RESUMEN
Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, â¼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6.81 × 106/kg (range, 0.98-29.78 × 106/kg) in a median of 3 infusions (range, 1-7). Median time between the onset of aGvHD and the first MSC infusion was 25.5 days (range, 6-153). Of the patients, 50% (23/46) presented clinical improvement. Of these, 3 patients (13%) had complete response, 14 (61%) had partial response and 6 (26%) had transient partial response. The estimated probability of survival at 2s year was 17.4%. Only 2 patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion. No patient had late or severe side effects because of MSC infusion. These results suggest that this therapeutic modality is safe and should be considered for steroid-refractory aGvHD, especially in countries where other second-line agents are less available.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Enfermedad Aguda , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Esteroides/administración & dosificación , Tasa de SupervivenciaRESUMEN
Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.
Asunto(s)
Apoptosis/genética , Proteína 5 Relacionada con la Autofagia/genética , Esclerosis Múltiple/genética , Adulto , Linfocitos T CD8-positivos/efectos de los fármacos , Ciclofosfamida/uso terapéutico , Femenino , Expresión Génica/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Adulto JovenRESUMEN
Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.
Asunto(s)
Galectina 1/genética , Galectina 3/genética , Janus Quinasa 2/genética , Policitemia Vera/genética , Mielofibrosis Primaria/genética , Trombocitemia Esencial/genética , Adulto , Sustitución de Aminoácidos , Antígenos CD34/genética , Proteínas Sanguíneas , Médula Ósea/patología , Neoplasias de la Médula Ósea/diagnóstico , Neoplasias de la Médula Ósea/genética , Neoplasias de la Médula Ósea/metabolismo , Línea Celular , Galectina 1/metabolismo , Galectina 3/metabolismo , Galectinas , Regulación Neoplásica de la Expresión Génica , Humanos , Janus Quinasa 2/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/metabolismo , Policitemia Vera/diagnóstico , Policitemia Vera/metabolismo , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/metabolismo , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/metabolismoRESUMEN
OBJECTIVES: Evaluate whether poor mobilisers had delayed haematopoietic (neutrophil and platelet) recovery despite receiving similar cell dose as good mobilisers. BACKGROUND: Autologous haematopoietic progenitor cell (HPC) transplantation is indicated to treat some haematological malignancies. This procedure requires HPC mobilisation from bone marrow to peripheral blood. Cell dose is important for a fast haematological recovery. Despite being poor mobilisers, some patients can collect enough cell numbers for transplantation. RESULTS: Fifteen poor mobiliser patients (peak of CD34+ cells ≤10 µL(-1) in peripheral blood) were transplanted at our institution. Haematological recovery (neutrophil ≥ 500 µL(-1) ) in this group was compared to that observed in the group of 16 patients of good mobilisers (peak of CD34+ cells ≥20 µL(-1) in peripheral blood) who received similar cell dose (2·637 ± 0·1744 × 10(6) kg(-1) vs 2·727 ± 0·1746 × 10(6) kg(-1) ; P = 0·7177). The poor mobiliser group had neutrophil and platelet recovery later than the good mobiliser group (on day 12, range 9-14 vs day 10, range 9-22, P = 0·0381 for neutrophil, and on day 22·89 ± 11·16 and 14·08 ± 4·821, P = 0·0193 for platelet). Mortality rates and transfusion requirements were not different between the groups. CONCLUSION: Poor mobilisers have delayed neutrophil and platelet recovery after autologous HPC transplantation despite having received the same cell dose as good mobilisers.
Asunto(s)
Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/sangre , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
Over the past 15 years, SCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies recently provided the proof-of-concept that restoration of immunological tolerance can be achieved by haematopoietic SCT in chronic autoimmunity through eradication of the pathologic, immunologic memory and profound reconfiguration of the immune system, that is, immune 'resetting'. Nevertheless, a number of areas remain unresolved and warrant further investigation to refine our understanding of the underlying mechanisms of action and to optimize clinical SCT protocols. Due to the low number of patients transplanted in each centre, it is essential to adequately collect and analyse biological samples in a larger cohort of patients under standardized conditions. The European society for blood and marrow transplantation Autoimmune Diseases and Immunobiology Working Parties have, therefore, undertaken a joint initiative to develop and implement guidelines for 'good laboratory practice' in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after SCT. The aim of this document is to provide practical recommendations for biobanking of samples and laboratory immune monitoring in patients with ADs undergoing SCT, both for routine supportive care purposes and investigational studies.
Asunto(s)
Enfermedades Autoinmunes/terapia , Bancos de Muestras Biológicas/normas , Trasplante de Células Madre Hematopoyéticas , Preservación Biológica/normas , Congresos como Asunto , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Guías de Práctica Clínica como Asunto , Índice de Severidad de la Enfermedad , Sociedades MédicasRESUMEN
Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T- and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4(+)CD25(hi)FoxP3(+) regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4(+)CD25(hi) T cells. We found transient increase in exhausted PD-1(+) T cells and of suppressive CD8(+)CD28(-)CD57(+) T cells. At baseline, CD4(+) and CD8(+) T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , MicroARNs/biosíntesis , Esclerosis Múltiple/genética , Esclerosis Múltiple/terapia , Acondicionamiento Pretrasplante/métodos , Adulto , Femenino , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Esclerosis Múltiple/metabolismo , Trasplante Autólogo , Adulto JovenRESUMEN
Primary myelofibrosis (PM) is a Philadelphia-negative clonal hematopoietic stem cell disorder characterized by intense reactive changes of bone marrow stroma with collagen fibrosis, osteosclerosis and angiogenesis. PM usually affects elderly people, and approximately half of the patients present JAK2V617F mutation. PM clinical course varies from 1 to 30 years, evolving from asymptomatic into progressive bone marrow failure, symptomatic splenomegaly or acute leukemia in 10-20 % of cases. PM risk stratification is based on parameters predicting survival, and several attempts have been made to identify clinical and laboratory features that could predict PM patient survival. This study applied five prognostic scores: Dupriez, Cervantes, Mayo, IPSS and DIPSS-Plus in 62 Brazilians patients from three centers, and compared their relevance and clinical usefulness considering the scores' parameters, fibrosis, JAK2V617F mutation, splenomegaly, hepatomegaly and treatment. According to the Cervantes, Dupriez and Mayo scores, most patients were stratified into low-risk group. However, when IPSS and DIPSS-Plus were applied, most patients were classified into an intermediate range, being low risk in only 11 and 13 % of patients, respectively. Overall survival at 4 years was 84 %. The Cervantes score was the only one that remained significantly associated with survival in a multivariate analysis. In conclusion, the Cervantes score remains important to the prognostication of PM.
Asunto(s)
Mielofibrosis Primaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mielofibrosis Primaria/clasificación , Mielofibrosis Primaria/enzimología , Mielofibrosis Primaria/genética , Pronóstico , Análisis de SupervivenciaAsunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Testículo/metabolismo , Adolescente , Adulto , Área Bajo la Curva , Niño , Ciclofosfamida/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Estudios Retrospectivos , Factores de Tiempo , Trasplante AutólogoAsunto(s)
Diabetes Mellitus Tipo 1/patología , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Recolección de Tejidos y Órganos/métodos , Adolescente , Adulto , Diabetes Mellitus Tipo 1/inmunología , Humanos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Esclerosis Múltiple/terapia , Acondicionamiento Pretrasplante/métodos , Adulto , Animales , Suero Antilinfocítico/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Rechazo de Injerto/prevención & control , Movilización de Célula Madre Hematopoyética , Caballos , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Calidad de Vida , ConejosRESUMEN
We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+. The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.
Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Leucemia Prolinfocítica de Células T/genética , Cromosomas en Anillo , Translocación Genética , Adulto , Inestabilidad Cromosómica/genética , Humanos , Masculino , Cariotipificación EspectralRESUMEN
Autologous or allogeneic SCT with conventional conditioning (chemotherapy with or without irradiation) has emerged as an effective and potentially curative therapy in patients with hematologic malignancies and in other selected solid tumors; however, several patients experience significant early and delayed side effects, including long-term endocrine imbalance and infertility. In spite of several reproductive recovery and pregnancy reports published in the oncology literature, review of medical literature reveals a paucity of comparable information in the SCT field. We report here four cases of ovarian recovery in patients who received hormonal replacement therapy after diagnosis of primary ovarian failure due to high-dose chemotherapy and SCT.
Asunto(s)
Terapia de Reemplazo de Estrógeno , Trasplante de Células Madre Hematopoyéticas , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Acondicionamiento Pretrasplante/efectos adversos , Adulto , Femenino , Humanos , Recién Nacido , Menstruación/efectos de los fármacos , Ovario/fisiología , Embarazo , Insuficiencia Ovárica Primaria/inducido químicamente , Resultado del TratamientoRESUMEN
We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lepra/etiología , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Lepra/diagnóstico , Lepra/patología , Masculino , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.
Asunto(s)
Bacteriemia/mortalidad , Resistencia a Múltiples Medicamentos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Brasil/epidemiología , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Niño , Preescolar , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de RiesgoAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/etiología , Trasplante de Células Madre/efectos adversos , Médula Ósea/metabolismo , Antígenos HLA/química , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante de Células Madre/métodos , Donantes de TejidosRESUMEN
This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma no Hodgkin/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Factores de Riesgo , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
In order to assess the effect of delaying G-CSF administration after autologous peripheral blood progenitor cell (PBPC) transplantation on the duration of neutropenia, 87 patients were randomized to receive G-CSF 5 microg/kg/day starting on day +1 (n = 45) or +5 (n = 42) following PBPC transplantation, until recovery of the neutrophils. The duration of neutropenia (<0.5 x 10(9)/l) was shorter in the day +1 group (7 vs 8 days; P = 0.02), especially in patients receiving melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg. These patients had a later onset of neutropenia after transplant. There were no differences in time to neutrophil and platelet engraftment, or in the incidence of fever and documentation of infection. Although the duration of antibiotic therapy (7 vs 10.5 days; P = 0.01) and time to hospital discharge (13 vs 15 days; P = 0.02) were shorter in the day +1 group, these differences could not be predicted by the day of G-CSF initiation in multivariate analysis. Starting G-CSF on day +1 does not result in faster neutrophil engraftment but in later onset and consequently, slightly shorter duration of neutropenia in patients who receive melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Adulto , Anciano , Esquema de Medicación , Femenino , Fiebre/etiología , Fiebre/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Hematopoyesis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/prevención & control , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Prospectivos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
We have determined the prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C in 71 children (< or = 15 years) with acute lymphoblastic leukaemia (ALL) and in 71 control subjects. Odds ratio (OR) for ALL linked to MTHFR C677T was 0.4 (95% CI 0.2-0.8); for heterozygotes it was 0.5 (95% CI 0.2-0.9) and for homozygotes it was 0.3 (95%CI 0.09-0.8). MTHFR A1298C yielded an overall OR for ALL of 1.3 (95% CI: 0.7-2.6); for heterozygotes it was 1.3 (95% CI: 0.7-7.6) and for homozygotes it was 2.8 (95% CI 0.5-15.6). In conclusion, MTHFR C677T was linked to a significant 2.4-fold decreased risk of developing childhood ALL, whereas MTHFR A1298C did not significantly affect the risk of ALL in our population.
Asunto(s)
Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Linfoma de Burkitt/genética , Estudios de Casos y Controles , Niño , Preescolar , Intervalos de Confianza , Femenino , Mutación de Línea Germinal , Heterocigoto , Homocigoto , Humanos , Lactante , Leucemia-Linfoma de Células T del Adulto/genética , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Oportunidad Relativa , Prevalencia , RiesgoRESUMEN
We report two cases of refractory chronic graft-versus-host disease after donor lymphocyte infusions in which the skin lesions improved dramatically with the use of intravenous pulses of lidocaine. This form of therapy has been used successfully for the cutaneous involvement of scleroderma and may have vasodilator and anti-inflammatory effects.