Performance evaluation of VRAIN: a brain-dedicated PET with a hemispherical detector arrangement.

Objective.For PET imaging systems, a smaller detector ring enables less intrinsic spatial resolution loss due to the photon non-collinearity effect as well as better balance between production cost and sensitivity, and a hemispherical detector arrangement is more appropriate for brain imaging than a conventional cylindrical arrangement. Therefore, we have developed a brain-dedicated PET system with a hemispherical detector arrangement, which has been commercialized in Japan under the product name of VRAINTM. In this study, we evaluated imaging performance of VRAIN.Approach.The VRAIN used 54 detectors to form the main hemispherical unit and an additional half-ring behind the neck. Each detector was composed of a 12 × 12 array of lutetium fine silicate crystals (4.1 × 4.1 × 10 mm3) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm2active area) with the one-to-one coupling. We evaluated the physical performance of VRAIN according to the NEMA NU 2-2018 standards. Some measurements were modified so as to fit the hemispherical geometry. In addition, we performed18F-FDG imaging in a healthy volunteer.Main results.In the phantom study, the VRAIN showed high resolution for separating 2.2 mm rods, 229 ps TOF resolution and 19% scatter fraction. With the TOF gain for a 20 cm diameter object (an assumed head diameter), the peak noise-equivalent count rate was 144 kcps at 9.8 kBq ml-1and the sensitivity was 25 kcps MBq-1. Overall, the VRAIN provided excellent image quality in phantom and human studies. In the human FDG images, small brain nuclei and gray matter structures were clearly visualized with high contrast and low noise.Significance.We demonstrated the excellent imaging performance of VRAIN, which supported the advantages of the hemispherical detector arrangement.

Design study of a brain-dedicated time-of-flight PET system with a hemispherical detector arrangement.

Time-of-flight (TOF) is now a standard technology for positron emission tomography (PET), but its effective use for small diameter PET systems has not been studied well. In this paper, we simulated a brain-dedicated TOF-PET system with a hemispherical detector arrangement. We modeled a Hamamatsu TOF-PET module (C13500-4075LC-12) with 280 ps coincidence resolving time (CRT), in which a 12 × 12 array of multi pixel photon counters (MPPCs) is connected to a lutetium fine silicate (LFS) crystal array of 4.1 × 4.1 mm2 cross section each, based on one-to-one coupling. On the other hand, spatial resolution degradation due to the parallax error should be carefully addressed for the small diameter PET systems. The ideal PET detector would have both depth-of-interaction (DOI) and TOF capabilities, but typical DOI detectors that are based on light sharing tend to degrade TOF performance. Therefore, in this work, we investigated non-DOI detectors with an appropriate crystal length, which was a compromise between suppressed parallax error and decreased sensitivity. Using GEANT4, we compared two TOF detectors, a 20 mm long non-DOI and a 10 mm long non-DOI, with a non-TOF, 4-layer DOI detector with a total length of 20 mm (i.e. 5 × 4 mm). We simulated a contrast phantom and evaluated the relationship between the contrast recovery coefficient (CRC) and the noise level (the coefficient of variation, COV) for reconstructed images. The 10 mm long non-DOI, which reduces the parallax error at the cost of sensitivity loss, showed better imaging quality than the 20 mm long non-DOI. For example, the CRC value of a 10 mm hot sphere at COV = 20% was 72% for the 10 mm long non-DOI, which was 1.2 times higher than that of the 20 mm long non-DOI. The converged CRC values for the 10 mm long non-DOI were almost equivalent to those of the non-TOF 4-layer DOI, and the 10 mm long non-DOI converged faster than the non-TOF 4-layer DOI did. Based on the simulation results, we evaluated a one-pair prototype system of the TOF-PET detectors with 10 mm crystal length, which yielded the CRT of 250 ± 8 ps. In summary, we demonstrated support for feasibility of the brain-dedicated TOF-PET system with the hemispherical detector arrangement.

Registration-directed phase 1/2 trial of irinotecan for pediatric solid tumors.

BACKGROUND: Although irinotecan hydrochloride (IRI) is a promising chemotherapeutic agent for pediatric solid tumors, its indications had been off-label in the USA, EU and Japan. Therefore, we conducted a phase 1/2 trial of IRI monotherapy in a registration-directed setting. METHODS: Children aged 2-18 years with solid tumors who were either refractory to or relapsed after standard chemotherapy were enrolled. Phase 1 was a conventional dose escalation study to determine the dose-limiting toxicity (DLT) and the recommended dose. IRI was given i.v. on days 1, 2, 3 and 8, 9, 10 in up to eight, 21 day cycles. RESULTS: The starting dose (40 mg/m2 /day) was determined to be the recommended dose because the next higher dose level (45 mg/m2 /day) resulted in two cases of DLT. Seventeen children (11 in phase 1 and six in phase 2) with a refractory solid tumor received IRI. Of the 12 patients treated with 40 mg/m2 /day, seven (58.3%) achieved a stable disease condition for >8 weeks. CONCLUSIONS: The RD of IRI in this treatment schedule was 40 mg/m2 /day. IRI did not cause tumor shrinkage but might help to stabilize refractory pediatric solid tumors. Based on the accumulating evidence from international studies of the efficacy of IRI against refractory pediatric solid tumors, the Japanese regulatory authority approved its use for this indication in 2011.

Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: report of an autopsy case.

We report clinicopathological features of a 23-year-old woman with Down syndrome (DS) presenting with subacute myelopathy treated with chemotherapy, including intravenous and intrathecal administration of methotrexate (MTX), and with allogenic bone-marrow transplantation for B lymphoblastic leukemia. Autopsy revealed severe demyelinating vacuolar myelopathy in the posterior and lateral columns of the spinal cord, associated with macrophage infiltration, marked axonal loss and some swollen axons. Pathological changes of posterior and lateral columns were observed from the medulla oblongata to lumbar cord. Proximal anterior and posterior roots were preserved. Cerebral white matter was relatively well preserved. There were no vascular lesions or meningeal dissemination of leukemia. Longitudinal extension of cord lesions was extensive, unlike typical cases of subacute combined degeneration (SACD), but distribution of lesions and histological findings were similar to that of SACD. DS patients show heightened sensitivity to MTX because of their genetic background. Risk factors for toxic myelopathy of DS are discussed, including delayed clearance of MTX despite normal renal function, alterations in MTX polyglutamation and enhanced folic acid depletion due to gene dosage effects of chromosome 21. Alteration of folate metabolism and/or vitamin B12 levels through intravenous or intrathecal administration of MTX might exist, although vitamin B12 and other essential nutrients were managed using intravenous hyperalimentation. To the best of our knowledge, this is the first report of an autopsy case that shows myelopathy mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case suggests a pathophysiological mechanism of MTX-related myelopathy in DS patients with B lymphoblastic leukemia mimicking SACD.

[Retrospective analysis of 157 patients with pediatric Hodgkin lymphoma in Japan: investigation by four pediatric cancer study groups].

Hodgkin lymphoma is an easily curable malignancy in the pediatric age group and is less frequently observed in Japan. No study with a large sample size of Japanese patients has been conducted. From 1985 to 2000, 157 Japanese patients with Hodgkin lymphoma were retrospectively analyzed based on their clinical characteristics, treatment regimen, and treatment outcome by 4 pediatiric cancer study groups. There were 107 male and 50 female patients with a median age of 10 years 1 month (range: 1 year 8 months to 17 years 8 months). Clinical stage I lymphoma was observed in 37 patients, stage II in 62, stage III in 40, and stage IV in 18. Fifty patients presented with B symptoms (32%). Most patients (n=125, 82%) received more than 6 courses of combination chemotherapy mainly comprising cyclophosphamide, vincristine, procarbazine, prednisolone (COPP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The 5-year overall and event-free survival rates were 81.5% and 94.8%, respectively. High-risk disease and age (>10 years) were considered to be poor prognostic factors.

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.

Critical infantile hepatic hemangioma: results of a nationwide survey by the Japanese Infantile Hepatic Hemangioma Study Group.

BACKGROUND: The current survey aimed to describe the clinical features of critical infantile hepatic hemangioma (IHH) and the implications of recent treatments. MATERIALS AND METHODS: A nationwide survey of critical IHH patients treated between 2005 and 2010 was performed in all 117 registered pediatric surgical hospitals in Japan. As a result, 19 patients were identified and reviewed using a statistical analysis. RESULTS: Abdominal distention (47.4%), high-output cardiac failure (47.4%), coagulopathy (42.1%), and respiratory distress (31.6%) were the major symptoms. Three patients died (1 of coagulopathy, 1 of cardiac failure, and 1 of both). An accompanying portovenous shunt was also highlighted. Infantile hepatic hemangioma was totally insensitive to steroid treatment in 3 (23.1%) of the 13 patients, and 9 (47.4%) of the 19 patients required other treatments. Surgical resection and ß-blocker improved the hematologic data, whereas hepatic arterial ligation and embolization seemed to produce a limited effect. Among the dead patients, several hematologic parameters were significantly worse: the thrombocyte count (pretherapeutic: 73,000 vs 300,000/mm(3), dead vs survivor, respectively [P < .03]; posttherapeutic: 66,000 vs 388,700/mm(3) [P < .003]) and the prothrombin time (posttherapeutic, 35.0 vs 12.1 seconds [P < .0001], dead vs survivor, respectively). CONCLUSION: For critical IHH cases with steroid-insensitive hematologic disorders, alternative treatments including ß-blocker therapy, surgery, and liver transplantation should be considered.

Impact of influenza A(H1N1) in pediatric patients with cancer and hematologic disorders: establishment of information sharing system for swine influenza.

In Japan, we encountered a pandemic expansion of novel influenza A(H1N1) in September 2009, but the impact on patients with underlying disease remained unclear. The Tokyo Children Cancer Study Group (TCCSG) established a "novel influenza information-sharing system" to share real time information on how the novel influenza affects pediatric patients with cancer or other hematologic disorders. To facilitate reporting, we limited the items to only the basic data (underlying disease, age, sex), influenza-associated data (diagnostic method, therapy and outcome) and allowed space for free comments. We could share the information promptly, and found that this system worked well. One hundred and fifteen patients were reported between September 2009 and February 2010. Although eight patients needed to be hospitalized, none of the patients died, were admitted to intensive care units or demonstrated sequelae. The novel influenza A(H1N1) did not have a strong impact on pediatric patients with cancer or hematologic disorder at least during the 2009-2010 season.

Neuroblastomas with discordant genotype-phenotype relationships: report of four cases with MYCN amplification and favorable histology.

MYCN amplification prevents cellular differentiation and promotes mitotic and karyorrhectic activities in neuroblastomas. Hence, MYCN-amplified tumors typically show an appearance of neuroblastoma of either an undifferentiated or a poorly differentiated subtype with a high mitosis-karyorrhexis index. In addition, they are classified as part of the unfavorable histology group, according to the International Neuroblastoma Pathology Classification. Large cell type and/or presence of prominent nucleoli is also reported to be an additional hallmark of MYCN amplification. However, there are few neuroblastomas having MYCN amplification and favorable histology. Four cases of MYCN amplification and favorable histology were identified in our file of 63 cases of neuroblastoma. The patients (M∶F  =  3∶1) were diagnosed between 6 and 13 months of age, and all had adrenal primary tumors and were treated with high-dose therapy and autologous stem cell rescue. Three patients (stages 1, 3, and 4) are alive and well 7 years, 26 months, and 19 months after diagnosis, respectively. One patient with stage 4 disease died 8 months after diagnosis. Their tumors showed the same histologic feature of neuroblastoma: poorly differentiated subtype with a low mitosis-karyorrhexis index; they were not qualified as large cell type and had no prominent nucleoli. MYCN amplification of those tumors was confirmed by fluorescence in situ hybridization in all 4 cases, but MYCN protein expression was not demonstrated by immunohistochemistry (4 cases) and MYCN mRNA was not detected by reverse transcriptase polymerase chain reaction (1 case). Those cases showed a discrepant genotype-phenotype that was not simply a laboratory observation but could indicate the concept that that MYCN amplification did not automatically equate to a poor prognosis in this group of patients.

Vaginal yolk sac (endodermal sinus) tumors in infancy presenting persistent vaginal bleeding.

Vaginal yolk sac (endodermal sinus) tumors were diagnosed in two girls (ages 12 and 46 months). In both, the only manifestation was persistent vaginal bleeding. Pelvic ultrasonography, computed tomography, and magnetic resonance imaging revealed solitary vaginal masses (diameter, 5 and 2 cm, respectively). Serum alpha-fetoprotein was highly elevated in one patient and normal in the other. Biopsy was performed in the first patient, and a tumor excision, in the second. Combination chemotherapy with cisplatin, etoposide, and bleomycin or carboplatin was administered to the first patient, and shortly thereafter, the tumor size decreased by more than half; serum alpha-fetoprotein was normalized after four chemotherapy cycles. After chemotherapy, magnetic resonance imaging revealed a small residual lesion, however the second biopsy revealed no viable tumor cells. In the second patient, no visible tumor was observed after chemotherapy by vaginoscopy. Both patients are well at 19 and 14 months after diagnosis, respectively.

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

BACKGROUND: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in pediatric patients are relatively rare. PROCEDURE: We performed a retrospective analysis in patients with PTCL over an 18-year period (1991-2008). RESULTS: We could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were female and 10 male. Median age of onset was 11 years (range: 1-21 years). There were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial lesions involved cervical lymph nodes in five patients, and the skin in five patients. In five patients, hemophagocytic syndrome (HPS) was the initial clinical feature. There were 12 patients with advanced stage disease (stages III and IV). Chemotherapy and radiation was administered in 18 and 2 patients, respectively. Among the two patients who did not receive chemotherapy and radiation, one patient died while being treated for HPS but another improved spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive without disease at last follow-up. Five-year overall survival rate was 85.2%. CONCLUSIONS: Generally, the outcome results of conventional chemotherapy for high-risk PTCL are poor in adult patients. However, the excellent results in our study suggest that PTCL of childhood is quite different from that of adulthood. Although this study is first report about PTCL of Asian children, the number of patients was small in this study. Larger studies are needed to confirm these findings.

Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation.

BACKGROUND: Preconditioning total body irradiation (TBI) prior to bone marrow transplantation (BMT) has been believed to be a safe procedure that does not cause late morbidity; yet, a recent report raises the suspicion that TBI-induced chondroosseous abnormalities do occur. OBJECTIVE: To evaluate the radiological manifestations of TBI-induced skeletal alterations and their orthopaedic morbidity. MATERIALS AND METHODS: Subjects included 11 children with TBI-induced skeletal changes, including 9 in our hospital and 2 in other hospitals. The former were selected from 53 children who had undergone TBI with BMT. Radiographic examinations (n=11), MRI (n=3), CT (n=2), and medical records in the 11 children were retrospectively reviewed. RESULTS: The skeletal alterations included abnormal epiphyseal ossification and metaphyseal fraying (8/11), longitudinal metaphyseal striations (8/11), irregular metaphyseal sclerosis (6/11), osteochondromas (4/11), slipped capital femoral epiphysis (2/10), genu valgum (3/10), and platyspondyly (2/3). MRI demonstrated immature primary spongiosa in the metaphysis. Of the 11 children, 9 had clinical symptoms. CONCLUSION: TBI can induce polyostotic and/or generalized bone changes, mainly affecting the epiphyseal/metaphyseal regions and occasionally the spine. The epi-/metaphyseal abnormalities represent impaired chondrogenesis in the epiphysis and growth plate and abnormal remodelling in the metaphysis. Generalized spine changes may lead to misdiagnosis of a skeletal dysplasia.

Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma.

PURPOSE: The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma. MATERIALS AND METHODS: Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically. RESULTS: The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05). CONCLUSIONS: The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery.

Outcome of childhood B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia treated with the Tokyo Children's Cancer Study Group NHL B9604 protocol.

From June 1996 to January 2001, 91 patients with B-cell non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia up to 18 years of age were enrolled in Tokyo Children's Cancer Study Group (TCCSG) NHL B9604 protocol study. Five-day intensive chemotherapy courses including high-dose methotrexate and high-dose cyclophosphamide were used for localized disease (Groups A and B). High-dose cytarabine was added for advanced disease (Groups C and D). Fifteen patients experienced an adverse event. There were three induction failures, eight relapses (three local, four bone marrow (BM), one BM + local), two toxic deaths and two second malignant neoplasm. Event-free survival at 6 years in Group D and in all patients was 82.4% +/- 9.2% and 81.9% +/- 4.4%, respectively. The TCCSG NHL B9604 protocol achieved an excellent treatment outcome especially in patients with the most advanced disease (Group D: high BM blast cell burden and/or central nervous system involvement).

A review of 331 rhabdomyosarcoma cases in patients treated between 1991 and 2002 in Japan.

BACKGROUND: To prepare for a Japanese nationwide group study of patients with rhabdomyosarcoma (RMS), we examined the characteristics and outcomes of RMS patients treated recently in Japan. METHODS: We classified 331 RMS patients treated between 1991 and 2002 at 63 institutions according to the Intergroup Rhabdomyosarcoma Study V (IRS-V) risk-group classification. RESULTS: Ten-year survival rates were 86.3% for patients in low-risk subgroup A, 80.7% for low-risk subgroup B, 62.7% for intermediate-risk subgroup A, 61.7% for intermediate-risk subgroup B, and 38.1% for the high-risk group. The outcomes of the patients in the former three groups were 8%, 12%, and 21% worse than the outcomes of the respective patients in the IRS-III and early IRS-IV data. The frequency of the alveolar histological subtype was 21.8%. Chimera genes, which are useful markers for the alveolar subtype, had been examined in only 10% of the patients treated in the period of this investigation. The survival rates of our patients with embryonal and alveolar histological subtypes (65.9% and 63.4%, respectively) were not significantly different. Among the patients in the high-risk group, the 5-year survival of patients who received high-dose chemotherapy (HDC; 58.2%) was significantly better than that of patients who did not receive HDC (18.4%). CONCLUSION: Patients in the lower-risk groups with embryonal-type tumors had poorer outcomes in this retrospective study. The better outcome of patients in the high-risk group is apparently due to the outstanding results obtained with an HDC regimen in a single institution. These results suggest that there is a need for: (1) a standard therapy, (2) a rapid central pathology review including a chimera gene analysis for the lower-risk group, and (3) evaluation of the efficacy of the high-dose regimen for the high-risk group in Japan.

[Neuroblastoma trial to overcome a rare malignant disease].

Neuroblastoma is one of the main causes of children's deaths in Japan and many developed countries, although it is a rather rare pediatric cancer. Many clinical studies have been carried out and reported. The clinical study system of Japan is much different from the systems of the other countries. In Japan, the main hospitals, where clinical study including clinical trials have been conducted, are not only national centers but also many regional or prefectural centers. Progression-free survival has been achieved in over 80% of low-risk patients,and in about 40% of high-risk patients. These are the same as the outcomes of neuroblastoma patients in European countries and North America. Further clinical studies and translational research should be planned especially regarding high-risk neuroblastomas.

X-linked severe combined immunodeficiency (X-SCID) with high blood levels of immunoglobulins and Aspergillus pneumonia successfully treated with micafangin followed by unrelated cord blood stem cell transplantation.

In this report, we describe a patient with X-linked severe combined immunodeficiency (X-SCID) who had high serum IgG, IgA, and IgM levels. The boy did well until 6 months of age, when he developed interstitial pneumonia caused by Aspergillus species, with a white cell count of 12,840/microL and only 10% lymphocytes; IgG, 991 mg/dL; IgA, 65 mg/dL; IgM, 472 mg/dL. Cell markers showed only 6.3% CD3, 2.1% CD4, 0.7% CD8, but 92% CD19 and 0.1% CD16+CD56+ (NK cells). A mutation was detected within exon 2 (C196 A-->C), leading to the substitution of proline for glutamine, which has not been reported previously. The boy was successfully treated with the new antifungal drug, micafangin (MCFG), at 5 mg/kg/day for 89 days. After resolution of the pneumonia, the patient underwent successful hematopoietic stem cell transplantation with completely matched unrelated female cord blood. The CD34 stem cell dose was 3.4 x 10(4) cells/kg. In conclusion, MCFG can be a first line agent for Aspergillus pneumonia in immunocompromised hosts.

Late complications after surgery in patients with neuroblastoma.

PURPOSE: The purpose of this study was 2-fold: to study the complications of neuroblastoma treatment and to establish surgical guidelines. MATERIALS AND METHODS: The medical records of 92 patients with neuroblastoma (stage 1 or 2, n = 33; stage 3, n = 21; stage 4, n = 31; stage 4S, n = 7) who had undergone surgery in our department between 1985 and 2001 were reviewed, with an emphasis on treatments and late complications. RESULTS: The disease-free survival rate was 98.3% (58/59) in infantile patients, whereas it was 36.4% (12/33) in advanced patients older than 1 year. The rate was improved up to greater than 50% after the introduction of intensive local therapy with intraoperative radiation (IOR). The treatment-associated morbidity rate was 15.0% in nonadvanced infantile patients, was 42.1% in advanced infantile patients, and was 33.3% in advanced older patients. In the advanced cases, renovascular problems were most frequently seen especially after IOR. Furthermore, pulmonary problems, cardiac problems, and second cancer were highlighted as fatal problems; thyroid dysfunction, vertebral deformity, and growth retardation were also noted. CONCLUSIONS: Higher incidences of late morbidity and treatment-associated mortality appeared to be more strongly related to disease stage rather than to patient age. Appropriate surgery and IOR with lower doses should be recommended as a surgical strategy for high-risk patients.

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan.

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10.5 months after the initial diagnosis. Twenty-four patients achieved a second remission. After a median follow-up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse-free survival rates were 61 +/- 12% and 51 +/- 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.