Recent childhood cancer treatment requires minimum late effects as well as treatment of the disease to improve the quality of survivorship. Fertility preservation has become an important issue in adolescent and young adult (AYA) cancer patients. Our fertility preservation strategy for AYA patients is to provide information on their estimated infertility risks on the basis of the treatment plan and consultation with an oncofertility specialist according to the patient’s decision. Seventeen patients from February 2006 to November 2015 were referred for fertility preservation (male:female=15:2; 15–24 years). The patients include 6 with acute leukemia, 4 with lymphomas, 4 with osteosarcomas and chondrosarcomas, 2 with rhabdomyosarcomas, and 1 with a medulloblastoma. Thirteen of the 17 patients, namely, those with lymphomas and solid tumors, consulted an oncofertility institute before starting chemotherapy and/or radiotherapy. Four acute leukemia patients underwent fertility preservation after the initiation of therapy. Twelve male patients out of 15 successfully cryopreserved their sperms. One female lymphoma patient underwent counselling and decided not to preserve her gametes since she prioritized an early start of chemotherapy. The patient with medulloblastoma was provided information about the choice of fertility preservation after a high infertility probability after the therapy was determined. She chose to cryopreserve her ovarian tissue. It would be essential for fertility preservation in AYA cancer patients to provide accurate information on the basis of the probability of infertility caused by the anticancer treatments and to promptly refer patients to fertility specialists when the patients decide to do so.
There are only a few reports of pediatric extracranial malignant germ cell tumors (MGCTs) in Japan. Thus, we retrospectively analyzed 50 cases of MGCTs in a single institute to assess the outcome, optimal therapy and prognostic factors. Our data included those of 50 cases of extracranial MGCTs from 1983 to 2015, and the median age at diagnosis was 2.0 (0.03–16.4). The median follow-up period from diagnosis was 2199 (76–7922) days. As for histopathological findings, there were 7 cases of dysgerminoma, 34 cases of yolk sac tumor, 4 cases of embryonal carcinoma, and 5 cases of mixed germ cell tumors. Front line therapies were a wait-and-see approach after total resection for 7 cases, carboplatin-based chemotherapy for 35 cases, VAC therapy for 6 cases (VCR, CPA, Act-D), and other therapies for 2 cases. The 5-year overall survival (OS) rates were 100% for all stages except stage IV (n=41) and 53.6% (13.2–82.5) for stage IV (n=7). There was a statistically significant difference between the two groups (p=6.84E-9). Among those diagnosed with MGCT after total resection, 7 out of 33 were selected for the wait-and-see approach after obtaining written informed consent from a person with parental authority. Two out of the 7 patients relapsed, treated with chemotherapy, and recovered. Stage IV was a strong unfavorable prognostic factor. The wait-and-see approach can be one of the optimal choices for stage I patients and those who have undergone total resection.
The prognosis of PTPN11 mutation-positive juvenile myelomonocytic leukemia (JMML) with blast crisis remains very poor. A 3-year-old girl presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. Bone marrow examination showed refractory anemia with excessive blasts, but we diagnosed her as having JMML with blast crisis on the basis of the finding of PTPN11 mutation positivity and spontaneous colony assay results. Because of graft failure after single-allele mismatch cord blood transplantation, we performed salvage transplantation of haploidentical peripheral stem cells from her mother. She achieved complete chimerism along with grade III acute GVHD; however, she developed donor-type aplasia thereafter. Since donor cell infusion from her mother did not lead to hematopoiesis recovery, she underwent haploidentical bone marrow transplantation from her father. She remains disease-free for more than one year after the last transplantation. Haploidentical hematopoietic stem cell transplantation (HSCT), via its potent GVL effects, may be effective for treating the most severe type of JMML such as PTPN11 mutation-positive JMML with blast crisis, which cannot be cured by conventional HSCT.
Diaphragmatic primary yolk sac tumor is an extremely rare disease. Since we experienced treating the case of an 11-month-old boy, we report it along with literature considerations. The initial symptoms of this disease are often chest-related symptoms such as coughing, chest pain, rapid breathing and pleural effusion. For the diagnosis of this disease, coronary MR images, sagittal images and 3D-CT images are useful. In the treatment of this disease, it is important to perform preoperative chemotherapy including platinum preparations to shrink the tumor followed by its complete surgical removal. Similarly in our patient, it developed primarily with chest symptoms such as coughing and pleural effusion, and was diagnosed as primary tumor of the diaphragm based on coronary MR images and sagittal images. After the histopathological diagnosis of yolk sac tumor, preoperative chemotherapy with a platinum preparation (cisplatin) was performed, and the tumor was completely excised after its shrinkage. Fifteen years have passed since the completion of the whole course of chemotherapy, and the patient has shown no recurrence of the disease or side effects of the chemotherapy.
The general treatment strategy for Wilms tumor in Japan consists of initial surgery for staging and pathological diagnosis, followed by chemotherapy. However, in many cases of bilateral or advanced Wilms tumor with extension to the right atrium, initial surgical resection of the tumor is not possible. Although treatment strategies for these cases have not yet been fully established, the efficacy of preoperative chemotherapy has been reported, and pathological diagnosis prior to chemotherapy is not always necessary. In our case of bilateral renal tumor in a one-year-old girl, and in the case of renal tumor extending to the right atrium in a four-year-old boy, chemotherapy was started without pathological diagnosis, and safe tumor resection was possible. In these two cases, Wilms tumor was diagnosed after surgery. In cases of advanced Wilms tumor, whose safe surgical removal at diagnosis is not possible, preoperative chemotherapy may be considered, and pathological diagnosis prior to the initiation of chemotherapy is not always necessary.
Hemophilia is characterized by suggillation or hematoma after 6 months of age and it rarely causes bleeding symptoms in the neonatal period. We report our experience of treating a male neonate with hemophilia A complicated by subgaleal hematoma and disseminated intravascular coagulation (DIC). The patient was born through vaginal delivery and had a subgaleal hematoma. He was subsequently transferred to us and was diagnosed as having DIC: concentrated erythrocytes and fresh frozen plasma were successfully administered. However, three days after administration, it was observed that his hematoma exacerbated, and the activated partial thromboplastin time (APTT) was extraordinarily prolonged. These findings prompted us to measure his plasma coagulation factor VIII activity. As a result, a decreased activity was found, which led to a diagnosis of severe hemophilia A. Although neonatal subgaleal hematoma is relatively common, we should have a high index of suspicion for hemophilia when a patient shows intractable courses or extraordinarily prolonged APTT.
Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Several studies have shown the efficacy of BV in relapsed or refractory anaplastic large cell lymphoma (ALCL). We present the case of a 14-year-old girl who experienced acute pancreatitis during the BV treatment of relapsed ALCL. The patient had stage 4 ALCL with cranial involvement at onset. She once achieved complete remission, but the disease relapsed only 1 month after the completion of chemotherapy. BV was effective against relapsed ALCL: she entered a second remission after the first administration of BV. After 4 cycles of BV treatment, however, she developed acute pancreatitis. As there were no signs of recurrence, the pancreatitis was likely due to BV treatment. Vinblastine was administered weekly to maintain remission until the recovery from pancreatitis, and allogeneic umbilical cord blood transplantation was finally performed. Although BV has been generally considered a safer drug, careful observation should be carried out for drug-induced pancreatitis.
A 12-year-old boy was referred to our hospital for the evaluation of abdominal pain. Abdominal computed tomography revealed a large tumor in the small bowel, and a histopathological study of biopsy material showed primary intestinal B-cell non-Hodgkin’s lymphoma (NHL). Nine days after the initiation of induction chemotherapy, the patient developed sudden severe abdominal pain. Our diagnosis was intestinal perforation, and we then immediately performed a simple closure with an omental patch. Because the perforation site was different from the biopsy area, we suspected that the rapid regression of NHL that infiltrated into the intestinal wall after the initiation of chemotherapy resulted in the perforation. Intestinal perforation after the initiation of treatment for NHL in childhood is rare, although some cases have been reported. However, intestinal perforation can have a fatal outcome; therefore, it is an important consideration during the treatment of intestinal NHL.