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Eltrombopag, a thrombopoietin receptor agonist, is approved for treating patients with immune thrombocytopenic purpura (ITP) refractory to corticosteroids and intravenous immunoglobulin (IVIg) therapy. We report a 32-years-old nulliparous Japanese woman with ITP and chronic hypertension who developed pulmonary edema due to superimposed preeclampsia at 27 weeks of gestation. She received therapy with corticosteroids, IVIg and Eltrombopag, but her platelet level was fluctuating and was difficult to achieve a well sustained response. A transient leukocytosis was noted but resolved by Eltrombopag dose reduction. Her pregnancy was complicated with preeclampsia with severe features required a prompt delivery. Although recent evidence supports the safety and efficacy of Eltrombopag use during pregnancy, unreported risks may underlie its use during pregnancy.
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We herein report an 83-year-old woman with filgrastim-associated aortitis during chemotherapy for relapsed diffuse large B-cell lymphoma. She had been treated with filgrastim as a prophylaxis for neutropenia during the fourth cycle of chemotherapy from day 9 to 18. On day 21, she developed a fever. Contrast-enhanced computed tomography revealed aortitis of the descending aorta. The fever abated with non-steroidal anti-inflammatory drug treatment. A literature review identified a small number of aortitis cases all caused by prophylactic use of granulocyte colony-stimulating factors (G-CSFs), among which short-acting filgrastim was rarely encountered. The present and previous findings imply a possible relationship between aortitis and prophylactic G-CSF usage.
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Aortitis , Neoplasias , Neutropenia , Femenino , Humanos , Anciano de 80 o más Años , Filgrastim/efectos adversos , Aortitis/inducido químicamente , Aortitis/diagnóstico por imagen , Aortitis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Neutropenia/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Objective Compared to prospective trials, the early death rate of newly diagnosed acute promyelocytic leukemia (APL) in the real-world clinical setting is higher. However, the early death rate was heterogeneous according to the reported institutes. Thus, the therapeutic approach at each institute may be important for preventing early death. This study evaluated the management strategy for untreated APL in our institute to avoid early death. Methods We identified consecutive 21 patients with untreated APL who received induction therapy including all-trans retinoic acid (ATRA) between July 2007 and December 2021 at the University of Tokyo Hospital. Results As therapeutic approaches, 16 patients (76%) received ATRA administration on the day of admission, and the remaining 5 received ATRA within 4 days from admission. Notably, all patients received conventional chemotherapy added to ATRA at a median of 1 day from admission (range: 0-9 days). As clinical outcomes, no patient died during induction therapy for untreated APL, and all achieved complete molecular remission. Conclusion Compared to the previous nationwide survey, a higher proportion of patients at our institute received conventional chemotherapy in addition to ATRA, and it was initiated more promptly, which may have helped prevent early death.
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Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tretinoina/uso terapéutico , Inducción de Remisión , Resultado del TratamientoRESUMEN
There have recently been a few case reports of cutaneous T-cell lymphomas following treatment of atopic dermatitis with dupilumab, which works binding to the interleukin (IL)-4 receptor and inhibiting the JAK/ STAT cascade located downstream of both IL-4 and IL-13. Here, we report the first case of Hodgkin lymphoma (HL) in a patient treated with dupilumab for one year. Based on multiple biopsies, this case was diagnosed as a rare combination of discordant lymphomas of HL and peripheral T-cell lymphoma. As both lymphomas are known to overexpress IL-13, future studies should carefully evaluate the effect of anti-IL-13 therapy. A literature review showed that dermatitis persisted or worsened in all reported lymphoma cases following dupilumab and cutaneous T-cell lymphoma was diagnosed within 2 years of the start of treatment with dupilumab. In these cases, with the addition of our own, the median interval was 12 months, and 31% needed multiple biopsies for diagnosis of lymphomas. Our results demonstrate a need to be alert to potential development of lymphomas associated with the IL-13 and IL-4 pathways in patients with poorly responsive atopic dermatitis receiving dupilumab, and to consider the possibility of composite or discordant lymphomas in diagnosis and treatment of lymphomas.
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Dermatitis Atópica , Enfermedad de Hodgkin , Linfoma de Células T Periférico , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Interleucina-4RESUMEN
To prevent early death, management of coagulopathy is important in patients with untreated acute promyelocytic leukemia (APL). This study aimed to clarify factors associated with in-hospital death in patients with coagulopathy during induction therapy for APL. We retrospectively identified patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) and developed coagulopathy, using a nationwide inpatient database in Japan. Of 1115 eligible patients, 175 (15%) died at a median of 13 days (interquartile range, 7-30) after admission. In the multivariable analysis, compared with younger patients (aged < 40 years), the occurrence of in-hospital death was significantly more common among older patients (aged ≥ 40 and < 60 years: odds ratio = 2.58 [95% confidence interval: 1.29-5.19]; aged ≥ 60 and < 80 years: 7.66 [3.89-15.10]; aged ≥ 80 years: 16.83 [7.41-38.21]). Delayed initiation of ATRA and no conventional chemotherapy were significantly associated with in-hospital death (1.79 [1.16-2.76] and 2.40 [1.47-3.92], respectively). A total of 699 patients (63%) received anticoagulant therapies, but none of these was significantly associated with lower mortality. Although the present study was constrained by a lack of laboratory findings because of database limitations, the results showed that untreated patients with APL, especially the elderly, had a poor prognosis. Immediate administration of ATRA may reduce in-hospital mortality.
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Antineoplásicos/uso terapéutico , Trastornos de la Coagulación Sanguínea/etiología , Quimioterapia de Inducción , Leucemia Promielocítica Aguda/complicaciones , Tretinoina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Femenino , Mortalidad Hospitalaria , Humanos , Quimioterapia de Inducción/efectos adversos , Japón/epidemiología , Leucemia Promielocítica Aguda/epidemiología , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tretinoina/efectos adversosRESUMEN
Secondary immune thrombocytopenic purpura (ITP) with non-Hodgkin lymphoma (NHL) is a rare disease. Although some treatment regimens are available for primary ITP, the treatment strategy for secondary ITP remains unconfirmed. We herein report a 79-year-old man who was diagnosed with secondary ITP with mantle cell lymphoma. Although intravenous immunoglobulin (IVIG) has been considered an effective option for secondary ITP, similar to the treatment of primary ITP, our patient did not benefit from IVIG. A literature review including the current report revealed that IVIG was ineffective in all treated patients. Secondary ITP with NHL should be treated differently from primary ITP.
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Linfoma no Hodgkin , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Anciano , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológicoRESUMEN
Bendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B-cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2-93.7) and 54.4% (40.7-67.6), respectively. Five-year overall survival (OS) and 5-years progression-free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4-6) than in 16 cases of the earlier cessation group (cycle 1-3) (p = 0.012, 5-years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty-one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5-years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorhidrato de Bendamustina/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Clorhidrato de Bendamustina/farmacología , Humanos , Persona de Mediana Edad , Rituximab/farmacologíaAsunto(s)
Coagulación Intravascular Diseminada , Leucemia Promielocítica Aguda , Coagulación Intravascular Diseminada/tratamiento farmacológico , Humanos , Quimioterapia de Inducción , Leucemia Promielocítica Aguda/tratamiento farmacológico , Trombomodulina/uso terapéutico , Tretinoina/uso terapéuticoRESUMEN
INTRODUCTION: There has been no comprehensive analysis of the age-specific efficacy of G-CSF to prevent febrile neutropenia (FN). We evaluated factors associated with FN occurrence according to patient age in rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) treatment. METHODS: We retrospectively reviewed diffuse large B-cell lymphoma (DLBCL) patients aged ≥50 years, who underwent the first R-CHOP cycle between July 2010 and March 2017, using a Japanese inpatient database. Multivariable logistic regression analysis was performed to identify the factors associated with FN. RESULTS: A total of 16,399 patients with untreated DLBCL were identified. Primary prophylaxis with pegfilgrastim was significantly associated with the lower occurrence of FN (odds ratio: 0.71 [95% confidence interval: 0.51-0.99]). Subgroup analysis according to age was then performed. Although there was no significance, primary prophylaxis with pegfilgrastim tended to have a lower odds ratio for the occurrence of FN in patients aged 50-60 years (0.86 [0.39-1.89]) and 61-70 years (0.64 [0.36-1.13]). In patients aged 71-80 years, primary prophylaxis with pegfilgrastim was significantly associated with reduced FN occurrence (0.46 [0.26-0.80]). Notably, in patients aged >80 years, the use of pegfilgrastim tended to be associated with a rather higher occurrence of FN (1.55 [0.84-2.87]). CONCLUSIONS: Preventing effect of G-CSF may be limited in patients aged >80 years.
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Factor Estimulante de Colonias de Granulocitos , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/efectos adversos , Doxorrubicina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Japón , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéutico , Vincristina/efectos adversosRESUMEN
The clinical impact of pegfilgrastim in day-to-day practice remains unclear. This study evaluated the effectiveness of pegfilgrastim compared with daily filgrastim in patients with DLBCL who received the first-cycle of R-CHOP treatment by using a Japanese national inpatient database. Patient characteristics were adjusted by using propensity-score matching and stabilized inverse probability of treatment weighting (IPTW). In 1295 propensity-score-matched pairs, the incidence of febrile neutropenia was significantly lower in the pegfilgrastim group (risk difference 6.1%, 95% CI 4.1%-8.1%) than in the filgrastim group. In the pegfilgrastim group, the length of hospital stay and the total costs were also significantly reduced (percent reduction 34% [95% CI: 31%-37%], percent reduction 12% [95% CI: 9%-15%], respectively). The stabilized IPTW showed comparable results. In day-to-day practice, the simple mode of pegfilgrastim administration may be advantageous.
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Linfoma de Células B Grandes Difuso , Neutropenia , Filgrastim , Factor Estimulante de Colonias de Granulocitos , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Polietilenglicoles , Puntaje de Propensión , Proteínas RecombinantesRESUMEN
Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. TKI combination may be required to treat double primary cancers, each having a targetable gene, or to treat a single malignancy with multiple targetable genes. Here, we demonstrate the first report of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). A 60-year-old man with an 8-year history of CML was diagnosed as advanced EGFR-mutated lung adenocarcinoma. Complete molecular response of CML had been achieved by imatinib, and ABL-TKI had been switched to nilotinib four years previously due to muscle cramps. We discontinued nilotinib and started afatinib. Although partial response of lung adenocarcinoma was achieved, cytogenetic relapse of CML was observed following nilotinib discontinuation. We applied the previously described framework of cytochrome P450 3A4-mediated oral drug-drug interactions and selected gefitinib and nilotinib to treat both malignancies. We effectively and safely administered this combination for seven months. The present report is the first to demonstrate the safety and efficacy of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and CML.
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Although several pedigrees of familial myelodysplastic syndromes/acute myeloid leukemia (fMDS/AML) have been reported, the epidemiology and clinical features has been poorly understood. To explore the epidemiology of this entity, we performed a retrospective nationwide epidemiological survey in Japan using questionnaire sheets. The questionnaire was sent to 561 institutions or hospitals certified by Japanese Society of Hematology, unearthing the existence of 41 pedigrees of fMDS/AML. Among them, we obtained the clinical information of 31 patients in 20 pedigrees. The median age of the initial diagnosis was 51 years (range 9-88 years) and the WHO classification 2008 ranged from refractory anemia (RA) to AML. Focusing on the familial MDS patients, refractory anemia with excess blasts (RAEB)-2 was the largest group (27.3%). The median overall survival (OS) of fMDS and fAML in this study were 71.6 and 12.4 months, and the five-year OS were 61.3 and 50%, respectively.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Humanos , Japón/epidemiología , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/genética , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Posterior reversible encephalopathy syndrome (PRES) and human herpesvirus (HHV)-6 encephalitis are both serious neurological complications post hematopoietic stem cell transplantation. Although infection is one of the important causes of PRES, only few cases have reported the relation between PRES and viral infection. Herein, we report the first adult case of PRES concurrent with HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. This case suggests that HHV-6 reactivation is associated with the pathogenesis of PRES. Also, PRES and HHV-6 encephalitis cause similar symptoms, and switching the immunosuppressant from calcineurin inhibitor to prednisolone for treating PRES may worsen HHV-6 encephalitis. Therefore, we should pay attention to the complication of HHV-6 encephalitis even after PRES is diagnosed.
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Encefalitis Viral/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 6/patogenicidad , Síndrome de Leucoencefalopatía Posterior/etiología , Infecciones por Roseolovirus/etiología , Antivirales/uso terapéutico , Encefalitis Viral/diagnóstico , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Foscarnet/uso terapéutico , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Síndrome de Leucoencefalopatía Posterior/tratamiento farmacológico , Síndrome de Leucoencefalopatía Posterior/virología , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/tratamiento farmacológico , Infecciones por Roseolovirus/virología , Trasplante Homólogo/efectos adversos , Resultado del TratamientoAsunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Linfoma de Células B/terapia , Adulto , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Biomarcadores , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/efectos adversos , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunohistoquímica , Linfoma de Células B/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Inducción de Remisión , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Granulocyte colony-stimulating factor (G-CSF) is commonly administered to prevent serious complications caused by chemotherapy-induced neutropenia; however, several cases of arteritis following the administration of G-CSF have been reported. Here, we report three cases of patients with non-Hodgkin lymphomas (NHLs) who developed arteritis after the administration of G-CSF, estimate the probability of adverse drug reaction caused by G-CSF with two distinct algorithms, and review the literatures. Both algorithms indicated a causal relationship between G-CSF and arteritis. In a literature review of seven reported cases, including our three patients, the time from the administration of G-CSF to the onset of arteritis ranged from 9 days to 6 months, and five patients were treated with steroids. In one of our three cases, a 62-year-old female with NHL developed arteritis twice in different courses of chemotherapy. Hydrocortisone was administered in the second event, leading to prompt relief of the manifestation and abnormal laboratory data. This finding suggests steroids may be effective for arteritis. In conclusion, although the number of reported cases is limited, there appears to be an association between arteritis and the administration of G-CSF, and steroids are an effective therapeutic option.
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Arteritis , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Linfoma no Hodgkin , Anciano , Arteritis/diagnóstico por imagen , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Objective The therapeutic approach for transfusion-independent non-severe aplastic anemia (NSAA) is undetermined. This study aimed to investigate the efficacy of immunosuppressive therapy (IST) for NSAA. Methods We retrospectively reviewed 42 consecutive patients with transfusion-independent NSAA. NSAA was further divided into two stages according to the degree of cytopenia. Progression was defined as transition to a transfusion-dependent state. Results Twelve (29%) patients received IST with cyclosporine A (CsA). Eleven (26%) patients became transfusion-dependent. In all patients, a univariate analysis revealed that a low hemoglobin level (p=0.006) and low reticulocyte count (p=0.005) were associated with a high probability of progression. The estimated transfusion-free survival (TFS) was significantly prolonged by IST among patients with advanced-stage NSAA (p=0.002), while IST did not reduce the incidence of progression in the overall cohort (p=0.349). In the non-IST group, an advanced clinical stage was significantly associated with progression (p=0.003). In contrast, the clinical stage was not related to progression in the IST group (p=0.318). None of the patients had to discontinue treatment with CsA due to renal failure. Conclusion IST is expected to be effective in patients with advanced-stage NSAA.