ABSTRACT
BACKGROUND: A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population. METHODS: A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed. RESULTS: Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event. CONCLUSIONS: In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting. TRIAL REGISTRATION: NCT04074187.
ABSTRACT
Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m2; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100.
ABSTRACT
Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Transplantation Conditioning , Humans , Transplantation Conditioning/methods , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/mortality , Retrospective Studies , Male , Female , Middle Aged , Adult , Hematopoietic Stem Cell Transplantation/methods , Japan , Aged , Prognosis , Transplantation, Homologous/methods , Adolescent , Young Adult , Societies, Medical , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Disease-Free Survival , AllograftsABSTRACT
Cytomegalovirus (CMV) reactivation is a prominent complication associated with adverse outcomes in allogeneic hematopoietic stem cell transplantation (HSCT). However, CMV reactivation after allogeneic HSCT may be associated with a lower incidence of relapse in some hematological malignancies. This study analyzed the Japanese registry data from 1082 patients with myelodysplastic syndrome (MDS) who underwent their first allogeneic HSCT and survived for 100 days after transplantation without graft failure or disease relapse to investigate this association. Patients who received cord blood transplants, demonstrated in vivo T cell depletion, underwent prophylactic anti-CMV treatment, or diagnosed with secondary MDS were excluded. CMV reactivation measured by pp65 antigenemia within 100 days after allogeneic HSCT was observed in 57.5% of patients, with a median time of 46 days from transplant. The 5-yr overall survival and cumulative incidence of relapse (CIR) in the cohort were 60.5% and 15.6%, respectively. The 5-yr CIR showed no significant difference between patients with and without CMV reactivation (14.4% versus 17.2%; P = .185). Interestingly, CMV reactivation within 100 days was significantly associated with a lower 5-yr CIR (7.6% versus 16.4%; P = .002) in patients with <5% myeloblasts in the bone marrow (BM) just before HSCT. Furthermore, this relevancy confirmed even when excluding patients with Grade II to IV acute GVHD (Hazard ratio: 0.38; 95% confidential intervals: 0.18-0.801; P = .011). Our findings indicate a correlation between early CMV reactivation and MDS relapse, based on the proportion of myeloblasts in the BM. These results may contribute to the development of effective CMV prophylaxis post-HSCT.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Recurrence , Transplantation, Homologous , Virus Activation , Humans , Myelodysplastic Syndromes/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Female , Middle Aged , Adult , Retrospective Studies , Transplantation, Homologous/adverse effects , Aged , Young Adult , Adolescent , Japan/epidemiologyABSTRACT
Background: Thoracic endovascular aortic repair (TEVAR) has been widely introduced. However, unestablished transfemoral approach due to true lumen obliteration disables endovascular option. Case summary: A 74-year-old male with a history of 15-year-ago type B aortic dissection presented with chronic bilateral lower extremity claudication. CT angiography revealed that a large entry tear was located at distal to the left subclavian artery. The thoracic aneurysmal degeneration progressed and eventually required repair. True lumen of infrarenal aorta to bilateral common iliac arteries was totally collapsed by false lumen, and the re-entry tear was open at external iliac artery. Initially, we performed recanalization to the collapsed true lumen. Bidirectional approach was taken from right brachial and bifemoral arteries. The covered endovascular reconstruction of aortic bifurcation (CERAB) technique and double D-shape moulding technique (DDMT) was performed to create covered stent configuration. As secondary treatment, 1-debranching TEVAR with axillary artery bypass was successfully performed by utilizing femoral approach. Discussion: This case demonstrated feasibility of two-stage endovascular therapy for thoracic aneurysmal degeneration concomitant with true lumen obliteration. This combined technique of CERAB and DDMT was absolutely effective to minimize type â ¢ endoleak in infrarenal segment. Hybrid endovascular treatment offered minimally invasive therapy to the patient.
ABSTRACT
This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients.
Subject(s)
Cord Blood Stem Cell Transplantation , Delirium , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human , Humans , Herpesvirus 6, Human/genetics , Quality of Life , Prospective Studies , Cord Blood Stem Cell Transplantation/adverse effects , Virus Activation , DNA, Viral , CognitionABSTRACT
This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months. A total of 147 patients (allo-SCT: 101; non-SCT: 46) were eligible for this analysis. In the multivariate analyses, allo-SCT was significantly associated with both superior overall survival (OS) (adjusted hazard ratio (aHR): 0.54; 95% CI: 0.30-0.97; p = .04) and relapse-free survival (RFS) (aHR: 0.21; 95% CI: 0.12-0.38; p < .001). The 5-year adjusted OS and RFS were 73% and 70% in the allo-SCT cohort, whereas they were 50% and 20% in the non-SCT cohort. Despite the higher non-relapse mortality (aHR: 3.49; 95% CI: 1.17-10.4; p = .03), allo-SCT was significantly associated with a lower relapse rate (aHR: 0.10; 95% CI: 0.05-0.20; p < .001). In addition, allo-SCT was also associated with superior graft-versus-host disease-free, relapse-free survival (aHR: 0.43; 95% CI: 0.25-0.74; p = .002). Propensity score-matched analyses confirmed the results of the multivariate analyses. In patients who achieved CMR within 3 months, allo-SCT in CR1 had superior survival and lower relapse compared with the non-SCT cohort.
Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Prospective Studies , Transplantation, Homologous , Hematopoietic Stem Cell Transplantation/methods , Stem Cell Transplantation/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Pathologic Complete Response , Retrospective StudiesABSTRACT
Human immunodeficiency virus (HIV)-associated CD8+ T-cell skin infiltrative disease with severe erythroderma has rarely been reported. While HIV-positive patients are prone to develop lymphoma, which is often associated with Epstein-Barr virus, polymorphic lymphoproliferative disorder is rare, accounting for <5% of cases. We herein report a 41-year-old HIV-positive man who presented with a fever, erythroderma, and lymphadenopathy and was diagnosed with the coexistence of both diseases. His condition improved significantly with continued antiretroviral therapy. This case suggests that HIV-induced immunodeficiency is central to the pathogenesis of both entities and that improvement of the immunodeficient state is an effective treatment.
Subject(s)
CD8-Positive T-Lymphocytes , Epstein-Barr Virus Infections , Lymphoproliferative Disorders , Humans , Male , Adult , CD8-Positive T-Lymphocytes/immunology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/drug therapy , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/diagnosis , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/immunology , Herpesvirus 4, Human/immunology , HIV Infections/drug therapy , HIV Infections/complications , HIV Infections/immunology , Treatment Outcome , Antiretroviral Therapy, Highly Active , B-Lymphocytes/immunologyABSTRACT
Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Humans , Male , Hematopoietic Stem Cell Transplantation/methods , Prognosis , Abnormal Karyotype , Risk Factors , Retrospective StudiesABSTRACT
There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era.
Subject(s)
Polycythemia Vera , Primary Myelofibrosis , Thrombocythemia, Essential , Humans , Aged , Polycythemia Vera/complications , Polycythemia Vera/diagnosis , Polycythemia Vera/therapy , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/drug therapy , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/etiology , Primary Myelofibrosis/drug therapy , Prospective StudiesABSTRACT
Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.
Subject(s)
Anemia, Refractory, with Excess of Blasts , Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Adult , Humans , Japan , Retrospective Studies , Siblings , Cord Blood Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Registries , Unrelated DonorsABSTRACT
BACKGROUND: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization.MethodsâandâResults: Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07). CONCLUSIONS: A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.
Subject(s)
Myocardial Infarction , Neoplasms , Percutaneous Coronary Intervention , Humans , Retrospective Studies , Aftercare , Patient Discharge , Myocardial Infarction/etiology , Coronary Angiography , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Risk Factors , Myocardial Revascularization/methods , Neoplasms/etiologyABSTRACT
Background: Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. Poor prognosis has been shown in patients with cGVHD after the failure of primary steroid-based treatments. A previous report demonstrated the efficacy and safety of ibrutinib in these patients, leading to the approval of ibrutinib for cGVHD in Japan. Here, we report the extended follow-up of patients in this study. Objectives: To evaluate the safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD. Study Design: An open-label, single-arm, multicenter study of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD (NCT No.: NCT03474679; Clinical Registry No.: CR108443). Results: At the time of the final data cutoff, 7/19 (36.8%) patients completed the study treatment, and 12/19 (63.2%) patients discontinued ibrutinib. After a median follow-up of 31.11 months (range:1.9 to 38.6 months), the best overall response rate was 84.2% (16/19 patients; 95% CI:60.4%, 96.6%) in all treated populations, with a median time to response of 2.81 (range:1.0 to 27.6) months. Of 15 responders with ≥2 organs involved at baseline, seven (46.7%) had responses in multiple organs. An improvement in the organ response rate was observed for the skin, eye, mouth, and esophagus compared with that in a previous report. The rate of sustained response for ≥20 weeks, ≥32 weeks, and ≥44 weeks were 68.8%, 62.5%, and 50.0%, respectively for 16 responders. The median daily corticosteroid dose requirement tended to decrease over time for all treated analysis sets. Twelve of 19 patients (63.2%) reached a corticosteroid dose of <0.15 mg/kg/day for at least one week, and four (21.1%) discontinued corticosteroid treatment for at least 28 days during the study. The failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively. The safety findings of this updated analysis were consistent with the safety profile observed at the time of the primary analysis and the known ibrutinib safety profile. Common grade ≥3 treatment-emergent adverse events (TEAEs) were pneumonia (6/19 [31.6%] patients), platelet count decreased, and cellulitis (3/19 [15.8%] patients each). After the primary analysis, no new TEAEs leading to death, treatment discontinuation, or dose reduction were reported, and no new patients reported major hemorrhage. Cardiac arrhythmia (Grade 2 atrial flutter) was reported in 1/19 (5.3%) patients. No new safety signs were observed despite prolonged ibrutinib exposure. Conclusions: The final results support previous conclusions, demonstrating a clinically meaningful response and acceptable safety profile of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.
ABSTRACT
Background: Endovascular treatment (EVT) is a well-established treatment for patients with chronic limb-threatening ischaemia, and below-the-knee (BTK) artery is its main target, although the re-intervention rate is still high. Understanding of the characteristics of BTK artery atherosclerosis would be required to overcome this issue. In this case series, we elucidated the characteristics of non-stenotic BTK artery atherosclerosis in the patients who received EVT of the superficial femoral artery (SFA) using optical frequency domain imaging (OFDI) and angioscopy. Case summary: We presented five patients who underwent EVT of SFA and subsequent observation of ipsilateral BTK artery using OFDI and angioscopy. Patients one and two had advanced atherosclerosis; however, patients three, four, and five had only mild atherosclerosis. Discussion: All patients had multiple risk factors for atherosclerosis and stenosis/occlusion of the SFA and ipsilateral BTK arteries. Furthermore, some patients had several other atherosclerotic vascular diseases suggesting the presence of advanced systemic atherosclerosis. On the other hand, some patients with multiple BTK artery stenosis/occlusion did not have advanced atherosclerosis in the examined BTK artery. The absence of significant atherosclerosis in a BTK artery in patients with multiple stenoses or occlusion in other ipsilateral BTK arteries may suggest some mechanism of vessel occlusion other than atherosclerosis. Further investigations are needed to clarify the mechanism.
ABSTRACT
Thrombotic thrombocytopenic purpura (TTP) can rapidly become a life-threatening condition, and the importance of its appropriate diagnosis and treatment cannot be overstated. Until recently, TTP has mainly been diagnosed by clinical findings such as thrombocytopenia and hemolytic anemia. In addition to these clinical findings, however, reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% has become internationally accepted as a diagnostic criterion for TTP. TTP is classified as immune-mediated TTP (iTTP) if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital TTP (cTTP) if ADAMTS13 gene abnormalities are detected. Fresh frozen plasma (FFP) transfusion is performed in patients with cTTP to supplement ADAMTS13. Plasma exchange therapy using FFP is conducted in patients with iTTP to supplement ADAMTS13 and to remove both anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. To suppress autoantibody production, corticosteroid therapy is administered in conjunction with plasma exchange. The monoclonal anti-CD-20 antibody rituximab is effective in patients with iTTP. In addition, caplacizumab, an anti-VWF A1 domain nanobody, has a novel mechanism of action, involving direct inhibition of platelet glycoprotein Ib-VWF binding. The recommended first-line treatments of iTTP in Japan are plasma exchange and corticosteroids, as well as caplacizumab.
Subject(s)
Purpura, Thrombotic Thrombocytopenic , Humans , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/therapy , Japan , von Willebrand Factor , Plasma Exchange , Autoantibodies , ADAMTS13 Protein/metabolismABSTRACT
Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.