RESUMEN
Refractory anemia with excess blasts in transformation (RAEB-T) is a subgroup of myelodysplastic syndrome (MDS) in which the bone marrow blast count ranges from 20% to 30%. The recently proposed World Health Organization Classification of Hematologic Malignancies eliminated this category from MDS by lowering the blast count cutoff for acute myeloid leukemia (AML) from 30% to 20%. However, MDS is distinguished from AML by a significant increase in apoptosis. To investigate the difference in apoptosis between RAEB-T, AML, and other categories of MDS, we prospectively analyzed fresh bone marrow samples using the Annexin V and mitochondrial potential assays. There was a significantly higher level of apoptosis in RAEB-T than in AML according to both assays, while no significant differences between RAEB-T and other categories of MDS were noted. The data suggest that RAEB-T is more likely to be an advanced stage of MDS and biologically different from AML.
Asunto(s)
Anemia Refractaria con Exceso de Blastos/patología , Apoptosis , Leucemia Mieloide/patología , Enfermedad Aguda , Anemia Refractaria con Exceso de Blastos/metabolismo , Anexina A5/metabolismo , Antígenos CD34/metabolismo , Médula Ósea/patología , Estudios de Casos y Controles , Citometría de Flujo , Humanos , Leucemia Mieloide/metabolismo , Potenciales de la Membrana , Mitocondrias/metabolismo , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Estudios ProspectivosRESUMEN
The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Differential expression of CD20 surface antigen in B-cell neoplasms at different sites is largely unknown. The number of CD20 antibodies bound per cell (CD20 ABC) in bone marrow (BM), peripheral blood (PB), and lymph node aspirate (LNA) samples from patients with B-cell chronic lymphocytic leukemia (B-CLL) or other B-cell disease was studied using quantitative flow cytometry. CD20 ABC differed significantly with the specimen type in B-CLL, being highest in PB (mean, 9,051) and lower in BM (mean, 4,067) and LNA (mean, 3,951). No difference in CD20 ABC between BM and PB samples was found in splenic lymphoma, mantle cell lymphoma, or follicular lymphoma. Also, we found a significant difference of CD20 ABC by type of disease: lowest in B-CLL; higher in splenic, follicular, and mantle cell lymphoma; and highest in hairy cell leukemia. The lower CD20 surface antigen levels in BM and LNA than in PB in B-CLL may have clinical relevance with regard to the efficacy of rituximab therapy.
Asunto(s)
Antígenos CD20/análisis , Linfocitos B/inmunología , Médula Ósea/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Ganglios Linfáticos/inmunología , Adulto , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Linfocitos B/patología , Médula Ósea/patología , Citometría de Flujo , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Ganglios Linfáticos/patología , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Linfoma de Células del Manto/inmunología , Linfoma de Células del Manto/patología , Rituximab , Neoplasias del Bazo/inmunología , Neoplasias del Bazo/patologíaRESUMEN
CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL. Peripheral blood samples from 218 patients with B-CLL were analyzed by flow cytometry for CD38 expression on CD5/19(+) leukemic cells. Various patient characteristics were studied including age, sex, Rai and Binet stages, splenomegaly, hepatomegaly, hemoglobin (Hgb) level, beta-2 microglobulin (beta2M) level in the serum, number of nodal sites involved with disease, and length of survival. The Kaplan-Meier method was used to construct survival curves, and the log-rank statistic was used to compare these curves. CD38 was expressed in 20% or more of leukemic cells in 43% of the patients. Patients with high CD38 expression (20% or more) had significantly shorter survival times (P =.00005). Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005). CD38 expression identified a group of patients with aggressive disease that was considered by Rai staging to be early-stage disease (Rai stages 0-II). Patients with CD38(+) samples have significantly aggressive disease regardless of their clinical stage. Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL.
Asunto(s)
Antígenos CD , Antígenos de Diferenciación/sangre , Leucemia Linfocítica Crónica de Células B/diagnóstico , NAD+ Nucleosidasa/sangre , ADP-Ribosil Ciclasa , ADP-Ribosil Ciclasa 1 , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Femenino , Citometría de Flujo , Humanos , Masculino , Glicoproteínas de Membrana , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
We report flow cytometric characterization of surface CD26 expression in 271 peripheral blood samples from 154 patients evaluated for the presence of a T-cell lymphoproliferative disorder, primarily mycosis fungoides/Sézary syndrome (MF/SS). The presence of morphologically identifiable tumor cells on peripheral blood smears was the criterion for lymphomatous involvement. In 66 of 69 samples from 28 patients, we identified an abnormal CD26-/dim T-cell population that was distinct from the variable CD26 expression seen in normal peripheral blood T cells. This population was CD26- in 23 patients and weakly CD26+ in 5 patients. CD7 was more variably expressed in MF/SS tumor cells, allowing recognition of a distinct, quantifiable abnormal T-cell population in only 34 of 69 involved samples. An increased CD4/CD8 ratio and lower surface expression of CD4 in tumor cells also helped separate the CD26-/dim atypical population for quantification. In 35 blood samples from other types of T-cell tumors, tumor cells in 10 of 11 morphologically involved cases showed absent/dim CD26. Although capable of detecting abnormalities in most cases of MF/SS, CD7 expression does not provide as clear a separation of the neoplastic population and can be replaced by CD26 staining in routine peripheral blood flow cytometric screening of MF/SS patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Dipeptidil Peptidasa 4/sangre , Micosis Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Antígenos CD7/sangre , Antígenos de Diferenciación de Linfocitos T/sangre , Citometría de Flujo , Humanos , Linfoma de Células T/sangre , Linfoma de Células T/diagnóstico , Trastornos Linfoproliferativos/sangre , Micosis Fungoide/sangre , Síndrome de Sézary/sangre , Subgrupos de Linfocitos T/clasificaciónRESUMEN
Eighty-one first-time normal donors underwent leukapheresis for peripheral blood progenitor cell (PBPC) collection after mobilization with filgrastim administered either twice-daily (6 microg/kg every 12 h; n = 40) or once-daily (12 microg/kg; n = 41) subcutaneously for 3 d. The groups were similar for age, donor blood volume and target CD34+ cell dose to be collected (>/= 4 x 106 CD34+ cells/kg recipient). There was no statistically significant difference in the apheresis yield of CD34+ PBPCs (x 106) per kg recipient weight (5.6 +/- 3.3 vs. 5.6 +/- 4.3; P = 0.94) and per litre of blood processed (30 +/- 17.2 vs. 30.4 +/- 19.5; P = 0.92).
Asunto(s)
Antígenos CD34 , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Células Madre/inmunología , Adulto , Donantes de Sangre , Esquema de Medicación , Femenino , Filgrastim , Humanos , Leucaféresis , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Trasplante HomólogoRESUMEN
The significance of terminal deoxynucleotidyl transferase (TdT) expression in acute myelogenous leukemia (AML) remains controversial. Therefore, we studied TdT expression by flow cytometry in 120 previously untreated patients with AML or myelodysplastic syndrome (MDS) to determine the distribution of TdT-positive blasts and the intensity of TdT expression and to seek clinically significant associations. TdT expression measured by flow cytometry (flow TdT%) was heterogeneous, ranging from 0.1% to 87% (median, 8.5%), and 74 patients (62%) had at least 5% TdT-positive blasts. TdT positivity was associated with the M0 or M1 subtype and with expression of CD34 and CD7. No significant correlation was found between TdT expression and type of cytogenetic abnormality or rearrangement of immunoglobulin or T-cell receptor genes. Remission lasted longer in patients with a flow TdT% < 5 than in patients with a flow TdT% > 5 (median, 95 weeks vs 55 weeks, p = 0.02); however, complete remission rates did not differ when patients were classified by initial flow TdT%. Survival was slightly better for patients with flow TdT% less than 5%. Among patients with a flow TdT% > 5%, those with a higher TdT intensity survived longer than those with a lower intensity. These data suggest that quantitative TdT measurement may contribute to prognostic estimate in AML patients.
Asunto(s)
ADN Nucleotidilexotransferasa/biosíntesis , Leucemia Mieloide Aguda/enzimología , Síndromes Mielodisplásicos/enzimología , Adulto , Femenino , Citometría de Flujo/métodos , Reordenamiento Génico de Linfocito B , Reordenamiento Génico de Linfocito T , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Mieloide Aguda/genética , Masculino , Síndromes Mielodisplásicos/genética , Resultado del TratamientoRESUMEN
CD38 is expressed in acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) blasts and its prognostic significance is unknown. We investigated CD38 expression in 304 AML and 138 ALL patients. CD38 was lower in AML-M3 compared to other FAB subtypes (5% vs. 41%; P < 0.001), but was similar among ALL subtypes (56.6%; P = 0.69). Ph + ALL and AML with t(15; 17) patients showed lower CD38 expression than the other cytogenetic groups. Overall survival favored AML and ALL patients with higher CD38 levels. Multivariate analysis revealed CD38 expression to be an independent outcome predictor in AML, but not in ALL.
Asunto(s)
Antígenos CD , Antígenos de Diferenciación/inmunología , Leucemia Mieloide/inmunología , NAD+ Nucleosidasa/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , ADP-Ribosil Ciclasa , ADP-Ribosil Ciclasa 1 , Enfermedad Aguda , Adulto , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Mieloide/genética , Glicoproteínas de Membrana , Persona de Mediana Edad , Análisis Multivariante , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Some transplant-related complications, such as the engraftment syndrome, are thought to be mediated by cytokines released during expansion of hematopoietic progenitors at the time of neutrophil recovery. Since there is an inverse correlation between CD34(+) cell dose and time to neutrophil recovery, we sought to determine if peritransplant toxicity and early mortality were adversely affected by high CD34(+) cell doses. METHODS: The study group included 186 women with breast cancer who received high-dose cyclophosphamide, carmustine, thiotepa and an autologous PBSC transplant. The median CD34(+) cell dose was 5.9 x 10(6)/kg (1.0-154.7 x 10(6)/kg). Patients were categorized by CD34(+) cell dose (1.0-3.5, 3.6-5.9, 6.0-19.9, and 20.0-154.7 x 10(6)/kg) for assessment of outcomes. RESULTS: Grades 2-4 mucositis occurred in 49%, cardiac toxicity in 7%, pulmonary toxicity in 5%, cystitis in 4%, diarrhea in 3%, renal toxicity in 1%, and central nervous system toxicity in 1%. A Grade 2-4 regimen-related toxicity occurred in 109 patients (59%) and Grade 3-4 in eight patients (4%). Overall survival was 100% at Day 30, 96% at Day 90, and 89% at 1 year. Treatment-related mortality was 3.8%. In multivariate analyses that included prior chemotherapy, disease status, visceral metastases, prior chest radiation and age, CD34(+) cell dose group was not an independent risk factor for Grade 2-4 mucositis, Grade 2-4 maximum toxicity, Grade > or =3 cumulative toxicity, 90 day survival or 1 year survival. DISCUSSION: We conclude that CD34(+) cell doses >20 x 10(6)/kg do not affect transplant outcome in a negative or positive fashion.
Asunto(s)
Antígenos CD34/metabolismo , Neoplasias de la Mama/sangre , Neoplasias de la Mama/terapia , Adulto , Anciano , Eliminación de Componentes Sanguíneos , Transfusión de Sangre Autóloga/efectos adversos , Transfusión de Sangre Autóloga/mortalidad , Neoplasias de la Mama/mortalidad , Femenino , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Persona de Mediana Edad , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Flow cytometry has revolutionized the study of hematopoietic cells. Immunophenotyping by multiparameter flow cytometry supplements conventional morphologic diagnosis by providing information on cell lineage and differentiation in ALL and helps monitor disease by improving sensitivity in detecting minimal residual disease. The use of multiple MoAbs and multicolor study by flow cytometry has revealed heterogeneity among ALL and mixed-lineage acute leukemia, which are assigned to the same diagnostic categories by morphology. As technology has improved, clinical and research applications of flow cytometry have expanded to include evaluation of nuclear markers, oncogene proteins, apoptosis, cytokine receptors, and drug resistance. Expanded identification of MoAbs against leukemia-specific markers and the use of QFCM be a significant in managing patients with ALL in the future. In addition, flow cytometry and flow cytometric sorting will be combined more and more with other technologies, such as molecular probing or fluorescence in situ hybridization (FISH). The sorting of rare malignant cells based on immunophenotype and subsequent confirmation by PCR or FISH has already been proven feasible. Ultimately, it is hoped that further definition of subgroups of ALL by immunophenotyping using prognostically significant markers and the use of hybrid technologies of flow cytometry and molecular analysis or cytogenetics will improve treatment strategies for patients with ALL.
Asunto(s)
Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Inmunofenotipificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adulto , Anticuerpos Monoclonales/inmunología , Examen de la Médula Ósea/métodos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patología , Diferenciación Celular , Linaje de la Célula , ADN Nucleotidilexotransferasa/análisis , Diagnóstico Diferencial , Citometría de Flujo , Antígenos HLA-DR/análisis , Humanos , Leucemia Bifenotípica Aguda/diagnóstico , Leucemia Bifenotípica Aguda/patología , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/patología , Proteínas de Neoplasias/análisis , Neoplasia Residual , Células Madre Neoplásicas/química , Peroxidasa/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
CD5 is a T-cell marker aberrantly expressed in B-cell chronic lymphocytic leukemia and mantle cell lymphoma. Other B-cell neoplasms, including Burkitt lymphoma, are usually CD5-. We report 4 cases of de novo CD5+ Burkitt lymphoma/leukemia in elderly patients, all of whom were in a leukemic phase and had variable lymph node and splenic involvement. The blasts were typically medium sized, with folded nuclei, distinct but not prominent nucleoli, and moderate amounts of somewhat vacuolated basophilic cytoplasm; they were terminal deoxynucleotidyl transferase--negative and surface immunoglobulin--positive. All 4 cases demonstrated c-myc rearrangement, but none had t(14;18), t(11;14), or cyclin D1 overexpression or rearrangement. Only 1 patient achieved complete remission after hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) therapy. One patient responded poorly to hyper-CVAD, and 2 patients died during induction chemotherapy. These rare cases of aggressive lymphoid malignancy with CD5 positivity and molecular features associated with Burkitt lymphoma/leukemia are best classified as Burkitt leukemia. However, the morphologic and immunophenotypic similarity to the blastoid variant of mantle cell lymphoma are diagnostically challenging. The diseases can be distinguished at the genetic level, since Burkitt lymphoma involves the rearrangement of c-myc, and mantle cell lymphoma usually the overexpression or rearrangement of cyclin D1.
Asunto(s)
Linfoma de Burkitt/diagnóstico , Antígenos CD5/análisis , Anciano , Linfocitos B/inmunología , Linfocitos B/patología , Médula Ósea/patología , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Nucléolo Celular/patología , Núcleo Celular/patología , Citoplasma/patología , Diagnóstico Diferencial , Femenino , Genes myc/genética , Humanos , Inmunofenotipificación , Recuento de Leucocitos , Ganglios Linfáticos/patología , Linfoma de Células del Manto , Masculino , Persona de Mediana Edad , Bazo/patologíaRESUMEN
We evaluated demographic characteristics and graft composition as risk factors for acute graft-versus-host disease (GVHD) in 160 adult recipients of HLA-identical allogeneic blood stem cell transplants. The patients received a median nucleated cell dose of 7.9 x 10(8)/kg and median C34(+) cell dose of 5.6 x 10(6)/kg. GVHD prophylaxis consisted of cyclosporine (CSA) and steroids, tacrolimus (FK506) and steroids, or FK506 and methotrexate. Grades 2 to 4 GVHD occurred in 31% (95% CI, 23% to 39%), and grades 3 to 4 GVHD in 14% (95% CI, 8% to 20%). In univariate analyses, GVHD prophylaxis with CSA and high CD34(+) cell doses were significant risk factors for grades 2 to 4 GVHD, but diagnosis, age, use of total body irradiation, donor sex, female donor for male recipient, donor parity, donor alloimmunization, viral serology, nucleated cell dose, CD3(+) cell dose, and CD56(+) cell dose did not alter the incidence of GVHD significantly. With a CD34(+) cell dose less than 8 x 10(6) CD34(+) cells/kg, the risk of grades 2 to 4 GVHD was significantly higher for those who received CSA (39%, 95% CI, 21% to 47%) in comparison with those on FK506 (18%, 95% CI, 10% to 26%) (P =.03), but GVHD prophylaxis regimen had less impact with a higher CD34(+) cell dose (overall grades 2 to 4 GVHD rate 52%, 95% CI, 37% to 67%). GVHD prophylaxis and CD34(+) cell dose are independent risk factors for acute GVHD after allogeneic blood stem cell transplantation.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Niño , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Trasplante HomólogoRESUMEN
Acute leukemia can be diagnosed when blasts constitute 30% or more of the nucleated cells in a patient's peripheral blood (PB) sample. To determine whether in such cases bone marrow (BM) aspirates are still necessary, we compared the results of diagnostic studies performed on PB samples with blast counts of 30% or more with those performed on the same patients' BM samples. We found no differences in morphologic features, cytochemistry, or immunophenotype between the blasts in PB and BM samples in any of 30 cases studied. However, in 10 (23%) of 44 cases in which cytogenetic analysis was performed, PB but not BM samples were insufficient for analysis. The converse never occurred. Five of the 10 cases had acute lymphoblastic leukemia and 5 had acute myeloid leukemia (41% of the patients with acute lymphoblastic leukemia and 17% of the patients with acute myeloid leukemia). In cases with adequate metaphases, there was strong correlation between the cytogenetic results for PB and BM samples. Some PB samples with blast counts of 30% or more are adequate for diagnosis of acute leukemia, especially when therapy can be delayed until it is known that an adequate number of analyzable metaphases are recovered from the PB samples.
Asunto(s)
Crisis Blástica/patología , Células de la Médula Ósea/patología , Leucemia/sangre , Leucemia/patología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Preescolar , Citogenética , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Lactante , Leucemia/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Information on the safety and efficacy of allogeneic peripheral blood progenitor cell (PBPC) collection in filgrastim-mobilized normal donors is still limited. STUDY DESIGN AND METHODS: The PBPC donor database from a 42-month period (12/94-5/98) was reviewed for apheresis and clinical data related to PBPC donation. Normal PBPC donors received filgrastim (6 microg/kg subcutaneously every 12 hours) for 3 to 4 days and subsequently underwent daily leukapheresis. The target collection was > or =4 x 10(6)CD34+ cells per kg of recipient's body weight. RESULTS: A total of 350 donors were found to be evaluable. Their median age was 41 years (range, 4-79). Their median preapheresis white cell count was 42.8 x 10(9) per L (range, 18.3-91.6). Of these donors, 17 (5%) had inadequate peripheral venous access. Leukapheresis could not be completed because of apheresis-related adverse events in 2 donors (0.5%). Of the 324 donors evaluable for apheresis yield data, 221 (68%) reached the collection target with one leukapheresis. The median CD34+ cell dose collected (first leukapheresis) was 462 x 10(6) (range, 29-1463). The main adverse events related to filgrastim administration in donors evaluable for toxicity (n = 341) were bone pain (84%), headache (54%), fatigue (31%), and nausea (13%). These events were rated as moderate to severe (grade 2-3) by 171 (50%) of the donors. In 2 donors (0.5%), they prompted the discontinuation of filgrastim administration. CONCLUSION: PBPC apheresis for allogeneic transplantation is safe and well tolerated. It allows the collection of an "acceptable" PBPC dose in most normal donors with one leukapheresis, with minimal need for invasive procedures.
Asunto(s)
Recolección de Muestras de Sangre/normas , Transfusión Sanguínea , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Antígenos CD34/análisis , Eliminación de Componentes Sanguíneos , Niño , Preescolar , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Cefalea/etiología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/metabolismo , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Factores de TiempoRESUMEN
BACKGROUND: Multiple days of apheresis are required for some normal peripheral blood progenitor cell (PBPC) donors, to ensure a sufficient collection of CD34+ cells for allografting. It would be of practical value to be able to identify the patients with poor mobilization on the basis of simple pretreatment clinical or hematologic variables. STUDY DESIGN AND METHODS: Clinical characteristics and laboratory data for 119 normal PBPC donors who underwent apheresis on Days 4 to 6 of treatment with granulocyte-colony-stimulating factor (filgrastim) were analyzed for correlations with CD34+ cell yield from the first day of apheresis. RESULTS: The CD34+ cell yield was significantly lower in donors who were more than 55 years of age, who underwent apheresis on Day 4 of filgrastim therapy, or who were not obese. There were weak direct correlations between CD34+ cell yield and the baseline white cell count, preapheresis white cell count, and preapheresis mononuclear cell count, and there was a weak inverse correlation with age. Twenty-one donors (18%) were considered to have poor mobilization (< 20 x 10(6) CD34+ cells/L blood processed). In the multivariate analysis, the only significant factor was age greater than 55 years, which conferred a 3.8 times greater risk (95% CI, 1.1-13.7) of poor mobilization (p = 0.04). However, poor mobilization occurred in all age groups, so the predictive value of the model was low. CONCLUSION: Donor variables correlated with CD34+ cell yield only weakly, so no particular clinical characteristic can be used to exclude an individual as a PBPC donor if he or she is otherwise suitable for the apheresis procedure.
Asunto(s)
Antígenos CD34/análisis , Donantes de Sangre , Células Madre Hematopoyéticas/inmunología , Adolescente , Adulto , Anciano , Recolección de Muestras de Sangre/economía , Movimiento Celular/efectos de los fármacos , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Madre Hematopoyéticas/citología , Humanos , Leucaféresis , Masculino , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
We report an unusual case of hairy cell leukemia variant with IgA and IgG-lambda biclonal gammopathy exhibiting light chain and a surface immunoglobulin class different from that of the paraproteins. In addition, we documented by gene rearrangement study that the hairy cell leukemia variant clone appears independent from the paraprotein-producing cells. The kappa light chain was expressed on the surface of hairy cell leukemia variant cells. Southern blot analysis revealed rearrangement of the kappa-light-chain gene and germline configuration of lambda-light-chain gene. We observed significant clinical improvement and reduction in the leukemic infiltrate in the patient after treatment with 2-chlorodeoxyadenosine (2-CdA). The intensity of the rearranged kappa-light-chain gene band decreased with therapy and increased at relapse without significant change of the paraproteins. Previously reported cases of hairy cell leukemia variant with paraproteins are reviewed, and our patient's contribution to the understanding of this association is stressed.
Asunto(s)
Leucemia de Células Pilosas/complicaciones , Leucemia de Células Pilosas/inmunología , Paraproteinemias/complicaciones , Paraproteinemias/inmunología , Anciano , Antineoplásicos/uso terapéutico , Southern Blotting , Células de la Médula Ósea , Cladribina/uso terapéutico , ADN/análisis , Reordenamiento Génico , Humanos , Inmunoelectroforesis , Cadenas kappa de Inmunoglobulina/análisis , Inmunoglobulinas/análisis , Inmunofenotipificación , Leucemia de Células Pilosas/tratamiento farmacológico , Leucocitos Mononucleares/citología , MasculinoRESUMEN
A patient with low-grade lymphoma presented 8 months after autologous marrow transplantation with dizziness, aphasia and hemiparesis. Magnetic resonance imaging (MRI) showed an abnormal T2 signal in the frontoparietal region unilaterally. Biopsy of the area demonstrated progressive multifocal leukoencephalopathy positive for JC virus and p53. Treatment with interleukin-2 at 0.5 MU/m2/day i.v. continuous infusion resulted in near complete resolution of symptoms and MRI abnormalities. The absolute number of CD3+CD4+ and CD3-CD56+ cells in the peripheral blood also increased, and the CD4/CD8 ratio normalized. She remains free of evidence of progressive multifocal leukoencephalopathy 1 year off therapy.
Asunto(s)
Interleucina-2/uso terapéutico , Virus JC/aislamiento & purificación , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/etiología , Infecciones por Papillomavirus/complicaciones , Infecciones Tumorales por Virus/complicaciones , Recuento de Células Sanguíneas , Trasplante de Médula Ósea , ADN Viral/aislamiento & purificación , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación in Situ , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/tratamiento farmacológico , Proteína p53 Supresora de Tumor/análisis , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/tratamiento farmacológicoRESUMEN
Structural abnormality of chromosome X is uncommonly seen in patients with acute leukemia, and translocation between chromosome X and 10 is an exceedingly rare event. In this report, we describe the occurrence of t(X;10)(p10;p10) in two patients with acute leukemia, one with acute monocytic leukemia and the other with myeloblastic relapse arising from bilineage leukemia. To our knowledge, similar chromosomal abnormality has been reported only twice in the literature.
Asunto(s)
Cromosomas Humanos Par 10 , Leucemia Monocítica Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética , Cromosoma X , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Monocítica Aguda/inmunología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunologíaRESUMEN
Fludarabine, the 5'-monophosphate of 9-beta-D-arabinofuranosyl-2- fluoroadenine (FaraAMP), is effective in the treatment of chronic lymphocytic leukemia (CLL) and has been demonstrated to increase natural killer (NK) cell lytic activity (NKa) in humans and mice. To determine the effect of FaraAMP on NK cells in CLL, we analyzed NKa toward K562 targets after in vitro incubation with FaraAMP and after in vivo exposure to fludarabine. Pretreatment analysis of peripheral blood from 12 CLL patients (9 untreated) revealed: median number of NK cells 500/microliter (range 290-1160); median NKa lytic unit30/10(6) cells (range 5-80). These results were similar to those from healthy adult donors. After exposure to 3, 30 or 300 microM FaraAMP, the median maximum stimulation index (NKa FaraAMP/NKa) was 1.2 (range 0.9-1.5), within the range observed in normal adults. FaraA also stimulated NKa in vitro toward autologous CLL cells in two of five patients as measured by a dye-exclusion assay. In three patients following three or more treatment courses of fludarabine (30 mg/m2 per day for 5 days) the NK cell number and NKa were maintained near pretreatment values. Phenotypic analysis of the peripheral mononuclear cells in 34 consecutive CLL patients revealed a marked reduction in CD5/CD20 and CD4 cell numbers after three courses of fludarabine with less effect on CD8 and CD56 cells. These results indicate that fludarabine spares NK cells and may stimulate NKa in some CLL patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Células Asesinas Naturales/inmunología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Adulto , Citotoxicidad Inmunológica , Citometría de Flujo , Humanos , Inmunofenotipificación , Células Asesinas Naturales/efectos de los fármacos , Leucemia Linfocítica Crónica de Células B/inmunología , Recuento de Linfocitos , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Células Tumorales Cultivadas , Vidarabina/uso terapéuticoRESUMEN
To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-host disease (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10 children with leukemia received high-dose thiotepa, cyclophosphamide and total body irradiation followed by transplantation of CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to treatment with steroids. Five of nine evaluable patients developed chronic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD. This may have been due to the high number of T cells infused with the marrow.