RESUMEN
Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.
Asunto(s)
Carbazoles , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma Anaplásico de Células Grandes , Piperidinas , Masculino , Humanos , Adulto , Linfoma Anaplásico de Células Grandes/terapia , Recurrencia Local de Neoplasia , Proteínas Tirosina Quinasas Receptoras/uso terapéuticoRESUMEN
We assessed the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction prior to autologous stem cell transplantation (ASCT) in newly diagnosed Japanese patients with multiple myeloma (MM). This regimen consisted of four 28-day cycles of once-weekly oral cyclophosphamide (300 mg/m2), subcutaneous bortezomib (1.3 mg/m2), and oral dexamethasone (40 mg). Responding patients underwent stem cell collection followed by ASCT. The primary endpoint was the postinduction rate of achieving a near complete response (nCR) or better. Among the 38 enrolled patients, a complete response (CR), an nCR, a very good partial response (VGPR), and a partial response (PR) were achieved in 10.5, 2.6, 23.7, and 36.8% of cases, respectively. A grade 4 hematological adverse event (AE) was observed in 1 patient. Grade 3-4 infection, including febrile neutropenia, was observed in 4 patients (10.5%). Although 2 patients dropped out due to AE, 94.7% of the patients completed the induction phase. However, because of a poor response to induction chemotherapy (Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Bortezomib/administración & dosificación
, Ciclofosfamida/administración & dosificación
, Dexametasona/administración & dosificación
, Mieloma Múltiple/tratamiento farmacológico
, Adolescente
, Adulto
, Anciano
, Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
, Bortezomib/efectos adversos
, Ciclofosfamida/efectos adversos
, Dexametasona/efectos adversos
, Esquema de Medicación
, Femenino
, Enfermedades Hematológicas/etiología
, Trasplante de Células Madre Hematopoyéticas
, Humanos
, Japón
, Masculino
, Persona de Mediana Edad
, Mieloma Múltiple/diagnóstico
, Mieloma Múltiple/mortalidad
, Análisis de Supervivencia
, Trasplante Autólogo
, Resultado del Tratamiento
, Adulto Joven
RESUMEN
Aplastic anemia is a hematopoietic deficiency disorder with pancytopenia, and immunosuppressive therapy is effective. We report a case in which plasma cells appeared in the peripheral blood during immunosuppressive therapy for aplastic anemia. Based on the results of morphology and flow cytometry, the plasma cells were considered reactive and disappeared spontaneously after follow-up. Thereafter, the patient had a good hematopoietic recovery. Reactive plasmacytosis has been reported in infectious and autoimmune diseases, but this is the first report of reactive plasmacytosis during immunosuppressive therapy for aplastic anemia, to our knowledge. In this case, reactive plasmacytosis was a sign preceding good hematopoietic recovery.
RESUMEN
Light chain proximal tubulopathy (LCPT) is a rare type of monoclonal gammopathy of renal significance. Clinicians should consider LCPT in the differential diagnosis of patients with renal or proximal tubular dysfunction with monoclonal gammopathy. They should confirm diagnosis by renal biopsy and initiate chemotherapy before disease progression.
RESUMEN
As hematopoietic progenitors supply a large number of blood cells, therapeutic strategies targeting hematopoietic progenitors are potentially beneficial to eliminate unwanted blood cells, such as leukemic cells and immune cells causing diseases. However, due to their pluripotency, targeting those cells may impair the production of multiple cell lineages, leading to serious side effects such as anemia and increased susceptibility to infection. To minimize those side effects, it is important to identify monopotent progenitors that give rise to a particular cell lineage. Monocytes and monocyte-derived macrophages play important roles in the development of inflammatory diseases and tumors. Recently, we identified human monocyte-restricted progenitors, namely, common monocyte progenitors and pre-monocytes, both of which express high levels of CD64, a well-known monocyte marker. Here, we introduce a dimeric pyrrolobenzodiazepine (dPBD)-conjugated anti-CD64 antibody (anti-CD64-dPBD) that selectively induces the apoptosis of proliferating human monocyte-restricted progenitors but not non-proliferating mature monocytes. Treatment with anti-CD64-dPBD did not affect other types of hematopoietic cells including hematopoietic stem and progenitor cells, neutrophils, lymphocytes and platelets, suggesting that its off-target effects are negligible. In line with these findings, treatment with anti-CD64-dPBD directly killed proliferating monocytic leukemia cells and prevented monocytic leukemia cell generation from bone marrow progenitors of chronic myelomonocytic leukemia patients in a patient-derived xenograft model. Furthermore, by depleting the source of monocytes, treatment with anti-CD64-dPBD ultimately eliminated tumor-associated macrophages and significantly reduced tumor size in humanized mice bearing solid tumors. Given the selective action of anti-CD64-dPBD on proliferating monocyte progenitors and monocytic leukemia cells, it should be a promising tool to target cancers and other monocyte-related inflammatory disorders with minimal side effects on other cell lineages.
Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Inmunoconjugados/farmacología , Células Precursoras de Monocitos y Macrófagos/efectos de los fármacos , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Humanos , Inmunoconjugados/uso terapéutico , Inmunofenotipificación , Ratones , Ratones Noqueados , Ratones Transgénicos , Células Precursoras de Monocitos y Macrófagos/metabolismo , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Células THP-1 , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismoRESUMEN
Nivolumab exerts therapeutic activity in patients with classic Hodgkin's lymphoma (CHL) but may cause several types of immune-related adverse events. Some rheumatoid arthritis (RA) patients develop CHL during methotrexate therapy (MTX-CHL); however, the efficacy and safety of nivolumab for these patients remain unclear. A 68-year-old woman was diagnosed with CHL after six years of MTX therapy for RA. The disease did not respond to any type of chemotherapy. Nivolumab was then initiated, and the patient was successfully treated without the reactivation of RA. The reactivation of RA always needs to be considered with the administration of nivolumab.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Antirreumáticos/efectos adversos , Enfermedad de Hodgkin/inducido químicamente , Enfermedad de Hodgkin/tratamiento farmacológico , Metotrexato/efectos adversos , Nivolumab/uso terapéutico , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Metotrexato/uso terapéuticoRESUMEN
BACKGROUND/AIM: Although various prognostic indices for follicular lymphoma (FL) have been proposed, they are designed specifically for patients requiring immediate therapy. We aimed to develop a new simple prognostic tool applicable for all patients with FL at diagnosis. MATERIALS AND METHODS: We retrospectively analyzed various clinical, pathological, and laboratory data, including soluble interleukin-2 receptor (sIL2R), from 140 patients with FL from two centers for their impact on prognosis. This study analyzed the impact of soluble interleukin-2 receptor (sIL2R) in order to develop a new simple prognostic tool applicable for all patients with FL at diagnosis. RESULTS: The initial management of these patients was watchful waiting (n=48) or immediate treatment (n=92). Event-free survival at 24 months predicted overall survival. When categorized into three groups according to the sIL2R levels at diagnosis, a very high sIL2R level identified about 20% of patients with a distinctively worse survival compared to the others. CONCLUSION: sIL2R is a very effective biomarker that can be easily applied in routine practice to predict survival for all patients with FL at diagnosis irrespective of initial management approach.
Asunto(s)
Biomarcadores de Tumor , Linfoma Folicular/sangre , Linfoma Folicular/mortalidad , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Manejo de la Enfermedad , Femenino , Humanos , Linfoma Folicular/diagnóstico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
To clarify the clinical features of adult patients with acute leukemia (AL) with 11q23 abnormalities, we performed a retrospective analysis of data from 58 adult Japanese patients: 51 with acute myeloid leukemia (AML), and 7 with acute lymphoblastic leukemia (ALL). The incidences according to fusion partners in AML were: t(9;11), 31.3%; t(11;19), 27.4%; t(6;11), 21.5%. The incidence of patients with t(11;19) was higher than those in the US and Europe, and the incidence of t(4;11) was lower than that in childhood. The results indicated the poor prognosis of AML with 11q23 abnormalities regardless of the fusion partners. AML patients with 11q23 aged <60 years in the first CR who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed a more favorable outcome than those treated without allo-HSCT, although the differences were not statistically significant (P = 0.322 for DFS, P = 0.138 for OS). This result suggests that treatment strategies including allo-HSCT may be considered in the first CR in cases of AML with 11q23 abnormalities. However, further studies involving a large number of cases are required to assess the effect of allo-HSCT on adult AL with 11q23 abnormalities.
Asunto(s)
Cromosomas Humanos Par 11/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética/genética , Adulto , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
T-cell prolymphocytic leukemia (T-PLL) is a rare postthymic T-cell disorder. The disease is characterized by lymphadenopathy, splenomegaly, skin lesions, a high white blood cell count, and an aggressive clinical course. The small cell variant of T-PLL occurs in approximately 20% of patients. Most T-PLL patients express membrane T-cell receptors (TCR) of the alphabeta phenotype. The diagnosis of small cell variant T-PLL in a 56-year-old woman was based on the findings of abnormal lymphocytosis, immunophenotype, lymphadenopathy, and aggressive clinical behavior. Immunophenotype analysis showed that lymphocytes were positive for CD2, CD3, CD5, CD7, CD8, and TCR gammadelta antigens and negative for CD1a, CD4, and TCR alphabeta antigens. Southern blot analysis revealed rearrangement of the TCR Jgamma and Jdelta-1 genes. A cytogenetic study of peripheral blood showed a normal karyotype. T-PLL with a TCR gammadelta phenotype is very rare. This case was typical T-PLL except for the morphologically small cell type and the lack of the typical chromosome aberration. If cases accumulate in the future, the specific features of the gamma8 type of T-PLL will become clearer.
Asunto(s)
Leucemia Prolinfocítica/patología , Leucemia de Células T/patología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Femenino , Humanos , Inmunofenotipificación , Leucemia Prolinfocítica/terapia , Leucemia de Células T/terapia , Persona de Mediana Edad , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
We report a patient with pseudo gray platelet syndrome. He was admitted to our hospital because of acute myocardial infarction. He had platelets that were stained poorly and appeared gray and agranular under a light microscope. This appearance is a characteristic feature of gray platelet syndrome. However, in this case, no bleeding tendency was observed and the abnormality was dependent on the presence of ethylenediamine tetra acetic acid (EDTA) and did not occur in a nonanticoagulant, trisodium citrate dihydrate and heparin. There are few reports of this pseudo gray platelet syndrome and, in fact, this is the first report of the syndrome in Japan, possibly because the phenomenon has been unrecognized and passed over in the past.
Asunto(s)
Trastornos de las Plaquetas Sanguíneas/diagnóstico , Plaquetas/efectos de los fármacos , Infarto del Miocardio/sangre , Anciano , Recuento de Células Sanguíneas , Trastornos de las Plaquetas Sanguíneas/patología , Plaquetas/patología , Plaquetas/ultraestructura , Diagnóstico Diferencial , Ácido Edético/farmacología , Reacciones Falso Positivas , Humanos , Masculino , SíndromeRESUMEN
We report a case of T-cell prolymphocytic leukemia in a 56-year-old woman who exhibited hemorrhaging with gastric involvement as the first manifestation. This patient's condition was diagnosed as T-cell prolymphocytic leukemia based on the findings of lymphocytosis, abnormal immunophenotype, hepatosplenomegaly, lymphadenopathy, and cutaneous involvement. Endoscopic examination of the upper gastrointestinal tract revealed hemorrhage from a gastric lesion with histological involvement. Cytogenetic analysis revealed chromosomal abnormalities, 46,XX,der(1), add(1)(p36), that have not previously been described in T-cell prolymphocytic leukemia. In spite of a transient response to chemotherapy, the patient died 15 months after onset of the disease.
Asunto(s)
Aberraciones Cromosómicas , Hemorragia Gastrointestinal/complicaciones , Leucemia Prolinfocítica/genética , Leucemia de Células T/genética , Linfocitos T/inmunología , Cromosoma X , Antígenos CD/sangre , Femenino , Hemorragia Gastrointestinal/genética , Hemorragia Gastrointestinal/patología , Reordenamiento Génico de Linfocito T , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Prolinfocítica/sangre , Leucemia Prolinfocítica/complicaciones , Leucemia Prolinfocítica/patología , Leucemia de Células T/sangre , Leucemia de Células T/complicaciones , Leucemia de Células T/patología , Persona de Mediana EdadRESUMEN
A 56-year-old woman was admitted because of anemia in April 2001. A diagnosis of malignant lymphoma (ML) (diffuse mixed, B-cell type) had been made in March 2000 whereafter she had been treated with CHOP chemotherapy and had achieved complete remission (CR). On examination, it was found she had concurrently developed pure red cell aplasia (PRCA) and warm type autoimmune hemolytic anemia (AIHA) without relapse of the ML. The PRCA and AIHA were successfully treated with prednisolone. To our knowledge, only 4 cases of PRCA and AIHA associated with ML have been reported. Moreover, this is the first report of the coexistence of PRCA and AIHA occurring during the CR of ML.
Asunto(s)
Anemia Hemolítica Autoinmune/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/complicaciones , Linfoma no Hodgkin/complicaciones , Aplasia Pura de Células Rojas/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Persona de Mediana Edad , Prednisona/administración & dosificación , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.
Asunto(s)
Inmunoglobulina E/sangre , Hígado/patología , Ganglios Linfáticos/patología , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/líquido cefalorraquídeoRESUMEN
A feasibility study on high-dose therapy with autologous peripheral blood stem cell transplantation (HDT/PBSCT) was performed in Japanese patients with multiple myeloma (MM). Twenty evaluable patients younger than 65 years old with stage II/III MM were enrolled in this study. Three courses of VAD were used as initial chemotherapy. High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSCH, and 1.2-89.3 (median 23.4) x 106/kg of CD34+ cells were collected. Single (11 patients) or tandem (9 patients) HDT with melphalan (MEL) 200 mg/m2 or MEL 140 mg/m2 plus TBI 10 Gy were performed. The incidence of grade 4 toxicity (COG) was 10% and treatment-related mortality was 5%. Complete response and tumor reduction of more than 75% were obtained in 4 (21%) and 16 (84%) out of 19 patients, respectively. The actuarial 3-year overall survival (OS) and event-free survival (EFS) after PBSCT/HDT were 65.6% and 22.0%, respectively. The median EFS duration was 18 months. These preliminary results indicated that HDT/PBSCT is feasible for Japanese MM patients. A prospective randomized clinical trial will be required to assess the efficacy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica , Adulto , Anciano , Antígenos CD34 , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Japón , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/mortalidad , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Vincristina/administración & dosificaciónRESUMEN
The IGH/CCND1 fusion gene has been reported in many hematologic tumors such as mantle cell lymphoma, chronic lymphocytic leukemia, prolymphocytic leukemia, multiple myeloma, and plasma cell leukemia. We report a case of plasma cell leukemia showing five IGH/CCND1 fusion signals by interphase fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis and multicolor spectral karyotyping showed a complex karyotype that did not include t(11;14). Metaphase FISH studies revealed three IGH/CCND1 fusion signals, two of which were amplified signals. These findings indicate that IGH/CCND1 fusion gene was amplified and interspersed in several chromosomes. The patient was treated with intensive chemotherapy. However, the clinical course was very aggressive. The amplification of the IGH/CCND1 fusion gene may contribute to the aggressive course of the disease. To our knowledge, this is the first case showing amplification of the IGH/CCND1 gene in plasma cell neoplasms.
Asunto(s)
Ciclina D1/genética , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia de Células Plasmáticas/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Cariotipificación EspectralRESUMEN
Malignant lymphoma around the orbit is very rare. We present a rare case of optic neuropathy caused by lymphoma. A 61-year-old Japanese woman was referred to our hospital for evaluation of idiopathic optic neuropathy affecting her right eye. The patient was treated with steroid pulse therapy (methyl-predonisolone 1 g daily for 3 days) with a presumed diagnosis of idiopathic optic neuritis. After she had been switched to oral steroid therapy, endoscopic sinus surgery had been performed, which revealed diffuse large B cell lymphoma of the ethmoidal sinus. Although R-CHOP therapy was immediately started, prolonged optic nerve compression resulted in irreversible blindness. Accordingly, patients with suspected idiopathic optic neuritis should be carefully assessed when they show a poor response, and imaging of the orbits and brain should always be done for initial diagnosis because they may have compression by a tumor.