RESUMO
An 84-year-old woman was diagnosed as having acute promyelocytic leukemia(APL)in July Year X-3. The test for promyelocytic leukemia- retinoic acid receptor alpha(PML-RARA)mRNA was positive, while that for CD56 was negative. Since her white blood cell( WBC) count was <3,000/µL, with a count of APL cells of <1,000/µL, she was started on monotherapy with all-trans retinoic acid(ATRA). In September Year X-3, complete hematological remission(CHR)was confirmed. she refused to provide consent for receiving consolidation therapy. In February Year X-2, hematological relapse occurred. She was started on re-induction therapy with arsenite(ATO), and in June Year X-2, complete molecular remission(CMR)was achieved. She was started on post-remission therapy with ATO. In August Year X-1, she developed molecular relapse and was started on tamibarotene(Am80). In October Year X-1, hematological relapse was detected, and the test for CD56 was positive. She was started on combined venetoclax(VEN)+azacitidine(AZA)(VEN+AZA). After completion of 1 course of treatment, CMR was achieved, but she developed hematological relapse after 5 courses of treatment. She died of gastrointestinal hemorrhage. This is considered a valuable case for accumulating information on the treatment of CD56-positive APL resistant to ATRA and ATO.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Promielocítica Aguda , Sulfonamidas , Humanos , Feminino , Idoso de 80 Anos ou mais , Leucemia Promielocítica Aguda/tratamento farmacológico , Trióxido de Arsênio/uso terapêutico , Azacitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tretinoína/uso terapêutico , RecidivaRESUMO
AIMS: Tissue eosinophilia is commonly observed in T-cell and classic Hodgkin lymphomas, but rarely in B-cell lymphomas. Herein, we present the first report of a case series on nodal marginal zone lymphoma (NMZL) with tissue eosinophilia. METHODS AND RESULTS: All 11 patients in this study had nodal disease at primary presentation. The mean age at diagnosis was 64 years. The mean follow-up period was 39 months, and all patients were alive. Nine of the 11 patients (82%) showed no recurrence, but the other two patients experienced recurrence in the lymph nodes or skin. Marked eosinophilic infiltration was observed in all biopsied lymph nodes. Nine of the 11 patients had a preserved nodular architecture with expanded interfollicular areas. The other two patients showed diffuse lymphoma cell infiltration with effacement of nodal architecture. One of them was diagnosed as having diffuse large B-cell lymphoma transformed from NMZL because large cells accounted for >50% of the lymphoma cells and formed sheet-like patterns. Cells were positive for CD20 and BCL2 and negative for CD5, CD10, and BCL6. Some patients showed myeloid cell nuclear differentiation antigen (MNDA) positivity. All patients showed B-cell monoclonality via flow cytometry, southern blotting, and/or polymerase chain reaction (PCR). CONCLUSION: All patients showed distinctive morphological features and could be misdiagnosed with peripheral T-cell lymphoma due to their eosinophil-rich backgrounds. The predominance of B cells, absence of histiocytes, and high endothelial venules in the interfollicular areas are key factors for diagnosis. B-cell monoclonality is the most reliable evidence of differentiation. We designated this type of lymphoma as an eosinophil-rich variant of NMZL.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Eosinófilos/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfonodos/patologia , Linfócitos B/patologia , Linfoma Difuso de Grandes Células B/patologiaRESUMO
Histiocytes and dendritic cells may display cytological atypia and an aberrant immunophenotype even in reactive processes. Herein, we describe two cases of "Hodgkinoid histiocytosis" that show distinctive clinicopathological features, mimicking morphologically classic Hodgkin lymphoma (CHL), but suggesting reactive histiocytic/dendritic cell proliferation in lymph nodes. Both the patients presented with peripheral lymphadenopathy and blood eosinophilia with skin manifestations. Lymph node biopsy revealed scattered large histiocytes resembling Hodgkin cells with a round or stellate shape, abundant cytoplasm, and distinct nucleoli admixed in a predominant inflammatory background. The Hodgkinoid histiocytes occasionally showed emperipolesis. They expressed CD30, S100, and PD-L1 proteins but lacked PAX5 and CD1a expressions, Epstein-Barr association, BRAF V600E mutation, and PD-L1 gene amplification. Neither of the patients showed overt progression to malignant haematopoietic neoplasms during the disease course. An identical case series of four patients has been reported to date. Both these series highlight the potential of being interpreted as CHL due to the presence of Hodgkinoid histiocytes with CD30 positivity.
Assuntos
Eosinofilia , Histiocitose , Doença de Hodgkin , Antígeno B7-H1 , Eosinofilia/complicações , Eosinofilia/patologia , Histiócitos/patologia , Histiocitose/complicações , Histiocitose/patologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Humanos , Antígeno Ki-1 , Proteínas S100RESUMO
BACKGROUND: Surgery is recommended for patients with high-risk submucosal invasive rectal cancer (SM-RC) after local resection but affects the quality of life due to stoma placement or impaired anal function; therefore, alternative treatment approaches are needed to prevent local metastasis. The purpose of this study was to assess the short-term safety of adjuvant chemoradiotherapy with capecitabine in patients with high-risk submucosal invasive rectal cancer after local resection. METHODS: This single-arm, multicenter, phase II trial included patients undergoing local resection for high-risk submucosal invasive rectal cancer within 12 weeks prior to enrollment. High-risk submucosal invasive rectal cancer was defined as the presence of at least one of the following factors: poor differentiation of adenocarcinoma, submucosal invasion depth > 1 mm, presence of lymphovascular invasion and grade-2 or -3 tumour budding. Protocol treatment comprised 45.0 Gy radiotherapy with conventional fractionation and 1650 mg/m2 capecitabine given twice daily until radiotherapy completion. The primary endpoint was treatment completion rate with an expected rate of 95% and a threshold of 80%. RESULTS: Twenty-nine patients from six institutions were enrolled between May 2015 and February 2018. One patient was ineligible. Twenty-three patients completed treatment, with a completion rate of 82% (80% confidence interval, 69-91%); the remaining five patients completed treatment with protocol deviation. The median relative dose intensity of capecitabine was 100% (range, 58-100%). Common adverse events included radiation dermatitis (54%), anal pain (39%) and anal mucositis (29%). No grade-3 or higher adverse events were reported. CONCLUSIONS: Adjuvant chemoradiotherapy using capecitabine demonstrated acceptable short-term safety profiles in patients with high-risk submucosal invasive rectal cancer after local resection.
Assuntos
Quimiorradioterapia Adjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Qualidade de Vida , Neoplasias Retais/patologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. METHODS: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. RESULTS: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. CONCLUSIONS: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.
Assuntos
Tumores Neuroendócrinos , Endoscopia Gastrointestinal , Trato Gastrointestinal , Humanos , Gradação de Tumores , Invasividade Neoplásica , Tumores Neuroendócrinos/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. CASE PRESENTATION: A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/µL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/µL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein-Barr virus (EBV) DNA level of 8.9 × 105 copies/µg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient's condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. CONCLUSIONS: sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.
Assuntos
Estado Terminal , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Complicações Hematológicas na Gravidez/diagnóstico , Infecções por Vírus Epstein-Barr/terapia , Feminino , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/terapia , Gravidez , Complicações Hematológicas na Gravidez/terapia , Resultado da Gravidez , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital. METHODS: According to the World Health Organization(WHO)diagnostic criteria. PATIENTS: All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019. RESULT: More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology. CONCLUSION: Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.
Assuntos
Policitemia Vera , Trombocitemia Essencial , Humanos , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiologia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/epidemiologiaRESUMO
A 42âyearâold woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"lowârisk"by IPSETâthrombosis, and as"ultralow"risk by revised IPSETâthrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.
Assuntos
Trombocitemia Essencial , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Cesárea , Feminino , Humanos , Período Pós-Parto , Gravidez , Trombocitemia Essencial/complicaçõesRESUMO
In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients. OBJECTIVE: The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated. METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted. RESULT: In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases. CONCLUSION: The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.
Assuntos
Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas , Pirazóis/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). BMbiopsy performed in 2016 showed overt fibrotic stage(Grade 2). She was classified according to the Dynamic International Prognostic Scoring System(DIPSS)as intermediate(Int)-â ¡risk. Ruxolitinib 10 mg daily was initiated. Ruxolitinib was suspended for hepatic dysfunction after the dose was increased to 15 mg. Subsequently, ruxolitinib was resumed at 10 mg. BM biopsy performed in 2017 showed progression of myelofibrosis(MF)to Grade 3. BM biopsy performed in 2018 showed improved to Grade 0-1, however, BM was fatty. Currently in 2019, she continues to be on ruxolitinib. Results of immunohistochemical staining of BM biopsy specimens for cytokines and CD34 suggested the role of cytokines in the pathogenesis of the PMF. It was speculated that ruxolitinib blocked the production of cytokines to ameliorate the MF and restore the hematopoietic function of the BM. Although the pathogenesis of the fatty marrow remained unclear, the possibility of involvement of ruxolitinib cannot be denied.
Assuntos
Mielofibrose Primária , Medula Óssea , Feminino , Fibrose , Humanos , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirazóis , PirimidinasRESUMO
A 72-year-old woman with chronic myeloid leukemia (CML) and cirrhosis complicated with blood blisters on her right upper arm and ascites was admitted. She presented with shock vital on admission. Initial gram staining of blood cultures showed gram-positive cocci in chains, suggesting streptococcal toxic shock syndrome (STSS). Amputation of the right upper arm was performed owing to necrotizing fasciitis. Despite continued antibiotic therapy and systemic management, the blood blisters rapidly spread to the skin of the whole body, and she died 41 h after admission. Blood and fluid cultures from the blisters showed group B streptococci. Reports of patients with leukemia complicated with STSS are rare, and all cases have followed fatal courses. Particularly in this case, various risk factors, such as neutropenia due to tyrosine kinase inhibitor, neutrophil dysfunction due to cirrhosis, and elderly CML, overlapped. In the future, we believe that the lives of patients with leukemia complicated with STSS may be saved by establishing treatment methods and determining the detailed pathogenesis of STSS.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Cirrose Hepática , Choque Séptico , Infecções Estreptocócicas , Idoso , Feminino , Humanos , Choque Séptico/etiologia , Streptococcus agalactiae , Streptococcus pyogenesRESUMO
OBJECTIVE: The clinical features(CF), laboratory data, disease transformation pattern and drug metabolism in essential thrombocythemia(ET)differ between Japan and Western countries. The CF of ET in clinical practice(CP)are more diverse than in prospective clinical studies. We should conduct retrospective analyses in CP. The present study was aimed at evaluating the efficacy, safety and tolerability of anagrelide(ANA)monotherapy and combined ANA plus hydroxycarbamide(HC)in Japanese ET. PATIENTS AND METHODS: We have a total of 35 cases. Sixteen patients received ANA monotherapy, 10 received ANA plus HC, and 9 received ANA plus other drugs. RESULTS: Comparison among three groups revealed the absence of differences in response rate(platelet count C60×10 / / 4/mL, platelet count C40×104/mL)(43.8%, 6.3% vs. 50.0%, 10.0% vs. 44.4%, 11.1%), treatment continuation rate(81.3% vs. 40.0% vs. 55.6%), median daily dose of ANA(1.00 mg in all three groups)or median treatment period(days)(259 vs. 198.5 vs. 161.0), the treatment continuation rate tended to be lower in the combined ANA plus HC. The incidence of all adverse events(AEs)was higher in the ANA monotherapy(45.7%)than ANA plus HC(28.6%)or ANA plus other drugs(25.7%), the AEs were mild in all groups. CONCLUSION: The tolerability of ANA monotherapy, ANA plus HC, and ANA plus other drugs were good.
Assuntos
Hidroxiureia/uso terapêutico , Quinazolinas/efeitos adversos , Trombocitemia Essencial , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Japão , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológicoRESUMO
A 59-year-old female was diagnosed as pulmonary aspergillosis(IPA)while remission induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia. Liposomal amphotericin B improved the fungal serodiagnostic markers, however,the IPA worsened. She also developed an Aspergillus brain abscess,which, while being undetectable on CT,was detected as multiple nodular lesions by MRI. A definitive diagnosis was made by polymerase chain reaction(PCR)of brain biopsy specimens. Voriconazole(VRCZ)was effective,and cord blood transplantation was performed. She has received VRCZ for a long time. There are no relapse of either the IPA or the Aspergillus brain abscess.
Assuntos
Abscesso Encefálico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Aspergilose Pulmonar Invasiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antifúngicos , Feminino , Humanos , Aspergilose Pulmonar Invasiva/complicações , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , VoriconazolRESUMO
Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.
Assuntos
Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco de Sangue Periférico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
OBJECTIVE: The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. METHODS: The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. RESULTS: Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. CONCLUSION: These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy.
Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crônica/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. METHODS: In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. RESULTS: PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p < 0.001 each). CONCLUSION: Our findings do not support the survival benefit of SP over S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Análise Multivariada , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Pontuação de Propensão , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Resultado do TratamentoRESUMO
The JAK2V617F mutation is the commonest major genetic mutation of myeloproliferative neoplasms (MPNs) and has been defined in the WHO diagnostic criteria for MPNs. However, there is still no approved in vitro diagnostic test kit available in Japan. We evaluated a JAK2V617F allele quantification kit (test method) in a prospective, multicenter clinical performance study involving patients with MPNs who were diagnosed with polycythemia vera, essential thrombocythemia, and primary myelofibrosis; healthy volunteers were also included in the analysis. Good correlation was observed between the allele burden determined using the test method vs. that determined using next-generation sequencing (NGS) in the patient group (r=0.998, y=1.071x-0.069; n=156). Furthermore, all allele burdens in the healthy group (n=54) were below the lower limit of the measurement range of the test method (0.042%). Our results confirmed that the test method could quantitatively measure the JAK2V617F allele burden in patients with MPN. Thus, the novel JAK2V617F allele quantification kit can be considered useful for the diagnosis of MPNs.
Assuntos
Testes Genéticos/instrumentação , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Estudos de Casos e Controles , Humanos , Japão , Mutação , Estudos ProspectivosRESUMO
BACKGROUND: Although patients with advanced gastric cancer (AGC) have a poor prognosis when conventional therapies fail, they are often candidates for phase I trials. However, there is no detailed report on clinical outcomes of patients with AGC treated in phase I trials. METHODS: We retrospectively reviewed the medical records of 66 consecutive patients with AGC enrolled in phase I trials between March 2008 and July 2014 at our institution in Japan. RESULTS: Median age was 66 years (range, 28-78 years) and median number of previous lines of conventional chemotherapy was 3 (range, 1-6). Five (8.6 %) and seven (12 %) patients showed objective response and stable disease >3 months, respectively. Although the time to treatment failure (TTF) of the best phase I treatment was shorter than that of the last line of conventional chemotherapy (median 1.5 vs. 2.3 months; P = 0.002), TTF of the best phase I treatment was longer than that of the last line of treatment in 21 patients (32 %). Severe adverse events and grade 3 or higher toxicities were reported in eight (12 %) and 13 patients (20 %), respectively. No treatment-related death was observed. Median survival time from the start of phase I treatment was 7.5 months, and four deaths (6 %) within 30 days after last administration were observed. CONCLUSION: Phase I trials of patients with AGC was acceptably feasible with some efficacy signal. Our results suggest that phase I trials might be one treatment option for patients with AGC when conventional therapies fail.
Assuntos
Ensaios Clínicos Fase I como Assunto , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Biópsia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estômago/patologia , Resultado do TratamentoRESUMO
A 67-year-old woman presented with a swelling on both sides of the neck. Biopsy of an enlarged cervical lymph node on the left side and flow cytometric analysis revealed CD56-positive CD4(+)CD8(+) abnormal NK/T cells. A Southern blot analysis of the cervical lymph node biopsy specimen showed a human T-cell leukemia virus type 1 provirus DNA monoclonal band. Based on these findings, the patient was diagnosed with CD56-positive adult T-cell leukemia/lymphoma. After five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, the general condition of the patient gradually declined, indicating resistance to treatment, and approximately 9 months after the onset of symptoms, the patient died. CD56 is recognized as an unfavorable prognostic marker in cases of acute myeloid leukemia with t(8;21), acute promyelocytic leukemia, and anaplastic large cell lymphoma. Only eight cases of CD56-positive adult T-cell leukemia/lymphoma have been reported so far in the literature. Most of these cases were in the advanced stage at diagnosis and had poor outcomes. It appears that the correlation between CD56 expression and outcomes in patients with adult T-cell leukemia/lymphoma should be clarified by investigating a larger number of cases in the future.