Summary
The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity ...in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft‐versus‐host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next‐generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate‐producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable treatment option for adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS). The study aim was to ...evaluate epidemiological data and identify prognostic factors for AYA patients with MDS undergoing allogeneic HSCT. Here, 645 patients were selected from patients enrolled in a multicenter prospective registry for HSCT from 2000 to 2015. The primary endpoint was 3-year overall survival (OS). Survival rates were estimated using the Kaplan-Meier method. Prognostic factors were identified using the multivariable Cox proportional hazards model. The 3-year OS was 71.2% (95% confidence interval CI: 67.4-74.6%). In multivariable analysis, active disease status (adjusted hazard ratio: 1.54, 95% CI: 1.09-2.18, p = 0.016), poor cytogenetic risk (1.62, 1.12-2.36, p = 0.011), poor performance status (2.01, 1.13-3.56, p = 0.016), human leukocyte antigen (HLA)-matched unrelated donors (2.23, 1.39-3.59, p < 0.001), HLA-mismatched unrelated donors (2.16, 1.09-4.28, p = 0.027), and cord blood transplantation (2.44, 1.43-4.17, p = 0.001) were significantly associated with poor 3-year OS. In conclusion, in AYA patients with MDS the 3-year OS following allogeneic HSCT was 71.2%. Active disease status, poor cytogenetic risk, poor performance status, and donor sources other than related donors were associated with poor 3-year OS.
Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially ...after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbβ3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.
Background
Although hepatopancreatoduodenectomy (HPD) is the only means of achieving R0 resection of widespread extrahepatic cholangiocarcinoma, its safety and oncological benefit remain ...controversial because of its inherent high risk of mortality and morbidity.
Objective
The aim of this study was to retrospectively analyze short- and long-term outcomes and evaluate the safety and oncological benefit of this advanced procedure.
Methods
The study cohort comprised 37 consecutive patients who had undergone major HPD. Portal vein embolization was performed before surgery in 20 (54%) patients with future remnant liver volume < 35%.
Results
The median operative time and blood loss were 866 min and 1000 mL, respectively. Concomitant vascular resection was performed in five patients (14%). The overall morbidity and mortality rates were 100% and 5.4% (
n
= 2), respectively. Nineteen patients (51%) had major (Clavien–Dindo grade III or higher) complications, the most common being intra-abdominal infection (49%) and post-hepatectomy liver failure (46%, grade B/C: 32%/5%), followed by postoperative pancreatic fistula (30%, grade B/C). R0 resection was achieved in 31 patients (84%). The 1-, 3-, and 5-year overall survival (OS) rates were 83%, 48%, and 37%, respectively. In patients with R0 resection, 5-year OS was comparable between patients who had undergone major HPD and major hepatectomy alone (41% vs. 40%,
p
= non-significant).
Conclusions
HPD is a valid treatment option for extensive cholangiocarcinoma, offering long-term survival benefit at the cost of relatively high but acceptable morbidity and mortality rates. HPD is advocated in selected patients provided that it is considered possible to achieve R0 resection.
Although haploidentical donor lymphocyte infusion (DLI) is a valid treatment option for relapsed acute myeloid leukemia (AML), the incidence and risk factors for graft-versus-host disease (GVHD) and ...the efficacy of haploidentical DLI have not been fully evaluated. We retrospectively analyzed the outcomes after haploidentical DLI for 84
patients
with AML using a nationwide database and additional questionnaires. The median number of DLI cycles and infused CD3
+
cell dose was 1 and 1.0 × 10
6
/kg, respectively. The infused CD3
+
cell count of 5.0 × 10
5
/kg or higher was associated with acute GVHD (grade II–IV, 32.1% vs. 10.5%,
p
= 0.03; grade III–IV, 21.4% vs. 5.3%,
p
= 0.10).
Patients
who developed grade III–IV acute GVHD more frequently succumbed to treatment-related mortality (46.7% vs. 15.8% at 1 year,
p
= 0.002), although the relapse-related mortality was significantly low (40.0% vs. 72.2% at 1 year,
p
= 0.025). The overall response to DLI was significantly higher in the preemptive DLI group (47.4%) than in the therapeutic group (13.9%,
p
= 0.002). In the multivariate analysis, preemptive DLI was the predictive factor for overall response (odds ratio, 5.58;
p
= 0.003). Our
results
indicated the substantial risk of acute GVHD after haploidentical DLI with CD3
+
cell count of 5.0×10
5
/kg or higher and the favorable outcomes after preemptive DLI.
Summary
Dysbiosis of the gut microbiota has been reported to increase early complications after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). However, it remains unclear whether ...gut microbial alterations persist during late complications, such as chronic graft‐versus‐host disease (cGVHD) or secondary cancers. Here, we analysed the gut microbiota of 59 patients who survived for 1–21.7 years (median, 6.4 years) after allo‐HSCT. Long‐term survivors showed lower gut microbial diversity than the age‐ and sex‐matched healthy controls. This decreased diversity was reflected in the reduced abundance of the butyrate‐producing bacteria. Patients with a history of grade 3 acute graft‐versus‐host disease (aGVHD) exhibited higher Veillonella abundance than patients with a history of grade 1–2 or non‐aGVHD cases. The abundance of Faecalibacterium showed no decrease only in limited cGVHD cases. Additionally, the microbial structure in the secondary cancer group was significantly different (p < 0.05) from that in the non‐secondary cancer group. This study is the first to show that microbial dysbiosis is present over a 10‐year lifetime after discharge following allo‐HSCT. Our results suggest that these prolonged gut microbial alterations may be associated with the development and exacerbation of late complications in post‐transplant survivors.
Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that exhibits significant efficacy in treating melanoma and other malignancies. However, various nivolumab-induced ...immune-related adverse events (irAEs) have been reported, and differentiating irAEs from tumor progression is sometimes difficult. Here, we report a case of reactive lymphadenopathy occurring after treatment with nivolumab. A 56-year-old man with stage IIIC melanoma received adjuvant therapy with nivolumab after wide local excision. He developed systemic lymphadenopathy and autoimmune hemolytic anemia 1 month after receiving seven cycles of nivolumab. Pathological analysis of a cervical lymph node biopsy specimen revealed no metastatic lesion or any other malignancy, including lymphoma. Thus, the patient was diagnosed with nivolumab-induced reactive lymphadenopathy. Systemic corticosteroids were administered to reduce hemolysis, which led to the resolution of lymphadenopathy. When progressive lymphadenopathy is observed in a patient who received immune checkpoint inhibitor therapy, reactive lymphadenopathy should be carefully distinguished from progression to lymphoid metastasis, and biopsy should be performed if needed.
Background
The management of positive ductal margins with carcinoma in situ (R1-CIS) after resection is controversial. The aim of this study was to evaluate the impact of R1-CIS on survival in ...patients who underwent resection for distal cholangiocarcinoma.
Methods
We enrolled 121 consecutive patients with distal cholangiocarcinoma. Poor prognostic factors were investigated by multivariable analysis, and we performed a stratified analysis to evaluate the impact of R1-CIS on survival in patients with or without prognostic factors.
Results
Multivariable analysis identified node-positive status as the prognostic factor (
P
= 0.003). Stratified by lymph node status, overall survival (OS) in the R0 group was significantly better than that in the R1-CIS group in node-negative patients (57.1% vs 30.0%;
P
< 0.050). Although OS was comparable between the two groups in node-positive patients (5-year OS: 22.2% vs 20.0%, respectively;
P
= not significant). Furthermore, OS in patients in whom R0 was achieved by additional resection was significantly better than that in patients with R1-CIS (5-year OS: 66.7% vs 30.0%, respectively;
P
< 0.050).
Conclusions
Remnant CIS is associated with a poor prognosis in patients with node-negative distal cholangiocarcinoma. Every effort should be made to achieve negative bile duct margins.
KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of ...some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting
mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients' prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of
mutations in AML, (2) the data in AML with
mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting
mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common,
mutations are attractive novel molecular targets in AML.
Background
Systemic inflammation may have prognostic value in some malignancies and association with lymph node metastasis. This study aimed to evaluate the impact of systemic inflammatory biomarkers ...on long‐term and oncological outcomes as well as to assess the association between biomarkers with lymph node metastasis in extrahepatic cholangiocarcinoma patients.
Methods
We enrolled 271 consecutive patients who underwent surgical resection for extrahepatic cholangiocarcinoma. Poor prognostic factors were compared to identify the biomarkers that were most associated with overall survival (OS) and disease‐free survival (DFS) using receiver operating characteristic curves and multivariable analysis. Furthermore, we evaluated the relationship between biomarkers and lymph node metastasis.
Results
Four and two biomarkers were predictive for OS and DFS, respectively, among which, the C‐reactive protein‐to‐albumin ratio (CAR) had the highest area under the curve values (OS: 0.631, DFS: 0.624). Multivariable analysis showed that a high CAR was an independent prognostic factor for both OS and DFS (P = .002 and P < .001, respectively). Although a high CAR was not significantly correlated with lymph node metastasis (P = .645), carbohydrate antigen 19‐9 showed a significant correlation (P < .001).
Conclusions
Preoperative CAR is the most accurate prognostic factor for OS and DFS in extrahepatic cholangiocarcinoma patients and is independent of lymph node metastasis.
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