RESUMEN
Relapse or progressive disease after chimeric antigen receptor T-cell (CAR-T) treatment remains a major issue for poor-risk aggressive large B-cell lymphoma. However, limited data are available on post-CAR-T use of polatuzumab vedotin. Here we describe the case of a patient with diffuse large B-cell lymphoma (DLBCL) who experienced relapse three months after CD19-directed CAR-T therapy with tisagenlecleucel. However, the relapsed lesions rapidly disappeared following treatment with polatuzumab vedotin and rituximab. Notably, long-term remission was achieved without severe cytopenia, infections or peripheral neuropathy, showing the therapeutic benefit of polatuzumab vedotin for CAR-T failure.
Asunto(s)
Inmunoconjugados , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Rituximab/uso terapéutico , Anticuerpos Monoclonales , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Enfermedad Crónica , Protocolos de Quimioterapia Combinada AntineoplásicaAsunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Melfalán/uso terapéutico , Bortezomib/uso terapéutico , Prednisolona , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Reino Unido , Resultado del Tratamiento , Prednisona/uso terapéuticoRESUMEN
Mogamulizumab (MOG), a humanized monoclonal anti-CCR4 antibody, exerts strong antibody-dependent cellular cytotoxic effects on CCR4-positive adult T-cell leukemia/lymphoma (ATLL) cells. As CCR4 is highly expressed on regulatory T cells as well as ATLL cells, pre-transplant MOG induces severe graft-versus-host disease (GvHD). However, limited data are available on post-transplant use of MOG for relapsed ATLL. Here we describe the case of a patient with ATLL who experienced post-transplant relapse with involvement of peripheral blood, skin, lungs, and lymph nodes. Neither tacrolimus dose reduction nor cytotoxic chemotherapy was effective, but a single dose of MOG (1 mg/kg) induced complete remission. After treatment with MOG, leukemic cells in the peripheral blood rapidly disappeared, and the skin, lymph node, and lung lesions gradually regressed. Most notably, the long-term remission was accompanied by recurrence of moderate acute GvHD (grade II, skin stage 2, gut stage 1, liver stage 0). Our findings indicate that MOG can augment allogeneic immune-mediated anti-tumor reactions through graft-versus-ATLL (GvATLL) even during post-transplant relapse involving the lymph nodes and lungs, along with inducing GvHD.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Linfoma , Adulto , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/patología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , RecurrenciaRESUMEN
BACKGROUND: The International Myeloma Working Group response criteria require two consecutive assessments of paraprotein levels. We conducted an exploratory analysis to evaluate whether a single response assessment could be a substitute for the International Myeloma Working Group criteria using data from JCOG1105, a randomized phase II study on melphalan, prednisolone and bortezomib. METHODS: Of 91 patients with transplant-ineligible newly diagnosed multiple myeloma, 79 patients were included. We calculated the kappa coefficient to evaluate the degree of agreement between the International Myeloma Working Group criteria and the single response assessment. RESULTS: Based on the International Myeloma Working Group criteria, 11 (13.9%), 20 (25.3%), 36 (45.6%) and 12 (15.2%) patients had stringent complete response/complete response, very good partial response, partial response and stable disease, respectively. Based on the single response assessment, 17 (21.5%), 19 (24.1%), 35 (44.3%) and 8 (10.1%) patients had stringent complete response/complete response, very good partial response, partial response and stable disease, respectively. The kappa coefficient was 0.76 (95% confidence interval, 0.65-0.88), demonstrating good agreement. The single response assessment was not inferior to the International Myeloma Working Group criteria in the median progression-free survival (3.8 and 2.9 years) in stringent complete response/complete response patients, suggesting that the single response assessment was not an overestimation. CONCLUSIONS: The single response assessment could be a substitute for the current International Myeloma Working Group criteria for transplant-ineligible newly diagnosed multiple myeloma.
Asunto(s)
Bortezomib/uso terapéutico , Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Prednisolona/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Humanos , Masculino , Supervivencia sin ProgresiónRESUMEN
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been accepted as a treatment option for aggressive (acute or lymphoma type) adult T cell leukemia/lymphoma (ATLL) patients with a poor prognosis, when a suitable HLA-matched donor is not available. However, haplo-HSCT carries a potential risk of treatment-related mortality including severe graft-versus-host disease (GVHD). Therefore, we conducted a prospective pilot study in order to evaluate the efficacy and safety of reduced-intensity haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with low-dose thymoglobulin (2.5 mg/kg only on day -2), fludarabine, melphalan, and total body irradiation 4 Gy for aggressive ATLL. Three consecutive acute type ATLL patients, who were ineligible for conventional myeloablative conditioning due to advanced age or comorbidities, were enrolled. One patient received pretransplant mogamulizumab therapy. All the patients were not in complete remission (CR) at the time of transplantation. Our transplantation protocol was safely carried out. CR was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. At a follow-up of 2 years, they were still in CR. However, T cell receptor repertoire diversities were low 1 year after transplantation in next-generation sequencing. Our results show encouraging therapeutic benefits of this pilot approach using reduced-intensity haplo-PBSCT with low-dose thymoglobulin for aggressive ATLL patients.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante , Anciano , Aloinjertos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/sangre , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Factores de Tiempo , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Carga Viral , Irradiación Corporal TotalRESUMEN
Stigmatic papillae develop at the apex of the gynoecium and play an important role as a site of pollination. The papillae in Brassicaceae are of the dry and unicellular type, and more than 15,000 genes are expressed in the papillae; however, the molecular and physiological mechanisms of their development remain unknown. We found that the papillae in Arabidopsis thaliana change their length in response to altered ambient humidity: papillae of flowers incubated under high humidity elongated more than those under normal humidity conditions. Genetic analysis and transcriptome data suggest that an abscisic acid-mediated abiotic stress response mechanism regulates papilla length. Our data suggest a flexible regulation of papilla elongation at the post-anthesis stage, in response to abiotic stress, as an adaptation to environmental conditions.
Asunto(s)
Flores/metabolismo , Polinización/genética , Polinización/fisiología , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brassicaceae/genética , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Humedad , Estrés Fisiológico/genética , Estrés Fisiológico/fisiología , Transcriptoma/genéticaRESUMEN
An 85-year-old male presented with 1-year history of a right breast mass. Needle biopsy of the mass revealed diffuse proliferation of large lymphoid cells that were positive for CD20, BCL2, BCL6, and MUM1 and negative for CD5, CD10, MYC, and EBER. The patient was diagnosed as having diffuse large B-cell lymphoma, a type of primary breast lymphoma (PBL). Sex hormone imbalance, which causes conditions such as gynecomastia, is associated with PBL development in males. Estramustine is a nitrogen mustard moiety linked to estradiol. For 5 years, the patient underwent estramustine therapy for treating prostate cancer. Our case suggests an important role of estrogen in PBL development.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Estramustina/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Humanos , MasculinoRESUMEN
BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin diffuse large B-cell lymphoma originally with a predilection to the oral cavity of patients infected with HIV. However, PBL of extraoral sites possesses clinicopathological characteristics distinct from oral PBL. Recently, therapeutic approaches using a proteasome inhibitor bortezomib to PBL of extraoral sites have been reported. We present a PBL patient with a bulky tumor of the oral cavity, who dramatically responded to bortezomib. CASE PRESENTATION: The patient was a 58 year-old Japanese male, who presented with a rapidly progressive history of a swelling on his left cheek and restricted mouth opening. He did not have a history or evidence of immunosuppression including HIV infection. A computed tomography demonstrated a bulky tumor in the oral cavity without enlarged lymph nodes. The tumor showed the proliferation of large lymphoid cells with centroblastic morphology, which were positive for CD138, CD38, CD56 and MUM-1, and negative for CD20, CD79a, BCL-6 and HHV8. The Ki-67 proliferation index was almost 100 %. Neither osteolytic lesions nor M-protein was observed. One week after the initiation of bortezomib, a marked regression of the oral tumor was obtained. CONCLUSIONS: Thus, our case demonstrated the effectiveness of bortezomib on PBL of the oral cavity as well as the extraoral sites.
RESUMEN
Cardiac involvement is by far the most relevant factor impacting poor outcomes of patients with systemic light-chain (AL) amyloidosis. Median survival of patients with symptomatic cardiac AL amyloidosis is less than 6 months. Approximately two-thirds of these patients die suddenly due to ventricular arrhythmias and electromechanical dissociation. We report a 56-year-old female with very severe cardiac AL amyloidosis (NT-proBNP 13,355 ng/l, troponin T 0.16 µg/l, and systolic blood pressure 100 mmHg), who was successfully treated with diuretics and an implantable cardioverter-defibrillator (ICD) and has survived for more than 4 years, to date. During the 4-year period after receiving the ICD, she experienced several episodes of sustained ventricular tachycardia and ventricular fibrillation, all successfully terminated by anti-tachycardia pacing or electrical shock. The benefit of ICD for cardiac AL amyloidosis is unclear since there have been only a few reports of successful use of this therapy for patients with cardiac AL amyloidosis. Recently, new treatment options for AL amyloidosis, such as bortezomib and lenalidomide, have shown high response rates and improved outcomes. It is important to identify those cardiac amyloidosis patients who might be more likely to benefit from ICD implantation.
Asunto(s)
Amiloidosis/etiología , Amiloidosis/terapia , Cardiomiopatías/etiología , Cardiomiopatías/terapia , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Mieloma Múltiple/complicaciones , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapia , Femenino , Humanos , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
We previously conducted a phase 1 study of bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy and determined the optimal dose of bortezomib to be 1.0 mg/m(2). We then conducted a multicenter phase 2 study in patients with relapsed or refractory myeloma. Bortezomib 1.0 mg/m(2) was administered intravenously on days 1, 4, 8 and 11, in combination with intravenous doxorubicin 9 mg/m(2) on days 1-4, and dexamethasone 20 mg orally on days 1-2, 4-5, 8-9 and 11-12 at a 3-week interval for six cycles. The primary endpoint of this study was the complete remission (CR) rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Twenty-seven patients, median age of 63, were enrolled. An overall response rate was 89 % with CR rate of 30 %. The median PFS time was 12.1 months, and the median OS time was not reached. One patient died of pneumonia. Although the incidence of hematological toxicities was high, these were transient and manageable. The most common non-hematological toxicity was sensory neuropathy; grade 3 toxicity was observed in six patients (22 %) and treatment was discontinued in four. We conclude that iPAD therapy is feasible, and shows efficacy by inducing high response rates and long response duration.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ácidos Borónicos/administración & dosificación , Doxorrubicina/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Pirazinas/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/efectos adversos , Bortezomib , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirazinas/efectos adversos , Tasa de SupervivenciaRESUMEN
We report a 73-year-old Japanese man with early onset pure red cell aplasia (PRCA) caused by subcutaneous administration of recombinant epoetin-ß. Two months after the start of epoetin therapy, he developed PRCA. Anti-erythropoietin (EPO) antibody, detected in the patient's serum by enzyme immunoassay and radioimmunoprecipitation method, inhibited EPO-dependent growth of AS-E2 cells in vitro. Treatment with prednisone (1 mg/kg) significantly reduced antibody levels 3 months later. It is important to have an awareness of antibody-mediated PRCA. Our case shows that subcutaneous epoetin administration produces this complication in the early period of therapy.
Asunto(s)
Anticuerpos , Eritropoyetina/inmunología , Aplasia Pura de Células Rojas/etiología , Anciano , Anemia/tratamiento farmacológico , Eritropoyetina/administración & dosificación , Eritropoyetina/efectos adversos , Humanos , Inyecciones Subcutáneas , Masculino , Prednisolona/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/inmunología , Aplasia Pura de Células Rojas/inmunología , Aplasia Pura de Células Rojas/terapia , Resultado del TratamientoRESUMEN
STAT4 is a critical mediator of IL-12-stimulated gene regulation in T-helper type 1 (Th1) cell. IL-12 activates the Janus family tyrosine kinases JAK2 and Tyk2, which in turn phosphorylate STAT4 on tyrosine 693. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is also activated in response to IL-12, followed by phosphorylation of STAT4 on serine 721, which is required for STAT4 full transcriptional activity. In the present study, we demonstrated constitutive activation of STAT4 in HTLV-I-transformed T-cell lines MT-2, MT-4 and HUT102 by immunoprecipitation, Western blotting and electrophoretic mobility shift assay (EMSA). In HTLV-I-transformed T-cell lines, STAT4 was constitutively phosphorylated not only on tyrosine 693 but also on serine 721, and formed a heterodimer with STAT3. Constitutive phosphorylation of its upstream activators, JAK2, Tyk2 and p38 MAPK was also observed in the cells. EMSA and transient transfection studies further showed that the high-affinity sis-inducible element (hSIE) preferentially binds the STAT3/STAT4 heterodimer and is constitutively transactivated in MT-2 cells in the absence of exogenous cytokine stimulation. When STAT4 expression vector was cotransfected along with STAT3 expression vector into MT-2 cells, STAT4 significantly synergized with STAT3 to transactivate hSIE, showing the functional importance of heterodimer formation between STAT4 and STAT3.
Asunto(s)
Factor de Transcripción STAT4/metabolismo , Serina/metabolismo , Linfocitos T/metabolismo , Tirosina/metabolismo , Western Blotting , Línea Celular , Transformación Celular Viral , Ensayo de Cambio de Movilidad Electroforética , Regulación de la Expresión Génica , Virus Linfotrópico T Tipo 1 Humano , Humanos , Inmunoprecipitación , Interferón gamma/metabolismo , Janus Quinasa 2 , Células Jurkat , Proteínas de la Membrana/metabolismo , Fosforilación , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Factor de Transcripción STAT3/metabolismo , Linfocitos T/enzimología , TYK2 Quinasa , Transcripción Genética , Activación Transcripcional , TransfecciónRESUMEN
In this study, we investigated the expression of six human DNA mismatch repair (MMR) genes, human MutS homologues 2 (hMSH2), 3 (hMSH3), and 6 (hMSH6), human MutL homologue 1 (hMLH1), human post-meiotic segregations 1 (hPMS1) and 2 (hPMS2), in primary leukemic cells obtained from 11 patients with acute-type adult T-cell leukemia (ATL) by using reverse transcription-polymerase chain reaction (RT-PCR). In contrast to normal peripheral lymphocytes, all primary ATL samples had reduced or loss of expression of two or more MMR genes, and the expression of several MMR genes was simultaneously suppressed in each ATL patient. Abnormal expression of hMSH2, hMSH3, hMSH6, hMLH1, and hPMS1 was observed more frequently than that of hPMS2. In particular, expression of hMSH2 and hPMS1 was reduced in all cases. Western blot analysis further showed reduced expression of both hMSH2 and hPMS1 proteins in all five cases examined. In three out of the 5 cases, both of the two proteins were undetectable. Interestingly, methylation-specific PCR indicated methylation of hPMS1 promoter in all of four ATL cases examined. hPMS1 expression, but not hMSH2 expression, was restored by treatment with a DNA demethylation agent, 5-aza-2'-deoxycytidine, suggesting that methylation plays a crucial role in inhibition of the hPMS1 gene expression in ATL. Our results demonstrate that defect of both human MutS and human MutL systems in primary ATL cells.
Asunto(s)
Adenosina Trifosfatasas/genética , Disparidad de Par Base/genética , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas Adaptadoras Transductoras de Señales , Anciano , Proteínas Portadoras , Metilación de ADN , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteínas MutL , Proteína 2 Homóloga a MutS , Proteína 3 Homóloga de MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogénicas/genéticaRESUMEN
A 71-year-old woman was admitted in December 2002 because of lymphadenopathy, hepatosplenomegaly and pleural effusion. She had severe anemia with hemoglobin 5.9 g/dl and a reticulocyte count of 1% per hundred. Direct/indirect Coombs tests and anti-double stranded DNA antibody were positive, her serum CH50 level was reduced and an increase in serum LDH isoenzyme 3 was observed. Bone marrow aspiration showed an almost total absence of erythroblasts and no pathological cell proliferation. The diagnosis of angioimmunoblastic T-cell lymphoma (AILT) was made based on the lymph node histological findings. Proliferation of arborizing small vessels with hyperplastic endothelium and infiltration of atypical T-lymphocytes were observed. After combination chemotherapy (THP-COP), remission was achieved in both the pure red cell aplasia (PRCA) and AILT. Remission was also accompanied by normalization of the Coombs tests, suggesting that autoimmune mechanisms in AILT may contribute to the development of PRCA.
Asunto(s)
Linfadenopatía Inmunoblástica/complicaciones , Aplasia Pura de Células Rojas/etiología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Prueba de Coombs , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/tratamiento farmacológico , Prednisolona/administración & dosificación , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
A 57-year-old woman with chronic myeloid leukemia showing severe basophilia (WBC 17.1 X 10(9)/L, basophils 23%) was treated with 400mg imatinib in June 2003. A high basophil count (WBC 10.6 X 10(9)/L, basophils 31%) was still observed after 1 week of therapy. After 9 days of therapy, she developed generalized pruritic skin erythema, chills and high fever. After terminating imatinib treatment, prednisolone therapy was initiated. The rash quickly disappeared. Four days after withdrawal of imatinib, leukocyte count was 13.0 X 10(9)/L with 3% of basophils, suggesting the possibility that rapid decrease in basophils following imatinib therapy may induce severe cutaneous reactions.
Asunto(s)
Antineoplásicos/efectos adversos , Basófilos , Eritema/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucopenia/inducido químicamente , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Benzamidas , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucocitosis/complicaciones , Leucopenia/complicaciones , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate-resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re-introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression.
Asunto(s)
Antineoplásicos/administración & dosificación , Crisis Blástica/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Benzamidas , Crisis Blástica/patología , Médula Ósea/patología , Aberraciones Cromosómicas , Genes abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Recuento de Leucocitos , Masculino , Neutropenia/inducido químicamente , Piperazinas/efectos adversos , Recuento de Plaquetas , Pirimidinas/efectos adversos , ARN Mensajero , Inducción de RemisiónRESUMEN
Graft-versus-lymphoma (GVL) effect has been described in patients with malignant lymphoma after allogeneic stem cell transplantation (alloSCT). The effect of interferon-alpha (IFN-alpha) on the GVL effect still remains unclear. Here we report on a 29-year-old woman with refractory diffuse large B-cell lymphoma (DLBL). Her clinical findings included multiple masses in the liver, stomach, bilateral kidneys, thyroid, vertebral bones and a bulky mediastinal mass. Since the patient did not respond to various combination chemotherapies and further developed superior vena cava syndrome, allogeneic peripheral blood stem cell transplantation (PBSCT) from a HLA-identical brother was carried out after a myeloablative TBI/CY-based conditioning regimen. DLIs have been also performed every 4 weeks since day +14. As a result, the lymphoma masses showed a partial response. In order to enhance the GVL effect, IFN-alpha was further given at a maximum of 3 MU four times per week. Although the patient only experienced graft-versus-host disease of the skin (grade II) even after both DLIs and IFN, complete clinical remission was observed. 200 days after transplantation, the patient is still disease-free and in good condition. This report suggests the curative potential of IFN-alpha combined with DLI after allogeneic SCT in refractory DLBL.
Asunto(s)
Efecto Injerto vs Tumor , Interferón-alfa/uso terapéutico , Transfusión de Linfocitos , Linfoma de Células B/terapia , Linfoma no Hodgkin/terapia , Trasplante de Células Madre de Sangre Periférica , Inducción de Remisión/métodos , Adulto , Femenino , Humanos , Inmunoterapia AdoptivaRESUMEN
The level of (1-->3)-beta-D-glucan in blood is a diagnostic index of fungal infection because it is released from the fungal cell wall. However, high levels of plasma (1-->3)-beta-D-glucan in patients administered blood components may give false positive results. High levels of (1-->3)-beta-D-glucan have been detected in blood components. We suspected that (1-->3)-beta-D-glucan from cellulose filters had been eluted into blood components by filtration in the manufacturing process. To investigate the contamination of blood components by (1-->3)-beta-D-glucan from cellulose filters, in vitro experiments were performed by using six cellulose filters and a nylon filter. Human serum albumin (HSA) solution (100 ml) was flowed through each filter after rinsing with 100 ml of distilled water, and (1-->3)-beta-D-glucan in each fraction was determined by Fungitec G test MK. The concentration of (1-->3)-beta-D-glucan eluted from cellulose filters in 100-ml distilled water fractions ranged from 6 to 207 pg/ml, and that of HSA fractions ranged from 33 to 20,784 pg/ml. These data showed that remarkably higher (1-->3)-beta-D-glucan levels were detected in HSA fractions flowed through cellulose filters in spite of advance rinsing with 100 ml of distilled water. In the case of a nylon filter, (1-->3)-beta-D-glucan was not eluted in either fraction. These results indicate that (1-->3)-beta-D-glucan contamination in blood components is caused by filtration with cellulose filters in the manufacturing process.