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1.
Leukemia ; 19(3): 449-55, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15674420

RESUMEN

The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the expression of a group of nine such molecules on both BMPC and the plasma of 61 newly diagnosed MG patients (30 MG of undetermined significance (MGUS), 27 multiple myeloma (MM) and four plasma cell leukemia (PCL)) and five normal individuals. Clonal PC from all MG displayed significantly increased levels of CD56, CD86 and CD126, and decreased amounts of CD38 (P<0.001). Additionally, HLA-I and beta2-microglobulin were abnormally highly expressed in MGUS, while CD40 expression was decreased in MM and PCL (P<0.05). Interestingly, a progressive increase in the soluble levels of beta2-microglobulin was found from MGUS to MM and PCL patients (P=0.03). In contrast, all groups showed similar surface and soluble amounts of CD126, CD130 and CD95, except for increased soluble levels of CD95 observed in PCL. Overall, those phenotypic differences are consistent with increased antigen presentation and costimulatory capacities in MGUS, which progressively deteriorate in malignant MG (MM and PCL).


Asunto(s)
Antígenos CD/genética , Médula Ósea/patología , Leucemia de Células Plasmáticas/genética , Mieloma Múltiple/genética , Paraproteinemias/inmunología , Células Plasmáticas/inmunología , Anciano , Antígenos CD/inmunología , Médula Ósea/inmunología , Células Clonales/inmunología , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Inmunofenotipificación/métodos , Leucemia de Células Plasmáticas/patología , Masculino , Mieloma Múltiple/patología , Paraproteinemias/genética , Paraproteinemias/patología , Células Plasmáticas/patología
2.
J Clin Oncol ; 11(6): 1165-71, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8501503

RESUMEN

PURPOSE: To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS: From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS: Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION: These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/administración & dosificación , Carmustina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversos
3.
J Clin Oncol ; 16(12): 3774-81, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9850021

RESUMEN

PURPOSE: The identification of immunophenotypic aberrancies through multiparametric flow cytometry makes the differentiation between normal and leukemic cells relatively simple and quick, and is therefore an attractive method for the investigation of minimal residual disease (MRD). In this report, we have analyzed the impact on relapse and relapse-free survival (RFS) of detecting immunophenotypical aberrant cells in acute lymphoblastic leukemia (ALL) patients in cytomorphologic complete remission (CR). MATERIALS AND METHODS: Two hundred eleven bone marrow (BM) samples from 53 consecutive ALL (37 precursor B-ALL and 16 T-ALL) patients were analyzed. The only selection criteria were to have at least one aberrant immunophenotypic feature at diagosis and to have achieved cytomorphologic CR after induction therapy. For MRD detection, all follow-up samples were analyzed with triple labelings using a two-step acquisition procedure, in which 106 cells were screened for the possible persistence of residual leukemic cells with the same phenotypic aberrancy as that identified diagnosis. RESULTS: Patients who displayed a gradual increase in MRD levels showed a higher relapse rate (90% v22%; P < .00001) and shorter median RFS (12 months v not reached; P < .0001) than those with stable or decreasing MRD levels. This adverse prognostic influence also was observed when children and adults, as well as B-ALL and T-ALL patients, were analyzed separately. An MRD level > or = or greater than 10(-3) discriminated two risk groups of ALL patients with significantly different relapse rates and RFS at all treatment phases (end of induction, consolidation, maintenance, and out of treatment). CONCLUSION: Multiparametric flow cytometry of MRD in ALL patients is a valuable tool for relapse prediction and for the identification of a cohort of patients with very poor prognosis.


Asunto(s)
Antígenos de Neoplasias/análisis , Células de la Médula Ósea/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Adulto , Anciano , Células de la Médula Ósea/inmunología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Valor Predictivo de las Pruebas , Recurrencia
4.
J Clin Oncol ; 14(7): 2167-73, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8683251

RESUMEN

PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Adulto , Terapia Combinada , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Estudios Prospectivos , Tasa de Supervivencia , Trasplante Autólogo , Vincristina/administración & dosificación
5.
Leukemia ; 16(8): 1460-9, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12145686

RESUMEN

Multiparameter immunophenotypic analysis of neoplastic cells has proven to be of great help for the investigation of minimal residual disease in acute leukemias; however, its utility has not been systematically explored in B cell chronic lymphoproliferative disorders. The aim of the present study was to investigate the incidence of phenotypic aberrations in a series of 467 consecutive leukemic B cell chronic lymphoproliferative disorders through the comparison of the phenotypic characteristics of tumor vs normal peripheral blood (n = 10) and bone marrow (n = 10) B cells, in order to explore the applicability of this strategy for minimal residual disease monitoring. An additional goal of our study was to evaluate the sensitivity of multiparameter flow cytometry for the detection of minimal residual disease in leukemic B cell chronic lymphoproliferative disorders through dilutional experiments (n = 19). From the patients analyzed 382 corresponded to B cell chronic lymphocytic leukemia/small lymphocytic lymphoma (353 typical and 29 atypical); five to prolymphocytic leukemia; 13 to hairy cell leukemias; 12 to lymphoplasmacytic lymphomas; 14 to splenic marginal zone lymphomas; 22 were follicular lymphomas; and 19 mantle cell lymphomas. The following triple stainings were systematically applied to both normal and leukemic samples: FMC7/CD5/CD19, CD22/CD23/CD19, CD103/CD25/CD19, CD10/CD11c/CD19 and sIg/sIg(lambda)/CD19. Overall, 98% of the leukemic B cell chronic lymphoproliferative disorders cases displayed aberrant phenotypes at diagnosis with no significant differences being found between cases analyzed in peripheral blood vs bone marrow samples. The most common types of aberrant criteria detected included asynchronous antigen expression (92%) and antigen over-expression (54%); abnormally light scatter characteristics were found in 17% of the cases. Most of the cases studied (90%) displayed four or more phenotypic aberrations. Once patients were divided according to the different diagnostic subgroups, the overall incidence of aberrant phenotypes ranged from 79 to 80% among atypical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia to 97% of follicular lymphoma and 100% of typical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma, hairy cell leukemia, lymphoplasmacytic lymphomas, splenic marginal zone lymphomas and mantle cell lymphomas. Based on the aberrant phenotypes detected unique four-color stainings could be built for the specific identification of aberrant phenotypes. These include CD22/CD23/CD19/CD5 and sIg(kappa)/sIg(lambda)/CD19/CD5 for lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia, CD103/CD25 or CD22/CD19/CD11c for hairy cell leukemia, FMC7/CD22/CD19/CD103 and sIg(kappa)/sIg(lambda)/CD22/CD19 for splenic marginal zone lymphomas, CD22/CD23/CD19/CD10 for follicular lymphomas and CD10/CD22/CD19/CD5 for mantle cell lymphomas. Serial dilutional experiments showed that the sensitivity level of immunophenotyping ranges between 10(-4) and 10(-5). In summary, the present study shows that immunophenotypic analysis allows the identification of aberrant phenotypes in 98% of leukemic B cell chronic lymphoproliferative disorders and these phenotypes can be used for minimal residual disease monitoring with a sensitivity limit of 10(-4)-10(-5).


Asunto(s)
Linfocitos B/patología , Citometría de Flujo/métodos , Inmunofenotipificación/métodos , Trastornos Linfoproliferativos/patología , Coloración y Etiquetado/métodos , Anticuerpos Monoclonales/inmunología , Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Linfocitos B/química , Enfermedad Crónica , Células Clonales/química , Células Clonales/patología , Técnica del Anticuerpo Fluorescente Directa , Colorantes Fluorescentes/análisis , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patología , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/patología , Trastornos Linfoproliferativos/diagnóstico , Neoplasia Residual , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Nefelometría y Turbidimetría , Sensibilidad y Especificidad
6.
Semin Oncol ; 30(2): 187-95, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12720134

RESUMEN

Immunophenotyping has become an essential tool for diagnosis of hematological malignancies. By contrast, for diagnosis of Waldenstrom's macroglobulinemia (WM) immunophenotyping is used only occasionally. From 150 patients with a IgM monoclonal gammopathy we have selected 60 cases with (1) morphological lymphoplasmocytoid bone marrow (BM) infiltration (>20%); (2) IgM paraprotein (>10g/L); and (3) absence of features of other lymphoma types. Immunophenotypic analysis was based on the use of the triple or quadruple monoclonal antibody (MoAb) combinations. To increase the sensitivity of the analysis of antigen expression, selected CD19(+)CD20(+) B cells were targeted. We have also explored the antigenic characteristics of both the plasma cell (PC) and mast cell (MC) compartments present in the BM from 15 WM patients. Clonal WM lymphocytes were characterized by the constant expression of pan-B markers (CD19, CD20, CD22, CD24) together with sIg, predominantly kappa (5:1, kappa:lambda ratio). A high proportion of cases (75%) were positive for FMC7 and CD25, but in contrast to hairy cell leukemia (HCL), these lymphocytes were always negative for CD103 and CD11c. CD10 antigen was also absent in all WM patients and less than one fifth of patients were positive for CD5 and CD23, while CD27, CD45RA, and BCL-2 were present in most malignant cells. In two cases, the coexistence of two different clones of B lymphocytes was identified, and in eight additional cases, intraclonal phenotypic heterogeneity was observed. As far as PCs are concerned, in most patients (85%) the number of PCs was within the normal range (median, 0.36%). The antigenic profile of these PCs differed from that observed in normal and myelomatous PC (CD38(++)CD19(++/-)CD56(-)CD45(++)CD20(+)). In three cases, PCs showed aberrant expression for CD5, CD22, or FMC7. Finally, the number of mast cells was significantly higher (0.058 +/- 0.13) as compared to normal BM (0.019 +/- 0.02) (P <.01), although they were immunophenotypically normal (CD117(+)CD2(-)CD25(-)).


Asunto(s)
Macroglobulinemia de Waldenström/inmunología , Macroglobulinemia de Waldenström/patología , Células de la Médula Ósea , Humanos , Inmunoglobulina M/inmunología , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/patología , Subgrupos Linfocitarios , Linfocitos , Mastocitos , Fenotipo , Células Plasmáticas
7.
Hematol J ; 2(3): 146-9, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11920239

RESUMEN

INTRODUCTION: A model of a stepwise malignant transformation has been proposed for the pathogenesis of monoclonal gammopathies. In this model, cell cycle regulators play a central role as a source of genetic events; particularly, p16/INK4a gene acts as a tumoral suppressor gene and, recently, inactivation of this gene through a methylation mechanism, has been observed in multiple myeloma patients. Under the diagnosis of monoclonal gammopathies there is a broad spectrum of disorders with very different outcomes, ranging from indolent courses, such as those of monoclonal gammopathy of undetermined significance, Waldeströn macroglobulinemia and smoldering multiple myeloma, to aggressive diseases such as symptomatic MM and primary plasma cell leukemia. To the best of our knowledge, the activity of p16 gene has not been evaluated and compared in these different subtypes of monoclonal gammopathies. MATERIALS AND METHODS: The methylation status of the p16 gene was analysed in a group of 159 patients with monoclonal gammopathies (40 monoclonal gammopathy of uncertain significance, eight Waldenström Macroglobulinemia, eight smoldering multiple myeloma, 98 symptomatic multiple myeloma and five primary plasma cell leukemia) using three different assays (restriction enzymes and PCR or S-B and modification by sodium bisulphite). RESULTS: Forty-one of 98 MM patients (41.8%) as well as four of the five (80%) primary PCL patients showed methylation of the p16 gene, while none of the patients with monoclonal gammopathy of undetermined significance, Waldenström Macroglobulinemia or smoldering multiple myeloma displayed a methylation status. CONCLUSION: These findings suggest that the methylation of the p16 gene could be a relevant oncogenic event in the monoclonal gammopathies evolution being associated with the most aggressive forms.


Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/fisiología , Metilación de ADN , Silenciador del Gen , Genes p16 , Paraproteinemias/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/deficiencia , ADN/química , ADN/efectos de los fármacos , ADN de Neoplasias/química , ADN de Neoplasias/efectos de los fármacos , Progresión de la Enfermedad , Leucemia de Células Plasmáticas/genética , Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Proteínas de Neoplasias/deficiencia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Paraproteinemias/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Sulfitos/farmacología , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/patología
8.
Hematol J ; 2(4): 272-8, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11920260

RESUMEN

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Carmustina/administración & dosificación , Causas de Muerte , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Prednisona/administración & dosificación , Inducción de Remisión , Análisis de Supervivencia , Tasa de Supervivencia , Vincristina/administración & dosificación
9.
J Biol Regul Homeost Agents ; 18(2): 161-5, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15471221

RESUMEN

The term "monoclonal gammopathy" (MG) includes a group of clonal plasma cell disorders, which show heterogeneous clinical behavior. While multiple myeloma (MM) and plasma cell leukemia (PCL) are incurable malignant diseases, most patients with MG of undetermined significance (MGUS) show an indolent/benign clinical course. Evidence has accumulated which supports the role of the bone marrow microenvironment in MG. Accordingly, the survival, drug-resistance and proliferation of MM cells have been shown to be largely dependent on a supportive microenvironment. Among the different environment-associated parameters, those related to the status/activity of the immune system are particularly relevant. This review focuses on the different ways clonal plasma cells (PC) interact with the immune system in different models of MG, to characterize crucial events in the development and progression of MG. These advances may support the design of novel therapeutic approaches in patients with MG.


Asunto(s)
Paraproteinemias/inmunología , Células Plasmáticas/inmunología , Médula Ósea/inmunología , Células de la Médula Ósea/inmunología , Células Clonales/inmunología , Humanos , Inmunofenotipificación , Leucemia de Células Plasmáticas/etiología , Leucemia de Células Plasmáticas/inmunología , Activación de Linfocitos/inmunología , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Mieloma Múltiple/etiología , Mieloma Múltiple/inmunología , Paraproteinemias/etiología , Linfocitos T/inmunología , Linfocitos T/fisiología
10.
Med Clin (Barc) ; 99(17): 645-8, 1992 Nov 21.
Artículo en Español | MEDLINE | ID: mdl-1447935

RESUMEN

BACKGROUND: The aim of the present study was to compare the prognostic influence of beta 2-microglobulin (B2M) corrected according to renal function versus the uncorrected form and relate these values with other characteristics of the disease in a series of patients with multiple myeloma (MM). METHODS: The serum levels of B2M were determined by the radioimmunoassay method (RIA) in 107 patients with newly diagnosed MM and the prognostic influence of B2M was statistically evaluated with univariant and multivariant analysis. RESULTS: The mean value of B2M obtained in patients with MM was 7.8 +/- 8.0 micrograms/ml, with a median of 5 micrograms/ml. Ninety percent of the patients studied presented serum values of B2M higher than the normal limit. The value of B2M corresponding to the median of the series (5 micrograms/ml) separated two groups of patients with different survival (48 vs 19 months) (p = 0.0001). Similarly, the most discriminative value of corrected B2M in agreement with creatinine (2.5 micrograms/ml) permitted the differentiation of two groups of patients although the differences in survival were less significant (36 vs 26 months, p = 0.03) demonstrating its lesser influence as a prognostic factor with respect to the uncorrected B2M. In contrast, a significant association was observed between high values of B2M and Bence Jones myeloma, clinical stage III, anemia, renal failure and intense involvement of the general state. Multivariant analysis demonstrated that B2M plays a greater prognostic role when used as a discrete rather than a continuous variable and that together with the degree of involvement of the general state, serum albumin and the proportion of plasma cells in the bone marrow, they make up the best set of variables for the prediction of prognosis in patients with MM. CONCLUSIONS: Beta 2-microglobulin is one of the most important independent prognostic factors in multiple myeloma with its prognostic value being greatest when used uncorrected according to the values of creatinine.


Asunto(s)
Mieloma Múltiple/inmunología , Microglobulina beta-2/inmunología , Proteína de Bence Jones/análisis , Humanos , Análisis Multivariante , Pronóstico , Radioinmunoensayo
11.
Med Clin (Barc) ; 97(10): 369-72, 1991 Sep 28.
Artículo en Español | MEDLINE | ID: mdl-1745085

RESUMEN

BACKGROUND: The aim of the present study was to analyze the blastic transformation occurring during chronic myeloproliferative diseases (CMPD) and to establish the differences between them. METHODS: The clinical and hematological characteristics of 54 patients in blastic crisis (BC) of a CMPD were analyzed: 40 chronic myelogenous leukemias (CML), 9 idiopathic myelofibroses (IMF), 4 polycythemia vera (PV), and one essential thrombocythemia (ET). The results were analyzed by the BMDP statistical program. RESULTS: The BC of CML appeared in younger patients (p less than 0.05). Only in this group did some patients achieve complete remission. Moreover, in this BC a greater incidence of visceromegalies and leukocytoses were observed. The BC of the IMF patients led to marked anemia (p less than 0.01) and bone marrow infiltration (p less than 0.05); these leukemias were more frequent in males and began with lymphadenopathies and visceromegalies. The transformations of PV were preceded by a longer chronic phase and had a lower incidence of visceromegalies and a nearly normal hemoglobin count value. The patient with acute leukemia secondary to ET did not display visceromegalies but did have anemia, leukopenia and a normal platelet count. None of the four groups responded to therapy, and their survival was short. CONCLUSIONS: Blast transformations of different myeloproliferative disorders have their own idiosynchratic clinical and hematological characteristics, some of these may be related to the chronic phase of disease.


Asunto(s)
Crisis Blástica , Trastornos Mieloproliferativos/patología , Factores de Edad , Femenino , Hemoglobinometría , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/diagnóstico , Recuento de Plaquetas , Policitemia Vera/sangre , Policitemia Vera/diagnóstico , Policitemia Vera/patología , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/patología , Trombocitemia Esencial/sangre , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/patología
12.
Arch Soc Esp Oftalmol ; 75(8): 515-21, 2000 Aug.
Artículo en Español | MEDLINE | ID: mdl-11151212

RESUMEN

PURPOSE: Mitomycin C is an antibiotic with a demonstrated antiproliferative capacity as an inhibitor of fibroblastic cells proliferation. Its use has been extended in glaucoma surgery. In the present study, we evaluated mitomycin C effect on cell culture monolayer of rabbit corneal endothelium. METHODS: The source of corneal endothelium for cell culture was New Zealand albino rabbit eyes. Desegregation of cells was carried out with mechanic and enzymatic dissociation from corneal endothelium and Descemet membrane. Culture medium was EMEM. Three treatment groups of plates were exposed to three different concentrations of mitomycin C 2x10(-3) mg/ml, 2x10(-2) mg/ml and 2x10(-1) mg/ml. Control and witness plate groups were also established. The morphometric study was performed through quantitative analysis with a video system connected to the light microscope. RESULTS: Different morphological changes related with cell size, cytoplasm and dyeing were seen at the morphological study and several degenerative signs were established indicating cellular death and a very decrease of the cellular population. In the groups treated with minimal dose (2x10(-3) mg/ml) and 3 days evolution time, cellular population was 434 cels/mm(2), 7 evolution days group cell density was 300.97cels/mm(2), and at 14 days it was 201.88 cels/mm(2). The percentage of survival in all the groups of treated cells was under 50%. CONCLUSIONS: Mitomycin C in concentrations and exposure time as used in this study has a potent lethal effect on this cellular type that compromises to a greater or smaller extent their function and integrity.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Endotelio Corneal/efectos de los fármacos , Mitomicina/farmacología , Animales , Células Cultivadas , Endotelio Corneal/patología , Masculino , Conejos
13.
An Med Interna ; 13(12): 580-3, 1996 Dec.
Artículo en Español | MEDLINE | ID: mdl-9063932

RESUMEN

Acute appendicitis is the most frequent etiology of abdominal laparotomy, and although it's thought that is a pathology of young patients, not only it isn't infrequent in elderly patients but it's increasing its incidence in the last decades, in part due to longer expectative of life in the general population. We studied the particularity of presentation and evolution in a group of 73 patients older than 60-year old, in comparason with a younger group. The clinical findings were typical in the most of patients, unrelated to the age, but problems as: delay in the clinical assistance, to have associated another diseases, and delayed diagnosis and operation, make the appendicitis in the older patient to have an increased incidence of complications. Moreover, post-operative complications occurred much more frequently, specially at the surgical incision, with a higher morbidity and hospital stay.


Asunto(s)
Apendicitis/diagnóstico , Factores de Edad , Anciano , Apendicitis/cirugía , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias , Factores de Tiempo
19.
Br J Haematol ; 136(1): 80-6, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17222197

RESUMEN

Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.


Asunto(s)
Deleción Cromosómica , Macroglobulinemia de Waldenström/genética , Adulto , Anciano , Anciano de 80 o más Años , Albuminuria , Anemia , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Distribución de Chi-Cuadrado , Citogenética , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina M/sangre , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Pronóstico , Estadísticas no Paramétricas , Macroglobulinemia de Waldenström/sangre , Macroglobulinemia de Waldenström/orina , Microglobulina beta-2/análisis
20.
Eur J Clin Invest ; 30(3): 210-4, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10691997

RESUMEN

BACKGROUND: The aim of this study was to determine the sensitivity of bone mineral density (BMD), ultrasounds (SOS) and resistance to torsion (T) to detect experimental osteopenia induced in rats 3 and 6 months after ooforectomy. MATERIALS AND METHODS: Seventy-four rats were used, divided into four groups, ooforectomized rats analysed 3 and 6 months after the operation and their respective control groups, in which BMD (Hologic QDR 1000 S/N 277), SOS (DBM Sonic 1200) and T (adapted test machine) were determined in the right femur. RESULTS: The results of the three techniques distinguished the ooforectomized groups from the controls, both 3 and 6 months after the ooforectomy, obtaining more significant differences with BMD (P = 0.0006, P = 0. 001, respectively) than SOS and T, where a significance of only P = 0.05 was obtained. In the correlation study among the three techniques, a significant correlation was observed between BMD and SOS (r = 0.39, P = 0.0008), as well as between BMD and T (r = 0.31, P = 0.03). However, significance was not observed between the SOS and T tests. CONCLUSION: In the study of sensitivity and specificity of the techniques used to detect the osteopenia caused by the ooforectomy, by means of calculation of the area under the receiver operation characteristic (ROC) curve, it was proven that although the three techniques distinguished between the two analysed populations, BMD presented an area under the ROC curve that was superior (0.87, 0.85) to that obtained with SOS (0.73, 0.67) and T (0.73, 0.68), both 3 and 6 months after the operation.


Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico , Huesos/fisiología , Animales , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/fisiopatología , Huesos/diagnóstico por imagen , Femenino , Osteoporosis/diagnóstico por imagen , Ovariectomía , Ratas , Ratas Wistar , Anomalía Torsional , Ultrasonido , Ultrasonografía
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