RESUMEN
Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy caused by the human T-cell lymphotropic virus, type I and it has an extremely poor prognosis. A 66-year-old man with severe hepatic damage, massive pleural effusion and ATL cell infiltration-induced ascites was referred to our department. Reduced-intensity cytotoxic chemotherapy was attempted, but could not continue due to persistent hyperbilirubinemia. Laboratory results also showed elevated lactate dehydrogenase (LDH) and serum albumin levels were profoundly decreased. A humanized monoclonal antibody against chemokine receptor type 4 (CCR4), mogamulizumab (Moga), was thereby challenged and it successfully resolved the hepatic damage. Finally, a standard dose of chemotherapy could be administered, and it induced a complete remission. The patient is still in remission more than three years after the final dosage of standard chemotherapy. These results indicate that Moga, whose pharmacokinetics are not significantly influenced by hepatic function or serum albumin, could be a promising treatment option for patients with ATL complicated by severe hepatic damage due to infiltration of ATL cells.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia-Linfoma de Células T del Adulto , Anciano , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Masculino , Pronóstico , Inducción de RemisiónRESUMEN
POEMS syndrome is often complicated by pulmonary hypertension. The standard therapy for patients with POEMS syndrome is high-dose chemotherapy followed by autologous stem cell transplantation. However, the safety of high-dose chemotherapy for patients complicated with pulmonary hypertension remains unclear, and the optimal therapy for these patients is yet to be establishment. Herein, we report the case of a 54-year-old woman with POEMS syndrome accompanied by pulmonary hypertension. We successfully and safely performed lenalidomide and dexamethasone (Ld) therapy followed by high-dose chemotherapy and autologous stem cell transplantation, which improved her pulmonary hypertension. Thus, Ld can be considered as safe and effective for pulmonary hypertension with POEMS syndrome.
Asunto(s)
Dexametasona/uso terapéutico , Hipertensión Pulmonar , Lenalidomida/uso terapéutico , Síndrome POEMS , Femenino , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Persona de Mediana Edad , Síndrome POEMS/complicaciones , TalidomidaRESUMEN
Adult T cell leukemia/lymphoma (ATL) is an aggressive peripheral T cell neoplasm with very poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported as a curative treatment modality for ATL. However, there are no reports comparing chemotherapy alone with allo-HSCT in ATL. In this report, we retrospectively analyzed data for patients treated with (n = 29, median age 55 years) or without allo-HSCT (n = 37, median age 58 years) for ATL in Kagoshima University Hospital, located in one of the most endemic areas of human T cell lymphotropic leukemia virus type 1 infection. Forty patients (61%) started coordination for allo-HSCT. Ten patients (34.4%) received allo-HSCT while in complete remission (CR), whereas the others were not in CR. Twenty-five patients (86.2%) received reduced-intensity conditioning, and the others received myeloablative conditioning. With a median follow-up period for survivors of 41 months (range, 5 to 125 months), the 3-year overall survival (OS) rate from first chemotherapy for all patients (with or without allo-HSCT) was 35.2%. The 3-year OS from first chemotherapy for patients who received allo-HSCT or only chemotherapy was 44.9% and 27.7%, respectively. Univariate analyses revealed that high serum soluble IL-2 receptor (sIL-2R) levels (≥ 2000 U/mL) just before the conditioning regimen and progressive disease (PD) status at HSCT (according to Japan Clinical Oncology Group Study 0907 criteria) were significant risk factors for OS in the allo-HSCT group. Multivariate analyses revealed that PD status was a significant risk factor for OS in the allo-HSCT group. In the chemotherapy-only group, the 3-year OS rate was 61.5% (95% CI, 30.8% to 81.8%) in patients with serum sIL-2R levels < 2000 U/mL for > 3 months. In contrast, the 3-year OS rate was 5.7% (95% CI, .4% to 22.4%) in patients who did not achieve serum sIL-2R levels < 2000 U/mL for >3 months. Our single-center cohort experience indicates that chemosensitivity is the most important prognostic factor for OS in ATL patients and the use of allo-HSCT is limited in chemorefractory patients with aggressive ATL disease. In the chemosensitive patients, allo-HSCT demonstrated a tendency toward better OS. Further clinical studies are warranted to determine optimal treatments for patients who are less sensitive to conventional chemotherapy.
Asunto(s)
Antineoplásicos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
A 79-year-old man presented with respiratory distress associated with a mediastinal mass and pleural effusion, and was diagnosed as having adult T-cell leukemia/lymphoma. The patient was highly refractory to anticancer drugs and radiotherapy from the time of onset and had progressive respiratory deterioration. However, his condition became stable with the administration of valemetostat for 11 days, and subsequent low-dose-anticancer agents led to a rapid improvement accompanied by high fever and a surge in C-reactive protein. In this case, the in vivo priming effect of valemetostat on tumor cells may have increased the sensitivity of these cells to conventional anti-cancer drugs.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Leucemia-Linfoma de Células T del Adulto , Enfermedades de la Piel , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/mortalidad , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/mortalidad , Tasa de SupervivenciaRESUMEN
OBJECTIVES: During therapeutic intervention for adult T-cell leukemia-lymphoma (ATLL), transient red blood cell (RBC) deformations and rapid anemia progression are often observed. These RBC responses are characteristically observed during the treatment of ATLL, and we examined the details and significance of these RBC responses. METHODS: Seventeen patients with ATLL were enrolled. Peripheral blood smears and laboratory findings were collected during the first two weeks after treatment intervention. We examined the transition of erythrocyte morphology and the factors associated with the induction of anemia. RESULTS: RBC abnormalities (i.e., elliptocytes, anisocytosis, and schistocytes) rapidly progressed following therapeutic intervention in five of the six cases for whom evaluable consecutive blood smears were available, with significant improvement evident after two weeks. Changes in RBC morphology were significantly associated with the red cell distribution width (RDW). Laboratory findings from all 17 patients showed various levels of anemia progression. A transient increase in RDW values was observed in 11 cases after therapeutic intervention. The degree of progressive anemia during the two-week period was significantly correlated with increased lactate dehydrogenase and soluble interleukin-2 receptor levels and an increase in RDW (P <0.01). CONCLUSIONS: In cases of ATLL, transient progression of RBC morphological abnormalities and RDW value were observed early after therapeutic intervention. These RBC responses may be associated with tumor and tissue destruction. RBC morphology or RDW values may provide important information about the tumor dynamics and general condition of the patients.
RESUMEN
A 66-year-old woman who had received tacrolimus for more than 11 years was admitted with high fever, generalized lymphadenopathy, and persistent gastrointestinal bleeding. Histopathological evaluation of the lymph nodes and colonic mucosa confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma. After discontinuation of tacrolimus, the lymphoma did not improve, and low-dose chemotherapy was introduced, which resulted in a recovery of lymphocyte counts and induction of complete remission. Low-dose anticancer treatments that suppress tumor growth while awaiting normal lymphocyte recovery for several weeks may be a useful therapeutic option even for aggressive lymphomas that develop during immunosuppressant therapy.
RESUMEN
A 56-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for six years visited our hospital with dyspnea and dizziness. Abdominal ultrasonography revealed mild splenomegaly. Laboratory examinations showed a marked elevation in soluble interleukin-2 receptor and lactate dehydrogenase levels. These abnormalities revealed a spontaneous regression after MTX discontinuation, however, they worsened again four months later. Skin biopsies revealed a diagnosis of intravascular large B-cell lymphoma (IVLBCL), and we diagnosed MTX-associated IVLBCL (MTX-IVLBCL) based on its characteristic course. Despite the recurrence of IVLBCL, it showed a good response to chemotherapy. MTX-IVLBCL should therefore be treated with consideration since it has different characteristics from that of de novo IVLBCL.
Asunto(s)
Artritis Reumatoide , Linfoma de Células B Grandes Difuso , Trastornos Linfoproliferativos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/efectos adversos , Persona de Mediana EdadRESUMEN
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm associated with the human T-cell leukemia virus type-I (HTLV-1); prognosis still remains very poor. We retrospectively reviewed the treatment of 198 patients with acute-, lymphoma- and unfavorable chronic-type ATL (aggressive ATL) diagnosed from 2005 to 2014 in a hospital located in an area of Japan in which HTLV-1 is highly endemic. One-hundred forty-three, and 35 patients were treated using OPEC/MPEC and VCAP-AMP-VECP, respectively. OPEC/MPEC was mainly used until around 2010, and gradually switched to VCAP-AMP-VECP, especially for younger patients. The 2-year overall survival for patients treated by VCAP-AMP-VECP was significantly higher than that using OPEC/MPEC for patients < 70 years old (y.o.), but not for patients ≥ 70 y.o. A less intensive chemotherapy OPEC/MPEC could be performed without reducing dose intensity, even in elderly patients, and its therapeutic outcome is not inferior to that of VCAP-AMP-VECP. It is difficult to draw definite conclusion from this small retrospective study; however, OPEC/MPEC may represent an alternative option for elderly patients with aggressive ATL.
Asunto(s)
Infecciones por Deltaretrovirus/epidemiología , Leucemia-Linfoma de Células T del Adulto/terapia , Progresión de la Enfermedad , Hospitales/estadística & datos numéricos , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/epidemiología , Estudios RetrospectivosRESUMEN
In the original publication of the article, Table 5 was published with incorrect contents. The correct Table 5 is given in this correction.
RESUMEN
We report 2 patients with chronic myeloid leukemia in the chronic phase showing diffusely increased F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow before treatment. Follow-up FDG positron emission tomography (PET) scans were performed in a patient after cessation of treatment and in the other under treatment. Both FDG PET findings showed reduced FDG uptake in the bone marrow. A series of these FDG PET findings suggest the usefulness of FDG PET for the diagnosis and monitoring of chronic myeloid leukemia after treatment.
Asunto(s)
Fluorodesoxiglucosa F18 , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico por imagen , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Pirimidinas/uso terapéutico , Anciano , Antineoplásicos/uso terapéutico , Benzamidas , Femenino , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Pronóstico , Radiofármacos , Resultado del TratamientoRESUMEN
Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/efectos adversos , Movilización de Célula Madre Hematopoyética/efectos adversos , Síndrome de Dificultad Respiratoria/inducido químicamente , Donantes de Tejidos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante HomólogoRESUMEN
A 61-year-old man with progressive adult T-cell leukemia/lymphoma (ATLL) successfully received reduced-intensity conditioning stem cell transplantation (RIST) without T-cell depletion (TCD) from his HLA-incompatible son, who had negative results for human T-lymphotropic virus type 1 (HTLV-1) (1-locus, 1-allele mismatch in the graft-versus-host [GVH] direction; 2-loci, 1-allele mismatch in the host-versus-graft direction). The preparatory regimen consisted of fludarabine, busulfan, and rabbit antithymocyte globulin. GVH disease (GVHD) prophylaxis consisted of short-term administration of methotrexate, tacrolimus, and methylprednisolone. The patient achieved complete donor chimerism on day 30 after transplantation. On approximately day 50 the patient started to experience steroid-refractory skin GVHD (grade IV), which was successfully managed with basiliximab (anti-CD25 monoclonal antibody) and mycophenolate mofetil (MMF). Serial analysis of HTLV-1 proviral load by quantitative polymerase chain reaction analysis using whole peripheral blood demonstrated undetectable levels from day 90. At the time of this writing the patient had been in complete remission for more than 16 months. The results in this case suggest the potential of non-TCD RIST from an HLA-incompatible relative donor as an alternative source of hematopoietic stem cells even for an elderly patient with advanced ATLL. In addition, basiliximab combined with MMF may be effective for the treatment of steroid-refractory skin GVHD without deteriorating the graft-versus-ATL effect.
Asunto(s)
Prueba de Histocompatibilidad , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/terapia , Trasplante de Células Madre , Linfocitos B/inmunología , Linfocitos T CD8-positivos/inmunología , Reacción Injerto-Huésped , Antígenos HLA/inmunología , Humanos , Masculino , Persona de Mediana Edad , Quimera por Trasplante , Resultado del TratamientoRESUMEN
Adult T-cell leukemia/lymphoma (ATL) is caused by human T-lymphotrophic virus type 1 infection and is one of the most refractory malignant T-cell lymphomas. Improvement of ATL therapy options requires the establishment of appropriate ATL animal models. In this study, we successfully generated an ATL mouse model by xenotransplantation of primary peripheral blood mononuclear cells (PBMCs) isolated from ATL patients (ATL cells) into nonobese diabetic/severe combined immunodeficiency/Jak3-null mice (NOJ mice). To generate the model, the ATL S1T cell line was subcutaneously injected into mice. Primary ATL cells were then transplanted subcutaneously, intraperitoneally, or intravenously. ATL cells infiltrated multiple organs, and elevated human soluble interleukin 2 receptor (IL-2R) levels were detected in peripheral blood. Injection of one million primary ATL cells was needed for successful engraftment into host mice. Thawed cells, frozen long-term in liquid nitrogen, could also be transplanted; however, more cells were required to achieve similar results. The median mouse survival time was proportional to the number of cells injected. Successful secondary transplantation of ATL cells from one NOJ mouse into another was achieved and confirmed by T-cell receptor analysis. Finally, we examined the effects of the antioxide pyrrolidine dithiocarbamate (PDTC) as an antitumor agent in vivo. PDTC administration inhibited the increase of soluble IL-2R and improved mouse survival, suggesting that this compound has potential as an anti-ATL agent. We demonstrated that ATL cells could be stably xenotransplanted into NOJ mice using primary cells. This model will be useful in the establishment of novel therapies to treat ATL.
Asunto(s)
Antioxidantes/farmacología , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Pirrolidinas/farmacología , Tiocarbamatos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Adulto , Animales , Xenoinjertos , Humanos , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , Ratones , Ratones Mutantes , Trasplante de Neoplasias , Células Tumorales CultivadasAsunto(s)
Carcinoma Neuroendocrino/radioterapia , Neoplasias Pulmonares/radioterapia , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Papulosis Linfomatoide/etiología , Linfopenia/etiología , Neoplasias Cutáneas/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biopsia , Nalgas , Carcinoma Neuroendocrino/diagnóstico , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico , Linfoma de Células B de la Zona Marginal/patología , Papulosis Linfomatoide/diagnóstico , Papulosis Linfomatoide/patología , Linfopenia/sangre , Linfopenia/diagnóstico , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
We examined human T-lymphotropic virus type I (HTLV-I) infection among patients with myelodysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB)/RAEB in transformation (RAEBt) and acute myelogenous leukemia (AML). The study population consisted of 151 patients: 46 with MDS RAEB/RAEBt and 105 with AML (M1, n = 15; M2, n = 39; M3, n = 18; M4, n = 19; M5, n = 9; M6, n = 3; M7, n = 2). As a reference, we examined 92 patients with refractory anemia (RA) and 405 patients with cardiovascular diseases (CVD). Thirteen patients with RAEB/RAEBt (28.3%), 11 with AML (11.6%), 27 with RA (29.3%), and 45 with CVD (11.0%) were positive for HTLV-I. Seven AML patients with HTLV-I infection had M3 acute promyelocytic leukemia (APL). The prevalences of HTLV-I infection among patients with RAEB/RAEBt (P < 0.001), APL (P = 0.001), and RA (P < 0.001) were significantly higher than that in patients with CVD. The prevalences of HTLV-I infection were still significantly higher in patients with RAEB/RAEBt (P = 0.007), APL (P = 0.017) and RA (P < 0.001) than in those with CVD matched by sex and age. Platelet counts and survival times of RAEB/RAEBt patients with infection were significantly lower than those of patients without infection.