Successful Emergency Decompressive Laminectomy for Burkitt Lymphoma with Metastatic Spinal Lesions: A Case Report.

Although Burkitt lymphoma (BL) usually arises in the abdomen or pelvis, it can also arise in the epidural space as a primary or secondary site and present with back pain or limb weakness. Emergency management is necessary to relieve spinal cord compression (SCC). Herein, we report a case of BL with metastatic spinal lesions in a 16-year-old female who presented with sudden-onset progressive walking difficulty. She was admitted to a previous hospital where she presented with abdominal pain and vomiting and was diagnosed with intussusception via a computed tomography scan. Laparoscopic small bowel resection was performed, during which a diagnosis of BL was made on the basis of pathological examination. Sudden numbness in the extremities and the complete inability to walk occurred ten days after surgery. Thoracolumbar MRI revealed a metastatic mass extending from C7 to T6 with evidence of SCC. Emergency decompressive laminectomies (from C7 to T6) and partial debulking of the tumor were performed 12 hours after the onset of her neurologic symptoms. She was subsequently treated with chemotherapy, and she made a complete neurologic recovery. Emergency decompressive laminectomies for BL with spinal lesions could effectively lead to the recovery of neurologic symptoms.

Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis.

Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen-activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/MAP2K signalling pathway in TAM pathogenesis.

Successful combination chemotherapy involving clofarabine, cyclophosphamide, and etoposide for pediatric relapsed acute myeloid leukemia: A case report.

Limited salvage chemotherapies are available for relapsed/refractory acute myeloid leukemia. Herein, we described successful reinduction chemotherapy, involving a combination of clofarabine, cyclophosphamide, and etoposide, in a 12-year-old male with relapsed acute myeloid leukemia prior to allogeneic bone marrow transplantation from his father. Although treatment with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin, and gemtuzumab ozogamicin had no positive effects, the aforementioned clofarabine-based chemotherapy induced complete remission and allowed the transplantation to go ahead. The abovementioned regimen may be useful for induction chemotherapy prior to hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia.

Anticoagulation treatment and prophylactic edoxaban for cerebral sinus venous thrombosis in an adolescent with acute lymphoblastic leukemia.

Pediatric acute lymphoblastic leukemia regimens include large L-asparaginase dosages and steroids, which are associated with an increased risk of venous thromboemboli in adolescents and young adults. Herein, we report the case of an 18-year-old male with acute lymphoblastic leukemia, who was treated with the pediatric regimen, in which edoxaban was employed as a prophylaxis against cerebral sinus venous thrombosis. The event happened on day 20 of induction therapy, when brain magnetic resonance imaging demonstrated a cerebral sinus venous thrombosis in the superior sagittal sinus. Anticoagulation therapy was initiated, and the patient's symptoms disappeared 3 days later. The induction therapy was restarted after an interruption of 16 days, and the consolidation therapies, which included L-asparaginase and steroids, were completed. Edoxaban was administered as a prophylaxis during the consolidation therapy. There were no further adverse events. Edoxaban could be an effective prophylaxis for coagulation complications in adolescents and young adults with acute lymphoblastic leukemia.

Pilot study of the combination of sorafenib and fractionated irinotecan in pediatric relapse/refractory hepatic cancer (FINEX pilot study).

BACKGROUND: Preclinical observations suggested a synergistic effect of sorafenib (SFN) and irinotecan (CPT-11) in hepatoblastoma (HB). Thus, we conducted a feasibility study of fractionated CPT-11 combined with SFN to develop a new therapy against relapsed/refractory pediatric hepatic cancer (HC). PROCEDURE: The study was originally designed as a phase I, standard 3+3 dose-finding study to evaluate dose-limiting toxicities (DLTs) for the regimen and the optimal CPT-11 dose in combination with SFN against relapsed/refractory pediatric HC, including HB and hepatocellular carcinoma (HCC). The enrolled patients received SFN at 200 mg/m2 every 12 hours or 400 mg/m2 every 24 hours daily combined with CPT-11 at 20 mg/m2 /day on days 1 to 5 as an initial level 1 dose. RESULTS: Six patients with HB (n = 4) or HCC (n = 2) were enrolled and treated with CPT-11 dose level 1. The median age at enrollment was 8.7 (6.2-16.3) years. All patients received platinum-containing chemotherapy, and five or two patients received CPT-11 or SFN before enrollment, respectively. Regimen toxicities were evaluable in all patients. One of six patients experienced a grade 4 transaminase levels increase, which was defined as a DLT per protocol. Grade 3/4 neutropenia and a grade 3 transaminase level increase occurred in three patients and one patient, respectively. All patients reported grade 1/2 toxicities such as anemia, skin toxicity, gastrointestinal symptoms, and hypoalbuminemia. CONCLUSIONS: Although the study was terminated before determining the maximum-tolerated CPT-11 dose, SFN and CPT-11 at the level 1 dose were concluded to be tolerable in pediatric patients with HC.

Successful Treatment of Pediatric Refractory/Relapsed AML with KIR-Ligand-Mismatched Cord Blood Transplant after FLAG-IDA Reinduction Therapy with or without the GO Regimen.

Prognosis in pediatric patients with refractory/relapsed acute myeloid leukemia (AML) is grim, and there is no standard treatment for such patients. Combined treatment with intensive chemotherapy and gemtuzumab ozogamicin (GO), a monoclonal anti-CD33 antibody conjugated with calicheamicin, is useful as reinduction therapy in refractory/relapsed AML. Here, we describe three cases of pediatric refractory/relapsed AML that were successfully managed with FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), with or without GO, as reinduction therapy before a KIR-ligand-mismatched cord blood transplant. This strategy relies on the fact that killer cell immunoglobulin-like receptors (KIR) on cord blood natural killer (NK) cells recognize human leukocyte antigen (HLA) class I alleles, and that donor KIR-ligand incompatibility may be associated with lower incidence of relapse and improved survival in AML, as cells that lack these inhibitory HLA ligands can activate NK cells. All three patients are currently alive and have been disease-free for 24-65 months, although one patient developed severe sinusoidal obstructive syndrome (SOS). Thus, our strategy can result in excellent outcomes in pediatric patients with refractory/relapsed AML.

Gastric antral vascular ectasia in a pediatric patient with neuroblastoma who underwent tandem stem cell transplantation.

Gastric antral vascular ectasia (GAVE) is an angiodysplastic disorder, which causes severe and prolonged gastric bleeding. Although GAVE has been described in adult patients treated with hematopoietic stem cell transplantation (HSCT), a few cases involving pediatric patients have also been reported. A 5-year-old boy with neuroblastoma (NB) developed severe hematemesis after undergoing tandem HSCT, i.e. autologous peripheral blood stem cell transplantation (auto-PBSCT), followed by allogeneic cord blood transplantation (allo-CBT). The patient suffered oral feeding difficulties because of the effects of chemotherapy and an unbalanced diet. Intravenous Busulfan (ivBU) was used as a conditioning regimen for the auto-PBSCT. The diagnosis of GAVE was made based on endoscopy of the upper gastrointestinal tract on day 31 after the allo-CBT. Argon plasma coagulation (APC) was performed twice, and the complete resolution of GAVE was confirmed by an endoscopic re-evaluation, conducted on day 87. GAVE in this case might have been associated with ivBU treatment. Atrophy of the gastric mucosa due to loss of appetite might also have contributed to GAVE. NB was treated using high-doses of alkylating agents, such as BU. Such treatment can cause significant mucositis of the oral cavity as well as vascular lesions and is associated with GAVE. Therefore, GAVE should be considered when gastrointestinal bleeding occurs in NB patients treated with HSCT. APC might be effective against HSCT-GAVE.

Prophylactic recombinant thrombomodulin treatment prevents hepatic sinusoidal obstruction syndrome in high-risk pediatric patients that undergo hematopoietic stem cell transplants.

Hepatic SOS is a potentially life-threatening complication of conditioning for allogeneic HSCT. rTM is a new drug for treating DIC. We report our experience of the use of rTM as a prophylaxis against SOS in high-risk pediatric patients that underwent HSCT. We evaluated the cases of 19 pediatric hematology and oncology patients who underwent HSCT at our institution between 2007 and 2016. The patients who received HSCT after 2012 (n = 8) were treated with rTM as a prophylaxis against SOS together with UDCA and LMWH, whereas the others (n = 11) were only treated with UDCA and LMWH. Although SOS occurred by post-HSCT day 35 in 3 (27%) patients in the control group, SOS was not seen in the rTM group. Two of the former three patients suffered severe SOS, and one died of the condition. The mean peak level of PAI-1 (a marker of endothelial damage) was significantly lower in the rTM group. rTM appears to be a safe prophylaxis for SOS. The present findings suggest that prophylactic rTM after HSCT might help to prevent SOS.

[Initial presentation of lymphoblastic crisis in a pediatric chronic myelogenous leukemia patient].

A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein. Based on these findings, she was diagnosed with a lymphoblastic crisis of chronic myelogenous leukemia (CML). Combined chemotherapy, involving imatinib, resulted in complete molecular remission. She received cord blood transplant (CBT) during the first complete remission; she is alive and has not suffered a relapse since two years after the CBT. The sudden onset of a blastic crisis in pediatric CML is rare, and it may be difficult to distinguish such cases from de novo Ph-positive leukemia. For diagnostic purposes, it is essential to consider a patient's clinical course and blood test results.