Natsuko Inazawa

Large-scale multiplex polymerase chain reaction assay for diagnosis of viral reactivations after allogeneic hematopoietic stem cell transplantation.

Viral reactivations following hematopoietic stem cell transplantation are thought to result from the breakdown of both cell‐mediated and humoral immunity. As a result, many viruses could be reactivated individually or simultaneously. Using a multiplex polymerase chain reaction (PCR), we prospectively examined many kinds of viral DNAs at a time in 105 patients who underwent allogeneic hematopoietic stem cell transplantation. In total, 591 whole blood samples were collected weekly from pre‐ to 42 days post‐transplantation and the following 13 viruses were tested; herpes simplex virus 1 (HSV‐1), HSV‐2, varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV‐6), HHV‐7, HHV‐8, adenovirus, BK virus (BKV), JC virus (JCV), parvovirus B19, and hepatitis B virus (HBV). Several viral DNAs were detected in 12 patients before hematopoietic stem cell transplantation. The detection rate gradually increased after transplantation and peaked at 21 days. The most frequently detected virus was HHV‐6 (n = 63; 60.0%), followed by EBV (n = 11; 10.5%), CMV (n = 11; 10.5%), and HHV‐7 (n = 9; 8.6%). Adenovirus and HBV were each detected in one patient (1.0%). Detection of HHV‐6 DNA was significantly more common among patients undergoing cord blood transplantation or with steroid treatment. EBV DNA tended to be more common in patients treated with anti‐thymocyte globulin. Multiplex PCR was useful for detecting many viral reactivations after hematopoietic stem cell transplantation, simultaneously. Cord blood transplantation, steroid treatment, or anti‐thymocyte globulin use was confirmed to be risk factors after transplantation. J. Med. Virol. 87:1427–1435, 2015.

An evaluation of peripherally inserted central venous catheters for children with cancer requiring long-term venous access

Long-term venous access is essential when treating malignant diseases. We reviewed our experience with peripherally inserted central venous catheters (PICC) in children suffering from various malignancies with regard to catheter life, reasons for removal, and complications. Ninety-three PICCs were inserted in 78 children. Median catheter life was 162 days (range 6–575 days) with a total of 16,266 catheter days. Seventy-five PICCs (80.6%) had been placed until the elective removal or patients’ death, whereas 18 PICCs (19.4%) were removed due to PICC-related complications; a rate of 1.11 per 1,000 catheter days. Complications requiring removal of PICCs included infection (n = 12), occlusion (n = 3), dislodgement (n = 2), and phlebitis (n = 1) with rates of 0.74, 0.18, 0.12 and 0.06 per 1,000 catheter days, respectively. We conclude that PICC provides reliable long-term intravenous access in children suffering from malignancies.

Platelet transfusion refractoriness attributable to HLA antibodies produced by donor‐derived cells after allogeneic bone marrow transplantation from one HLA‐antigen‐mismatched mother

Hatakeyama N, Hori T, Yamamoto M, Inazawa N, Iesato K, Miyazaki T, Ikeda H, Tsutsumi H, Suzuki N. Platelet transfusion refractoriness attributable to HLA antibodies produced by donor‐derived cells after allogeneic bone marrow transplantation from one HLA‐antigen‐mismatched mother. 
Pediatr Transplantation 2011: 15: E177–E182.

An infant with self-healing cutaneous Langerhans cell histiocytosis followed by isolated thymic relapse

Thymic involvement with Langerhans cell histiocytosis (LCH) typically occurs in children as part of multi‐system (M‐S) LCH. Patients who develop skin‐only LCH during infancy may either follow a self‐healing course with spontaneous regression or may progress to M‐S involvement. We describe a male infant who developed isolated thymic LCH after spontaneous complete regression of isolated cutaneous lesions. His erythrocyte sedimentation rate and C‐reactive protein increased temporarily during the skin‐only stage of LCH, and increased again considerably during the thymic relapse. Even for patients with skin‐only LCH, these laboratory data might indicate possible relapse or late progression of the disease. Pediatr Blood Cancer 2009;53:229–231.

HHV-6 encephalitis may complicate the early phase after allogeneic hematopoietic stem cell transplantation: Detection by qualitative multiplex PCR and subsequent quantitative real-time PCR

Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post‐HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first‐line screening test and real‐time PCR for subsequent quantitative evaluation. Five hundred ninety‐one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV‐6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV‐7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV‐6 DNA levels demonstrated four of the six HHV‐6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV‐6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV‐6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV‐6 encephalitis can be improved by confirming high HHV‐6 DNA load in blood. J. Med. Virol. 88:319–323, 2016.

Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay.

Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) are frequent, but viral reactivations after autologous HSCT (auto‐HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto‐HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre‐ to 42 days post‐HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV‐1), HSV‐2, varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV‐6), HHV‐7, HHV‐8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV).  Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV‐6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto‐HSCT patients, which was similar to the incidence in allo‐HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto‐HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto‐HSCT patients. J. Med. Virol. 89:358–362, 2017.

Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced-intensity conditioning cord blood transplantation

Hatakeyama N, Hori T, Yamamoto M, Inazawa N, Hirako Y, Tsutsumi H, Suzuki N. Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced‐intensity conditioning cord blood transplantation.
Pediatr Transplantation 2010: 14: E4–E10.

Treatment of an infant with severe acute refractory immune thrombocytopenic purpura using combination therapy including rituximab

Some infants with acute immune thrombocytopenic purpura (ITP) do not respond to first‐line therapy, and currently there is no consensus on therapy for these refractory cases. We describe a 12‐week‐old infant with acute ITP who was unresponsive to intravenous immunoglobulin and corticosteroid, and developed gastrointestinal bleeding. Several combination therapies were unsuccessful. After four doses of rituximab followed by intravenous immunoglobulin and corticosteroid, his platelet counts gradually increased. Combined therapy which includes rituximab may be a promising treatment for severe acute refractory ITP. Pediatr Blood Cancer 2009;53:203–205.

Extramedullary relapse in RARA rearrangement-negative acute promyelocytic leukemia successfully treated in combination with chemotherapy, local radiotherapy, and cord blood transplantation.

RARA rearrangement-negative acute promyelocytic leukemia (APL) is uncommon, and its extramedullary relapse is extremely rare. We report a 5-year-old girl with RARA rearrangement-negative APL, which recurred solely at the external auditory canal and mastoid air cells. She was successfully treated with chemotherapy, local radiotherapy, and unrelated cord blood transplantation. She has maintained complete remission for 24 months after transplantation. The clinical features and our therapeutic strategy in this patient will provide valuable information for extramedullary relapse of RARA rearrangement-negative APL.

Use of recombinant thrombomodulin in disseminated intravascular coagulation complicated hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is frequently lethal in its early phase due to complicating disseminated intravascular coagulation (DIC). The authors report a 14-mo-old girl with severe DIC complicating Epstein-Barr virus associated HLH. She was successfully treated with immunochemotherapy consisting mainly of etoposide and additional recombinant thrombomodulin (r-TM), a newly developed anticoagulant. Although the efficacy of r-TM cannot be proven in a single case report, additional anticoagulation therapy with r-TM is safe and may reduce early deaths in patients with DIC-complicated severe HLH. More clinical experience is required, although r-TM is currently licensed only in Japan.