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High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC/ASCT) has been useful in relapsed or refractory classic Hodgkin lymphoma (RRcHL). Furthermore, a ranimustine, cytarabine, etoposide, and cyclophosphamide (MCVAC) conditioning regimen has been effective in diffuse large B-cell lymphoma. However, limited data are available regarding this conditioning regimen for cHL. In this study, we investigated the efficacy and toxicity of MCVAC for RRcHL. We retrospectively analyzed 10 patients with RRcHL who underwent ASCT preceded by the MCVAC conditioning regimen between January 2009 and December 2021 at our institution. A total of 10 patients (median [range] age, 36 [23-64] years), including 5 (50%) men and 5 (50%) women, were treated with the MCVAC regimen followed by ASCT. The median follow-up duration of the 10 patients was 25.0 months. The 36-month PFS and OS rates were 43.8% (95% CI, 11.9%-72.6%) and 64.0% (95% CI, 22.6%-87.5%), respectively. Two patients died because of treatment-related factors, and one patient died because of disease progression. Based on our findings, recognizing the risk factors for adverse events (AEs) associated with this treatment, MCVAC may be a valid treatment option for the management of RRcHL.
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The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.
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Neoplasias de Células Plasmáticas , Humanos , Estudios Prospectivos , Anciano , Femenino , Persona de Mediana Edad , Masculino , Japón , Neoplasias de Células Plasmáticas/terapia , Trasplante Autólogo , Pronóstico , Tasa de Supervivencia , Adulto , Trasplante de Células Madre Hematopoyéticas , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Despite high response rates to initial therapy, most patients with mantle cell lymphoma (MCL) experience relapsed or refractory (R/R) disease. Here, we report the efficacy, safety, and pharmacokinetics of the Phase 2, single-arm M20-075 study (NCT04477486) of ibrutinib and venetoclax combination therapy in Japanese patients with R/R MCL. METHODS: Patients received 560 mg ibrutinib and 400 mg venetoclax (after a 5-week ramp-up from 20 mg) once daily for up to 104 weeks. Primary endpoint was complete response (CR) rate by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) rate, progression-free survival (PFS), overall survival (OS), safety including dose-limiting toxicity (DLT) assessment in the first six patients, and pharmacokinetic parameters. Full analysis set (FAS) comprised all treated patients. Per protocol set (PPS) excluded treated patients with non-evaluable disease at baseline by IRC. RESULTS: Thirteen patients were treated (FAS n = 13; PPS, n = 12). Median age was 71 years, patients had a median of two prior treatments. After a median follow-up of 9.6 months, IRC-assessed CR rate and ORR were both 83% (PPS). All six MRD-evaluable patients had uMRD. Median DOR, PFS, and OS were unreached. The most common Grade ≥ 3 treatment-emergent adverse event (TEAE) was neutropenia (23%); 1 patient discontinued due to squamous cell carcinoma of the lung. No DLTs, tumor lysis syndrome, or deaths related to TEAEs were observed. CONCLUSION: Ibrutinib plus venetoclax exhibited high response rates and a well-tolerated safety profile in Japanese patients with R/R MCL.
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Adenina/análogos & derivados , Compuestos Bicíclicos Heterocíclicos con Puentes , Linfoma de Células del Manto , Sulfonamidas , Adulto , Humanos , Anciano , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Japón , Piperidinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized disease entity characterized by EBV-positive atypical B-cell proliferation. EBVMCU is a localized self-limited disease that affects mucosa and skin, especially the oral cavity. EBVMCU develops in immunosuppressive patients, such as those with methotrexate (MTX)-administrated rheumatoid arthritis (RA). Here we clinicopathologically analyzed 12 EBVMCU patients in a single institution. All cases were administrated MTX for RA, and five cases occurred in the oral cavity. All cases except one had demonstrated spontaneous regression after withdrawal of the immunosuppressive agent. We found 4 of 5 cases in the oral cavity had preceding traumatic events in the same site within a week before the onset of EBVMCU. Although there is no detailed and large study that has analyzed the trigger of EBVMCU, a traumatic event would indeed be a significant trigger for EBVMCU in the oral cavity. The cases were histologically classified; six cases were diffuse large B-cell lymphoma-type, five were polymorphous-type, and one was Hodgkin-like lesion type due to morphological appearance and immunophenotype. The PD-L1 expression was also examined by two antibodies for PD-L1 (E1J2J and SP142). Both antibodies revealed identical results for PD-L1 expression, and three cases were positive for PD-L1. The application of SP142 for evaluating the immune status of lymphomagenesis has also been proposed. Nine of 12 cases were negative for PD-L1, which implies that most EBVMCU cases may be caused by an immunodeficiency, rather than an immune-evasion, mechanism. However, as three cases were positive for PD-L1, immune escape may underly the pathogenesis in a subset of EBVMCU cases.
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Artritis Reumatoide , Infecciones por Virus de Epstein-Barr , Humanos , Metotrexato/efectos adversos , Infecciones por Virus de Epstein-Barr/inducido químicamente , Infecciones por Virus de Epstein-Barr/complicaciones , Úlcera , Herpesvirus Humano 4/metabolismo , Antígeno B7-H1 , Inmunosupresores/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicacionesRESUMEN
ABL1-tyrosine kinase inhibitors (TKIs) are an established treatment choice for patients with chronic myeloid leukemia in the chronic phase (CML-CP). However, effects of TKI dose modification have not been well investigated. In this study, we retrospectively analyzed 178 patients with newly diagnosed CML-CP who were treated with dasatinib or nilotinib, focusing on age and dose effects. Efficacy as measured by cumulative major molecular response (MMR) and molecular response 4.5 rates did not differ significantly between the younger group and elderly group. Elderly patients who started nilotinib at a reduced dose had similar or better efficacy outcomes (including cumulative MMR and continuation ratios) than other groups, and elderly patients who started dasatinib at a reduced dose had the lowest MMR ratio and longest MMR duration. Effects of dose modification based on age and TKI selection can be attributed to flexible management of TKI therapy in real-world practice, but further studies are required to validate the findings of this study.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Anciano , Dasatinib/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pirimidinas , Resultado del TratamientoRESUMEN
Objective Pleural effusion (PE) is a common adverse event that occurs during dasatinib therapy for chronic myeloid leukemia (CML). However, the pathomechanism of PE and appropriate management of Asian patients with CML have not been elucidated. This study investigated the incidence rate, risk, and appropriate management of PE in Asian patients with CML treated with dasatinib. Methods We retrospectively collected data on patients in the chronic phase of CML who received first-line dasatinib therapy and were registered in the CML-Cooperative Study Group database. Patients We identified 44 cases of PE in a series of 89 patients and analyzed previously reported risk factors and effective management of PE. Results A univariate analysis revealed that age, diabetes mellitus, chronic renal failure, hypertension, the history of cardiovascular events, and dasatinib dose were significantly associated with PE. A multivariate analysis revealed that age ≥65 years old was the only independent risk factor for PE. Dasatinib dose reduction and switching to a tyrosine kinase inhibitor showed a statistically significant difference in effectively reducing PE volume compared to single diuretic use. Conclusion Although further studies are warranted, our observations showed that advanced age is a significant risk factor for PE, and tyrosine kinase inhibitor dose reduction or replacement of dasatinib may be an effective management strategy for PE in Asian CML patients who received first-line treatment with dasatinib in real-world clinical practice.
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Dasatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Derrame Pleural , Anciano , Humanos , Dasatinib/efectos adversos , Pueblos del Este de Asia , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Derrame Pleural/inducido químicamente , Derrame Pleural/epidemiología , Derrame Pleural/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Anciano , Humanos , Proteínas de Fusión bcr-abl , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
A 76-year-old woman with leukocytosis and thrombocytopenia was admitted to our hospital. A bone marrow examination showed a composition of 82.0% blasts, i.e., positive for TdT, CD10, CD19, CD34, and HLA-DR and negative for cyCD3, CD13, CD33, MPO, and cyµ. The reverse transcription-polymerase chain reaction analysis revealed a minor BCR-ABL1 fusion gene, leading to a diagnosis of acute lymphocytic leukemia (ALL) with a BCR-ABL1 fusion gene. G-band assay was negative for Philadelphia (Ph) chromosome and also revealed add (21) (q22. 1) and del (20) (q11. 2q13.3). Fluorescence in situ hybridization (FISH) assaying revealed a positive BCR-ABL1 fusion signal. Thus, this patient was diagnosed as Ph chromosome-negative and BCR-ABL1-positive fusion gene ALL, which suggested the presence of ALL with the "masked" Ph chromosome found in approximately 1% of chronic myeloid leukemia. Therefore, the FISH analysis may complement cytogenetic analysis when cytogenetic and molecular genetic findings are contradictory in ALL.
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Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Hibridación Fluorescente in Situ , Citogenética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
Aim: To evaluate the safety and effectiveness of carfilzomib in a real-world setting. Methods: A post-marketing surveillance of Japanese patients with relapsed or refractory multiple myeloma who received carfilzomib treatment was performed. Results: Overall incidences of adverse events of any grade, ≥grade 3 treatment-related adverse events and serious adverse events were 63.5, 44.6 and 37.7% of patients, respectively. No new safety findings were observed. Treatment-related adverse events of special interest (≥5%) were hematological toxicities, infectious disease, cardiac disorders (including cardiac failure, myocardial infarction and QT prolongation), renal disorders, liver failure or liver dysfunction, and hypertension or hypertensive crisis. The overall response rate was 46.5%. Conclusion: Carfilzomib was found to be a safe and effective treatment for relapsed or refractory multiple myeloma in Japanese patients.
Carfilzomib is a medicine that was recently approved for the treatment of cancer of bone marrow (multiple myeloma) that comes back or does not respond to previous treatment (relapsed or refractory). Data gathered from the hospitals, where the medicine is commonly used, was used to generate evidence. We looked at how well carfilzomib works in Japanese participants and if it is safe. Overall, 63.5% of participants treated with carfilzomib had side effects and 37.7% had serious side effects. Death occurred in 3.1% of participants during the study. Decrease in bone marrow and blood cells, infections, heart and kidney disorder, liver failure or dysfunction, and high blood pressure occurred in 5% or more participants. In 46.5% of participants the tumors had disappeared or shrank. In Japanese participants, carfilzomib was found to be safe and effective treatment for cancer of bone marrow that comes back or does not respond to previous treatment.
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Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Humanos , Japón/epidemiología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/epidemiología , Oligopéptidos/efectos adversos , Vigilancia de Productos ComercializadosRESUMEN
We report the case of an 82-year-old male with subacute sensorimotor neuropathy associated with Epstein-Barr virus (EBV) infection, who presented with diplopia followed by gait disturbance due to limb weakness. Pathological findings of a biopsied cervical lymph node showed a high frequency of EBV-positive cells. EBV-DNA was detected in blood. A nerve conduction study suggested a mixture of axonal damage and demyelination. Brain MRI showed multiple microbleeds in cerebellar cortices, but cerebrospinal fluid EBV-PCR was negative, suggesting bleeding due to EBV-related vasculitis. Corticosteroid therapy improved the neurological symptoms and the patient was able to walk independently four months later. The main pathogenesis of the neuropathy in this case is likely to be a mixture of vasculitic neuropathy and immune-mediated demyelinating neuropathy, which are considered to be due to EBV reactivation.
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Infecciones por Virus de Epstein-Barr , Enfermedades del Sistema Nervioso Periférico , Vasculitis , Anciano de 80 o más Años , Herpesvirus Humano 4 , Humanos , MasculinoRESUMEN
Therapeutic improvements are needed for patients with acute myeloid leukemia (AML), particularly those who have relapsed or who have treatment-refractory (R/R) AML or newly diagnosed patients with poor prognostic factors. Alvocidib (DSP-2033), a potent cyclin-dependent kinase 9 inhibitor, has previously demonstrated promising clinical activity for the treatment of AML. In this multicenter, open-label, uncontrolled, 3 + 3 phase I study, we investigated the safety and tolerability of alvocidib administered in combination with either cytarabine and mitoxantrone (ACM) for R/R AML or cytarabine/daunorubicin (A + 7 + 3) for newly diagnosed AML. Alvocidib was administered to all patients as a 30-min intravenous (i.v.) bolus (30 mg/m2 /d), followed by a continuous i.v. infusion over 4 h on days 1-3 (60 mg/m2 /d). A total of 10 patients were enrolled: six received ACM (at two dose levels of cytarabine and mitoxantrone) and four received A + 7 + 3. Alvocidib was tolerated and no dose-limiting toxicities were observed. All patients experienced adverse events, of which diarrhea was the most frequent (100%); hematologic events were also common. Alvocidib concentration peaked at the end of dosing (4.5 h after start of administration), plasma accumulation after repeated dosing was minimal and urinary excretion was negligible. The rate of complete remission/complete remission with incomplete hematologic recovery was 66.7% with the ACM regimen in R/R AML, including four complete remission (median duration 13.6 months), and 75% (three complete remission) with the A + 7 + 3 regimen. Further development of alvocidib in hematologic malignancies is warranted. The trial is registered with Clinicaltrials.gov, NCT03563560.
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Citarabina , Leucemia Mieloide Aguda , Humanos , Citarabina/efectos adversos , Leucemia Mieloide Aguda/patología , Daunorrubicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inducción de Remisión , JapónRESUMEN
Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country's aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% > 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with > 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.
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Leucemia Mieloide Aguda , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/uso terapéutico , Citarabina , Humanos , Japón , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Few studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively analysed the clinical features, treatment response, and long-term outcomes of 42 AYA patients, in comparison to older patients. The initial therapies of AYA patients between 2001 and 2016 included imatinib (n = 24), dasatinib (n = 13) and nilotinib (n = 5). RESULTS: In AYA patients, the peripheral blood (PB) white blood cell count and percentage of blasts at the diagnosis were significantly higher, haemoglobin levels were lower and the spleen size was larger. The major molecular response (MMR), event-free survival (EFS) and overall survival (OS) rates were comparable. A sub-analysis comparing imatinib to second-generation TKIs as the initial therapy also showed that their prognosis was comparable. DISCUSSION: In conclusion, the tumour burden at the diagnosis of CML-CP is higher in AYA patients; however, their prognosis was not worse in comparison to older patients treated with TKIs. KEY MESSAGESFew studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). This study showed the tumour burden at the diagnosis of CML-CP is higher in AYA pa tients; however, their prognosis was not worse in comparison to older patients treated with TKIs. Understanding the biological and non-biological features of AYA patients with CML-CP on TKI therapy is essential for better management and to improve the outcomes.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide de Fase Crónica , Adolescente , Humanos , Mesilato de Imatinib/efectos adversos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/diagnóstico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Adulto JovenRESUMEN
The tumor microenvironment (TME) is a critical regulator of the development of malignant lymphoma. Therapeutics targeting the TME, especially immune checkpoint molecules, are changing the treatment strategy for lymphoma. However, the overall response to these therapeutics for diffuse large B-cell lymphoma (DLBCL) is modest and new targets of immunotherapy are needed. To find critical immune checkpoint molecules for DLBCL, we explored the prognostic impact of immune checkpoint molecules and their ligands using publicly available datasets of gene expression profiles. In silico analysis of three independent datasets (GSE117556, GSE10846, and GSE181063) revealed that DLBCL expressing CD24 had a poor prognosis and had a high frequency of MYC aberrations. Moreover, gene set enrichment analysis showed that the 'MYC-targets-hallmark' (false discovery rate [FDR] = 0.024) and 'inflammatory-response-hallmark' (FDR = 0.001) were enriched in CD24-high and CD24-low DLBCL, respectively. In addition, the expression of cell-specific markers of various immune cells was higher in CD24-low DLBCL than in CD24-high DLBCL. CIBERSORT analysis of the datasets showed fewer macrophages in CD24-high DLBCL than in CD24-low DLBCL. Additionally, immunohistochemical analysis of 335 cases of DLBCL showed that few TME cells were found in CD24-high DLBCL, although statistical differences were not observed. These data indicate that CD24 expression suppresses immune cell components of the TME in DLBCL, suggesting that CD24 may be a target for cancer immunotherapy in aggressive large B-cell lymphoma.
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Antígeno CD24 , Proteínas de Punto de Control Inmunitario , Linfoma de Células B Grandes Difuso , Antígeno CD24/genética , Antígeno CD24/inmunología , Humanos , Proteínas de Punto de Control Inmunitario/inmunología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Fenotipo , Pronóstico , Microambiente TumoralRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma characterized by the selective growth of lymphoma cells within the lumen of vessels. We describe the case of a 69-year-old male who presented with marked pain in the left facial region. Gadolinium-enhanced magnetic resonance imaging revealed a swollen left trigeminal nerve (TN) and positron emission tomography/computed tomography demonstrated fluorodeoxyglucose-only uptake at the same site. The patient had high serum lactate dehydrogenase and soluble interleukin-2 receptor levels. As random skin biopsy and bone marrow biopsy detected no abnormal pathogenesis, open biopsy of the TN was performed, revealing diffuse large B-cell lymphoma (DLBCL). However, ground glass opacities rapidly developed in both lung fields with severe respiratory failure. The patient died of progressive disease before the initiation of chemotherapy. Postmortem examination revealed widespread lymphoma cells in the lumen of vessels in multiple organs, including the lungs, excluding the bone marrow and skin. Lymphoma cells formed a mass in the TN and left lumbar plexus. A diagnosis of IVLBCL was made based on the postmortem pathological analysis. DLBCL of abnormal sites, such as the peripheral nervous system, should be considered in cases of IVLBCL as a differential diagnosis.
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Linfoma de Células B Grandes Difuso , Autopsia , Fluorodesoxiglucosa F18 , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Nervio Trigémino/patologíaRESUMEN
DSP-7888 is an immunotherapeutic cancer vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of DSP-7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP-7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2-4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose-limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty-seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher-risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8-10.3) months. Median OS was 10.0 (90% CI, 7.6-11.4) months in patients with a WT1-specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3-8.1) months in those without a WT1-specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP-7888 dosing emulsion.
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Vacunas contra el Cáncer , Síndromes Mielodisplásicos , Azacitidina/uso terapéutico , Vacunas contra el Cáncer/efectos adversos , Emulsiones/uso terapéutico , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológico , Resultado del Tratamiento , Vacunas de Subunidad/efectos adversos , Proteínas WT1RESUMEN
A 62-year-old woman was presented at our hospital with visual disturbance. An ocular examination revealed bilateral Roth spots. Laboratory data revealed leukocytosis (236,200 µl) with an excess blast (11%). Physical examination and computed tomography (CT) showed systemic lymphadenopathy. A bone marrow examination revealed a composition of 9.2% blast. Chromosomal analysis on bone marrow cells revealed 46,XX,t (3;12)(q26.2;p13),t (9;22)(q34.1;q11.2) in 80% of metaphases (16/20). Inguinal lymph node biopsy revealed diffuse proliferation of myeloperoxidase (MPO)-positive abnormal cells. Fluorescence in situ hybridization analysis was used to detect the BCR-ABL1 fusion gene and split the signals of MECOM and ETV6. She was diagnosed with de-novo chronic myeloid leukemia (CML) extramedullary blast crisis. She received tyrosine kinase inhibitor (TKI) combination chemotherapy and allogeneic hematopoietic stem cell transplantation and achieved a major molecular response. In this study, we reported a case of CML in blast-phase initially presenting as extramedullary, in which cytogenetic and molecular analyses were useful in the staging method.
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Crisis Blástica , Leucemia Mielógena Crónica BCR-ABL Positiva , Femenino , Humanos , Persona de Mediana Edad , Crisis Blástica/genética , Crisis Blástica/patología , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Análisis Citogenético , Ganglios Linfáticos/patologíaRESUMEN
We compared the two methods of assessing CD30 protein expression in DLBCL and TCL specimens routinely employed at our hospital, immunohistochemistry (IHC) and flow cytometry (FCM), using the same clone of the anti-CD30 antibody (Ber-H2) in 123 patients with DLBCL and 28 patients with TCL. FCM was more sensitive than IHC, especially in cases with low expression. In three cases of TCL and two cases of DLBCL, there was discordance between these two methods. Two of these TCL cases were ALCL and one was peripheral T-cell lymphoma, NOS, but ALCL was unable to be excluded. One of two cases of DLBCL was an anaplastic variant of DLBCL. The data suggested that CD30 was undetectable, though rare, by FMC in several cases. Based on this study, a combination of IHC and FCM is recommended for the reliable and quantitative detection of CD30.