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Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/µL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events - cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.
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Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.
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Neoplasias Hematológicas , Leucemia-Linfoma de Células T del Adulto , Adulto , Humanos , Anciano , Proteína C-Reactiva , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Estudios Retrospectivos , AlbúminasRESUMEN
Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Neoplasias Cutáneas , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Cutáneas/etiología , Trasplante Homólogo/efectos adversos , Voriconazol/uso terapéuticoRESUMEN
Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2-34.5), 33.1 (21.2-40.3) and 27.7 (13.6-29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.
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Imidazoles/farmacocinética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacocinética , Piridazinas/farmacocinética , Adulto , Anciano , Terapia Combinada , Monitoreo de Drogas , Femenino , Proteínas de Fusión bcr-abl/genética , Trasplante de Células Madre Hematopoyéticas , Humanos , Imidazoles/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Leucemia Mieloide de Fase Crónica/diagnóstico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridazinas/administración & dosificación , Resultado del TratamientoRESUMEN
Anti-thymocyte globulin (ATG) is an important component of preparative regimens for allogeneic bone marrow transplantation (BMT) for aplastic anemia (AA). However, the pharmacokinetics (PK) of ATG are unclear. A 38-year-old woman with severe AA underwent BMT using a fludarabine (Flu)-based and reduced-dose cyclophosphamide (CPA)-conditioning regimen comprising rabbit ATG (2.5 mg/kg, days -7 and -6), Flu (30 mg/sqm, days -5 to -2), CPA (25 mg/kg, days -5 to -2), and total body irradiation (2 Gy, day -1), following a human leukocyte antigen-match with an unrelated donor. Notably, ATG was administered earlier than that recommended by conventional schedules. The engraftment was achieved on day 15 without reactivation of the Epstein-Barr virus and residual recipient cells. Absolute lymphocyte recovery (>0.5×109/L) was achieved on day 22. The ATG concentration on day 0 and the area under the concentration-time curve (AUC) for ATG after allogeneic BMT were 21.8 µg/mL and 464 µgã»day/mL, respectively. The patient remained disease-free for 6 years after BMT without acute or chronic graft-versus-host disease. Moreover, based on serum PK monitoring of ATG, including ATG concentration on day 0 and the AUC for ATG after BMT, the patient safely underwent the less-toxic, Flu-based, reduced-dose CPA regimen containing a low dose of ATG. In conclusion, we present the first report that analyzed the PK of ATG in a patient with AA treated with BMT from a matched unrelated donor. These findings might be helpful to determine ATG dosages for such patients receiving similar transplantations.
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BACKGROUND: Although anthracycline-related cardiomyopathy is a life-threatening complication during intensive treatment for hematological malignancies, clinical features and outcomes of this type of cardiomyopathy have been unclear because of limited reports in the literature. METHODS: We analyzed three cases of anthracycline-related cardiomyopathy among 996 patients with either acute myelogenous leukemia (285), acute lymphoblastic leukemia (37), or malignant lymphoma (674) at our hospital during the period from 2006 to 2016. RESULTS: All patients showed accumulation of anthracycline within a proper range (< 500 mg/sqm). Two patients (Hodgkin lymphoma and acute lymphoblastic leukemia) showed acute heart failure (AHF) with ejection fraction (EF) of 30 and 40% after 4.5 and 5 years after diagnosis, respectively. For AHF, diuretics and carperitide were administered to control in-out balance. The remaining patient (follicular lymphoma) showed ventricular fibrillation (VF)/ventricular tachycardia (VT) with EF of 40% at 5 years after diagnosis. In this patient, immediate cardioversion made VF/VT to normal sinus rhythm, and then, amiodarone was given. Furthermore, implantable cardioverter defibrillator was set up for VF/VT. In all patients, ß blocker and/or angiotensin-converting enzyme inhibitor (ACE-I) were administrated to prevent recurrence of anthracycline-related cardiomyopathy. Consequently, two of three patients showed mild improvement of cardiac function. CONCLUSION: Our study indicates that late-onset (4 to 5 years) anthracycline-related cardiomyopathy can develop, though range of anthracycline accumulation is in proper range. Thus, a cautious follow-up by ECG and UCG is required. Furthermore, the early treatment after the onset of anthracycline-related cardiomyopathy should be also needed to improve the poor outcome.
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Neoplasias Hematológicas , Taquicardia Ventricular , Antraciclinas/efectos adversos , Estudios de Seguimiento , Humanos , Fibrilación VentricularRESUMEN
The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.
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Recurrencia Local de Neoplasia/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Neoplasias Uterinas/patología , Útero/patología , Médula Ósea/patología , Femenino , Humanos , Cariotipo , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Neoplasias Uterinas/genéticaRESUMEN
As opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia/lymphoma (ATL) pose a serious problem, it is necessary to clarify their clinical characteristics and outcomes in these patients. We retrospectively analyzed the clinical features and outcomes of opportunistic infections in 127 HTLV-1 carriers and 153 ATL patients between 2006 and 2016. The cumulative incidence rates of opportunistic infections among HTLV-1 carriers and ATL patients were 1.5% (2/127) and 6.5% (10/153), respectively. The etiology of opportunistic infections was as follows: fungal infections (3 cases), pneumocystis pneumonia, and cytomegalovirus (CMV) infections. Even after aggressive treatment, the prognosis of opportunistic infections was poor (50% of overall survival at 28 days). Regarding prognostic factors affecting the OS of opportunistic infections, higher SOFA scores (especially the respiratory subscore) and higher LDH values were identified by univariate analysis. Moreover, 3 out of 6 patients achieved spontaneous remission of ATL as the short-term outcome after the development of opportunistic infection. However, 5 out of 6 surviving patients exhibited ATL progression or relapse after a median of 194 days (133-226) after contracting an opportunistic infection as the long-term outcome of ATL. In conclusion, opportunistic infections should be carefully followed among HTLV-1 carriers and ATL patients because of their aggressive clinical course and poor outcomes. Furthermore, early diagnosis and subsequent prompt treatment are necessary in clinical practice.
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Infecciones por Citomegalovirus , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Infecciones Oportunistas , Neumonía por Pneumocystis , Adulto , Anciano , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/terapia , Neumonía por Pneumocystis/mortalidad , Neumonía por Pneumocystis/terapia , Tasa de SupervivenciaRESUMEN
Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Advanced-stage mycosis fungoides (MF) has a generally poor prognosis. Allogeneic hematopoietic stem cell transplantation improves the outcome of advanced-stage MF. Recently, cord blood has been used as an alternative stem cell source; however, there are few reports of MF patients treated using cord blood transplantation. Here, we report a rare case of refractory folliculotropic MF, which was treated with reduced-intensity conditioning followed by cord blood transplantation.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Micosis Fungoide/terapia , Neoplasias Cutáneas/terapia , Acondicionamiento Pretrasplante , Adulto , Biopsia , Resultado Fatal , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Micosis Fungoide/patología , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Piel/patología , Neoplasias Cutáneas/patología , Tomografía Computarizada por Rayos X , Acondicionamiento Pretrasplante/métodosRESUMEN
We present the case of a 62-year-old Japanese woman with relapsed adult T-cell leukemia/lymphoma (ATLL) who was treated with humanized anti-CCR4 monoclonal antibody (KW-0761). Although this antibody was highly effective against refractory ATLL, 6 months after the final KW-0761 infusion, the patient complained of hypoxia due to diffuse panbronchiolitis. Physicians should remain vigilant to the possibility of such previously unreported late-onset adverse effects associated with KW-0761 therapy.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Bronquiolitis/inducido químicamente , Infecciones por Haemophilus/inducido químicamente , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Receptores CCR4 , Femenino , Humanos , Hipoxia , Leucemia-Linfoma de Células T del Adulto/patología , Persona de Mediana Edad , Factores de TiempoRESUMEN
A 76-year-old man suffered from swelling stoma for several weeks. A biopsy sample revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, bcl-6, and MUM1. The patient was diagnosed with diffuse large B-cell lymphoma, with a non-germinal center B-cell pattern. A whole-body PET-CT scan revealed that the lymphoma was restricted to the stomal site. Bladder reconstruction was undertaken using the ileal conduit: this is the first reported case of lymphoma that developed primarily at the stoma. During the long-term maintenance after bladder reconstruction, clinicians should consider the possibility of lymphoma at the stomal site.