Allografting in patients with severe, refractory aplastic anemia using peripheral blood stem cells and a fludarabine-based conditioning regimen: the Mexican experience.

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 x 10(6) CD34(+)/kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 x 10(9)/L was reached; and by day +12, the platelet count had reached >20,000 x 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 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.

Primary thrombophilia in Mexico. V. A comprehensive prospective study indicates that most cases are multifactorial.

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 C-->T 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.

[Monoclonal gammopathy of undetermined significance (MGUS) in Mexican mestizos: one institution's experience]. / Gamapatía monoclonal de significado indeterminado (GMSI) en mestizos mexicanos. Experiencia de una sola institución.

Monoclonal gammopathy of undetermined significance (MGUS) is defined as presence of serum monoclonal protein at a concentration of 3 g per deciliter or less, no monoclonal protein or only moderate amounts of monoclonal light chains in urine, absence of lytic bone lesions, anemia, hypercalemia, and renal insufficiency related with monoclonal protein, and with a proportion of plasma cells in bone marrow of 10% or less. In Caucasian population, MGUS affects about 3% of individuals > 70 years of age, whereas in Mexican mestizos this figure is substantially lower (0.7%); on the other hand, MGUS represents in Mexico only 2.4% of all monoclonal gammopathies. In a total of 9081 individuals studied prospectively at the Centro de Hematología y Medicina Interna de Puebla throughout a 20-year period, 11 patients with MGUS were identified. Median age was 70 years (range 43-83 years). Patients have been followed in periods ranging from 6 to 3270 days (median, 308 days). Two patients evolved into overt multiple myeloma at 308 and 1687 days after diagnosis of MGUS. Overall median survival (SV) of the group has not been reached, whereas 3270 days overall SV is 91%. After discussing underreporting, biasing, and other confounding factors, it would seem that MGUS, like other monoclonal gammopathies, is less frequent in Mexican mestizos than in Caucasians. Routine screening studies to identify the condition should result in increased numbers of patients.

Gamapatía monoclonal de significado indeterminado (GMSI) en mestizos mexicanos: Experiencia de una sola institución / Monoclonal Gammopathy of Undetermined Significance (MGUS) in Mexican Mestizos: One Institution's Experience

La gamapatía monoclonal de significado indeterminado (GMSI) se define como la presencia de una proteína sérica monoclonal a una concentración de 3 g por decilitro o menor; sin proteína monoclonal en la orina o solamente cantidades moderadas de cadenas ligeras monoclonales, sin lesiones líticas óseas, anemia, hipercalcemia, ni insuficiencia renal relacionada a la pro teína monoclonal y con una proporción de células plasmáticas en la médula ósea de 10% o menor. En poblaciones caucásicas, la GMSI afecta a 3% de la población mayor a 70 años, en tanto que en mestizos mexicanos esta proporción es considerablemente menor (0.7%); por otro lado, de todas las para proteinemias monoclonales en México, la GMSI representa sólo 2.4%. En un total de 9081 pacientes estudiados en el Centro de Hematología y Medicina Interna de Puebla en un período de 20 años, se identificaron 11 pacientes con GMSI. La mediana de edad es de 70 años, con márgenes de 43 a 83. Los pacientes han sido vigilados por periodos que oscilan entre 6y 3270 días (mediana 308). Dos pacientes desarrollaron mieloma múltiple 308 y 1687 días después de haberse identificado la GMSI. La mediana de supervivencia (SV) del grupo no se ha alcanzado y la SV a 32 70 días es de 91%. Después de discutir causas potenciales de error como son la falta de reporte y varios sesgos, parece que la GMSI, al igual que otros padecimientos inmunoproliferativos malignos, es probablemente menos frecuente en mestizos mexicanos que en individuos de origen caucásico. Es posible que hacer estudios rutinarios para identificar esta condición permita diagnosticar más casos.

Monoclonal gammopathy of undetermined significance (MGUS) is defined as presence of serum monoclonal protein at a concentration of 3 g per deciliter or less, no monoclonal protein or only moderate amounts of monoclonal light chains in urine, absence oflytic bone lesions, anemia, hypercalemia, and renal insufficiency related with monoclonal protein, and with a proportion of plasma cells in bone marrow of 10% or less. In Caucasian population, MGUS affects about 3% of individuals > 70 years of age, whereas in Mexican mestizos this figure is substantially lower (0.7%); on the other hand, MGUS represents in Mexico only 2.4% of all monoclonal gammopathies. In a total of 9081 individuals studied prospectively at the Centro de Hematología y Medicina Interna de Puebla throughout a 20-year period, 11 patients with MGUS were identified. Median age was 70 years (range 43-83 years). Patients have been followed in periods ranging from 6 to 3270 days (median, 308 days). Two patients evolved into overt multiple myeloma at 308 and 1687 days after diagnosis of MGUS. Overall median survival (SV) of the group has not been reached, whereas3270 days overall SV is 91%. After discussing underreporting, biasing, and other confounding factors, it would seem that MGUS, like other monoclonal gammopathies, is les sfrequent in Mexican mestizos than in Caucasians. Routine screening studies to identify the condition should result in increased numbers of patients.

Multiple myeloma in Mexico: a 20-year experience at a single institution.

BACKGROUND: In a 20-year period at a single institution, 66 cases of multiple myeloma (MM) were identified. The disease was less frequent in Mexico because in a multicenter study it represented 4.2% of all hematologic malignancies, whereas during this experience it was found to represent 7.7%. These figures contrast with those reported in Caucasians-10-15%. METHODS: There were two patients <40 years of age; median age was 66 years. Bone pain was present in 54%, fatigue in 66%, and weight loss in 47%. Anemia was present in 75% of females and in 96% of males at diagnosis; median hemoglobin was 10.2 g/dL; abnormal monoclonal spike had a median of 2.87 g/dL (range 0-9.9). Four cases (6%) of nonsecretory myelomas were identified. Bence Jones proteinuria was present in 51 cases (77%). Forty six individuals were followed for >3 months (97-7,054 days, median 2,371 days). RESULTS: Their survival (SV) was 51% at 540 days. Patients treated with melphalan/prednisone had a median SV of 33 months with a 72-month SV of 30%. Patients treated with vincristine/adriamycin/dexamethasone had an SV of 40% at 42 months, whereas those given high-dose chemotherapy and autologous stem cell rescue had an SV of 80% at 22 months. CONCLUSIONS: Clinical features of Mexican patients with MM were not significantly different from those reported for other populations; best results from treatment were observed in patients administered autologous stem cell transplantation.

Primary thrombophilia in Mexico IV: frequency of the Leiden, Cambridge, Hong Kong, Liverpool and HR2 haplotype polymorphisms in the factor V gene of a group of thrombophilic Mexican Mestizo patients.

The activated protein C resistance (APCr) phenotype is found in around 40% of thrombophilic Mexican Mestizo individuals; since only very few display the factor V gene Leiden (Arg506Gln) mutation, it was considered of interest looking for other factor V gene mutations associated to thrombophilia: The HR2 haplotype, the factor V Cambridge (Arg306Thr), the factor V Hong Kong (Arg306Gly) and the FV Liverpool (Ile359Thr). In 39 individuals, the FV Leiden was found in 10%, the HR2 haplotype in 28%, the FV Hong Kong in 2%, whereas the FV Cambridge and FV Liverpool gene mutations were not found in any individual. In the subset of 10 patients with the APCr phenotype, the FV Leiden mutation was found only in 4 (40%) whereas the HR2 haplotype in 3 (30%); all the patients with the factor V Leiden mutation and 27% of those with the HR2 phenotype displayed the APCr phenotype. It is concluded that these polymorphisms of the factor V gene are not major contributors to the thrombophilia observed in Mexican Mestizos and that additional mutations in the FV gene should be looked for in those who display the APCr phenotype.

Long-term results of the immunosuppressive treatment of patients with severe acquired aplastic anemia: a single institution study.

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.