RESUMEN

The aim of the study was to evaluate the efficacy and safety of the conversion of MMF to EC-MPS in pediatric renal transplant recipients. We included 12 patients with stable graft function who were receiving MMF treatment. In the first visit, a complete medical examination was performed, which included a GSRS, a nine-point pharmacokinetic profile, samples for renal, liver and hematological tests and evaluation of IMPDH2 gene expression. The patients were transferred to an equimolar dose of EC-MPS. Two wk later, a clinical evaluation and blood collection, as in the first visit were performed. There was no change in serum creatinine, leukocyte count, serum albumin, or transaminase levels, but we found a statistically significant reduction of hemoglobin after conversion (13.2 +/- 1.6 g/dL with MMF vs. 12.5 +/- 1.3 g/dL when receiving EC-MPS). The GSRS total mean score was 16 +/- 12 with MMF vs. 8 +/- 5 with EC-MPA (p < 0.05). There was no statistically significant difference between formulations in the gene expression of IMPDH 2, in the AUC(0-12h) or in C(max). However, peak concentration occurred later with EC-MPS.

Asunto(s)

Sustitución de Medicamentos , Inmunosupresores/farmacocinética , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Adolescente , Área Bajo la Curva , Niño , Femenino , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Masculino , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Comprimidos Recubiertos

RESUMEN

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.

Asunto(s)

Trasplante de Células Madre/métodos , Adolescente , Adulto , Eliminación de Componentes Sanguíneos/métodos , Niño , Preescolar , Transfusión de Eritrocitos , Femenino , Humanos , Lactante , Leucemia/terapia , Linfoma no Hodgkin/terapia , Masculino , México , Persona de Mediana Edad , Mieloma Múltiple/terapia , Trasplante Autólogo , Trasplante Homólogo

RESUMEN

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.

Asunto(s)

Donantes de Sangre , Neoplasias Hematológicas/terapia , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante , Femenino , Prueba de Histocompatibilidad , Humanos , Masculino , México , Hermanos , Donantes de Tejidos , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

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.).

Asunto(s)

Enfermedad de Hodgkin/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Examen de la Médula Ósea , Niño , Preescolar , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/clasificación , Enfermedad de Hodgkin/terapia , Humanos , Masculino , México , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Antígenos CD34 , Recuento de Células Sanguíneas , Niño , Preescolar , Femenino , Neoplasias Hematológicas/terapia , Hematopoyesis , Humanos , Inmunosupresores/administración & dosificación , Leucaféresis/normas , Recuento de Leucocitos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Factores de Tiempo , Trasplante Homólogo/métodos , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados

RESUMEN

BACKGROUND: The molecular follow-up of patients with chronic myelogenous leukemia (CML) has been described as useful in other countries, but there are not data reported in Mexico. METHODS: All patients studied at Laboratories Clínicos de Puebla/Centro de Hematología y Medicina Interna de Puebla in which the BCR-ABL hybrid gene was identified by means of polymerase chain reaction were analyzed. In 22 individuals the molecular marker of the disease was studied at diagnosis and in different instances afterwards; these patients were treated with chemotherapy, interferon, autologous or allogeneic bone marrow transplantation. RESULTS: Only the six patients that were allografted from HLA-identical siblings cleared the molecular marker of the disease; the rest of them did not achieve molecular remissions. The median survival (SV) of the whole group has not been reached, whereas the 53-month SV is 68%. One of the allografted patients died as a result of complications of graft versus-host disease. CONCLUSIONS: We have found useful the molecular monitoring of the treatment of patients with CML. Using this approach, we found that molecular remissions can be accomplished only with allografting; however, other therapeutic approaches may also result in long-lasting hematologic remissions.

Asunto(s)

Proteínas de Fusión bcr-abl/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Homólogo

RESUMEN

BACKGROUND: The prevalence of beta-thalassemia in Mexico is not known in detail. METHODS: Data of studies investigating abnormal hemoglobins between September 1987 and November 2000 were analyzed; in addition, data of red-blood-cell indices and clinical features were analyzed in patients identified as carriers of beta-thalassemia. RESULTS: In 1,639 prospective studies looking for abnormal hemoglobins, 429 disclosed some abnormality; of these, 319 cases displayed abnormally high levels of hemoglobin A2, thus consistent with the diagnosis of beta-thalassemia. This hemoglobin abnormality represented 74.2% of all abnormalities, both quantitative and qualitative, of the molecule of hemoglobin. There were 317 heterozygotes and only two homozygotes. We have previously shown that the most frequent cause of anemia as the iatrotropic condition in Mexican mestizos is iron deficiency. We found that iron deficiency is 11.5 times more frequent than beta-thalassemia and that the latter is 1.3 times more frequent than macrocytic/megaloblastic anemia. CONCLUSIONS: beta-thalassemia should not be considered as infrequent in Mexico, and individuals with red blood cell microcytosis and/or hypochromia with or without anemia should be screened for thalassemia.

Asunto(s)

Heterocigoto , Talasemia beta/epidemiología , Anemia Hipocrómica/diagnóstico , Anemia Hipocrómica/epidemiología , Anemia Megaloblástica/epidemiología , Diagnóstico Diferencial , Pruebas Genéticas , Genotipo , Hemoglobinopatías/epidemiología , Hemoglobinopatías/genética , Hemoglobinas Anormales/análisis , Humanos , Deficiencias de Hierro , México/epidemiología , Prevalencia , Estudios Prospectivos , Rasgo Drepanocítico/epidemiología , Rasgo Drepanocítico/genética , Talasemia alfa/epidemiología , Talasemia beta/diagnóstico , Talasemia beta/genética

Asunto(s)

Trasplante de Médula Ósea/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante de Médula Ósea/estadística & datos numéricos , Humanos , Acondicionamiento Pretrasplante/estadística & datos numéricos , Resultado del Tratamiento

RESUMEN

Indirect evidence of hemolysis has been described in patients with autoimmune thrombocytopenic purpura. In order to collect more data, another method to assess red blood cell destruction in these patients was employed: measurement of free haptoglobin levels. In 17 individuals with autoimmune thrombocytopenic purpura the levels of free haptoglobins were assessed after carefully ruling out microangiopathic hemolysis, systemic lupus erythematosus or overt Evans syndrome. Abnormally low levels of free haptoglobins were found in five individuals (29%) as indirect evidence of hemolysis. The long-term thrombocytopenia-free status was lower in patients with low haptoglobin levels than in those with normal levels (40 versus 58%). These data, added to previous evidence, support the observation of Evans made 50 years ago: "there is a spectrum-like relationship between primary thrombocytopenia and haemolytic anemia".". Accordingly, the concept of "attenuated" variants of the Evans syndrome could be entertained.

Asunto(s)

Anemia Hemolítica Autoinmune , Haptoglobinas/metabolismo , Hemólisis , Trombocitopenia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Hemolítica Autoinmune/sangre , Anemia Hemolítica Autoinmune/clasificación , Anemia Hemolítica Autoinmune/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Trombocitopenia/sangre , Trombocitopenia/clasificación , Trombocitopenia/diagnóstico

RESUMEN

Along a 5-year period in a single institution, specific molecular markers were prospectively looked for in consecutive patients with acute leukemia, by means of polymerase chain reaction (PCR): In patients with acute lymphoblastic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-ETO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular markers were identified in 15/75 patients: Four with ALL (three with clonotypic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein--M3 AML-, and two with the AML1/ETO fusion protein--M2 AML-). During follow-up periods ranging from 1 to 60 months, seven patients cleared the residual disease assessed by PCR (RD-PCR), whereas eight patients had either persistence of RD-PCR or a molecular relapse. For patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respectively (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PCR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected without an overt morphological relapse. It is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.

Asunto(s)

Biomarcadores de Tumor/análisis , Leucemia/patología , Proteínas de Fusión Oncogénica/análisis , Reacción en Cadena de la Polimerasa/métodos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Preescolar , ADN Complementario/genética , Femenino , Humanos , Inmunofenotipificación , Leucemia/genética , Leucemia/mortalidad , Tablas de Vida , Masculino , Persona de Mediana Edad , Neoplasia Residual , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , Análisis de Supervivencia