RESUMEN
BACKGROUND: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. PATIENTS AND METHODS: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). RESULTS: NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(-)] (defined as <10-6) in post-ASCT BM cases (n = 26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) cases (n = 7) where MRD was not detected by ASO-PCR (P = 0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10-7) (n = 19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents (n = 49) had a significantly better PFS (P = 0.001) and tended to have a better OS (P= 0.214) than those that were untreated (n = 33). CONCLUSIONS: Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.
Asunto(s)
Trasplante de Médula Ósea/métodos , Melfalán/uso terapéutico , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Trasplante de Células Madre/métodos , Antineoplásicos Alquilantes/uso terapéutico , Supervivencia sin Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Neoplasia Residual/genética , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Estudios Retrospectivos , Trasplante Autólogo , Resultado del TratamientoAsunto(s)
Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Japón/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver-operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.
Asunto(s)
Cadenas Ligeras de Inmunoglobulina/análisis , Linfoma de Células B/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Cadenas Ligeras de Inmunoglobulina/clasificación , Cadenas kappa de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/análisis , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The range of survival duration in myeloma patients is wide and several percent of patients live longer than 10 years. Therefore, a precise prediction of survival for the individual patient is required to decide treatment. We evaluated possible prognostic factors at diagnosis for 116 Japanese patients with multiple myeloma. Twelve parameters reported to affect survival were analyzed using a log rank test and stepwise Cox proportional hazards regression. Factors identified as adversely affecting survival were age over 60 years, male sex, blood hemoglobin less than 8.5 g/dl, platelets less than 100 x 10(9)/l, serum creatinine level more than 2.0 mg/dl, serum C-reactive protein (CRP) level more than 6.0 mg/l, and serum beta2-microglobulin level more than 6.0 mg/l. Among them, only high age and high serum CRP level were independently prognostic for poor survival. In conclusion, we have established a simple prognostic model for Japanese myeloma patients only, using factors that can be determined in routine examinations without the need of subjective information.
Asunto(s)
Mieloma Múltiple , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Creatinina/sangre , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/mortalidad , Mieloma Múltiple/fisiopatología , Análisis Multivariante , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Microglobulina beta-2/sangreRESUMEN
Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow and rarely cured by chemotherapy. Villunger et al. showed that the neoplastic plasma cells express Fas ligand (FasL), which transmits a signal of apoptosis upon ligation to Fas, and suggested that the FasL suppresses the T-cells activated against malignant cells, resulting in escape from tumour immunity. We examined serum soluble FasL (sFasL) levels in 35 multiple myeloma patients to evaluate the correlation between sFasL levels and clinical characteristics. The serum sFasL levels were not affected by the disease status, serum monoclonal protein levels, or other prognostic factors. We could not determine whether the expression of FasL is involved in the poor clinical course of the disease.
Asunto(s)
Glicoproteínas de Membrana/sangre , Mieloma Múltiple/sangre , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Sanguíneas , Proteína Ligando Fas , Femenino , Humanos , Inmunoglobulinas/sangre , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Proteínas de Mieloma/análisis , Proteínas de Mieloma/metabolismo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Solubilidad , Estadísticas no ParamétricasRESUMEN
C-reactive protein (CRP) is an acute phase reactant of inflammation. We evaluated the clinical value of serial measurement of CRP in neutropenic patients. CRP was shown to be useful to monitor the response to therapy for febrile episodes in neutropenia. However, we failed to show statistically significant differences in CRP levels between febrile episodes with or without clinically documented infection (p= 0.10) and with or without bacteremia (p = 0.55). Also, we could not predict febrile episodes within three days by the elevation of CRP value. The area under receiver-operating characteristic curve depicting the relationship between CRP levels and forthcoming febrile episodes was only 0.60. In conclusion, serial measurement of CRP was considered to be not useful to predict fever within three days, or to differentiate the types of infection.
Asunto(s)
Proteína C-Reactiva/metabolismo , Neutropenia/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Bacteriemia/sangre , Bacteriemia/inducido químicamente , Biomarcadores/sangre , Femenino , Fiebre/sangre , Fiebre/inducido químicamente , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Valor Predictivo de las Pruebas , Curva ROC , Estudios RetrospectivosRESUMEN
We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998. Distant extraosseous involvement was found in 33 patients (63.5%). Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection. Amyloidosis was shown in 8 patients. Second malignancies were observed in 4 cases. The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients. Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection.
Asunto(s)
Mieloma Múltiple/patología , Anciano , Anciano de 80 o más Años , Autopsia , Causas de Muerte , Técnicas de Laboratorio Clínico , Femenino , Hemorragia/etiología , Humanos , Infecciones/etiología , Enfermedades Renales/etiología , Enfermedades Renales/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Invasividad Neoplásica/patología , Células Plasmáticas/patología , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
BACKGROUND: Fluconazole is used widely for fungal prophylaxis. Although studies with bone marrow transplantation (BMT) recipients clearly showed the usefulness of oral fluconazole, results of the studies in neutropenic patients other than BMT recipients have been inconsistent. Therefore, the authors performed a meta-analysis to evaluate the efficacy of fluconazole prophylaxis during chemotherapy-induced neutropenia. METHODS: The authors identified reports that were not restricted to those in English and not restricted to published trials through MEDLINE, CANCERLIT, or the data base of the Pfizer company. The authors included prospective, randomized studies comparing oral fluconazole with placebo, no treatment, or oral polyenes as prophylaxis for fungal infections in neutropenic patients. Two independent authors extracted data from 16 trials with 3734 patients enrolled. The outcome measures were the development of fungal-related death, systemic and superficial fungal infections, the use of empiric intravenous amphotericin-B, and infections or colonization with fluconazole-resistant fungi. The summarized odds ratios (ORs) were calculated using the Mantel-Haenszel method and the DerSimonian-Laird method. RESULTS: Prophylactic fluconazole was not effective in reducing fungal-related death or in reducing proven, systemic fungal infections in non-BMT patients (OR, 0.91; 95% confidence interval [CI], 0.30-2.82 and OR, 0.85; 95% CI, 0.47-1.55, respectively). However, fluconazole was very effective in reducing superficial fungal infections (OR, 0.44; 95% CI, 0.24-0.80), even when it was given in lower doses (50-200 mg per day). There was no increase in proven, systemic infection of fluconazole-resistant fungi, although colonization of those fungi increased. When the results were combined in studies in which the incidence of systemic fungal infections was > 15%, fluconazole was effective in reducing such infections (OR, 0.23; 95% CI, 0.15-0.36). CONCLUSIONS: The current analyses failed to find an effect of fluconazole on both fatal fungal infection and systemic fungal infection in non-BMT patients. Further studies on severely neutropenic patients are warranted because prophylactic fluconazole seemed to be effective when the incidence of systemic fungal infection was expected to be > 15%.
Asunto(s)
Antifúngicos/uso terapéutico , Fluconazol/uso terapéutico , Micosis/tratamiento farmacológico , Neutropenia/inducido químicamente , Neutropenia/complicaciones , Administración Oral , Antineoplásicos/efectos adversos , Humanos , Micosis/etiología , Neoplasias/tratamiento farmacológico , Neutropenia/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Cyclophosphamide (CPA) is widely used for peripheral blood stem cell mobilization, and a dose adjustment of CPA in the presence of renal failure has not been suggested. However, we describe a myeloma patient with renal failure (serum creatinine 4.2 mg/dl, creatinine clearance 11.2 ml/min) receiving CPA 2 g/m2 for 2 days, who developed unexpectedly severe toxicity, including myopericarditis and prolonged myelosuppression. The serial serum concentrations of CPA metabolites were persistently much higher than those in a myeloma patient with normal renal function. We consider, therefore, that the dose of CPA should be reduced in the presence of severe renal failure when used as high-dose therapy or to mobilize peripheral blood stem cells.
Asunto(s)
Antineoplásicos Alquilantes/efectos adversos , Ciclofosfamida/efectos adversos , Movilización de Célula Madre Hematopoyética/efectos adversos , Miocarditis/inducido químicamente , Pericarditis/inducido químicamente , Insuficiencia Renal/complicaciones , Adulto , Antineoplásicos Alquilantes/sangre , Antineoplásicos Alquilantes/farmacocinética , Ciclofosfamida/farmacocinética , Femenino , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Mieloma Múltiple/sangre , Mieloma Múltiple/metabolismo , Mieloma Múltiple/terapia , Derrame Pericárdico/inducido químicamente , Insuficiencia Renal/sangre , Insuficiencia Renal/metabolismoRESUMEN
We evaluated possible prognostic factors just before salvage therapy with vincristine, doxorubicin, and dexamethasone (VAD) for 36 patients with refractory multiple myeloma. The median duration from diagnosis to the first VAD salvage was 14 months (range 2-76 months). Among parameters that have been shown to be associated with poor survival, a high serum lactate dehydrogenase (LDH) level was the sole significant predictor of survival. The median survival of patients with high LDH levels was 4 months, whereas that of patients with low LDH levels was 20 months. A multivariate analysis identified high LDH and high age as independent prognostic factors. More aggressive therapies might be indicated for high-LDH patients with refractory myeloma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , L-Lactato Deshidrogenasa/sangre , Mieloma Múltiple/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Terapia Recuperativa , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Adult T-cell leukemia/lymphoma (ATL) is a neoplastic disorder of T lymphocytes associated with human T lymphotropic virus type I (HTLV-I). The prognosis of ATL is generally poor. We present here a 79-year-old woman with spontaneous remission of acute type ATL. Spontaneous remission was preceded by surgical biopsy and pneumonia and lasted for two years until she died with pancreas cancer. Monoclonal integration of HTLV-I provirus DNA became undetectable after remission.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/diagnóstico , Adulto , Anciano , Células Clonales , ADN Viral , Femenino , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/fisiología , Humanos , Inmunofenotipificación , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Persona de Mediana Edad , Remisión Espontánea , Integración ViralRESUMEN
Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.
Asunto(s)
Trasplante de Médula Ósea , Trasplante Homólogo , Filtros de Vena Cava , Vena Cava Superior , Trombosis de la Vena/terapia , Anticoagulantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cateterismo Venoso Central/efectos adversos , Trastornos de las Proteínas de Coagulación/complicaciones , Terapia Combinada , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Endotelio Vascular/lesiones , Heparina/uso terapéutico , Humanos , Inmovilización/efectos adversos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Radiografía , Terapia Recuperativa , Trombofilia/etiología , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/patología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/etiología , Vincristina/administración & dosificación , Warfarina/uso terapéuticoRESUMEN
BACKGROUND: Although many studies have been performed to evaluate the prognostic significance of CD34 expression in acute myeloid leukemia (AML), the findings have been inconsistent. In this study, the authors reviewed such previous studies to establish a definite conclusion. METHODS: Using MEDLINE, the authors identified studies that evaluated the prognostic significance of CD34 expression in AML. The outcome measure was the complete remission rate. They used the random-effect method to combine the results. Results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The ORs were less than 1 if the complete remission occurred more frequently in the CD34 negative group. RESULTS: Twenty-two studies including 2483 patients were reviewed. The combined OR was 0.38 (95% CI, 0. 26-0.57), which suggested that CD34 expression was associated with a poor remission rate. However, the authors found statistical evidence of marked heterogeneity among trials (P < 0.001), especially according to time of publication. The combined OR in studies published in or after 1994 was 0.70 (95% CI, 0.47-1.09). The authors divided the studies into several subgroups, but they could not determine the reason for the heterogeneity. CONCLUSIONS: At present, CD34 expression should not be considered a marker of poor prognosis because it is not supported by the combined data from recent studies. Further studies should be conducted to investigate the intensity of CD34 expression in specific populations of patients, such as those with t(8;21) or t(15;17) translocations or the AML-M0 subtype.
Asunto(s)
Antígenos CD34/metabolismo , Antígenos de Neoplasias/metabolismo , Leucemia/metabolismo , Enfermedad Aguda , Intervalos de Confianza , Humanos , Leucemia/mortalidad , Oportunidad Relativa , PronósticoRESUMEN
Oral complications occur frequently after bone marrow transplantation (BMT). Some of them are caused by regimen-related toxicity of the preparative regimen, and others by infections. In addition, oral tissues are targets of graft-versus-host disease (GVHD). Oral granulomatous lesions are not a common complication after BMT, and are especially rare on the tongue. Such rare lesions reported in the literature, developed late after BMT with oral chronic GVHD. We present here a patient who developed pyogenic granuloma of the tongue early after allogeneic BMT done for multiple myeloma. Regimen-related mucositis, oral acute GVHD, the administration of cyclosporine A, and the preexisting macroglossia might be responsible for the formation of granuloma.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Granuloma Piogénico/etiología , Mieloma Múltiple/terapia , Enfermedades de la Lengua/etiología , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Interleukin 2 receptor is expressed not only on the surface of activated T or B lymphocytes, but also on certain lymphoid malignancies. The receptor is released from the cell membrane as soluble form (sIL-2R). Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation or specific tumor cell growth including non-Hodgkin's lymphoma (NHL). However, the relevance of serum sIL-2R levels relating to clinical outcome in adult patients with NHL remains uncertain. Therefore, we investigated the serial serum sIL-2R levels in 28 untreated patients with NHL to evaluate its correlation with clinical characteristics. High serum sIL-2R level (>1000 U/ml) at diagnosis was associated with a high incidence of treatment failure (p=0.03) and poor overall survival (p=0.057). The serum sIL-2R levels decreased significantly after achieving complete remission (p=0.003). Further larger studies are required to evaluate whether serum sIL-2R level is an independent prognostic factor or not. However, adding this parameter to those already employed in the International Prognostic Index would perhaps provide a better prognostic index for adult patients with NHL.
Asunto(s)
Linfoma no Hodgkin/sangre , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Japón , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
We describe a patient with leukocytosis with all the stages of neutrophilic series, peripheral dominant myeloblast proliferation, marked dysplasia of myeloid and erythroid series, and extramedullary hematopoiesis of the lymph nodes. A cytogenetic study of the bone marrow cells showed normal karyotype, and molecular analysis of the leukemic cells showed negative for BCR-ABL by RT-PCR. After chemotherapy, the patient went into complete remission with a normal blood and bone marrow profile with no dysplasia. On relapse, the hematological findings showed a typical bone marrow dominant acute myeloid leukemia, with the leukemic cells having a chromosomal abnormality. The patient exhibited the combined features of myeloproliferative disorder, myelodysplastic syndrome, peripheral dominant myeloblast proliferation (so-called peripheral leukemia) and typical acute myeloid leukemia throughout the clinical course. This is thought to be a rare overlapping disease involving these distinct hematological conditions that do not usually occur in the same patient.
Asunto(s)
Leucemia Mieloide/patología , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/patología , Preleucemia/patología , Enfermedad Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Citarabina/administración & dosificación , Citarabina/análogos & derivados , Daunorrubicina/administración & dosificación , Progresión de la Enfermedad , Hematopoyesis Extramedular , Humanos , Masculino , Mercaptopurina/administración & dosificación , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Trastornos Mieloproliferativos/tratamiento farmacológico , Prednisolona/administración & dosificación , Inducción de RemisiónRESUMEN
An 84-year-old woman was admitted with acute non-lymphoblastic leukemia transformed from myelodysplastic syndrome. We examined the signal transduction of the leukemic blasts. Stimulation of the blasts by macrophage colony-stimulating factor (M-CSF) resulted in tyrosine phosphorylation of several cellular proteins. In vitro proliferation of leukemic blasts was stimulated by M-CSF, but not by granulocyte colony-stimulating factor. Based upon these findings, combined therapy with M-CSF and low dose cytosine arabinoside (ara-C) was successful. After her recovery, we confirmed marked reduction of blasts and disappearance of M-CSF-responsive cells. These results suggest that M-CSF could enhance the cytotoxic effect of ara-C on leukemic blasts via its intracellular signaling pathway linked to proliferation.