Factors associated with employment status among mothers of survivors of childhood cancer: a cross-sectional study.

PURPOSE: To identify the factors associated with employment status among mothers of childhood cancer survivors (CCSs). METHODS: We conducted a questionnaire survey on mothers of survivors of childhood cancer to clarify practical factors such as care demands, psychological factors such as motivation to work, and support. After calculating descriptive statistics for all variables, binary logistic regression analysis was performed. RESULTS: Of 171 mothers, 129 (75.4%) were employed. The most common form of employment was non-regular (n = 83; 48.5%), including part-time, dispatched, and fixed-term workers. At the time of the survey, compared with nonworking mothers, working mothers tended to be more motivated to work and have lower scores for "Long-term Uncertainty" on the Parent Experience of Child Illness Scale. The results of the binary logistic regression analysis indicated that employment was related to higher motivation to work, the continuation of employment during treatment, more outpatient visits, and a higher amount of support. CONCLUSION: As employment of CCSs' mothers is associated with psychological factors such as motivation to work and long-term uncertainty, psychological support for CCSs' mothers might promote employment. In addition, because the continuation of employment during treatment affects the employment of mothers after the end of cancer treatment, a leave system that covers the treatment period for childhood cancer needs to be established.

A comprehensive study of the distressing experiences and support needs of parents of children with intractable cancer.

OBJECTIVE: The primary endpoints of this study were: (1) to explore the distressing experiences of parents of patients with intractable pediatric cancer in Japan from disclosure of poor prognosis to the present and (2) to explore support they regarded as necessary. METHODS: A multi-center questionnaire survey was conducted that included 135 bereaved parents of patients with pediatric cancer in Japan. RESULTS: The top five distressing experiences shared by over half of the bereaved parents were: 'Realize that the child's disease was getting worse' (96.7%), 'Witness the child's suffering' (96.7%), 'Make many decisions on the basis that the child will die in the not-so-distant future' (83.6%), 'Feel anxious and nervous about the child's acute deterioration' (82.0%) and 'Realize that there was nothing that I could do for the child' (78.7%). The top five support regarded as necessary were: 'Visit the room and speak to the sick child every day' (90.2%), 'Provide up-to-date information' (80.3%), 'Sufficiently explain the disadvantages of each treatment option' (80.3%), 'Show a never-give-up attitude until the end' (78.7%) and 'Make arrangements to allow the sick child to spend time with his/her siblings' (73.8%). CONCLUSIONS: This study identified the common distressing experiences of parents and the support regarded as necessary by them. To provide efficient support with limited manpower in pediatric setting, healthcare professionals should recognize these tasks as high priorities when engage parents of intractable pediatric cancer patients.

Efficacy of micafungin in pediatric immunocompromised patients with invasive fungal infection.

BACKGROUND: Micafungin, an antifungal echinocandin, has been indicated for pediatric patients with invasive fungal infection (IFI) in Japan and Europe. Its efficacy in immunocompromised pediatric patients with IFI, however, has not been fully investigated. METHODS: The safety and efficacy of micafungin as an antifungal therapy were analyzed in nine consecutive severe immunocompromised patients with IFI. RESULTS: Three patients with proven or probable Candida infections had complete response to micafungin therapy. Of the other six patients with proven, probable or possible Aspergillus infection, four had complete response and one had partial response to micafungin treatment. No severe adverse events were observed. CONCLUSIONS: In this small series, micafungin was effective for IFI caused by both Candida and Aspergillus species and no severe adverse events were observed in these immunocompromised patients.

Allogeneic hematopoietic stem cell transplantation against recurrent rhabdomyosarcoma.

The prognosis of high-risk rhabdomyosarcoma (RMS) with metastatic or recurrent disease remains poor. We report a 6-year-old girl who successfully underwent allogeneic hematopoietic stem cell transplantation against recurrent metastatic alveolar RMS. The disease recurred at distant lymph node metastasis with bone marrow involvement. After chemotherapy and radiotherapy for the metastatic site, she underwent allogeneic bone marrow transplantation during complete remission from her 5/8 HLA-matched father. She developed acute graft-versus-host disease after preemptive donor lymphocyte infusion and remains in a disease-free condition for 31 months after transplantation. A graft-versus-tumor effect through allogeneic immune cells might produce a beneficial effect for high-risk RMS.

Living-donor, single-lobe lung transplantation and simultaneous contralateral pneumonectomy in a child.

An 8-year-old girl became ventilator-dependent due to severe bronchiolitis obliterans/interstitial pneumonia caused by cord-blood cell transplantation for neuroblastoma. Her mother's right lower lobe was twice as large as her right chest cavity. She successfully underwent living-donor, right, single-lobe lung transplantation and simultaneous left pneumonectomy under conditions of cardiopulmonary bypass. At 18 months after transplantation, the patient returned to school life and is currently able to carry out daily activities without supplemental oxygen.

Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning for a child with recurrent anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence is frequently observed. Allogeneic hematopoietic stem cell transplantation (HSCT) has recently been reported to be effective against recurrent disease, suggesting a graft-versus-lymphoma effect. We present a 3-year-old child with recurrent ALCL who underwent HSCT from an HLA-1-locus mismatched cord blood unit following reduced intensity conditioning with fludarabine, melphalan, and low-dose thoraco-abdominal irradiation. Engraftment was uneventful, but grade III acute graft-versus-host disease was observed. He is well and free of disease 25 months after HSCT, which implies that reduced intensity conditioning may allow a sufficient graft-versus-lymphoma effect against ALCL while lessening treatment-related toxicities.

Retropharyngeal neuroblastoma in an infant: management without surgery.

SUMMARY: Retropharyngeal neuroblastoma is rare. We report a 3-month-old infant with retropharyngeal neuroblastoma presenting with airway compression, which had an unresectable localized tumor without N-myc amplification. He was promptly treated with chemotherapy, resulting in a dramatic resolution. Subsequently, he received no surgical intervention and is well without evidence of recurrence 10 months after completion of chemotherapy. A review of the literature reveals that retropharyngeal neuroblastoma in infants has a good prognosis, but with some risk of surgical complication. Thus, it might be better to treat unresectable, localized disease accompanied by life-threatening symptoms with chemotherapy alone.

Hemophagocytosis after bone marrow transplantation for JAK3-deficient severe combined immunodeficiency.

HSCT is the optimal treatment for patients with SCID. In particular, HSCT from a HLA-identical donor gives rise to successful engraftment with long survival. We report a six-month-old girl with JAK3-deficient SCID who developed hemophagocytosis after BMT without conditioning from her HLA-identical father. She had suffered from pneumonia and hepatitis before BMT. Prophylaxis for GVHD was short-term methotrexate and tacrolimus. On day 18 after BMT, the patient developed hemophagocytosis in bone marrow when donor lymphocytes were increasing in peripheral blood. Analysis of chimerism confirmed host origin of macrophages and donor origin of lymphocytes. Thus, host macrophage activation was presumably induced in response to donor lymphocytes through immunoreaction to infections and/or alloantigens. HSCT for SCID necessitates caution with respect to hemophagocytosis.

Antifungal prophylaxis with micafungin in patients treated for childhood cancer.

BACKGROUND: Invasive fungal infections (IFIs) remain a major cause of infectious morality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation (HSCT). Micafungin exhibits broad antifungal activity against both Aspergillus and Candida species. We performed a retrospective study to determine the efficacy and safety of prophylactic micafungin against IFI in pediatric neutropenic patients during chemotherapy or HSCT. PROCEDURE: Forty patients were given micafungin (3 mg/kg/day) intravenously for neutropenia: 131 patient-cycles (39 patients) after chemotherapy and 15 patient-cycles (14 patients) after HSCT. Median duration of neutropenia and micafungin prophylaxis was 13 and 23 days after chemotherapy and HSCT, respectively. RESULTS: Treatment success rate, defined as absence of proven, probable, possible, or suspected IFIs, was 93.9% (121/131) and 80.0% (12/15) for chemotherapy and HSCT, respectively. Proven or probable IFI was documented in only one patient after HSCT. No adverse events were observed that could be related to micafungin prophylaxis. CONCLUSIONS: These results suggest that prophylactic micafungin is well tolerated and may prevent IFIs in pediatric patients with neutropenia receiving chemotherapy or HSCT.

WT1 (Wilms tumor 1) peptide immunotherapy for childhood rhabdomyosarcoma: a case report.

Immunotherapy using a Wilms tumor (WT1) peptide has been undergoing clinical trials for adulthood leukemia and solid cancer with promising results. In this study, the authors used WT1 peptide vaccination to treat a 6-year-old girl with metastatic alveolar rhabdomyosarcoma. She received weekly intradermal injection with HLA-A*2404-restricted, 9-mer WT1 peptide against residual bone disease. After 3 months her bone disease disappeared, concurrent with an increase in the frequency of WT1-specific cytotoxic T lymphocytes (CTLs). A high proportion of WT1-specific CTLs with effector or effector memory phenotype were detected in peripheral blood of this patient. She is currently still on continued WT1 peptide immunotherapy in a disease-free condition for 22 months. WT1 peptide-based immunotherapy should be a promising option for high-risk rhabdomyosarcoma in childhood.

Ex vivo-expanded donor CD4(+) lymphocyte infusion against relapsing neuroblastoma: A transient graft-versus-tumor effect.

High-risk neuroblastoma has a poor prognosis despite multimodal treatment including high-dose chemotherapy. A 7-year-old male with neuroblastoma received ex vivo-expanded donor CD4(+) T lymphocyte infusion (CD4(+) DLI) after recurrence in the bone marrow following allogeneic hematopoietic stem cell transplantation from his HLA-identical mother. The disease transiently responded to CD4(+) DLI with reduction of tumor cells and a decrease of serum neuron-specific enolase. The response was associated with development of continued high fever and an increase of cytotoxic T lymphocytes in peripheral blood. This case suggests a possibility of a graft-versus-tumor effect against neuroblastoma.

Pediatric post-transplant diffuse large B cell lymphoma after cardiac transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) occur in 3.5-9% of patients after pediatric cardiac transplantation. Caution is needed when treating patients with PTLD because of the risk of allograft rejection frequently caused by withdrawal of immunosuppression. In this report, we describe a 47-month-old boy who developed PTLD as an ileocecal mass 29 months after cardiac transplantation. Immunosuppressive therapy with cyclosporine A (CyA) had been reduced due to an elevation of Epstein-Barr virus (EBV) titer for 8 months before development of PTLD. Histology of the tumor was diffuse large B cell lymphoma. EBV was detected by in situ hybridization assay. Cytogenetic analysis revealed t(8;14)(q24;q32) and Southern blot analysis detected a c-Myc rearrangement. He was treated with rituximab and combination chemotherapy with excellent response. CyA dose was maintained at reduced levels during chemotherapy and later minimized with introduction of everolimus. The child is free of both PTLD and allograft rejection 41 months after the diagnosis of PTLD.

Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: Single-institute experience.

We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m2), CY (200 mg/kg IV), and fludarabine (180 mg/m2 IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21-25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.

NK-cell repertoire is feasible for diagnosing Epstein-Barr virus-infected NK-cell lymphoproliferative disease and evaluating the treatment effect.

Epstein-Barr virus (EBV) occasionally infects T and NK cells and causes EBV-infected T/NK-cell lymphoproliferative disease (LPD), which comprises chronic active EBV infection, EBV-associated hemophagocytic syndrome, mosquito allergy, hydroa vacciniforme, aggressive NK-cell leukemia, and NK/T-cell lymphoma. The diagnosis is proven by the monoclonal proliferation of EBV-infected T or NK cells, which is a time-consuming and complicated method. T-cell monoclonality is helpful for the screening of EBV-infected T-cell LPD in patients with EBV-genome burden and is easily shown with T-cell-receptor rearrangement or the T-cell repertoire, whereas NK-cell monoclonality is difficult to prove due to its lacking such rearranged receptors. We investigated a set of killer immunoglobulin-like receptors (KIRs) and also CD94-NKG2 heterodimers on NK cells, namely the NK-cell repertoire. Skewed repertoires were seen in all patients with EBV-infected NK-cell LPD, but not in any patients with EBV-infected T-cell LPD and were restored only after successful treatment. The normal KIR repertoire is variable for each individual and it seems difficult to detect minimal residual EBV-infected lymphocytes. However, the NK-cell repertoire is feasible for identifying EBV-infected NK-cell LPD and evaluating the treatment effect.