[Evaluation of the correlation between JAK2V617F allele burden by Quenching Probe-Tm method and allele-specific quantitative PCR method].

The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densyTM IS-5320 genetic analyzer with the quenching probe-Tm (QP-Tm) method. However, since 2020, allele-specific quantitative PCR (AS-qPCR) is being performed in clinical settings for measuring V617F allele burden. To investigate the clinical usefulness of the QP-Tm method in patients with MPNs, we evaluated the V617F allele burden measured by both the methods. A good correlation was observed between the V617F allele burden determined using QP-Tm and that determined using AS-qPCR (P<0.001, rs=0.952). The median mutant allele burden, as determined using the QP-Tm method, was significantly higher in patients with polycythemia vera than in those with essential thrombocythemia. The results of this study suggested that the QP-Tm method will continue to be useful clinical ancillary test for measuring V617F allele burden.

[Relationship between Coombs-positive autoimmune hemolytic anemia and development of malignant tumors: a retrospective study].

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.

High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Central Nervous System Lymphoma: Data From the Japan Society for Hematopoietic Cell Transplantation Registry.

High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has been shown to improve the prognosis of patients with central nervous system (CNS) lymphoma. We queried the Japan Society for Hematopoietic Cell Transplantation Registry for 2006 to 2015 to analyze the outcomes of 102 patients with primary CNS lymphoma (PCNSL) who underwent first HDT/ASCT. The median patient age was 54 years (range, 20 to 74 years), and 65 patients were treated in an upfront setting. With a median duration of follow-up of 44 months, the 5-year overall survival (OS) and progession-free survival (PFS) were 54.9% and 38.4%, respectively. There were no significant differences in OS and PFS between upfront and salvage HDT/ASCT. Because thiotepa, a key agent in HDT/ASCT for PCNSL, has been unavailable since 2011 in Japan, the HDT regimens used were not uniform. Thiotepa-containing HDT was received by 16 out of 32 patients before 2010, but by only 2 of 70 patients after 2011. Thiotepa-containing HDT was associated with better PFS (P = .019), lower relapse (P = .042), and a trend toward a survival benefit. In multivariate analysis, noncomplete remission at HDT/ASCT was an independent predictor for OS (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.25 to 4.58; P = .008) and thiotepa-containing HDT remained significant for PFS (HR, .42; 95% CI, .19 to .95; P = .038). These results confirm the activity of thiotepa-containing regimens.

Efficacy of prophylactic irradiation to the contralateral testis for patients with advanced-stage primary testicular lymphoma: an analysis of outcomes at a single institution.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. METHODS: We retrospectively identified 15 patients (median age 66 years; range 39-81) diagnosed with diffuse large B-cell PTL in the period 2000-2014. Characteristics and outcomes of these cases were evaluated. RESULTS: All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8-190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I-II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III-IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. CONCLUSIONS: The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I-II and stage III-IV PTL.

Sphingosine-1-phosphate receptor 1 as a prognostic biomarker and therapeutic target for patients with primary testicular diffuse large B-cell lymphoma.

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.

[Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].

In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 µmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.

Severe Colitis Associated with both Epstein-Barr Virus and Cytomegalovirus Reactivation in a Patient with Severe Aplastic Anemia.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD.