Keita Igarashi

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.

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.

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.

Extramedullary Tumor of Cerebral Falx: An Unusual Presentation of Acute Megakaryocytic Leukemia.

In childhood acute myelogenous leukemia, extramedullary tumor is an occasional clinical symptom. However, extramedullary acute megakaryocytic leukemia is extremely rare. Here, we report an extremely rare case of acute megakaryocytic leukemia in a patient who presented with extramedullary tumor of cerebral falx as a first manifestation before the diagnosis of systemic bone marrow leukemia.

Primary orbital neuroblastoma in a 1-month-old boy.

Neuroblastoma is a malignant tumor predominantly occurring in children and usually arising from the adrenal gland or sympathetic ganglia. We describe a neuroblastoma in a 1‐month‐old boy arising from his left orbital cavity. This tumor was refractory to chemotherapy or radiotherapy, requiring enucleation of the left eye for complete removal of the intraorbital tumor. Thereafter, he received high‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation, and has been in complete remission for 3 years. Unlike neuroblastomas arising from the adrenal gland or sympathetic ganglia, primary orbital neuroblastoma may be refractory even in early infancy.

Successful treatment of childhood hypocellular acute myeloid leukemia.

Hypocellular acute myeloid leukemia (AML) is extremely rare in childhood. We report on a 7-year-old girl with hypocellular AML who was treated successfully with granulocyte-colony stimulating factor (G-CSF) and combined chemotherapy. High-dose G-CSF induced complete remission and she subsequently received reduced intensity conditioning and unrelated cord blood transplantation; however, this resulted in early rejection. After a complete hematological recovery, she received 3 courses of combination chemotherapy oriented toward AML. She has remained in complete remission for over 1 year after the completion of the therapy. G-CSF effectively induced remission, and combination chemotherapy has been proven to be feasible for patients with childhood hypocellular AML.

Response to ponatinib before hematopoietic stem cell transplantation in a child with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia

to achieve best cosmesis. Lipomas with small pedunculated lesions did not influence functional outcome in the literature, but several patients with large lipomas did have functional outcome affected. Wester and Rintala reported on functional outcome in three patients >4 years of age with large lipomas and described severe constipation and soiling. The effects of lipoma on functional outcome may involve distortion of the sphincter, thereby worsening function and complicating the surgery, resulting in a less than satisfactory outcome. In conclusion, perineal lipoma with ARM affects operative management of anorectoplasty and functional outcome.

Non-alcoholic steatohepatitis induced by induction chemotherapy for pediatric acute lymphoblastic leukemia

An 8-year-old boy presented with acute lymphoblastic leukemia (ALL). He had been obese from early childhood, and the degree of obesity was 56.8% at onset of ALL. On admission, his initial complete blood cell count showed a white blood cell count of 14.4 × 109/L with 61% lymphoblasts, hemoglobin of 8.6 g/dL, and a platelet count of 37 × 109/L. Biochemical tests showed a marked elevation of transaminase (AST 428 IU/L, ALT 403 IU/L) and lactate dehydrogenase (LDH 5490 IU/L); however, serum bilirubin and uremic acid were within the normal range. Hepatitis B or C viruses were serologically negative. A computed tomography scan showed hepatosplenomegaly and mild fatty liver on admission (Fig. 1a). Bone marrow examination showed hyperplasia with 99.2% lymphoblasts with an immunophenotype positive for CD10, CD19, CD22, CD58, cytoplasmic-CD79a, HLA-DR, TdT, and cytoplasmic-Igμ. The karyotype of leukemic blasts was 46, XY, der(19)t(1;19) (q23;p13.3). Chimeric gene analysis revealed E2A/PBX1. After a diagnosis of B-precursor ALL, a BFM-based induction chemotherapy including prednisolone, intrathecal methotrexate, vincristine, daunorubicin, and l-asparaginase was started. Thirty-two days after the start of steroid administration, laboratory examination showed hyperbilirubinemia (total bilirubin 3.9 mg/dL), elevated transaminase (AST 294 IU/L, ALT 287 IU/L), lactate dehydrogenase (LDH 363 IU/L) and γ-glutamyl transpeptidase (γ-GTP 907 IU/L) with hypertriglyceridemia (4834 mg/dL). Computed tomography scan on day 36 after the start of treatment showed severe fatty liver and hepatosplenomegaly, and the thickness of the bile tract wall suggested complication by cholangitis (Fig. 1b). Maximum γ-GTP was 1066 IU/L on day 36, and the maximum total bilirubin level was 8.2 mg/dL on day 42. He was treated with supportive care. The induction chemotherapy was completed on day 57. However, we had to adjust the schedule of chemotherapy due to severe fatty liver, and we also had to omit the final administration of l-asparaginase. After induction therapy, he achieved complete remission. However, his fatty liver and elevation of transaminase persisted. We performed a liver biopsy, and the pathological examination showed severe fatty liver (80%) and ballooning of hepatic cells. The NAFLD activity score was 6 (steatosis: 3, lobular inflammation: 1, hepatocyte ballooning: 2) (Fig. 1c). A diagnosis of non-alcoholic steatohepatitis was made. ALL is usually associated with elevated transaminase and LDH at onset. Induction chemotherapy for ALL commonly contains prednisolone and vincristine, which often induces hyperbilirubinemia and fatty liver. Our patient had dietinduced obesity and probably fatty liver before developing ALL. Steroids, vincristine and l-asparaginase may induce severe NASH [1]. NAFLD is fairly common in childhood cancer survivors, but it is rare in pediatric patients during induction chemotherapy for ALL. We initially reduced the dose of chemotherapeutic agents according to his adjusted

Candida krusei arthritis in a boy with acute lymphoblastic leukemia

Fungal arthritis is a relatively rare complication, which occurs in patients with hematological disease and cancer. Recently non-albicans Candida species have emerged as clinically important agents; however, Candida krusei (C. krusei) arthritis is still rare. We report a 6-year-old boy who developed C. krusei arthritis associated with acute lymphoblastic leukemia. He was given oral fluconazole and broad-spectrum antibiotics prophylactically, but nevertheless, he developed fungemia with C. krusei and subsequently developed arthritis in his right hip. He was successfully treated with liposomal amphotericin B and micafungin combined with surgical drainage. This is the youngest case with C. krusei arthritis.