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1.
Ann Hematol ; 100(12): 2989-2995, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34430990

RESUMEN

Minimal residual disease (MRD)-negative status in multiple myeloma (MM) is associated with favorable outcomes. Although EuroFlow next-generation flow (NGF) is a global standard for MRD detection, its operating cost is high. Therefore, it is desirable to develop a less expensive method with equivalent sensitivity to that of EuroFlow-NGF. In this study, we compared the analytical ability of our BML 10-color multiparameter flow cytometry (MFC) to that of EuroFlow-NGF. Bone marrow samples collected from 51 patients with MM were subjected to MRD detection using BML 10-color-MFC and EuroFlow-NGF. Our antibody panel consisted of CD38 multiepitope, CD138, CD45, CD56, CD19, CD27, CD81, CD117, cytoplasmic immunoglobulin (cIg) κ, and cIgλ in a single tube. The median percentages of total plasma cells, as per 10-color-MFC and EuroFlow-NGF, were 0.2148% and 0.2200%, respectively, with a good correlation between the methods (r = 0.950). The median percentages of myeloma cells determined via 10-color-MFC and EuroFlow-NGF were 0.0012% and 0.0007%, respectively, with a strong correlation (r = 0.954). Our 10-color-MFC demonstrated high sensitivity to detect MRD; the results showed a good correlation with those obtained using EuroFlow-NGF. Therefore, our cost-effective single-tube MFC (approximately 100 USD/sample) is a promising alternative method for the detection of MRD in patients with MM.


Asunto(s)
Citometría de Flujo/métodos , Mieloma Múltiple/diagnóstico , Neoplasia Residual/diagnóstico , Adulto , Anciano , Antígenos CD/análisis , Médula Ósea/patología , Femenino , Humanos , Inmunoglobulinas/análisis , Masculino , Persona de Mediana Edad
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.
Eur J Haematol ; 104(2): 110-115, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31733155

RESUMEN

OBJECTIVES: Bortezomib with lenalidomide and dexamethasone (VRd) is a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). However, some patients discontinue VRd because of severe adverse events, despite its high efficacy. We aimed to study the efficacy of modified dose of VRd (VRd lite) in transplant-eligible patients with NDMM. METHODS: Forty-eight transplant-eligible patients with NDMM were included. VRd lite was administered every 4 weeks. Bortezomib 1.3 mg/m2 was administered subcutaneously on days 1, 8, 15 and 22, and dexamethasone 20 mg was administered orally on the day of and the day after bortezomib administration. Lenalidomide was omitted on days 1, 8 and 15, which are the days of bortezomib administration. RESULTS: The overall response rate (ORR) after four cycles of VRd lite was 83%, including a complete response of 25%. Thirty-eight among the 45 patients who completed at least four cycles of VRd lite received autologous stem cell transplantation (ASCT). The ORR and very good partial response or better were upgraded to 100% and 74%, respectively, following ASCT. CONCLUSION: Our strategy consisting of VRd lite followed by ASCT is, thus, a highly effective and well-tolerated regimen resulting in durable responses in patients with NDMM.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Autoinjertos , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Lenalidomida/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Estudios Retrospectivos
4.
Rinsho Ketsueki ; 61(11): 1563-1569, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33298647

RESUMEN

Plerixafor is increasingly used in combination with granulocyte-colony-stimulating factor (G-CSF) for peripheral blood stem cell collection. Although it is an expensive drug, its cost-benefit performance is not well investigated. Thus, we analyzed its cost-effectiveness in our hospital. A retrospective observational analysis was performed in patients who underwent stem cell collection between December 2013 and November 2018. A total of 203 patients were investigated and classified into three groups according to their pre-mobilization regimen: G-CSF alone, G-CSF and cyclophosphamide (G+CY), and G-CSF and plerixafor (G+plerixafor). The cost-effectiveness of apheresis of the collected cluster of differentiation (CD) 34+ cells was assessed based on two viewpoints: cost of drugs and cost of equipment. Due to the high cost of plerixafor, the cost of apheresis was higher in patients who received G+plerixafor. However, the difference narrowed when we calculated the cost to collect 2.0×106 CD34+ cells/kg body weight required for a single transplant. The number of stem cells collected from patients who received G+plerixafor was higher than those who received other regimens (median CD34+ cells harvested/day were 2.90 for G-CSF, 2.13 for G+CY, and 4.63 for G+plerixafor, ×106/kg body weight, P<0.01). Our results show that plerixafor enables efficient apheresis.


Asunto(s)
Compuestos Heterocíclicos/uso terapéutico , Células Madre de Sangre Periférica , Antígenos CD34 , Bencilaminas , Análisis Costo-Beneficio , Ciclamas , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Humanos , Mieloma Múltiple/terapia , Estudios Retrospectivos
5.
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
6.
Rinsho Ketsueki ; 60(10): 1411-1417, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31695000

RESUMEN

Because multiple myeloma is rare in young people, there are fewer reports on the same. Thus, its clinical aspects and prognosis remain unelucidated. We retrospectively evaluated 30 patients with multiple myeloma aged ≤ 45 years at diagnosis. We divided them into three groups based on their cytogenetic risks: standard risk (SR), high risk (HR), and unknown risk. The frequency of HR patients was 36.6%, the highest of the three groups, unlike the previous report. The median progression-free survival (PFS) was 35 months (SR vs. HR, 46 vs. 29 months), and the median overall survival (OS) was not reached (NR) (SR vs. HR, NR vs. 82 months). The OS was significantly worse, and the PFS also appeared inferior in HR patients. The International Staging System score was not associated with OS. Thus, young patients with myeloma appeared to have a higher frequency of HR features, suggesting that instead of age, the cytogenetic risk was a significant prognostic factor.


Asunto(s)
Mieloma Múltiple/diagnóstico , Citogenética , Supervivencia sin Enfermedad , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
7.
Rinsho Ketsueki ; 60(12): 1635-1640, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31902813

RESUMEN

Although elotuzumab (ELO) is associated with improved outcomes in patients with relapsed/refractory multiple myeloma (MM), no data are available for the usage of ELO following allogeneic stem cell transplantation (allo-SCT). Here, we report two cases of relapsed MM treated with ELO in combination with lenalidomide (LEN) and dexamethasone (ELd) following allo-SCT. Case 1 had been treated with 11 lines of therapy followed by cord blood transplantation resulting in partial response. ELd was introduced 140 days post-transplantation and continued for eight cycles until disease progression. No worsening in graft-versus-host disease (GvHD) was observed under ELd treatment. Case 2 had received unrelated bone marrow transplantation due to primary refractory disease after undergoing six regimens. Carfilzomib-based maintenance therapy had to be discontinued owing to severe myelosuppression. Subsequently, ELd treatment was initiated 544 days following the allo-SCT, which led to an improvement in serum paraprotein level and amelioration in GvHD. In both cases, immunosuppressants were tapered off. Several studies have shown exacerbation of GvHD under LEN monotherapy following allo-SCT. However, an ELd regimen may be one of the safer options for treating post-allo-SCT relapse.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia , Trasplante de Células Madre , Trasplante Homólogo
8.
Rinsho Ketsueki ; 60(3): 165-170, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31068511

RESUMEN

Failure of autologous peripheral blood stem cell collection (PBSCH) can affect the treatment modality for patients with hematological malignancies. The clinical efficacy of plerixafor in PBSCH was analyzed in our institution. The medical records of 61 patients were retrospectively reviewed. The use of plerixafor was determined according to the CD34+ cell count in the peripheral blood (PB CD34+) on day 4 of G-CSF administration and patients' backgrounds. A total of 47 patients received G-CSF plus plerixafor: 31 with multiple myeloma, 8 with AL amyloidosis or POEMS syndrome, and 8 with non-Hodgkin lymphoma. The median fold increase in PB CD34+ following the first dose of plerixafor was 7.18 times. The median number of collected CD34+ cells on day 5 was 4.1×106/kg and 5.3×106/kg in total. Among the 47 patients, 44 (93.6%) yielded the minimum required cell collection of 2.0×106/kg within an average of 1.3 days. Plerixafor enables rapid and efficient mobilization, and sufficient numbers of CD34+ cells were successfully collected.


Asunto(s)
Movilización de Célula Madre Hematopoyética , Compuestos Heterocíclicos/farmacología , Células Madre de Sangre Periférica/citología , Amiloidosis/terapia , Antígenos CD34 , Bencilaminas , Ciclamas , Factor Estimulante de Colonias de Granulocitos/farmacología , Humanos , Linfoma no Hodgkin/terapia , Mieloma Múltiple/terapia , Síndrome POEMS/terapia , Estudios Retrospectivos , Trasplante Autólogo
9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
Int J Hematol ; 110(4): 431-437, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31236823

RESUMEN

Red blood cell distribution width (RDW) has been used for the differential diagnosis of anemia, but high RDW may also be associated with several human disorders. We evaluated the prognostic relevance of RDW in patients with light-chain (AL) amyloidosis. We retrospectively analyzed all patients with AL amyloidosis who were newly diagnosed at the Japanese Red Cross Medical Center between December 2011 and June 2018. RDW was evaluated in 94 patients; 48% (n = 45) of patients had a high RDW (≥ 13.8%) and 52% (n = 49) had a low RDW (< 13.8%). Overall survival (OS) was significantly lower in patients with a high RDW (P < 0.001). On multivariate analysis, increased RDW was an independent predictor for OS. Even in patients without cardiac amyloidosis, the OS was significantly lower in the high-RDW group (P = 0.0064). The survival rate of high-RDW patients without cardiac involvement was as poor as that of patients with cardiac involvement. In addition, in patients with revised Mayo stage I or a normal level of N-terminal pro-B-type natriuretic peptide, high RDW was negatively correlated with OS (P = 0.0086, 0.025). RDW is a simple and strong predictor of early death, and is a prognostic biomarker in patients with AL amyloidosis without cardiac involvement.


Asunto(s)
Índices de Eritrocitos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
20.
Transplant Proc ; 51(10): 3437-3443, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31733801

RESUMEN

OBJECTIVE: The refined disease risk index (R-DRI) is a well-designed prognostic parameter that is based on only the disease type and status and is used for stratifying patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT) into 4 risk groups. However, the application of the R-DRI for rare diseases has remained unclear. METHODS: We evaluated 135 patients who underwent allo HSCT for hematological malignancies including rare diseases, such as acute leukemia of ambiguous lineage, acute T-cell leukemia/lymphoma, extranodal natural killer T-cell lymphoma, and lymphoblastic lymphoma, at our institute. RESULTS: According to the R-DRI, overall survival (OS) and progression-free survival at 2 years for patients with the low, intermediate, high, and very high groups were 66.7% and 66.7%, 60.8% and 56.0%, 27.1% and 23.7%, and 5.9% and 5.1%, respectively (P < .0001 and P < .0001, respectively). OS showed no significant difference between B-cell non-Hodgkin lymphoma (B-NHL) and T-cell non-Hodgkin lymphoma (T-NHL) (P = .71). Moreover, OS at 1 year was 80%, 14.3%, 60%, and 0% for the intermediate risk group, the very high-risk group of B-NHL, the intermediate risk group, and the high-risk group of T-NHL, respectively (P = .035). CONCLUSION: We showed the applicability of the R-DRI for hematological malignancies, including rare disorders. However, we suggest that T-NHL patients may be better to be assigned between the nodal group and the extranodal group in the R-DRI.


Asunto(s)
Neoplasias Hematológicas/clasificación , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Enfermedades Raras/clasificación , Enfermedades Raras/terapia , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
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