Continued complete remission without systemic therapy for isolated testicular relapse after bone marrow transplantation in a boy with acute lymphoblastic leukemia.

ITR after BMT in cases of acute lymphoblastic leukemia is relatively rare. Treatment for ITR after BMT generally consists of a combination of local irradiation, orchiectomy, and systemic chemotherapy. However, the effectiveness of these modalities has not been established. Both irradiation and systemic chemotherapy including a second transplantation would result in additional toxicity. In this report we describe a boy with ITR 91 months after BMT who has remained in complete remission more than two yr after a unilateral orchiectomy. We did not treat this patient with systemic chemotherapy, as his ITR developed very late. Our experience suggests that orchiectomy alone is a reasonable option for very late ITR after BMT.

Rapid progression of metastatic osteosarcoma after initiation of a reduced-intensity conditioning regimen with immunosuppressive fludarabine.

Indications for RIST have not been established in patients with solid tumors. In this study, we performed RIST as immunotherapy in a 13-yr-old girl with intractable but not progressive osteosarcoma, which originated from the inter-costal region. Carcinomatous pleurisy suddenly developed after the start of a conditioning regimen that included Flu and BUS. She died of respiratory failure on day +19 without signs of engraftment. This case suggests that unexpected acceleration of tumor growth may occur following RIST with immunosuppressive drugs before the development of a beneficial GVT effect.

Successful treatment of an endodermal sinus tumor of the vagina by chemotherapy alone: a rare case of an infant diagnosed by pathological examination of discharged tumor fragment.

A 7-month-old infant was noted to have vaginal bleeding that was accompanied by a discharged tumor fragment. The histological diagnosis was endodermal sinus tumor. Her serum alpha-fetoprotein (AFP) was increased to 358.7 ng/mL, and magnetic resonance imaging showed a 1.8 x 1.0 cm tumor in the vagina. She received combination chemotherapy with cyclophosphamide, pirarubicin, carboplatin, and etoposide. The tumor in the images disappeared and the serum level of AFP returned to the normal range after 2 cycles. Treatment was complete without surgical or radiological therapy. More than 45 months after the completion of chemotherapy, she is alive without signs of recurrence.

Response of heavily treated and relapsed hepatoblastoma in the transplanted liver to single-agent therapy with irinotecan.

We describe here a patient with relapsed hepatoblastoma after LDLT who developed heart failure, which was treated with irinotecan hydrochloride (CPT-11). His native liver was replaced by a liver graft from his mother at 26 months from the onset. However, LDLT failed to induce complete remission and he was diagnosed as relapsed hepatoblastoma six months after LDLT. We again administered cisplatin and doxorubicin. After six courses of chemotherapy, he developed congestive heart failure because of anthracycline toxicity. The chemotherapy regimen was therefore switched to irinotecan at 35 mg/m2 daily for three days/wk for two consecutive weeks, and repeated every 28 days. After four courses of irinotecan, metastatic lesions were remarkably reduced in size, and the serum level of AFP decreased from 0.7 million to 927 ng/mL. No severe side effects were documented and congestive heart failure improved. These results suggest that irinotecan may be safely given to a patient with relapsed hepatoblastoma after LDLT without serious side effects and may contribute to prolonging the survival.

Identical reconstitution after bone marrow transplantation in twins who received fresh and cryopreserved grafts harvested at the same time from their older brother.

We report here the reconstitution after bone marrow transplantation (BMT) in identical infant twins with acute myelogenous leukemia (AML). They were diagnosed at 8 and 9 months of age. Complete remission was induced after two courses of chemotherapy. After four and five courses of chemotherapy, respectively, they received BMT at 2-month interval from the same HLA-identical older brother. The total dose of marrow nucleated cells (NC) harvested was 77.7 x 10(8). The first patient was transplanted with half of the total dose of NC. The remaining cells were cryopreserved without the use of a programmed freezer and transplanted into the second patient 2 months later. The number of days for neutrophil (>0.5 x 10(9)/L), platelet (>50 x 10(9)/L), and reticulocyte (>1%) recovery were, respectively, 15, 21, and 14 in the first case and 12, 21, and 15 in the second case. The clinical courses after BMT were uneventful in both cases, except for mild acute GVHD, and complete remission has been maintained >4 yr with full recovery of immune and marrow function. Based on the results in these cases, we confirmed that marrow cells that have been cryopreserved without the use of a programmed freezer could reconstitute immune and marrow function as well as non-cryopreserved cells.

Fetal ultrasonography to prevent irreversible neurological sequelae of neonatal neuroblastoma.

An intra-abdominal mass was observed by fetal ultrasonography at 32 weeks of gestation. The baby was diagnosed as having neuroblastoma at the time of delivery at 39 weeks and its lower extremities were completely paralyzed. The chemotherapy after birth was quite effective to reduce the mass volume but neurological sequelae failed to improve. By carefully monitoring the movement of extremities, it may have been possible to prevent irreversible by inducing delivery before that state was reached.

Minimal residual disease in early phase of chemotherapy reflects poor outcome in children with acute lymphoblastic leukemia--a retrospective study by the Children's Cancer and Leukemia Study Group in Japan.

We analyzed the minimal residual disease (MRD) in 50 children with acute lymphoblastic leukemia (ALL) by amplifying the clonally rearranged T-cell receptor (TCR) gamma/delta chain and/or immunoglobulin (Ig) kappa chain gene using the allele-specific-PCR method. All children were treated according to the protocols of the Children's Cancer and Leukemia Study Group of Japan (CCLSG). The patients were stratified into four risk-groups according to the leukocyte count and age at diagnosis. We prospectively sampled the patients' bone marrow at 1 month (point 1) and 3 months (point 2) after the initiation of chemotherapy and quantitated the MRD retrospectively. The results of MRD were closely related with the clinical outcome. The relapse rate of the patients MRD-positive at points 1 and 2 was 46% (6/13) and 86% (6/7), respectively, whereas those MRD-negative results at point 1 and 2 were 13% (3/13) and 3% (3/30), respectively. We found significant differences in the event-free survival between MRD-positive children and MRD-negative children like the reports, which have been made by BFM and EORTC groups. We conclude that MRD in an early phase of chemotherapy can be a good predictor of the prognosis of childhood ALL regardless of the protocol of chemotherapy or race.

GCV resistance due to the mutation A594P in the cytomegalovirus protein UL97 is partially reconstituted by a second mutation at D605E.

A ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) was isolated from an AIDS patient. Molecular analysis of the HCMV UL97 gene revealed two point mutations, A594P and D605E, respectively. In order to evaluate quantitatively the impact of the individual mutations on GCV phosphorylation, recombinant vaccinia viruses (rVVs) were generated carrying either the two mutations (rVV-594/605) or only one mutation (rVV-594 or rVV-605, respectively). In cells infected with the rVV-594/605 double mutant, the GCV phosphorylation was decreased to 50% compared with the phosphorylation in cells infected with the rVV-UL97 wild-type. In cells infected with the rVV-594, however, the GCV phosphorylation was further decreased to 30%. Interestingly, the mutation D605E led to an even better GCV phosphorylation than that measured in cells infected with the rVV-UL97 wild type. These results were confirmed by plaque reduction assays, indicating that rVV-594 was more resistant to GCV than rVV-594/605. In contrast, rVV-605 was more sensitive to GCV than the rVV-UL97 wild type. Therefore, our results demonstrated for the first time that compensatory mutations can also occur in HCMV, as already shown for human immunodeficiency virus type 1.