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Chronic Epstein-Barr virus–associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor.

Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.

Newly diagnosed children with ALL (n = 32) were treated on a protocol incorporating minimal residual disease (MRD)-based treatment decisions. MRD was monitored at 4 time points by semi-quantitative PCR detection of antigen receptor gene rearrangement, flow cytometry, quantitative RT-PCR detection of chimeric gene transcripts and overexpressed WT1 mRNA. Four patients positive for MRD at week 5 were treated with an intensified regimen. Median follow-up was 5.0 years (range 3.8–6.6 years) with a 4-year event-free survival rate of 93.8 ± 4.3%. This MRD-based treatment strategy seems to be highly successful and may improve the outcomes of children with ALL. A large study is warranted.

Background/Purpose Neuroblastoma (NB) detected by mass screening (MS) usually shows favorable prognosis and sometimes regresses spontaneously. Therefore, the authors started an observation program for these patients to avoid overtreatment. In this study, the authors analyzed the profile of NB resected after observation to elucidate the nature of NB detected by MS. Methods Between 1994 and 2004, 22 NB patients matched the following criteria and entered the observation program after obtaining informed consent: stage I or II, less than 5 cm in diameter, and without involvement of large vessels or organs. If increase in size, elevation of tumor markers, or evidence of metastasis was observed, the tumor was immediately resected. Results Thirteen (59%) of 22 cases showed spontaneous regression. In the remaining 9 cases, tumors were resected because of parents' request, increase in size, and/or elevation of tumor markers. Four tumors had at least one unfavorable biologic feature, and 3 of them had more than 2. According to Shimada's system, 2 had unfavorable histology. One was diploid tumor, 3 had 1p deletion, and Trk-A expression was low in 4 tumors. All patients survived without evidence of recurrence. Conclusions The observation program has shown that at least one third of the NB detected by MS regressed spontaneously. On the other hand, MS may detect some cases with unfavorable tumor in early stage, which benefit from screening.

In 1985, a nationwide single protocol (cyclophosphamide, vincristine, tetrahydropyranyl Adriamycin, and cisplatin) for the treatment of advanced neuroblastoma was begun in Japan and was found to significantly increase the 3-year survival rate—to 70% for stage III, and to 45% for stage IV. In this study, the authors investigated the efficacy of this protocol for advanced neuroblastoma with or without N- myc amplification. In 159 of the 233 patients with advanced neuroblastoma treated with this protocol (between January 1985 and March 1993), genomyc amplification of N- myc was determined. These 159 patients were divided into two groups according to the number of N- myc copies, ie, those with fewer than 10 copies (105 patients) and those with 10 or more copies (54 patients). The survival curves for the two groups were significantly different. The 5-year survival rate for patients with 10 or more copies was 43.9%; this is surprisingly high in comparison to results of previous studies in which no survivors were expected in cases of advanced neuroblastoma with highly amplified N- myc . Persistent bone marrow suppression was common, but there were no deaths attributable to drug side effects. Five patients with fewer than copies of N- myc amplification died more than 3 years after initial treatment. Three of the five had tumors with an unfavorable Shimada classification, and two had diploid nuclear DNA content. The authors conclude that the protocol resulted in dramatic improvement in the patients with advanced neuroblastoma, even with high N- myc amplification. However, a more aggressive approach is needed to increase the survival rate for the patients without N- myc amplification who have other poor prognostic factors.

Of 125 children with acute lymphoblastic leukemia (ALL), who had been in continuous remission for three years on chemotherapy, 108 patients received biological response modifiers (BRM) such as Bestatin, N-CWS, OK-432 and/or PSK in order to prevent relapse after treatment suspension. From 20 patients who were treated with PSK, 6 relapsed within 13 months. This relapse rate was quite similar to the rate observed with those children who were off therapy (4 relapses in 17 patients within 13 months). In contrast to these 37 patients, only 3 out of 31 patients who received Bestatin (p less than 0.05) and 8 out of 57 patients who received N-CWS or OK-432 relapsed. Based on these findings, BRMs used in the present study seems to be effective to prevent relapse of leukemia among childhood ALL who have electively stopped chemotherapy.

Purpose To report a case of hemophagocytic syndrome, which is characterized by hemophagocytosis of histiocytes, optic nerve involvement, and unusual retinal white patches. Method Case report. A 10-year-old boy had repeated relapses of hemophagocytic syndrome. He complained of swelling of the right upper eyelid and bilateral visual disturbance. RESULTS: Ophthalmoscopic examination disclosed bilateral optic disk edema, retinal hemorrhages, and multiple perivenous white patches in the retina. Magnetic resonance imaging demonstrated enlargement of both optic nerves. After chemotherapy and bone marrow transplantation, his visual acuity improved in both eyes, and retinal patches changed to inactive-appearing scars. Conclusion Hemophagocytic syndrome may manifest with ophthalmic findings such as optic nerve involvement, retinal hemorrhages, and multiple white perivenous retinal patches.

Background The clinical aspects and problems in adolescents and young adults (AYA) with cancer in the western countries have been elucidated. These patients have benefited less from therapeutic advances partly because of less opportunity to participate in clinical trials. And AYA cancer patients have many social problems such as school, employment and expense. This situation is called as AYA gap and some programs have been started in the USA to improve the outcome of AYA cancer patients as an orphaned population. AYA cancer patients have not been studied in Japan and we do not have any available nation-wide data of this population. Here, we report AYA cancer patients who were treated at Osaka Medical Center and Research Institute for Maternal and Child Health (OMCRI). Method Sixteen AYA cancer patients aging from 15 to 29 years were treated at OMCRI during 2005–2009. These cases were analyzed in terms of diagnosis, age, treatment, and outcomes. Result Ten cases (62.5%) were diagnosed with hematological malignancies, four (25%) were soft tissue sarcomas. Fifteen of 16 patients were between 15 and 20 years old. A multimodal therapy consisting of chemotherapy, radiotherapy, and/or hematopoietic stem cell transplantation was applied for most of them. The overall survival rate with a median follow-up of 6.3 years is 62.5% (10/16). Discussion Although the number of patients in this series is small, it appears that incidence and characteristics of AYA cancer patients in Osaka is similar to that of USA. These results suggest the importance of a multimodal combination therapy for the treatment of AYA cancer patients. Approximately 250 young people aged 15–29 are annually diagnosed with cancer in Osaka prefecture, and cancer is the leading cause of death in this age population. Therefore, it is important to analyze the incidence, situation of medical-examination, treatment and outcome of AYA cancer patients in the large scale. We recently organized an AYA cancer information-sharing system (Osaka AYA Cancer Network) including specialists such as pediatric or adult hemato-oncologist, epidemiologist, and so on to understand and investigate AYA cancer patients in Osaka area in an attempt to improve the outcomes and quality of life for these patients.

We report a case of botryoid Wilms’ tumor that occupied the renal pelvis and extended into the bladder. A 3-year-old boy was referred to us with a chief complaint of gross hematuria and micturition pain. Computed tomography showed tumor occupying the right renal pelvis and ureter and extending into the bladder. Right radical nephroureterectomy was performed. The resected specimen showed a botryoid sarcoma-like appearance, occupied the right renal pelvis and ureter, and protruded into the bladder. Histologic findings showed typical triphasic Wilms’ tumor. Botryoid Wilms’ tumor has been reported in only 16 cases in the literature and in only 3 cases extended into the bladder.