilized with G-CSF in healthy donors and the dose of iNKT cells and FoxP3 and CD62L+ regulatory T cells is of clinical importance in human HSCT.

The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene Is Associated with Idiopathic Ischemic Stroke in the Young Mexican-Mestizo Population

Background and Purpose: Previous studies have demonstrated that a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk for stroke. However, this relation remains controversial. Our aim was to investigate the possible association between the C677T polymorphism in the MTHFR gene and idiopathic ischemic stroke in the young Mexican-Mestizo population. Methods: One hundred seventy-eight patients <45 years with idiopathic ischemic stroke and 183 controls were tested for the C677T polymorphism in the MTHFR gene. Causes of primary thrombophilia as well as classical risk factors for atherothrombotic disease were also evaluated. Results: There was a significant difference in the genotype distribution between patients and controls (p = 0.01), but the allele frequency was similar in both groups (p = 0.09). The univariate analysis identified the T allele as a risk factor for ischemic stroke (TT and CT carriers), as compared with homozygous for C allele (p = 0.01). Hypertension and smoking prevalences were significantly higher in the group of patients. Also the T allele was significantly associated with large-vessel ischemic stroke. The postoral methionine load homocysteine levels were higher in patients with ischemic stroke versus controls (p < 0.001). There was a low prevalence of primary thrombophilia markers. Conclusions: The T allele from the C677T polymorphism of the MTHFR gene represents an independent risk factor for idiopathic ischemic stroke at young age in the Mexican-Mestizo population. Also, hypertension and smoking were independent risk factors in our study population. Primary thrombophilic risk factors were not associated with ischemic stroke in our population.

Activated protein C resistance and factor V Leiden in Mexico.

A common cause of hereditary thrombophilia is activated protein C resistance (APCR), and most cases result from factor V Leiden mutation. An APCR phenotype without association with factor V Leiden has been described. This transversal, observational, nonrandomized study evaluated these 2 phenomena in healthy indigenous and mestizo Mexican subjects (n = 4345), including 600 Mexican natives. No indigenous subjects had APCR, but 82 mestizo subjects did. After retesting, 50 subjects had a negative test. The remaining 32 subjects had factor V Leiden, giving a 0.85% prevalence of factor V Leiden in the mestizo Mexican population. Only 31% of APCR carriers had factor V Leiden. These results show a very low prevalence of APCR and factor V Leiden in Mexico. Except for factor V Leiden, there are no other mutations in the factor V gene responsible for the APCR phenotype. Acquired APCR is nearly twice as prevalent as the inherited variant.

von Willebrand's disease in Mexico: a pilot study

von Willebrands disease (VWD) is the most commonly inherited bleeding disorder. For a long time, it has been said that VWD was absent in some countries due to ethnical differences. Information about the prevalence of VWD in Mexico remains unclear, owing largely to poor awareness and diagnosis of the disease. The aim of this study was to objectively diagnose VWD in a cohort of highly selected Mexican patients with a chronic history of bleeding. Mexican Mestizos were recruited between July 2010 and August 2011. Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty‐three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for female patients was 19.5 years (range 3–44 years) and 18.5 years (range 4–63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1–61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty‐six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and plasma concentrates.

Awareness regarding venous thromboembolism among internal medicine practitioners in Mexico: a national cross-sectional study.

Venous thromboembolism (VTE) affects millions of patients worldwide and is responsible for thousands of hospitalisations annually.

IFN-α as Induction and Maintenance Treatment of Patients Newly Diagnosed with Waldenström's Macroglobulinemia

Waldenstroms macroglobulinemia is a rare malignant disorder of B lymphocytes. There are no studies on the use of interferon-α (IFN-α) as frontline therapy in this disease. Between April 1991 and September 2000, we treated 21 newly diagnosed patients using 8 mg/m2 chlorambucil and 40 mg/m2 prednisone p.o. daily for 10 days and 3 megaU/m2 IFN-α three times a week. Patients who responded after induction continued receiving IFN until relapse or death. We found a high frequency of peripheral neuropathy (43%) and grade 3 diffuse marrow fibrosis (43%). Objective response was achieved in 12 (57%) patients, including 4 (19%) complete responders. Median time from treatment to response was 8 months (range 3-18). Median progression-free survival was 70 months (95% CI 47-93), and overall survival was 91 months (95% CI 50-132). Patients who achieved objective response lived longer (91 vs. 33 months, p < 0.03), as did patients who had lactic dehydrogenase (LDH) < 180 U/L (89 vs. 54 months, p < 0.01). Grade 3 hematologi...