Local Anesthesia With General Anesthesia for Pediatric Bone Marrow Procedures.

BACKGROUND: Pediatric patients with cancer undergo repeated painful procedures, including bone marrow aspirations and biopsies (BMABs). Optimal management of procedure-related pain can reduce discomfort, anxiety, and distress. METHODS: Children with neuroblastoma were randomly assigned to 1 of 2 arms on a prospective, single-blind, crossover trial conducted at Memorial Sloan Kettering Cancer Center from October 2016 to January 2018 (www.clinicaltrials.gov, identifier NCT02924324). Participants underwent 2 sequential BMABs: one with general anesthesia (GA) alone, the other with GA plus local anesthesia (LA) (GA + LA). The objective was to assess procedure-related pain and its interference with quality of life (QoL) with GA versus GA + LA. Primary outcome was percentage of participants requiring postprocedural opioids. Secondary outcomes were total opioid and nonopioid analgesics, pain scores, time to first analgesic, QoL, and toxicity. Management of postprocedural pain was standardized. RESULTS: Of 56 participants randomly assigned (3-16.5 years old), 46 completed both procedures. There was no significant difference in percentage of participants requiring opioids with GA versus GA + LA (24% vs 20%, P = .5). Pain scores in the recovery room were significantly lower for GA + LA versus GA (median [IQR]: 0 [0-2] vs 2 [0-4], P = .002). There were no statistically significant differences in total opioid or nonopioid analgesic, 6- and 24-hour pain scores, median time to first analgesic, or pain interference. No adverse events occurred. CONCLUSIONS: LA was associated with significant improvement in pain scores in the immediate recovery period. LA did not reduce postprocedural opioid use, nor did it improve QoL for patients undergoing BMAB with GA.

A potent tetravalent T-cell-engaging bispecific antibody against CD33 in acute myeloid leukemia.

Acute myeloid leukemia (AML), the most common acute leukemia in adults and the second most common cancer in children, is still a lethal disease in the majority of patients, but immunologic approaches have improved outcome. Bispecific antibodies (BsAbs) are novel immunotherapeutics that can redirect immune cells against AML. We now report a tetravalent (2+2) humanized BsAb in the immunoglobulin G light chain single chain fragment variable [IgG(L)-scFv] format to engage polyclonal T cells to kill CD33+ AML targets. In vitro, this BsAb demonstrated strong antigen-specific T-cell-dependent cell-mediated cytotoxicity (TDCC) with an 50% effective concentration (EC50) in the femtomolar range that translated into treatment of established human AML IV xenografts in vivo. Importantly, it could redirect intraperitoneally injected T cells to ablate established and rapidly growing extramedullary subcutaneous AML xenografts in vivo. Furthermore, internalization of CD33 upon BsAb binding was identical to that of a bivalent (1+1) heterodimer, both being substantially less than anti-CD33 IgG. In contrast to the heterodimer, the tetravalent IgG-scFv BsAb was >10-fold more efficient in TDCC of AML cells in vitro and in vivo. This BsAb did not react with and did not kill CD38-CD34+ hematopoietic stem cells from cord blood. We conclude that the novel anti-CD33 IgG(L)-scFv BsAb construct reported here is a potential candidate for clinical development.

Long-term survival after autologous peripheral blood stem cell transplantation in two patients with malignant rhabdoid tumor of the kidney.

A 5-month-old male with stage II malignant rhabdoid tumor of the kidney (MRTK) and a 24-month-old male with stage III MRTK were treated with surgical resection of tumors and chemotherapy of alternating ICE (ifosfamide, carboplatin, and etoposide) and VDC (vincristine, doxorubicin, and cyclophosphamide), followed by high-dose chemotherapy using etoposide, carboplatin, and melphalan with autologous hematopoietic stem cell transplantation (SCT). Two patients have been alive without any evidence of disease for 30 and 37 months after diagnosis, respectively, and require no medication. Consolidation with SCT should be further studies for selected patients with high-risk MRTK.

Graft-versus-lymphoma effect after reduced intensity allogeneic hematopoietic stem cell transplantation from HLA-two loci mismatched father in a patient with refractory non-Hodgkin lymphoma.

A 10-year-old female developed a mediastinal mass and was diagnosed as mixed lineage lymphoblastic lymphoma. The tumor was extremely refractory, and she never achieved remission despite intensive therapy using 12 anti-lymphoma agents and local irradiation. She received reduced-intensity allogeneic peripheral blood stem cell transplantation from her HLA-two loci mismatched father, and achieved complete remission. However, the lymphoma relapsed four months later, and we abruptly discontinued immunosuppressive drugs. Concurrent with the development of grade III graft-versus-host disease, the lymphoma completely disappeared with an increase of activated T-cells in peripheral blood. The clinical course suggested the graft-versus-lymphoma effect against aggressive/refractory lymphoma.

Epstein-Barr virus-associated bronchial leiomyoma in a boy with cellular immunodeficiency.

Bronchial leiomyoma is a rare disease in children. Recently, the association of leiomyoma and HIV infection was reported. We describe a boy with a cellular immunodeficiency, who had endobronchial leiomyoma. The tumor cells were positive for Epstein-Barr virus-encoded RNA-1 (EBER-1) and Epstein-Barr virus-determined nuclear antigen-2, suggesting a role of Epstein-Barr virus in the pathogenesis of leiomyoma.

Long-term use of peripherally inserted central venous catheters for cancer chemotherapy in children.

BACKGROUND: Peripherally inserted central venous catheters (PICCs) have been increasingly used in pediatric patients. However, little is known about the incidence and risk of complications when using this device in children with cancer. The purposes of this study are to assess the feasibility of PICCs and to determine the risk factors for PICC-related complications in pediatric patients with various types of malignancies. PATIENTS AND METHODS: We attempted to place PICCs in 53 patients with a median age of 5 years ranging from 2 months to 20 years. PICCs were used to administer fluid, parenteral nutrition, anticancer agents, antibiotics, and blood products and also for the through-line blood sampling. The duration of catheterization and the incidence of PICC-related complications requiring removal were retrospectively evaluated in association with the diagnosis, sex, age and body weight of the patients, size, insertion site and tip location of the catheters, type of treatment, and duration of leukopenia. RESULTS: PICCs were successfully placed in 109 of 112 attempts (97.3%) in 53 patients, and they were followed for a total of 11,797 catheter days (median placement, 87 days; range, 3 to 512 days). Fifty five PICCs (50.5%) were removed as a result of PICC-related complications with a rate of 4.66 per 1,000 catheter days. The most common reasons for catheter removal were occlusion (n=18), breakage/leakage (15), and infection (10). More than 70% of such complications occurred more than 30 days after placement. The catheter tip location in the superior vena cava or the right atrium might decrease the risk of complications. Other parameters did not influence the incidence of complications. CONCLUSIONS: PICCs were found to provide a reliable access for prolonged intravenous administration and blood sampling in children intensively treated for hematologic and solid malignancies, thus leading to a reduction of physical pain and psychological stress in such patients. However, the long-term placement of PICCs may also be related to an increased risk of complications.

Prolonged severe pancytopenia preceding the cutaneous lesions of juvenile xanthogranuloma.

We report a case of juvenile xanthogranuloma (JXG) having progressive pancytopenia for 6 months until the proliferating skin lesions. A 2-month-old infant presented recurrent fever, anemia, and hepatosplenomegaly mimicking hemophagocytic lymphohistiocytosis (HLH) or juvenile myelomonocytic leukemia (JMML). At 8 months of age, the biopsy of a growing papule on the elbow made the diagnosis. Bone marrow (BM) specimens showed clustering foamy cells including hemophagocytosis by histiocytes. Treatment with etoposide followed by vinblastine plus prednisolone (PSL) therapy improved the disease. Although JXG is a benign non-Langerhans cell histiocytosis, the multisystem-visceral form should be considered as a potential aggressive disease when associated with BM failure in early infancy.