RESUMO
BACKGROUND AND OBJECTIVES: In Japan, cord blood transplantations exceed those done with adult-sourced unrelated stem cells. This study analyses cord blood (CB) storage criteria to maintain high-quality CB units. MATERIALS AND METHODS: The Kanto-Koshinetsu Cord Blood Bank received 29,795 units from 2014 to 2021, mostly >60 mL, and 5486 (18.4%) were stored as transplantable units. We investigated the mother's gestational period, CB volume, total nucleated cells (TNCs), CD34+ cells, total colony-forming units (CFUs), time from collection to reception and cryopreservation, cell viability, and the reasons for not storing a unit. RESULTS: The average time from collection to reception of 29,795 units was 18.0 h. The most common reason for not storing a CB unit was low cell numbers (pre-processing TNC count <1.2 billion), accounting for 67.9% of the units received. There was no correlation between the CB volume and the CD34+ cell count. The shorter the gestational period, the lower the TNC count, but the higher the CD34+ cell count. There was no correlation between the time from collection to cryopreservation, within a 36-h time limit, and the CD34+ cell recovery rate. CONCLUSION: We could accept units with a TNC count <1.2 billion and a CB volume <60 mL from a gestational period of 38 weeks or less if we did a pre-processing CD34+ cell count. This would secure more units rich in CD34+ cells.
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Bancos de Sangue , Preservação de Sangue , Criopreservação , Sangue Fetal , Humanos , Sangue Fetal/citologia , Japão , Bancos de Sangue/normas , Preservação de Sangue/métodos , Feminino , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Antígenos CD34 , Gravidez , MasculinoRESUMO
BACKGROUND AND OBJECTIVES: In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer). MATERIALS AND METHODS: A total of 538 male apheresis donors and 538 age-matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations. RESULTS: About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow-up of the 19 donors for 4 months revealed a progressive decrease in sFer. CONCLUSION: Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered.
RESUMO
BACKGROUND AND OBJECTIVES: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation. MATERIALS AND METHODS: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first-time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up. RESULTS: About one-third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre-menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post-menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer. CONCLUSION: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan.
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BACKGROUND: Antibodies against human neutrophil antigen (HNA) are involved in the pathogenesis of neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion-related acute lung injury. The present methods for anti-HNA antibody identification strongly depend on the presence of standard antisera with known allo/isospecificities. Here, we aimed to produce recombinant humanized antibodies to HNA from available mouse monoclonal antibodies (MoAbs). STUDY DESIGN AND METHODS: RNAs were extracted from available hybridoma cells producing mouse anti-HNA antibodies recognizing HNA-1a (TAG-1), -1b (TAG-2), -2 (TAG-4), and FcγRIIIb, and the cDNA was synthesized. Recombinant fragments consisting of the variable regions of the H and L chains of the mouse MoAb ligated to the constant region of human IgG were incorporated into an expression vector and transfected into CHO cells. Antibody specificity of the selected humanized monoclonal antibodies was confirmed, and tested by the participants of the ISBT Granulocyte Immunobiology Working Party (GIWP) workshop 2020. RESULTS: GIFT results confirmed the specific reactivity of TAGH-1 to -4, except for a cross-reactivity of TAGH-2 with HNA-1a/a neutrophils, only in flow-cytometry. MAIGA results showed clear specificity of all humanized antibodies, but the selection of the appropriate capture monoclonal antibody was essential for the test. The results of the ISBT GIWP showed high concordance among the labs. CONCLUSIONS: These are the first humanized monoclonal antibodies to HNA-1 and HNA-2 antigens produced and they will be important standard reagents for laboratories testing for neutrophil antibodies. We plan to have these humanized MoAbs available through WHO.
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Neutropenia , Neutrófilos , Recém-Nascido , Cricetinae , Humanos , Animais , Camundongos , Cricetulus , Isoantígenos , Anticorpos Monoclonais , Anticorpos Monoclonais HumanizadosRESUMO
BACKGROUND AND OBJECTIVES: In Japan, the prevalence of haptoglobin deficiency is approximately 1 in 4000. Haptoglobin-deficient individuals may produce anti-haptoglobin from allo-immunization, leading to serious transfusion reactions. Therefore, implementation of a consistent supply of haptoglobin-deficient fresh frozen plasma is crucial. We developed a novel reagent to facilitate large-scale identification of haptoglobin-deficient individuals as potential donors of plasma products. MATERIALS AND METHODS: We established mouse monoclonal anti-haptoglobin-producing cell lines (three clones) using the hybridoma method by immunizing mice with the haptoglobin protein. Purified antibodies were conjugated with carboxylate-modified polystyrene latex beads and used for haptoglobin measurements by the latex agglutination method using an automatic analyser (LABOSPECT008). Samples with low protein concentrations were re-examined by enzyme-linked immunosorbent assay to confirm the results. Additionally, the haptoglobin gene was amplified by polymerase chain reaction to confirm the haptoglobin deletion allele (Hpdel ). RESULTS: From February to October 2022, 7476 blood donor samples were screened. Two haptoglobin-deficient and 21 low-haptoglobin-expressing individuals were identified. Two haptoglobin-deficient donors were found homozygous for Hpdel , and 19 (90%) of the 21 low-haptoglobin-expressing individuals were heterozygous for Hpdel , which includes the first reported case of heterozygous Hpdel /HpJohnson . CONCLUSION: We developed a new reagent for the detection of haptoglobin deficiency, which is automatable and inexpensive and appears useful for large-scale screening of blood donors.
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Doadores de Sangue , Haptoglobinas , Animais , Humanos , Camundongos , Ensaio de Imunoadsorção Enzimática , Haptoglobinas/química , Haptoglobinas/genética , Heterozigoto , Reação em Cadeia da Polimerase/métodos , Anticorpos Monoclonais/químicaRESUMO
BACKGROUND AND OBJECTIVES: Previously (2007), it was reported that ABO antibody titers in Japanese blood donors had decreased significantly compared to 20 years before. Here we evaluated whether further decrease of antibody titers had occurred in recent years, and the potential factors associated with changes in antibody titers. MATERIALS AND METHODS: Serum/plasma from random blood donors in 2010 and 2021 (2010: 3369, 2021: 5796 donors) was classified into low, middle, and high ABO antibody titers according to the reactivity of diluted serum/plasma (2.5-fold and 20-fold) by an automated microplate system. The rates of low/high titer in the two periods were compared. Logistic regression and age-gender-BMI subgroup analyses were conducted to identify the factors that contributed to changes in antibody titers. RESULTS: Compared to 2010, the rate of donors with high ABO antibody titers wasãdecreased in 2021 for both anti-A and anti-B (anti-A, 2010: 23.8%, 2021: 19.3%; anti-B, 2010: 23.8%, 2021: 16.4%). In logistic regression analysis, age was found to significantly affect both anti-A and anti-B antibody titers (anti-A, adjusted odds ratio 0.36, 95% CI 0.31-0.41; anti-B, 0.42, 0.37-0.47), and BMI (0.82, 0.73-0.92) and other time-related factors (0.79, 0.71-0.88) significantly affect anti-B antibody titers. Subgroup analysis revealed decreased rate of high anti-B titers in the higher age group in 2021. CONCLUSION: The rate of high ABO antibody titers, especially high anti-B titers, was significantly decreased in 2021, and our results suggested an association with aging and obesity of blood donors as well as other time-related factors.
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Anticorpos , Doadores de Sangue , Humanos , Japão , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos SanguíneosRESUMO
BACKGROUND AND OBJECTIVES: The Xg blood group is composed of two antigens, Xga (XG1) and CD99 (XG2 and MIC2). The XG and CD99 are homologous genes located on pseudoautosomal region 1 of the X and Y chromosomes. The expressions of Xga and CD99 are co-regulated by a single nucleotide polymorphism (rs311103) in the GATA-1 binding region. Another mechanism of the Xg(a-) phenotype is the genomic deletion of approximately 114 kb, including the XG gene. Anti-Xga seems to be naturally occurring by detection in males who have never been transfused. MATERIALS AND METHODS: In this study, we identified 23 anti-Xga producers among 580,115 donors (0.004%). Additional 12 anti-Xga producers were also identified from a separate cohort. RESULTS: All 35 anti-Xga producers were male. Genomic DNA was obtained from 34 of 35 producers, and all 34 producers were confirmed to carry the XG-gene-deficient allele (XGdel). The breakpoints of all 34 producers were identical. The XGdel was also identified in 12 non-producers of anti-Xga among 860 donors who have no antibodies against RBCs, and the breakpoints were also identical with the anti-Xga producers. CONCLUSION: Our results will serve as the basis for a more complete understanding of Xg blood group polymorphisms.
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Antígenos de Grupos Sanguíneos , Doadores de Sangue , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/metabolismo , Feminino , Patrimônio Genético , Humanos , Japão , Masculino , FenótipoRESUMO
BACKGROUND: Transfusion-associated circulatory overload (TACO) is an adverse reaction associated with a high risk of mortality. The actual incidence of TACO and hypertension associated with transfusion in Japan is unknown. METHODS: A multicentre retrospective observational study was conducted across 23 institutions during the 1-year period of 2016. Patients were included if they developed TACO or their blood pressure (either systolic or diastolic) increased by at least 30 mmHg during the transfusion. TACO was confirmed by the primary physicians and transfusion medicine teams and recorded in the data on passive surveillance, and additional data were extracted from electronic medical records. RESULTS: In our patient cohort of 31 384 patients who underwent transfusion, the incidence of TACO and hypertension was 0·03% and 0·2%, respectively. However, 43% of the participating institutions didn't report any cases. When comparing risk factors between the TACO and hypertension groups, there were significant differences in comorbidities, such as abnormal findings on chest x-ray. Significant differences between the two groups were observed post-transfusion pulse rate, body temperature and oxygen saturation (P < 0·01). In the group of patients with hypertension, the level of BNP increased significantly after transfusion in 45% (5/11) of the patients. We identified 4 patients in the hypertension group who met the new ISBT's TACO criteria. CONCLUSION: Our study suggests that more attention should be given to TACO in Japan, particularly in terms of improving surveillance systems. For the early diagnosis of TACO, it is crucial to carefully monitor vital signs including blood pressure.
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Hipertensão , Reação Transfusional , Transfusão de Sangue , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/etiologia , Japão/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Hematopoietic cell infusion-related adverse events (HCI-AEs) in hematopoietic stem cell transplantations (HSCTs) have been largely attributed to toxicity of dimethyl sulfoxide (DMSO) for cryopreservation, but HSC products also contain various cells and plasma components. Our recent prospective study of 1125 HSCT recipients revealed the highest overall HCI-AE rate in bone marrow transplantation (BMT) using fresh/noncryopreserved products, although products of peripheral blood stem cell transplantation and cord blood transplantation (CBT) are generally cryopreserved with DMSO containing smaller plasma volumes. We aimed to clarify if product volume and component effects are more substantial in small recipients including children. STUDY DESIGN AND METHODS: We performed subgroup analysis on 219 recipients of 45 kg or less body weight (whole small recipients), including 90 children (pediatric recipients), from the original cohort (general recipients). RESULTS: Whereas overall HCI-AE rates did not differ among hematopoietic stem cell sources in the general recipients, bradycardia most often occurred after CBT in whole small recipients. Conversely, whole small and general recipients shared the same trend of having the highest rate of hypertension in BMT. The overall HCI-AE rate was higher in allogeneic HSCT compared with autologous HSCT. Notably, pediatric recipients showed a 10-fold higher incidence of nausea and vomiting in allogeneic HSCT compared with autologous HSCT, suggesting a possible role of allogeneic antigens. Multivariate analysis identified a relatively large infusion volume per body weight as a significant factor correlating with HCI-AE in whole small recipients. CONCLUSIONS: We should be aware of product volume and specific HCI-AEs such as nausea and vomiting in small patients including children.
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Peso Corporal/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Reação Transfusional/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Pré-Escolar , Estudos de Coortes , Criopreservação/métodos , Criopreservação/estatística & dados numéricos , Crioprotetores/efeitos adversos , Dimetil Sulfóxido/efeitos adversos , Feminino , Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Reação Transfusional/etiologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Adulto JovemRESUMO
The amount of infused CD34+ cells has been reported to be the strongest predictor of platelet recovery after autologous stem cell transplantation (ASCT). However, the timing of platelet recovery varies widely among patients even after the infusion of similar amounts of CD34+ cells. Therefore, we retrospectively assessed 99 patients who underwent their first ASCT for lymphoma or myeloma at our center. Thirteen patients (13%) did not achieve platelet engraftment, defined as a platelet count of at least 2.0 × 104/µL without transfusion, at day 28 after transplantation, whereas 58 of 60 patients (97%) who received at least 2.0 × 106/kg CD34+ cells achieved platelet engraftment within 28 days. Multivariate analysis identified the following significant risk factors for delayed platelet recovery: hemoglobin level and platelet count before stem cell harvest, body temperature of > 39 °C within 5 days after ASCT, and infusion of a small amount (< 2.0 × 106/kg) of CD34+ cells. In a subgroup analysis of 39 patients infused with < 2.0 × 106/kg CD34+ cells, a need for repeated apheresis for stem cell harvest and a body temperature of > 39 °C within 5 days after ASCT were identified as independent factors for delayed platelet recovery. In summary, platelet recovery following ASCT was affected by insufficient hematopoietic recovery at stem cell harvest, a need for repeated apheresis, and high fever early after ASCT, particularly when the amount of infused stem cells was insufficient.
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Plaquetas/fisiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/sangue , Linfoma/terapia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Adulto JovemRESUMO
Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.
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Púrpura Trombocitopênica Idiopática , Trombose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Trombose/etiologia , Trombose/mortalidadeRESUMO
BACKGROUND AND OBJECTIVES: It is sometimes difficult to obtain antigen-negative red blood cells (RBCs) for patients with antibodies against RBCs. However, the frequency and severity of the adverse reactions have not been well elucidated. Here, we conducted a multi-institutional collaborative study to clarify the background, frequency and clinical significance of antigen-positive RBC transfusions to patients with the respective antibodies. MATERIALS AND METHODS: The survey included the background of patients, antigens on RBCs transfused, total amount of antigen-positive RBCs transfused, results from antibody screen and direct antiglobulin tests, specificity of antibodies, adverse reactions and efficacies. All antibodies were surveyed regardless of their clinical significance. RESULTS: In all, 826 cases containing 878 antibodies were registered from 45 institutions. The main reasons for antigen-positive RBC transfusions included 'negative by indirect antiglobulin test' (39%) and 'detection of warm autoantibodies' (25%). In 23 cases (3% of total), some adverse reactions were observed after antigen-positive RBC transfusion, and 25 antibodies (9 of 119 clinically significant and 16 of 646 insignificant antibodies) were detected. Non-specific warm autoantibodies were detected in 9 cases, anti-E in 5 cases, 2 cases each of anti-Lea , anti-Jra or cold alloantibodies, and 1 case each of anti-Dib , anti-Leb or anti-P1. Other antibodies were detected in 2 further cases. Five (22%) of these 23 cases, who had anti-E (3 cases) or anti-Jra (2 cases), experienced clinically apparent haemolysis. CONCLUSIONS: Adverse reactions, especially haemolysis, were more frequently observed in cases with clinically significant antibodies than those with clinically insignificant antibodies (P < 0·001).
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Antígenos de Grupos Sanguíneos/imunologia , Transfusão de Sangue , Hemólise , Isoanticorpos/sangue , Autoanticorpos/sangue , Autoanticorpos/imunologia , Teste de Coombs , Transfusão de Eritrócitos , Eritrócitos/imunologia , Feminino , Humanos , Isoanticorpos/imunologia , Japão , Masculino , Gravidez , Sensibilidade e Especificidade , Reação TransfusionalRESUMO
The speed of neutrophil recovery following allogeneic hematopoietic cell transplantation (allo-HCT) varies widely among patients. We retrospectively evaluated the slope of neutrophil recovery (N slope) in 120 patients who underwent a first unrelated bone marrow transplantation with granulocyte-colony-stimulating factor support between 2009 and 2018. The median N slope was 205.5/µl/day. We classified patients into low (n = 59) and high (n = 61) N slope groups with a cutoff value of 200/µl/day. The high N slope group correlated with older patients, RIC regimen, high CD34+ cells, and recent transplantation. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly higher in the high N slope group than in the low N slope group (44.3% vs. 16.9%, P < 0.001). In multivariate analysis, high N slope was identified as a significant independent risk factor for grade II-IV aGVHD, irrespective of the involved organs. There were no differences in relapse, nonrelapse mortality, or overall survival between the two groups. In conclusion, the difference in N slope after allo-HCT may predict the risk of aGVHD. Prevention and treatment of GVHD according to the changes in the neutrophil count may improve post-transplant complications.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neutrófilos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.
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Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Neoplasias Hematológicas/sangue , Heparitina Sulfato/uso terapêutico , Inibidores de Proteases/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Componentes Sanguíneos , Sulfatos de Condroitina/efeitos adversos , Dermatan Sulfato/efeitos adversos , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Neoplasias Hematológicas/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/mortalidade , Heparitina Sulfato/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Inibidores de Proteases/efeitos adversos , Tempo de Protrombina , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Receptores de Interleucina-2/sangue , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Vimblastina/administração & dosagemRESUMO
It is controversial whether blast percentage based on all nucleated cells (ANC) or non-erythroid cells (NEC) more accurately reflects the prognosis of patients with myelodysplastic syndromes (MDS). We considered that the impact of blast percentage on survival should be similar in MDS with erythroid hyperplasia (MDS-E) and MDS with no erythroid hyperplasia (MDS-NE), and from this perspective, we retrospectively analyzed 322 patients, including 44 with MDS-E and 278 with MDS-NE. Overall survival was similar between the MDS-E and MDS-NE groups (P = 0.94). In a subgroup of patients with bone marrow (BM) blasts of < 5%, no difference in survival was found between MDS-E and MDS-NE by either calculation method. However, in patients with a blast percentage between 5 and 10%, a significant difference in survival was observed only when the blast percentage in MDS-E was calculated from ANC (P < 0.001 by ANC and P = 0.66 by NEC). A similar result was observed when we analyzed the remaining patients with higher blasts together with those with blasts between 5 and 10%. These results suggest that the calculation of the BM blast percentage based on NEC in MDS-E provides a blast percentage value with a clinical impact consistent with that in MDS-NE.
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Crise Blástica , Células da Medula Óssea , Leucócitos Mononucleares , Síndromes Mielodisplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Crise Blástica/classificação , Crise Blástica/metabolismo , Crise Blástica/mortalidade , Crise Blástica/patologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Intervalo Livre de Doença , Feminino , Humanos , Hiperplasia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.
Assuntos
Autoanticorpos , Hiperplasia do Linfonodo Gigante , Doenças do Mediastino , Púrpura Trombocitopênica Idiopática , Tomografia Computadorizada por Raios X , Autopsia , Hiperplasia do Linfonodo Gigante/sangue , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Evolução Fatal , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/terapia , Doenças do Mediastino/sangue , Doenças do Mediastino/diagnóstico por imagem , Doenças do Mediastino/patologia , Doenças do Mediastino/terapia , Pessoa de Meia-Idade , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Derrame Pleural/terapia , Mielofibrose Primária/sangue , Mielofibrose Primária/diagnóstico por imagem , Mielofibrose Primária/patologia , Mielofibrose Primária/terapia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico por imagem , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/terapiaRESUMO
Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4+ and CD8+ T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rgnull mice. CD4+ T cells and, to a lesser extent, CD8+ T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4+ T cells also supported the activation and proliferation of CD8+ T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4+ T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4+ T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC)+/+ mice but not in MHC-/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD.
Assuntos
Apresentação de Antígeno , Células Apresentadoras de Antígenos , Doença Enxerto-Hospedeiro/imunologia , Xenoenxertos/imunologia , Linfócitos T/citologia , Animais , Proliferação de Células , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Cinética , Ativação Linfocitária , Camundongos SCID , Linfócitos T/imunologia , Transplante Homólogo/efeitos adversosRESUMO
Transplants using peripheral blood hemopoietic stem/progenitor (PBHS) cells are widely performed for the treatment of patients with hematologic disorders in routine practice and clinical trials. Although the process from mobilization to infusion of PBHS cells has been mostly established, optimal conditions for each process remain undetermined. Adverse reactions caused by PBHS cell infusions have not been systematically recorded. In transplants using PBHS cells, a number of problems still exist. In this section, the current status of and future perspectives regarding PBHS cells are described.
Assuntos
Fator Estimulador de Colônias de Granulócitos/imunologia , Células-Tronco/imunologia , Adolescente , Adulto , Linhagem Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This retrospective multicenter study evaluated the efficacy and safety of released washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs were prepared by washing leukoreduced apheresis PCs with the platelet additive solution, BRS-A, using automated cell processors. RESULTS: Clinical data were obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were used in 94.5% of the patients with a history of recurrent or severe transfusion reactions for preventing such reactions. Responses of RWPCs were evaluated as complete response (91.6%), partial response (8.2%), no-change (0.2%), and progression (0%) and overall response was equal across subgroups divided by patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post-transfusion were 13.5 (range, 1.9-35.4) × 109/L and 3.5 (range, -13 to 53.6) × 109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) × 109/L in patients without risk factors associated with platelet transfusion refractoriness. Transfusion reactions to RWPCs were observed in only nine transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This study demonstrated that RWPCs were effective and safe in patients with a history of transfusion reactions. Further prospective studies on efficacy together with cost-benefit analysis in RWPCs are needed.