Over a 36-month period, 46 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were prospectively assessed by searching for the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 CfiT mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3¢-untranslated region of the prothrombin gene. Of the 46 consecutive patients prospectively accrued in the study, only 12 (26%) were males, the median age being 38 years (range 10-63 years). In only four individuals (8%) could we not record any abnormality. In 5/42 patients with abnormal results (12%), a single abnormality was recorded, whereas in the remaining 37, two to five co-existing abnormalities were identified. We found 22 (48%) patients with the SPS, 11 (24%) with the aPCR phenotype, 5 (11%) with the factor V Leiden mutation, 7 (15%) with the prothrombin gene mutation, 29 (63%) with the MTHFR gene mutation, 11 (24%) with the factor V HR2 haplotype, 11 (24%) with antiphospholipid antibodies, 4 (9%) with PS deficiency, 6 (13%) with PC deficiency, one with the FV Hong Kong mutation, and one with AT-III deficiency. The results are consonant with the idea that most cases of thrombophilia in Mexico are multifactorial. Am.

Acute promyelocytic leukemia is characterized the PML/RARalpha chimeric fusion gene, transcript and protein; the breakpoint cluster regions (bcr) in the PML gene may occur in 3 different sites: Intron 6 (bcr1), exon 6 (bcr2) or intron 3 (bcr3). In a 10-year period in a single institution, we studied prospectively the breakpoint cluster regions of the PML/RARalpha fusion gene in 43 Mexican Mestizo patients with APL, and found that the bcr1 represented 62.7%, the bcr2 9.3% whereas the bcr3 27.9%. The prevalence of the bcr1 subtype is significantly higher than that informed in Caucasians and similar to that in Asians; these data are consonant with those described in other Latin-American patients with APL. Since other Asian genetic markers have been found in the Indian component of the Mexican mestizos, it is possible that the Asian immigration into the Americas through the strait of Behring 12,000 years ago may account for a possible genetic susceptibility to suffer certain forms of APL.

We studied the effectiveness of a fludarabine/cyclophosphamide-based conditioning regimen without anti-thymocyte globulin in 23 aplastic anemia patients who had no response to previous conventional pharmacologic treatment. Patients received oral busulphan 4 mg/ kg/day/2 days, IV cyclophosphamide 350 mg/m 2 /day/3 days, and fludarabine 30 mg/m 2 /day/ 3 days. For GVHD prophylaxis, patients received MTX 5 mg/m 2 days +1, +3, +6, and +11 and oral cyclosporin A (CyA) 5 mg/kg/day, starting on day -1. Peripheral blood stem cell products were used with a median dose of 5.5 · 10 6 CD34 + /kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 · 10 9 /L was reached; and by day +12, the platelet count had reached >20,000 · 10 9 /L. Acute grade I-II GVHD occurred in 4 patients, whereas limited chronic GVHD presented in 6 cases. Twenty-one patients (91.3%) achieved engraftment. Two patients failed to engraft, and 4 developed late rejection; 2 of these individuals died, 2 have survived with high transfusion requirements, whereas 2 received a second peripheral blood stem cell infusion and achieved sustained engraftment. Currently 21 (91%) of the 23 patients are alive, whereas 19 of 21 (90%) remain in complete remission. The average cost was about USD 15,000 for this kind of reducedintensity allotransplant. Reduced-intensity stem cell transplantation represents an affordable alternative to traditional more cytotoxic conditioning for severe aplastic anemia (SAA) patients. Long-term effects however, remain to be evaluated. Am.

We studied the effectiveness of a fludarabine/cyclophosphamide‐based conditioning regimen without anti‐thymocyte globulin in 23 aplastic anemia patients who had no response to previous conventional pharmacologic treatment. Patients received oral busulphan 4 mg/kg/day/2 days, IV cyclophosphamide 350 mg/m2/day/3 days, and fludarabine 30 mg/m2/day/3 days. For GVHD prophylaxis, patients received MTX 5 mg/m2 days +1, +3, +6, and +11 and oral cyclosporin A (CyA) 5 mg/kg/day, starting on day −1. Peripheral blood stem cell products were used with a median dose of 5.5 × 106 CD34+/kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 × 109/L was reached; and by day +12, the platelet count had reached >20,000 × 109/L. Acute grade I–II GVHD occurred in 4 patients, whereas limited chronic GVHD presented in 6 cases. Twenty‐one patients (91.3%) achieved engraftment. Two patients failed to engraft, and 4 developed late rejection; 2 of these individuals died, 2 have survived with high transfusion requirements, whereas 2 received a second peripheral blood stem cell infusion and achieved sustained engraftment. Currently 21 (91%) of the 23 patients are alive, whereas 19 of 21 (90%) remain in complete remission. The average cost was about USD 15,000 for this kind of reduced‐intensity allotransplant. Reduced‐intensity stem cell transplantation represents an affordable alternative to traditional more cytotoxic conditioning for severe aplastic anemia (SAA) patients. Long‐term effects however, remain to be evaluated. Am. J. Hematol. 81:157–161, 2006. © 2006 Wiley‐Liss, Inc.

No abstract