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Biomedical subjects

G J Ruiz-Argüelles

Publications and source records attributed to G J Ruiz-Argüelles.

At least 19 recordsLinked to original sources

Significance of one human leukocyte antigen mismatch on outcome of nonmyeloablative allogeneic stem cell transplantation from related donors using the Mexican schedule.

Using the Mexican approach to conduct nonablative stem cell transplantation (NST), we have prospectively performed 58 allografts in individuals with various malignant and nonmalignant hematological diseases using sibling donors, either HLA identical (6/6) or compatible, with one mismatch (5/6). When comparing allografts obtained from HLA identical (n=40) or compatible (n=18) siblings, respectively, the overall median survival was found to be 33 vs 8 months (P<0.01), the 52-month survival was 47 vs 38% (P>0.2), the prevalence of acute graft-versus-host disease (GVHD) 57 vs 38%, that of chronic GVHD 25 vs 11% and the relapse rate 45 vs 55%. The two patients who failed to engraft were both 5/6 matches. Probably stemming from the low number of patients, and despite a trend toward worse results in patients allografted from HLA compatible (5/6) siblings, most differences in outcome were not significant. It seems that NST can be offered to individuals with either an HLA identical or a compatible sibling donor.

Blood Donors↗

Bloodless (transfusion-free) hematopoietic stem cell transplants: the Mexican experience.

We have analyzed the transfusion requirements of a group of 132 peripheral blood stem cell transplants from a single institution (73 allografts and 59 autografts) over a 10-year period. The allografts were conducted using the 'Mexican' nonmyeloablative conditioning regimen, while the autografts were given single-day high-dose melphalan. For the allografts, the median number of transfused packed red blood (PRBC) cell units was 1 (range 0-22), while the median number of platelet transfusion (PLT) sessions was 1 (range 0-9); 45% of allografted individuals did not require PRBC transfusions and 35% did not require PLT. For autografts, the median number of PRBC units was 2 (range 0-21), while the median number of PLT was 2 (range 0-21); 33% of autografted individuals did not require PRBC and 25% did not require PLT. We conclude that, by using certain preparative regimens, both allo and auto hematopoietic stem cell grafts can be conducted without the transfusion of blood products.

Adolescent↗

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study.

Using a reduced-intensity stem cell transplantation (RIST) schedule, 24 patients with Philadelphia (Ph1) (+) chronic myelogenous leukemia (CML) in first chronic phase (CP) were prospectively allografted in four Latin American countries: México, Brazil, Colombia and Venezuela, using HLA-identical siblings as donors. The median age of the patients was 41 years (range 10-71 years); there were eight females. Patients received a median of 4.4 x 10(6)/kg CD34 cells. The median time to achieve above 0.5 x 10(9)/l granulocytes was 12 days, range 0-41 days, and the median time to achieve above 20 x 10(9)/l platelets was also 12 days, range 0-45 days. In all, 22 patients are alive 81-830 (median 497) days after RIST. The 830-day probability of survival is 92%, and the median survival has not been reached, being beyond 830 days. A total of 11 patients (46%) developed acute graft-versus-host disease (GVHD), and seven of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after RIST, one as a result of sepsis and the other of chronic GVHD. The 100-day mortality was 4.4%, and transplant-related mortality was 8%. RIST for patients with CML in CP appears to be an adequate therapeutic option.

Adolescent↗

Role of bone marrow examination in staging Hodgkin's disease: experience in México.

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).

Adolescent↗

Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos.

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), <1% and 51% (+/-5%, alpha = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients.

3' Untranslated Regions↗

Results of an outpatient-based stem cell allotransplant program using nonmyeloablative conditioning regimens.

Using nonmyeloablative, immunosuppressive, fludarabine (FLU)-based conditioning regimens, we have performed allogeneic peripheral blood stem cell transplants in 26 patients (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 10 with acute lymphoblastic leukemia, 1 with myelodysplasia, and 1 with thalassemia major). Conditioning consisted of FLU/busulphan/cyclophosphamide/cyclosporin-A (CyA)/methotrexate, or FLU/melphalan/CyA/methotrexate. The median granulocyte recovery time to 0.5 x 10(9)/l was 11 days, whereas the median platelet recovery time to 20 x 10(9)/l was 12 days. Twelve patients did not need red blood cell transfusions, and 8 did not need platelet transfusions. In 21 individuals (81%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 30 and 600 days: one patient failed to engraft and recovered endogenous hemopoiesis; six out of 26 patients developed acute graft-versus-host disease (GVHD) whereas 7/22 developed chronic GVHD. Twelve patients (46%) have died, nine of them with a relapsing disease and three with GVHD; median post-transplant survival (SV) was 300 days, whereas the 12-month SV was 42%. The 100-day mortality was 3.8% and the transplant-related mortality was 11.5%. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and it may represent another approach in the management of patients requiring an allogeneic stem cell transplant.

Adolescent↗

Features of the engraftment of allogeneic hematopoietic stem cells using reduced-intensity conditioning regimens.

The features of the engraftment in 26 patients allografted using reduced-intensity conditioning regimen (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 9 with acute lymphoblastic leukemia, 1 with hybrid acute leukemia, 1 with myelodysplasia and 1 with thalassemia major) were analyzed. Patients received a median of 10 x 10(8)/Kg mononuclear cells (range 1.6 to 22.9), and a median of 4.2 x 10(6)/Kg CD34 cells (range 0.3 to 14). There was a linear correlation between the number of infused mononuclear cells (MNC) and that of CD34 cells (r = 0.78, p = 0.002). Three patients (11%) failed to engraft; in those who engrafted, the median time to achieve > 500 granulocytes was 11 days (range 10 to 22), and the median time to achieve > 10,000 platelets was 12 days (range 10 to 41). The three patients who failed to engraft received less than 5 x 10(8)/Kg MNC (1.6, 4.6 and 4.9) and less than 0.5 x 10(6)/Kg CD34; however, five of eight patients who received less than 5 x 10(8)/Kg MNC still engrafted successfully. On the other hand, all the patients who received less than 0.5 x 10(6)/Kg CD34 cells failed to engraft. Within the group of patients who engrafted, it was found that those who received more than 7 x 10(6)/Kg CD34+ cells tended to earlier recover > 20 x 10(9)/L platelets (p = 0.02), and > 0.5 x 10(9)/L neutrophils (p = 0.06) before day 15, than those who received less than 7 x 10(6)/Kg CD34+ cells. No such association could be established between the number of MNC and the time for recovery. In these patients allografted using reduced-intensity conditioning regimens, the target doses of hematopoietic cell used were similar to those described for conventional allografts: The number of CD34 infused cells was significantly related to the possibility of failure to engraft and to the recovery rate of the hemopoiesis.

Adolescent↗

Hematopoietic stem cell allografts using a non-myeloablative conditioning regimen can be safely performed on an outpatient basis: report of four cases.

Using a non-myeloablative, immunosuppressive, fludarabine-based conditioning regimen, we performed allogeneic peripheral blood stem cell transplants totally on an outpatient basis in four patients (two with chronic myelogenous leukemia, one with acute myelogenous leukemia and one with thalassemia major). The median granulocyte recovery time to 0.5 x 109/l was 10 days and the lowest absolute neutrophil count was 0.064 x 109/l; only one patient developed thrombocytopenia below 20 x 109/l. No patient required red blood cell transfusions and one was given a single prophylactic platelet transfusion. All patients are alive at 210-390 (median 285) days and have definite evidence of chimerism; one developed biopsy-proven GVHD on day 50, with a limited cutaneous rash. The procedure is less costly than its counterpart using myeloablative conditioning regimens and may represent another approach in the management of patients requiring an allogeneic stem cell transplant. Bone Marrow Transplantation (2000) 25, 131-133.

Adolescent↗

PML/RAR alpha(+) hypergranular acute promyelocytic leukemia (M3) developing into an M3 acute myelocytic leukemia without PML/RAR alpha.

The case of an adult with PML/RARalpha(+) hypergranular acute promyelocytic leukemia (M3) that evolved into a rapidly fatal M3 acute myelocytic leukemia without PML/RARalpha after a complete and molecular remission had been achieved, is presented. Only 7 such cases have been published in the literature. The possible origin of this either leukemic relapse or secondary malignancy is briefly discussed, focusing on the fact that this diagnosis could only be defined by adequate molecular biology studies in the leukemic cells.

Adult↗

Primary thrombophilia in Mexico: a prospective study.

A group of 102 Mexican Mestizo patients with appropriate clinical features suggestive of primary thrombophilia was prospectively studied. Thirty-nine percent of them had activated protein C resistance, but only four patients displayed the factor V Leiden mutation. Five percent of the individuals were found to be protein C deficient, whereas 2% had protein S deficiency. No cases of abnormalities in antithrombin III, plasminogen, tissue-type plasminogen activator or plasminogen activator inhibitor were found. The low prevalence of the activated protein C resistance genotype, probably stemming from the genetic admixture of the Mexican Mestizo group is noteworthy.

Activated Protein C Resistance↗

All trans-retinoic acid decreases early mortality in patients with promyelocytic leukemia and can be given entirely on an outpatient basis.

The results of the treatment of 43 patients with acute promyelocytic leukemia (PML) are reported: 27 were treated initially with all-trans-retinoic acid (ATRA), whereas 16 were treated with conventional chemotherapy. All patients received myelosuppressive chemotherapy after the initial treatment. Respectively, the complete remission rate was 92% and 37% (P < 0.01), the 5-day mortality rate was 0% and 44% (P < 0.001), and the 28-day mortality rate was 4% and 44% (P < 0.001). The median disease-free survival was 12 and 1 months (P < 0.01), whereas the 12-month disease-free survival was 50% and 13% (P < 0.01) and the 36-month disease-free survival was 41% and 9% (P < 0.01). Thirteen of the patients treated with ATRA were given the treatment fully as outpatients. ATRA given as initial therapy decreased significantly early mortality in promyelocytic leukemia patients; because some promyelocytic leukemia patients given ATRA as initial therapy can be treated as outpatients, the costs of this treatment modality may be diminished.

Adolescent↗

Impaired metoclopramide-induced pituitary prolactin release in men with human immunodeficiency virus infection.

To investigate whether metoclopramide-induced prolactin release is impaired in HIV-infected men, we studied 10 clinically healthy HIV-negative adult men (group 1) and 10 consecutive HIV-positive adult men (group 2) with anti-HIV antibodies confirmed by Western blot analysis and a CD4 cell count from 13 to 570x10(6)/L. After a 10- to 12-hour overnight fast, three basal blood samples were obtained at 15-minute intervals (-30, -15, and 0 minutes) and thereafter at 15, 30, 60, 90, 120, 180, and 240 minutes after a 10-mg intravenous bolus of metoclopramide. Duplicate serum prolactin concentrations were measured in each sample with commercially available radioimmunoassay kits. No significant differences between groups were observed in basal prolactin levels. Group 2 had lower serum prolactin concentrations than group 1 throughout the test (P< or =.002). The area under the prolactin curve (mean +/- SD) was also lower in group 2 than in group 1 (7156+/-1433 ng/mL/240 min vs. 12430+/-2454 ng/mL/240 min, P<.0001), and the area under the prolactin curve had a significant correlation with the CD4 cell counts (r = 0.7912, P<.001). These findings suggest that the hypothalamic dopaminergic tone, although present, was clearly diminished in these HIV-positive men regardless of their clinical stage.

Adult↗

The G20210A polymorphism in the 3'-untranslated region of the prothrombin gene in Mexican mestizo patients with primary antiphospholipid syndrome.

In an effort to identify alleles associated with an increased risk of venous thrombosis in patients with primary antiphospholipid syndrome, we studied the G20210A polymorphism (the G-->A mutation at nucleotide position 20210) in the 3'-untranslated region of the prothrombin gene in a group of 14 patients with primary antiphospholipid syndrome. We did not find any patient with the mutated gene. Since the prothrombin mutation is more prevalent in white populations, this finding may be related with the genetic composition of the Mexican mestizos, in whom the white component is low. The polymorphism of the prothrombin gene in Mexican mestizo patients with antiphospholipid syndrome does not seem to be related to the thrombophilia observed in these patients.

3' Untranslated Regions↗

Chronic lymphocytic leukemia is infrequent in Mexican mestizos.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults living in Western countries, and accounts for approximately 30% of adult leukemias. In a 15-year period in a single institution, we identified 19 patients with CLL in a group of 211 adults with leukemia (9% of adult leukemias). Of these 19 CLL patients, 8 had a Caucasian phenotype, 4 were born outside the country, and only 11 were Mexican mestizos. On the other hand, in a multicenter experience involving 1968 Mexican adults with leukemia, CLL represented 6.6% of the cases, a figure significantly lower than that reported in Caucasians (P < 0.01). CLL is the least frequent type of leukemia in Mexican mestizos, and this low prevalence may stem from the genetic origin of this racial group. The data also suggest a genetic predisposition of Caucasians to suffer from this disease.

Adult↗

Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis.

We have prospectively performed peripheral blood stem cell autotransplants in six patients with hematological malignancies on an entirely outpatient basis. Patients were conditioned with high-dose melphalan and received a median of 4.2 x 10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of 3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl was 21 days, with a range of 16 to 40, whereas the median time to achieve > 20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three patients were transfused with platelets whereas packed red blood cells were transfused in two. All patients survived 60 days after the autograft and three are alive at 450, 690, and 1,950 days after the autotransplant. One patient was given an allogeneic bone marrow transplant when relapsing after the autotransplant. One patient had to be admitted to the hospital on day +10 because of fever. A median of 6,500.00 USD per patient was calculated as the total cost of each outpatient autotransplant. Since outpatient autologous transplants with non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Adult↗