Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVE: Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. METHODS: Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. RESULTS: Median PA-IgG was 285 ng/107 cells (range, 45.5-18,200 ng/107 cells), and median IPF was 15.5% (range, 5.4-62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0-46 ng/107 cells; IPF, 1.1-9.5%). First-line therapy was performed using standard-dose prednisolone (0.5-1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125-1,000 mg/day, 3-4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (p = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4-41.5%) and nonresponders (16.7%; range, 6.3-62.1%; p = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/107 cells; range, 101-18,200 ng/107 cells) than among responders (254.5 ng/107 cells; range, 45.5-470 ng/107 cells; p = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000-1.010; p = 0.029). CONCLUSION: Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

Kinetics and clinical significance of human herpesvirus 6 DNA shedding in saliva after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Little is known about the kinetics and clinical significance of saliva human herpesvirus-6 (HHV-6) DNA after hematopoietic stem cell transplantation (HSCT). METHODS: In this observational study, we quantified HHV-6 DNA in serially collected plasma and saliva from allogeneic HSCT recipients. Associations between the status of salivary HHV-6 DNA and the development of HHV-6 encephalitis, depression, and oral mucosal graft-versus-host disease (GVHD) were retrospectively analyzed. RESULTS: A total of 787 plasma and 434 saliva samples were collected from 56 patients. The cumulative incidence of HHV-6 DNA in plasma and saliva at 60 days after transplantation was 51.8% and 83.9%, respectively. The peak level of salivary HHV-6 DNA was significantly higher in patients who displayed plasma HHV-6 DNA than in those who did not (median, 51,584 copies/mL vs 587 copies/mL; P < .0001). Salivary HHV-6 DNA levels increased after positive plasma HHV-6 DNA was detected and remained high during observation period. Despite the frequent occurrence of positive salivary HHV-6 DNA, no patient developed depression. Positivity of salivary HHV-6 DNA was not significantly associated with the development of HHV-6 encephalitis (P = 1.00, Fisher's exact test) or oral mucosal GVHD (P = .71, Grey's test). No significant relationship between salivary HHV-6 DNA and these diseases was found even when comparing higher HHV-6 DNA loads in saliva. CONCLUSION: Salivary HHV-6 DNA levels increased after HHV-6 DNA was detected in the blood. However, no epidemiological evidence was shown to support a role of salivary HHV-6 in the development of HHV-6 encephalitis, depression, and oral mucosal GVHD.

Development of diffuse large B-cell lymphoma from duodenal type follicular lymphoma: a retrospective study of 23 cases.

The incidence and clinical characteristics of histological transformation (HT) from duodenal type follicular lymphoma (DFL) are unclear. A retrospective analysis was conducted to identify the incidence and clinical features of HT from DFL in 23 cases with DFL. The median follow-up duration was 4.6 years (range, 0.8-20 years). HT to diffuse large B-cell lymphoma was observed in 2 of 23 cases during follow-up (8.7%). One of two cases transformed at 21 months later with increased serum lactate dehydrogenase (LDH; 1655 U/L) and abdominal lymphadenopathy. Partial response was achieved after R-THP (pirarubicin)-COP therapy, but the disease progressed. The other case transformed at 8.3 years with an increase of serum LDH (4022 U/L), abdominal lymphadenopathy, and bone marrow involvement. The disease was refractory to DA-EPOCH-R and a high-dose methotrexate/cytarabine regimen. The patient received allogenic peripheral blood stem cell transplantation and finally achieved complete response. Both cases developed HT at nodal or other intestinal lesions with no progression of the primary duodenal lesion. No significant factors for the occurrence of HT were identified. Although the incidence is low, HT could occur in DFL with aggressive clinical manifestations.

L-asparaginase-induced Parotitis in an Elderly Patient with Acute Lymphoblastic Leukemia.

A 67-year-old woman received induction chemotherapy comprising vincristine, daunorubicin, cyclophosphamide, L-asparaginase and prednisolone for acute lymphoblastic leukemia with a common B-cell phenotype. The administration of L-asparaginase at 3,000 U/m2 for 6 days was planned. Before the fourth administration on day 16, left parotid swelling was identified along with increased serum amylase (991 U/L; 94% derived from salivary glands). An enlarged left parotid gland was apparent on computed tomography. The symptoms resolved after cessation of L-asparaginase, with serum amylase normalizing by day 20. This rare adverse event should be recognized as improving within a week after ceasing L-asparaginase.

Prognostic implications of TdT expression in acute myeloid leukemia with an intermediate-risk karyotype.

Terminal deoxynucleotidyl transferase (TdT) is expressed on precursor lymphoblastic neoplasms and some acute myeloid leukemia (AML) cells. The clinical impact of TdT expression on AML outcomes remains unclear. Here, we conducted a retrospective analysis to identify prognostic implications of TdT expression in AML with an intermediate-risk karyotype. Forty-eight cases of intermediate-risk AML were enrolled. TdT positivity was defined as expression on ≥ 10% of the gated cells. Of 48 cases, 12 (25%) were positive for TdT [median expression rate of TdT 0.9% (range 0-86.9%)]. No significant differences in patient characteristics or complete remission rate were observed between TdT-positive and TdT-negative cases. The probability of overall survival (OS) and event-free survival (EFS) at 1 year was not significantly different between TdT-positive and TdT-negative cases (OS: 58.3% vs. 65.2%, p = 0.32; EFS: 33.3% vs. 57.1%, p = 0.06). Relapse-free survival (RFS) probability at 1 year was significantly lower for TdT-positive than TdT-negative cases (10% vs. 71.3%, p = 0.002). Multivariate analyses revealed that TdT positivity was an independent significant adverse factor for RFS [hazard ratio: 3.309, 95% confidence interval: 1.334-8.209, p = 0.009]. Our results suggest that TdT expression is associated with increased risk of relapse in patients with intermediate-risk AML.

[Concurrent subcutaneous panniculitis-like T-cell lymphoma and myelodysplastic syndrome with fibrosis].

A 66-year-old male presented with fever and erythema at our hospital, and leukoerythroblastosis, anemia, thrombocytopenia, and multiple low-density lesions in the moderately enlarged spleen were detected. Skin tissue revealed CD8+ T cells with the expression of cytotoxic molecule markers involving fat lobules, and subcutaneous panniculitis T-cell lymphoma (SPTCL) was diagnosed. The bone marrow displayed no infiltration of lymphoid tumor cells, but hyperplasia of granulocytes and megakaryocytes with grade 2 stromal fibrosis. In addition, the bone marrow exhibited diffuse 18F-fluorodeoxyglucose (FDG) accumulation on FDG positron-emission tomography/computed tomography (FDG-PET/CT). Although chemotherapy improved SPTCL, the patient died from leukocytosis with leukoerythroblastosis. We obtained negative results for the JAK2 V617F mutation, and CD34+ cells were elevated in the bone marrow compared with the levels at initial examination. The final diagnosis was concurrent myelodysplastic syndrome (MDS) with fibrosis and SPTCL. This report highlights that it is essential to consider MDS or other myeloproliferative neoplasms (MPN) as possible complications when malignant lymphoma complicates myelofibrosis in the absence of bone marrow infiltration of lymphoma cells. Perhaps, the assessment of clonal markers of MPN and FDG accumulation patterns in the bone marrow by FDG-PET/CT could enable differentiation.

[Ibrutinib therapy for a blastoid variant mantle cell lymphoma patient with early extranodal relapse after autologous stem cell transplantation].

A 65-year-old man with multiple lymphadenopathy presented to our hospital and was diagnosed with StageIVA blastoid-variant mantle cell lymphoma (MCL), with a Ki-67 index of 93%. Partial response was achieved after four courses of CHASER (cyclophosphamide, cytarabine, dexamethasone, etoposide, and rituximab) chemotherapy, and complete response was achieved after autologous stem cell transplantation (ASCT). Six months after ASCT, the MCL relapsed with occurrence of tumors one on the left upper arm and one in the cerebrum, which were proved to be resistant to the conventional chemotherapy and progressed rapidly. These tumors disappeared with scarring following the local irradiation (45 Gy). However, the unirradiated regions became enlarged. The bulky abdominal lesion was treated with local irradiation (41 Gy) combined with 560 mg of ibrutinib but still resulted in progressive disease 1 month after initiating the ibrutinib treatment. Finally, the patient died 5 months post-relapse. The prognosis of patients with blastoid-variant MCL with high Ki-67 index is extremely poor. Furthermore, the risk of central nervous system (CNS) involvement is very high. Therefore, ibrutinib maintenance therapy post ASCT might be a treatment option to prevent CNS involvement. Further efforts might be needed to improve the outcomes of blastoid-variant MCL with a high Ki-67 index.

[Successful treatment of myelodysplastic syndrome-associated autoinflammatory lymphedema with azacytidine].

An 84-year-old woman presented pancytopenia. She was diagnosed with myelodysplastic syndromes (MDS) with excess blasts-1, however, she declined treatment with azacitidine (AZA). Ten months later, bilaterally symmetrical, non-pitting edema appeared on the lower legs. A skin biopsy of the lower leg revealed lymphedema. The appearance and location of the lymphedema suggested an immunologic etiology; however, tests for autoimmune diseases yielded negative results. Therefore, a relationship between MDS and lymphedema was, therefore, speculated. Consequently, treatment with AZA was started, which led to marked improvement in both the lymphedema and pancytopenia. Based on the skin tissue pathology and the improvement in MDS after treatment with AZA, MDS-related autoinflammatory lymphedema was diagnosed.

[Successful diagnosis of lymphoplasmacytic lymphoma with IgG paraprotein using MYD88 L265P mutation analysis].

A 76-year-old woman presented to our hospital with leukocytosis and abnormal lymphocytes. M protein of the immunoglobulin G (IgG) type was detected using immunoelectrophoresis. A bone marrow biopsy revealed infiltration of small mature lymphocytes, lymphoplasmacytoid cells with Dutcher bodies, grape cells, and Russell bodies. The MYD88 L265P mutation was detected in the abnormal peripheral lymphocytes, and a diagnosis of lymphoplasmacytoid lymphoma was established. MYD88 L265P mutation analysis is useful for making a diagnosis of non-IgM lymphoplasmacytoid lymphoma because it enables the differentiation from other low-grade B-cell malignancies.

Complete Sequences of the Human T-Cell Leukemia Virus Type 1 Proviral Genomes from Newly Established Adult T-Cell Leukemia Cell Lines in Oita Prefecture, Japan.

We report two complete proviral genome sequences of human T-cell leukemia virus type 1 (HTLV-1) isolated from the peripheral blood specimens of acute type adult T-cell leukemia (ATL) patients in Oita Prefecture, Japan.

Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder, Hodgkin Type, following Epstein-Barr Viral Hepatitis in a Patient with Rheumatoid Arthritis.

A 59-year-old man with an 18-year history of rheumatoid arthritis who had been treated with steroids, methotrexate, and infliximab presented with a high-grade fever, cervical lymphadenopathy, and hepatosplenomegaly. Epstein-Barr virus (EBV) hepatitis was diagnosed based on the liver histology and EBV antibody titer. The symptoms improved temporarily, but five months later, the fever, skin rash, jaundice, and thrombocytopenia relapsed. Bone marrow and liver biopsies demonstrated infiltration with Reed-Sternberg cells. Based on these findings, the patient was diagnosed with other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD), Hodgkin lymphoma type. This case followed a rare clinical course, in that acute hepatitis preceded the diagnosis of OIIA-LPD.

Successful Cord Blood Stem Cell Transplantation for an Adult Case of Chronic Active Epstein-Barr Virus Infection.

A 41-year-old man was referred to our hospital for treatment of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Chronic active Epstein-Barr virus (CAEBV) was diagnosed based on the findings of elevated EBV antibody titers and positive EBV-DNA in the peripheral blood, and cord blood stem cell transplantation (CBT) was performed. The EBV-DNA levels in the blood fell below the limit of detection. His lymphoma relapsed on Day 165 with the appearance of eruptions, which disappeared after the withdrawal of tacrolimus. One year after transplantation, there were no signs of recurrence. This encouraging result suggests that CBT should be considered for adult cases of CAEBV with aggressive clinical manifestations.