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1.
Emerg Infect Dis ; 26(1): 11-19, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31855136

RESUMEN

Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.


Asunto(s)
Infecciones por Mycoplasma/microbiología , Mycoplasma , Adulto , Eritema/microbiología , Eritema/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Japón/epidemiología , Masculino , Microscopía Electrónica , Mycoplasma/genética , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/patología , Prurito/microbiología , Prurito/patología , Piel/patología
2.
Biol Blood Marrow Transplant ; 26(2): 367-372, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31678538

RESUMEN

Methotrexate (MTX) in combination with a calcineurin inhibitor has been commonly used for prophylaxis of graft-versus-host disease (GVHD) following umbilical cord blood transplantation (UCBT) in Japan. However, the appropriate prophylactic MTX dosage in UCBT has not been established to date. To determine the preferential GVHD prophylaxis in UCBT, this study retrospectively investigated the administration of short-term MTX for 2 days versus 3 days. Of 103 adult patients submitted to UCBT enrolled in the study, 73 received tacrolimus (TAC) with 2 days of MTX given at 10 mg/m2 on day 1 and 7 mg/m2 on day 3 (very short-term [vs] MTX), whereas 30 patients received TAC with 3 days of MTX given at 10 mg/m2 on day 1, 7 mg/m2 on day 3, and 7 mg/m2 on day 6 (short-term [s] MTX). In univariate analysis, neutrophil engraftment was shown to be significantly better (P = .039) in the vsMTX/TAC group. Among high-risk patients, the vsMTX/TAC group also exhibited earlier neutrophil engraftment (P = .042); however, the incidence of acute GVHD was higher in the vsMTX/TAC group (P = .035) on univariate analysis. In multivariate analysis, compared with sMTX/TAC, vsMTX/TAC was associated with lower risk of relapse (hazard ratio, .27; 95% confidence interval, .11 to .64; P = .003) . These results suggest that vsMTX/TAC can be appropriate GVHD prophylaxis after UCBT, especially in higher-risk patients.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Adulto , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Japón , Metotrexato/uso terapéutico , Estudios Retrospectivos , Tacrolimus/uso terapéutico
3.
Blood ; 131(2): 215-225, 2018 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-29084771

RESUMEN

Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.


Asunto(s)
Regulación Leucémica de la Expresión Génica , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/genética , Mutación , Cariotipo Anormal , Anciano , Epigénesis Genética , Femenino , Dosificación de Gen , Humanos , Factores Reguladores del Interferón/genética , Masculino , Persona de Mediana Edad , Modelos Moleculares , Polimorfismo de Nucleótido Simple , Pronóstico , Factor de Transcripción STAT3/genética
4.
Biol Blood Marrow Transplant ; 25(5): 861-867, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30639819

RESUMEN

After allogeneic stem cell transplantation (alloSCT), several immune checkpoints play an important role in the antileukemic immune response in the bone marrow (BM) microenvironment. However, immune checkpoint expression levels in the BM have not been reported after alloSCT in patients with acute myeloid leukemia (AML). We investigated the clinical impact of immune checkpoint expression in BM samples after alloSCT for AML. Higher expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) was associated with a decreased incidence of acute graft-versus-host disease (P = .048) and poor overall (P = .046) and progression-free survival (P = 0.024). In addition, higher expression of TIGIT at engraftment after alloSCT was correlated with a decreased number of natural killer cells in BM (P = .019). Monitoring TIGIT expression in the BM could be useful for predicting outcome after alloSCT for AML. Our findings raise the possibility that blockade of TIGIT would improve survival.


Asunto(s)
Antígenos de Diferenciación de Linfocitos T/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Monitorización Inmunológica/métodos , Receptores Inmunológicos/metabolismo , Receptores Virales/metabolismo , Médula Ósea/metabolismo , Enfermedad Injerto contra Huésped , Humanos , Inmunidad , Células Asesinas Naturales/citología , Sobrevida , Trasplante Homólogo
5.
Int J Mol Sci ; 20(9)2019 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-31027331

RESUMEN

The most common cause of death in patients with acute myeloid leukemia (AML) who receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) is AML relapse. Therefore, additive therapies post allo-HSCT have significant potential to prevent relapse. Natural killer (NK)-cell-based immunotherapies can be incorporated into the therapeutic armamentarium for the eradication of AML cells post allo-HSCT. In recent studies, NK cell-based immunotherapies, the use of adoptive NK cells, NK cells in combination with cytokines, immune checkpoint inhibitors, bispecific and trispecific killer cell engagers, and chimeric antigen receptor-engineered NK cells have all shown antitumor activity in AML patients. In this review, we will discuss the current strategies with these NK cell-based immunotherapies as possible therapies to cure AML patients post allo-HSCT. Additionally, we will discuss various means of immune escape in order to further understand the mechanism of NK cell-based immunotherapies against AML.


Asunto(s)
Inmunoterapia/métodos , Células Asesinas Naturales/metabolismo , Leucemia Mieloide Aguda/terapia , Animales , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Trasplante Homólogo/métodos
6.
Rinsho Ketsueki ; 60(6): 577-581, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31281147

RESUMEN

Cardiac involvement during lymphoma often causes complications, including arrhythmia. A 68-year-old male with cardiac tamponade was diagnosed with diffuse large B-cell lymphoma with cardiac involvement based on the presence of the tumor mass in the myocardium and lymphoma cells in the pericardial effusion. He developed atrial fibrillation, ventricular tachycardia, and atrial flutter after initiating chemotherapy. Following chemotherapy, sinus rhythm was restored without invasive treatment for arrhythmia, while the cardiac mass disappeared. No recurrent arrhythmias were observed. In lymphoma with cardiac involvement, unexpected arrhythmias can emerge after initiation of chemotherapy, which could potentially be related to accelerated cardiac remodeling owing to the rapid relief of cardiac damage. Follow-up using electrocardiogram is thus necessary during chemotherapy for cardiac lymphoma, despite the absence of arrhythmia at the time of diagnosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Taponamiento Cardíaco/inducido químicamente , Neoplasias Cardíacas/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Arritmias Cardíacas , Neoplasias Cardíacas/tratamiento farmacológico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Derrame Pericárdico
7.
Biol Blood Marrow Transplant ; 24(9): 1841-1847, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29753837

RESUMEN

Rapid immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for clinical outcome prediction. In most studies, immune recovery after allo-HSCT is monitored via peripheral blood. However, few reports regarding the status of absolute lymphocyte subsets in the bone marrow (BM) microenvironment have been undertaken. Therefore, we evaluated the clinical impact of immune recovery in the early period following allo-HSCT using BM samples. We showed that delayed natural killer cell recovery was independently associated with a poor prognosis for overall survival (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.37- 6.89; P = .007), progression-free survival (HR, 3.42; 95% CI, 1.47-7.94; P = .004), and nonrelapse mortality (HR, 6.68; 95% CI, 1.82-25.0; P = .004) by multivariate analysis. In addition, low NK cell counts were associated with the presence of 1 or more bacterial, viral, or fungal infections. Our results indicate that investigating absolute lymphocyte subsets in BM in the early phase following allo-HSCT can be useful for predicting and improving survival outcomes.


Asunto(s)
Médula Ósea/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Células Asesinas Naturales/inmunología , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
8.
Haematologica ; 103(12): 1980-1990, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30093396

RESUMEN

Chromosomal translocation t(8;21)(q22;q22) which leads to the generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in approximately 10% of acute myelogenous leukemia (AML). To identify somatic mutations that co-operate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in depth the role of ASXL2 in normal hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid hyperplasia, splenomegaly, extramedullary hematopoiesis, and poor reconstitution ability in transplantation models. Parallel analyses of young and >1-year old Asxl2-deficient mice revealed age-dependent perturbations affecting, not only myeloid and erythroid differentiation, but also maturation of lymphoid cells. Overall, these findings establish a critical role for ASXL2 in maintaining steady state hematopoiesis, and provide insights into how its loss primes the expansion of myeloid cells.


Asunto(s)
Diferenciación Celular/genética , Proliferación Celular/genética , Hematopoyesis/genética , Células Mieloides/metabolismo , Proteínas Represoras/genética , Enfermedad Aguda , Animales , Perfilación de la Expresión Génica/métodos , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Mielopoyesis/genética
9.
Acta Haematol ; 139(1): 12-18, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29301121

RESUMEN

Bendamustine has demonstrated favourable efficacy in relapsed or refractory indolent lymphoma and mantle cell lymphoma. We retrospectively evaluated the pre-treatment clinical and laboratory factors and their correlation with the clinical outcome of these lymphomas. We analysed 53 patients who had been treated with bendamustine alone (n = 6) or rituximab plus bendamustine (n = 47). The overall response rate was 81.1%, with a complete response (CR) rate of 39.6%. The CR rate was significantly low in patients who had elevated levels of soluble interleukin-2 receptor (p = 0.024) and C-reactive protein (CRP; p = 0.004). The 1-year overall survival (OS) rate was 79.3%. An elevated CRP was associated with a short OS (p = 0.056). The present findings suggest that the lymphoma microenvironment and immune response were involved in the effects of bendamustine. These findings are also important in order to understand the pathophysiology of refractory lymphoma and to find effective strategies using bendamustine.


Asunto(s)
Clorhidrato de Bendamustina/uso terapéutico , Proteína C-Reactiva , Linfoma de Células del Manto/sangre , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma/sangre , Linfoma/tratamiento farmacológico , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma/mortalidad , Linfoma/patología , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Resultado del Tratamiento
10.
Support Care Cancer ; 26(1): 269-274, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28766099

RESUMEN

PURPOSE: Few studies have investigated the effect of palonosetron on delayed chemotherapy-induced nausea and vomiting in lymphoma patients receiving the CHOP regimen. We conducted a prospective clinical trial to assess the efficacy of palonosetron in patients receiving the CHOP regimen. METHODS: Complete control (CC: emesis-free and mild nausea) during delayed phase (24-120 h) was the primary endpoint. The secondary endpoint was complete response (CR: emesis-free) during acute (0-24 h), delayed, and overall phases (0-120 h), and CC during acute and overall phases. Palonosetron (0.75 mg) was administered before chemotherapy on day 1 of both the first and second CHOP cycles. RESULTS: The efficacy of palonosetron in preventing emesis was evaluated in 40 patients. Across two cycles, over 85% of patients achieved CR. As the primary endpoint, the proportion of patients achieving CC in the delayed phase increased from 70% (cycle 1) to 85% (cycle 2). CR rate in the delayed phase increased from 85% (cycle 1) to 95% (cycle 2). CONCLUSION: These results suggest that the antiemetic effects during the delayed phase were inferior to those in the acute phase during the first cycle. However, even at the same dose of palonosetron, CR and CC rates increased in the second cycle.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Isoquinolinas/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Náusea/inducido químicamente , Quinuclidinas/uso terapéutico , Vómitos/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Isoquinolinas/administración & dosificación , Isoquinolinas/farmacología , Masculino , Persona de Mediana Edad , Palonosetrón , Prednisona/administración & dosificación , Prednisona/farmacología , Prednisona/uso terapéutico , Estudios Prospectivos , Quinuclidinas/administración & dosificación , Quinuclidinas/farmacología , Vincristina/administración & dosificación , Vincristina/farmacología , Vincristina/uso terapéutico , Adulto Joven
11.
Rinsho Ketsueki ; 59(11): 2423-2427, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-30531137

RESUMEN

Hyponatremia occurs while receiving bortezomib-containing combination therapy in multiple myeloma (MM) ; however, the mechanism of hyponatremia remains unclear. A 65-year-old female with MM was treated with bortezomib, lenalidomide, and dexamethasone. Fourteen days after chemotherapy initiation, she developed hyponatremia (serum sodium, 127 mEq/l, compared with 136 mEq/l before chemotherapy) with plasma hypo-osmolality and urine hyper-osmolality. She exhibited neither dehydration nor adrenal insufficiency. Her serum arginine vasopressin peptide (AVP) level was 1.5 pg/ml. She was diagnosed with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), wherein causative roles of inflammatory cytokines were strongly suggested in the development because (1) SIADH was triggered by the cessation of the dexamethasone treatment and (2) hyponatremia was successfully treated with prednisolone, which was administered for the complication of drug eruption. Perhaps, bortezomib-induced immune reactions could be involved in a subset of hyponatremia during bortezomib-containing antimyeloma chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Síndrome de Secreción Inadecuada de ADH , Mieloma Múltiple , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Femenino , Humanos , Síndrome de Secreción Inadecuada de ADH/inducido químicamente , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Mieloma Múltiple/tratamiento farmacológico
12.
Rinsho Byori ; 63(5): 548-56, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26524893

RESUMEN

In the present retrospective single-center study, we examined the efficacy and safety of eltrombopag, a thrombopoietin (TPO) -receptor agonist (TPO-RA), and found clinical factors associated with its efficacy in Japanese patients with chronic immune thrombocytopenia (ITP). According to the definition of a response, which is to attain a platelet count of more than 50,000/µL at least once during eltrombopag treatment, 42 enrolled patients were divided into two groups: responders (29 patients, 69%) and non-responders (13 patients, 31%). In analyses of the clinical and laboratory data of these two groups, we extracted two factors that are significantly associated with a better response to eltrombopag, which have not been recognized previously, namely, (1) an older age of patients at eltrombopag initiation (≥ 70 years old) and (2) normal or decreased cellularity of iliac bone marrow (BM) biopsy at diagnosis. The significance of patient age contradicts previous findings from studies in which the Caucasian population was the major focus. However, factors such as changes of pharmacokinetics might modulate the effects of eltrombopag in older patients in Japan because East Asians show higher bioavailability of eltrombopag by as-yet-unknown mechanisms. BM cellularity in ITP may represent an impairment and/or lower responsiveness of pluripotent hematopoietic stem cells, not limited to the megakaryocyte (MgK) -platelet axis, to endogenous TPO, because recent evidence shows that TPO-RA can successfully restore hematopoiesis in aplastic anemia. These results should be useful for the therapeutic use of TPO-RA for ITP and also related thrombocytopenia in Japan.


Asunto(s)
Benzoatos/administración & dosificación , Células de la Médula Ósea , Hidrazinas/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/administración & dosificación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Benzoatos/farmacocinética , Femenino , Células Madre Hematopoyéticas , Humanos , Hidrazinas/farmacocinética , Masculino , Persona de Mediana Edad , Células Madre Pluripotentes , Pirazoles/farmacocinética , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
13.
Int J Hematol ; 118(5): 636-641, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37439996

RESUMEN

Chronic neutrophilic leukemia (CNL) is primarily diagnosed by excluding myelodysplastic syndromes (MDS). We report the case of a patient who developed secondary CNL 3 years after hypoplastic MDS. We used droplet digital polymerase chain reaction mutation detection assay to analyze genomic alterations during the progression from MDS to CNL. At the time of MDS diagnosis, U2AF1 Q157P and SETBP1 D868N were dominant and additional mutation of ASXL1 1934_insG was observed. CSF3R T618I and SETBP1 D868N were increasing at the time of CNL diagnosis. We revealed the accumulation of multiple gene mutations during CNL development from MDS. This suggests that CNL was clonally developed from the founding clone of MDS and CSF3R mutation contributes to the development of CNL in the present case. These findings provide insights into the pathology of CNL.


Asunto(s)
Leucemia Neutrofílica Crónica , Síndromes Mielodisplásicos , Humanos , Leucemia Neutrofílica Crónica/complicaciones , Leucemia Neutrofílica Crónica/genética , Leucemia Neutrofílica Crónica/diagnóstico , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Mutación
14.
Eur J Haematol ; 89(4): 350-5, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22805426

RESUMEN

In diffuse large B-cell lymphoma (DLBCL), a CD20-negative relapse is clinically significant because it is associated with chemo-refractory phenotypes and loss of a therapeutic target. The alteration of the CD20 gene is reported as infrequent in CD20-negative relapse in B-cell lymphoma. We established a DLBCL cell line with loss of CD20 expression (SD07) from a patient at CD20-negative relapse. She was initially diagnosed with CD20-positive DLBCL and received repeated immuno-chemotherapy that included rituximab. SD07, which has an immunoglobulin κ rearrangement identical to that of lymphoma cells at CD20-negative relapse, showed homozygous deletion of the CD20 gene with loss of the copy number of 11q12. SD07 is the first case in which it is proven that the loss of CD20 expression in relapsed DLBCL is the result of deletion of the CD20 gene. Deletion of the CD20 gene is a molecular mechanism of CD20-negative relapse in a subset of DLBCL.


Asunto(s)
Antígenos CD20/genética , Eliminación de Gen , Anciano , Femenino , Humanos , Cariotipificación , Reacción en Cadena de la Polimerasa
15.
Rinsho Ketsueki ; 52(12): 1882-7, 2011 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-22241156

RESUMEN

A 44-year-old male patient was diagnosed with acute lymphoblastic leukemia (CD10+, CD19+, CD20 weak) and underwent unrelated bone marrow transplantation (uBMT) with a conditioning regimen of cyclophosphamide plus total body irradiation during first complete remission (CR). Twenty months post-uBMT, the serum creatinine level (Cre) increased gradually, up to ≥ 1.5 mg/dl at 23 months. Since the increase in Cre was observed continuously, imaging examinations were performed and showed significant bilateral enlargement of the kidneys. Renal biopsy showed diffuse invasion of TdT, CD10 and CD19 positive lymphoid cells in the tubulo-interstitial region. Since leukemia cells were observed in the bone marrow, it was diagnosed as relapse in the bone marrow and kidney. Following reinduction chemotherapy, both kidneys returned to normal size. The patient entered into a second CR, but relapse occurred 6 months thereafter. The patient underwent uBMT again with a reduced-intensity conditioning regimen and CR has been maintained up to 5 months post-second uBMT. Although it is considered rare for relapse to occur with diffuse enlargement of both kidneys, as shown in this case, it is important to confirm the state of the kidney by performing blood tests and image diagnosis during the early phase, when renal dysfunction of an uncertain cause occurs after transplantation.


Asunto(s)
Riñón/patología , Infiltración Leucémica , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trasplante de Células Madre , Adulto , Humanos , Masculino , Trasplante Homólogo
16.
Int J Hematol ; 114(4): 441-448, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34227058

RESUMEN

Inflammatory cytokines play a role in hematopoiesis and development of myelodysplastic syndromes (MDS). Although increased serum levels of inflammatory cytokines are associated with poor survival in MDS patients, clinical management does not include assessment of inflammation. We investigated the significance of inflammation in MDS using serum C-reactive protein (CRP) levels, an indicator of the degree of systemic inflammation that can be used in routine practice. We hypothesized that serum CRP levels can be used to further classify low-risk MDS. We conducted a retrospective analysis of 90 patients with low-risk MDS, defined by the international prognostic scoring system (IPSS). We examined the prognostic relevance of CRP and known prognostic factors at diagnosis. Increased serum CRP (≥ 0.58 mg/dL) was associated with poor survival (hazard ratio [HR]: 17.63, 95% confidence interval [CI] 5.83-53.28, P < 0.001) both overall and among the 73 patients with low-risk MDS as defined by the revised IPSS (HR: 28.05, 95% CI 6.15-128.04, P < 0.001). Increased CRP might predict poor prognosis and serum CRP levels can indicate clonal hematopoiesis and non-hematological comorbidity in patients with low-risk MDS.


Asunto(s)
Biomarcadores/sangre , Proteína C-Reactiva , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Curva ROC , Adulto Joven
17.
Int J Hematol ; 113(5): 693-702, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33385294

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is an uncontrolled hyperinflammatory disorder driven by an overactive immune system that results in high mortality. Post-transplant-associated hemophagocytic lymphohistiocytosis (PT-HLH) is a type of secondary HLH that occurs following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical features of PT-HLH remain unclear and diagnostic and prognostic tools have not yet been established. Here, we retrospectively evaluated the clinical manifestations and outcomes of PT-HLH in 94 patients who underwent allo-HSCT. According to our PT-HLH criteria (hyperferritinemia and increased macrophage count in bone marrow), PT-HLH occurred in 12 patients (12.8%). The PT-HLH patients showed splenomegaly (P = .001), a higher risk of engraftment failure (P = .013), and an increased percentage of macrophages and hemophagocytes in bone marrow aspirates (P = .0009 and P = .0006, respectively). Moreover, univariate and multivariate analyses revealed that the survival rate was lower in PT-HLH patients than non-PT-HLH patients (P = .0017 and P = .034, respectively). This study defines the clinical features of PT-HLH and PT-HLH criteria that could be useful tools for diagnosing PT-HLH.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfohistiocitosis Hemofagocítica/etiología , Adolescente , Adulto , Anciano , Médula Ósea/patología , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Adulto Joven
18.
J Clin Exp Hematop ; 61(3): 120-125, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34511544

RESUMEN

Post-transplant lymphoproliferative disorder (PTLD) and other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are iatrogenic lymphoproliferative disorders (LPD) that develop in association with immunosuppressive treatment in the setting of organ transplantation and autoimmune disease, respectively. Each has a spectrum of pathologies ranging from lymphoid hyperplasia to lymphoma. To clarify the characteristics of the diffuse large B-cell lymphoma (DLBCL) subtype in a cohort of 25 patients with PTLD or OIIA-LPD from our institute, we selected 13 with a histological subtype of DLBCL, including 2 cases of PTLD and 11 of OIIA-LPD. The median patient age at diagnosis was 70 years, with a female predominance. Both PTLD cases developed after kidney transplant. Of the patients with OIIA-LPD, 10 had rheumatoid arthritis, 1 had mixed connective tissue disease, and 8 were treated using methotrexate. Both of the PTLD patients and 6 of the OIIA-LPD patients had extranodal manifestations. All patients except for one were classified as having the non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Tissue samples from 8 patients were positive for CD30 and 8 were positive for Epstein-Barr virus (EBV)-encoded small RNA. Seven patients had MYC-positive tissue samples, but none had MYC translocation. Our study suggests that extranodal manifestations and the non-GCB subtype are common, that EBV is associated with the DLBCL subtype of PTLD and OIIA-LPD, and that anti-CD30 therapy is applicable. In addition, our patients with the DLBCL subtype of PTLD and OIIA-LPD exhibited MYC overexpression without MYC translocation, suggesting an alternative mechanism of MYC upregulation.


Asunto(s)
Regulación de la Expresión Génica , Genes myc , Enfermedad Iatrogénica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Anciano , Anciano de 80 o más Años , Susceptibilidad a Enfermedades , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos
19.
Eur J Haematol ; 84(5): 448-52, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20050882

RESUMEN

We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1alpha in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-alpha, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1alpha significantly stimulated (3)H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1alpha. In the present case, MIP-1alpha, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1alpha is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1alpha is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma.


Asunto(s)
Quimiocina CCL3/sangre , Hipercalcemia/metabolismo , Linfoma de Células del Manto/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimiocina CCL3/genética , Humanos , Hipercalcemia/complicaciones , Linfoma de Células del Manto/complicaciones , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/genética , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Int J Hematol ; 112(3): 341-348, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32524308

RESUMEN

Although follicular lymphoma (FL) is a pathological entity characterized by relatively uniform histological and molecular findings, its clinical course is highly variable. Establishment of therapeutic strategies based on a simple and practical prognostic model is important. C-reactive protein (CRP) is an adverse prognostic marker for various tumors and aggressive lymphomas. However, the significance of serum CRP levels as a prognostic index in low-grade lymphomas, such as FL, has not been thoroughly investigated. We retrospectively analyzed the relationship between serum CRP levels at diagnosis and the prognosis in patients with FL (n = 61) undergoing rituximab-containing chemotherapy. Elevated CRP levels showed a significant association with elevated fibrinogen (P = 0.002) in univariate analysis. Patients with higher CRP levels (> 5 mg/L) had a significantly shorter progression-free survival in multivariate analysis (P = 0.044). We concluded that serum CRP levels are important in prognostic stratification of patients with FL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteína C-Reactiva/análisis , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Rituximab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Fibrinógeno/análisis , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico
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