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/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.

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.

No abstract

In México, only few patients can afford adequate treatment for aplastic anemia. In a single institution 61 individuals with severe aplastic anemia (SAA) were identified; of these, 33 were followed for at least 3 months, 26 could be treated with immunosuppression (IS), 20 with antithymocyte globulin and cyclosporin A (ATG + CyA) and 6 with CyA, whereas 7 individuals were given only anabolic androgens. In the patients treated with IS a complete remission was achieved in 12 and a partial remission in 6, the overall response rate being 69%. The 5,729-day overall survival (SV) was 54%; it was superior for the patients who received both ATG and CyA (58 vs. 50%). These data contrast with those of the patients who were given only androgens: 14% SV at 5,510 days. Within the group of patients who received IS, one developed acute myelogenous leukemia, another paroxysmal nocturnal hemoglobinuria and another a primary Sjögren’s syndrome-associated low-grade, B cell, non-Hodgkin’s lymphoma. Two individuals who received IS were allografted from HLA-identical siblings and survived 70 and 413 days after the allograft. On the other hand, we also found that, for several reasons, mainly economic ones, only 41% of individuals with SAA finally benefited from the best immunosuppressive therapeutic approach. IS was a good therapeutic choice for some patients with SAA, clearly better than androgen treatment.

Of a group of 149 patients who underwent allogeneic stem cell transplantation using the "Mexican approach", a nonablative preparative regimen, 49 individuals developed bone marrow relapse, and 8 patients developed extramedullary relapse (EMR). All EMR cases presented in patients who received allografts for myeloid malignancies. In contrast, bone marrow relapses presented in patients with myeloid or lymphoid malignancies. EMR presented 60 to 1010 days after the allograft and appeared in 3 cases as subcutaneous nodules in different parts of the body, in the vertebrae in 3 cases, and in the kidney and the breast in 1 case each. One patient had both subcutaneous nodules and epididymis EMR. When EMR was noted, acute graft-versus-host disease (GVHD) had presented in 4 patients, and limited forms of chronic GVHD were present in 3 patients. All but 1 of the patients were full chimeras when the EMR ensued, and the EMR preceded an overt hematologic relapse in all but 1 of the patients. Patients who experienced an overt hematologic relapse died 20 to 180 days (median, 40 days) after the EMR. The only individual alive 240 days after relapse shows no evidence of a full-blown hematologic relapse. An EMR after allogeneic hematopoietic stem cell transplantation usually has a bad prognosis and presents mainly in individuals with high-risk malignancies.

Gilbert's syndrome (GS) is a benign, familial condition characterized by recurrent asymptomatic non-hemolytic low-grade indirect hyper-bilirubinemia. Conditions related to fasting, stress or co-morbidity might reveal the disease in asymptomatic individuals. Seven patients who were treated for a hematological malignancy were identified with reversible indirect hyper-bilirubinemia. Liver function tests in all of them, including bilirubin levels were normal before the therapeutic maneuver, which was the delivery of combined chemotherapy in three cases and a bone marrow transplantation in four (three allografts and one autograft). Bilirubin levels returned to normal in all five patients following treatment. GS should not be overlooked in individuals exposed to these treatments who develop hyperbilirubinemia and jaundice.