Long-Term Outcomes of Cementless Bipolar Hemiarthroplasty in Young Patients With Osteonecrosis of the Femoral Head: The Impact of Implant Improvements and Preoperative Stage.

Introduction Advancements in bipolar hemiarthroplasty (BHA) implants in the mid-1990s contributed to favorable short-term outcomes for osteonecrosis of the femoral head (ONFH), particularly in cases without acetabular cartilage lesions. Nevertheless, long-term results remain unclear. In this study, we investigated (i) the impact of new-generation BHA implants and (ii) the effect of the preoperative stage on long-term outcomes in young patients with ONFH. Methods The records of consecutive patients with ONFH who underwent cementless BHA were retrospectively reviewed. Patients aged ≥60 years, with <10 years of follow-up, or who underwent acetabular reaming during surgery were excluded. Radiographical and clinical outcomes of patients who received first-generation BHAs and new-generation BHAs (developed after 1998) were compared by stratifying based on preoperative stage 2/3A and 3B/4, according to the Japanese Investigation Committee classification. Results Overall, 50 hips from 39 patients (mean age: 44.6 years; 64% male) with an average follow-up of 18.6 years were included. The frequency of advanced-stage patients was significantly higher in the first-generation BHA group than in the new-generation group. Regarding postoperative outcomes, the first-generation BHA group had higher acetabular erosion grades (p<0.001) and more femoral component loosening than those in the new-generation group (p<0.001). Revisions were performed in eight hips (seven in the first-generation and one in the new-generation BHA groups, p<0.001). In the new-generation BHA group, there were no significant differences in patient background between stage 2/3A and 3B/4 groups, and only one case in the stage 3B/4 group required revision. In the new-generation group, the grade of acetabular erosion was significantly higher for stage 3B/4 than stage 2/3A (p<0.001); other radiographical and clinical outcomes did not differ significantly between stages. Conclusion New-generation BHAs have significantly better implant survival rates for early-stage ONFH than those of first-generation BHAs. These findings indicate that BHA is an acceptable treatment option for early-stage ONFH in young patients.

Long-term outcomes of the mayo conservative hip system in patients aged 30 years or less with osteonecrosis of the femoral head: mean follow-up of more than 10 years.

INTRODUCTION: Historically, total hip arthroplasty (THA) in very young patients has been associated with lower survivorship. However, the long-term outcomes of THA using short stems for osteonecrosis of the femoral head (ONFH) in very young patients remain unclear. Therefore, this study aimed to investigate the long-term outcomes of the Mayo conservative hip system, a short metaphyseal stabilised stem, in patients with ONFH aged ≦30 years. MATERIALS AND METHODS: We retrospectively reviewed 104 joints in 76 patients with ONFH who underwent THA using the Mayo conservative hip system with a minimum follow-up of 8 years. The mean follow-up period was 12.5 (range, 8-19) years. Patients were categorised into two age groups (≦30 years, n = 21 and > 30 years, n = 83). Radiographic evaluation was used to assess stem sinking, stress shielding, and spot welds. The clinical evaluations were performed using the Japanese Orthopedic Association (JOA) hip score. Postoperative major complication and revision surgery rates were also assessed. RESULTS: The patient characteristics were similar between the two groups, except for the age. Revision surgeries were performed in five cases, with similar implant survival rates between the groups. Dislocations occurred in the older age group alone (four joints). One case of intra-operative periprosthetic femoral fracture was found in the younger age group. Stem sinking of > 3 mm occurred in one and seven joints in the younger and older age groups, respectively. Spot welds were observed in most joints (93.2%) in modified Gruen zones 2 and 6 without significant differences between the groups. Stress shielding showed no significant differences in the frequency of occurrence or location between the two groups. Furthermore,the JOA score showed no significant difference between the two groups. CONCLUSION: The use of short stems in patients aged ≤ 30 years with ONFH showed favourable long-term outcomes.

TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.

High-degree posterior rotational osteotomy for extensive collapsed femoral head osteonecrosis in teenagers: remodeling and results with a mean of 10-year follow-up.

INTRODUCTION: This study evaluated the effectiveness of high-degree posterior rotational osteotomy for teenagers with extensively collapsed femoral head osteonecrosis. MATERIALS AND METHODS: We reviewed 40 hips in 35 patients with severely collapsed femoral head osteonecrosis treated by this procedure with a mean follow-up period of 9.7 years (range 5-25 years). Thirteen hips had a history of steroid administration. Nine had slipped capital femoral epiphysis. Nine had femoral neck fracture. Two had traumatic dislocation and fracture. Seven had no apparent risk factors. The mean age of the patients (18 women and 17 men) was 14.8 years. All femoral heads were extensively collapsed below the acetabular roof, and 20 hips showed preoperative joint space narrowing (ARCO stage 4). Lateral radiographs of the femoral head revealed extensive lesions from the posterior to anterior portion. The mean degree of posterior rotation was 118° with intentional varus positioning [mean: 19° (range 10-30)]. The pre- and postoperative extent of the viable area of the femoral head was assessed using conventional anteroposterior radiographs and 45-degree flexion radiography. Further collapse, joint space narrowing, femoral head morphology, and congruency with the acetabulum based on the Stulberg classification were assessed using conventional anteroposterior radiographs. The clinical assessment was conducted using the Merle d'Aubigné hip scores at the last follow-up. RESULTS: The viable area of the femoral head on the loaded portion was seen during a short period after operations. The necrotic lesions were gradually improved postoperatively. The mean extent of viable bone below the acetabular roof was 48% at less than 6 months after surgery and 92% at the final follow-up. The mean extent on 45° flexion radiography was 54% at less than 6 months after surgery and 89% at the final follow-up. Further collapse was prevented in 38 hips (95%). In 19 of 20 hips with preoperative narrowing of the joint space, the joint space was first improved, but narrowing progressively observed in 9 of 40 hips at the final follow-up. Thirty-four hips had excellent or good clinical outcomes, whereas 6 had fair or poor outcomes. CONCLUSIONS: We concluded that this procedure is effective at delaying the progression of degeneration if adequate area of viable bone can be moved under the loaded portion of the acetabulum in teenagers with severe femoral head osteonecrosis.

Case Report: Juvenile Myelomonocytic Leukemia Underlying Ornithine Transcarbamylase Deficiency Safely Treated Using Hematopoietic Stem Cell Transplantation.

Background: Juvenile myelomonocytic leukemia (JMML), which is predominantly found in infants, is a clonal abnormality of pluripotent hematopoietic stem cells and presents with the symptoms of both myeloproliferative tumors and myelodysplastic syndromes. Estimates have shown that ~20 cases of JMML occur annually in Japan. Ornithine transcarbamylase deficiency (OTCD), the most common among all urea cycle disorders (UCDs), occurs in 1 of 80,000 people in Japan. Case Presentation: A 10-month-old infant who had fever, vomiting, and diarrhea for 2 days was referred to our hospital for the following abnormalities in blood tests: white blood cell count, 48,200/µL; hemoglobin, 9.0 g/dL; and platelet count, 135,000/µL. Bone marrow examination showed a nucleated cell count of 396,000/mm3 and blast cell count of 5.0%, as well as decreased mature granulocyte count and slightly myeloperoxidase stain-negative blasts but no monoclonal cell proliferation on May-Giemsa staining. Colony assay showed the proliferation of spontaneous colony and high sensitivity to granulocyte-macrophage colony-stimulating factor. Genetic analysis of peripheral blood mononuclear cells showed that the patient was positive for neuroblastoma RAS (NRAS) mutation. The patient was ultimately diagnosed with JMML. Approximately 170 days after his first hematopoietic stem cell transplantation (HSCT), the patient's JMML relapsed. Shortly after the recurrence, nausea, vomiting, hyperventilation, and decreased vitality were observed, followed by a decrease in the level of consciousness. The patient's ammonia level was 472 µmol/L. A test for seven different genetic mutations for the UCD showed the presence of c. 119G>A (amino acid change p. Arg40His). As such, late-onset OTCD was added to his diagnosis. Administration of sodium phenylacetate, l-arginine hydrochloride, and carnitine was continued following the diagnosis of OTCD, after which hyperammonemia was not observed. Regarding JMML relapse, HSCT was performed on day 405 after the first transplantation. Conclusion: Hyperammonemia should be considered a differential diagnosis when unexplained and non-specific symptoms occur during the treatment of hematologic malignancies. Patients should be tested for UCD as a cause of hyperammonemia, and treatment for hyperammonemia should be continued until the cause is identified. The patient shows normal developmental progress, has an intact neurological status, and has not experienced another hyperammonemia attack. His JMML has remained in remission for over 3 years.

Changes in bone marrow and peripheral blood lymphocyte subset findings with onset of hepatitis-associated aplastic anemia.

RATIONALE: Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow. PATIENT CONCERNS: A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/µL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%. DIAGNOSIS: HAAA. INTERVENTIONS: Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered. OUTCOMES: The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered. LESSONS: This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA.

Isolated Septic Arthritis of the Hip Due to Fusobacterium Nucleatum in An Immunocompetent Adult: A Case Report and Review of the Literature.

INTRODUCTION: Hip septic arthritis is more common in children than in adults. Staphylococcus aureus and Streptococcus spp. are commonly found in association with septic joints. In contrast, Fusobacterium nucleatum septic arthritis in adults is extremely rare. To the best of our knowledge, only five cases have been reported in the literature in English, and three of them were cases of periprosthetic joint infection. We report a rare case of hip septic arthritis due to F. nucleatum in an immunocompetent adult. CASE PRESENTATION: A 56-year-old Asian man with a history of bilateral Perthes' disease and mild alcoholic liver disease presented to our hospital complaining of worsening right hip pain and difficulty in walking for the previous 3 weeks. On presentation, his temperature was 38.7°C, and laboratory results showed a white blood cell count of 19 200 cells/µL and a C-reactive protein level of 43.56 mg/dL. Hip movements were limited due to pain. Contrast-enhanced computed tomography and magnetic resonance imaging showed fluid retention, suggesting infection. F. nucleatum was detected in the culture test from joint aspirate. Surgical drainage was performed 3 times in combination with antibiotherapy. Finally, we performed two-stage total hip arthroplasty, and the post-operative course was uneventful without implant loosening or infection relapse. CONCLUSION: The patient had a history of Perthes' disease and had hip osteoarthritis, which may have contributed to the development of hip septic arthritis. We treated this rare case of hip septic arthritis due to F. nucleatum with two-stage revision surgery and antibiotherapy. Clinicians should be aware that F. nucleatum could be the etiologic agent of hip septic arthritis in an immunocompetent patient.

Unexpected Complications after Corrective Spinal Fusion Surgery for Adult Spinal Deformity with Severe Hip Contracture.

INTRODUCTION: In cases with markedly decreased hip function, patients predominantly utilize spine movement while standing up to compensate for the hip malfunction. However, spinal fusion surgeries might lead to the disruption of this compensatory mechanism, resulting in difficulties in walking and standing up as well as proximal junctional failure (PJF) due to the excessive stress on the spine caused by the pendulum-like motion needed for standing up. Hence, in patients with severe hip pathology, surgeons should be cautious about the indication for spinal fusion, which inevitably affects spinal mobility. This is the first report presenting a case that supports the aforementioned theory. CASE REPORT: In this study, we report the case of a 76-year-old Japanese woman who underwent corrective spinal fusion surgery for spinal scoliosis secondary to hip contracture. The patient exhibited post-operative complications, such as unexpected difficulty in walking and standing up and PJF. The patient underwent a revision spinal surgery with an extension of spinal fusion for PJF and muscle release around the hip for hip contracture which resulted in improved walking and standing movements with no reports of pain. CONCLUSION: Spinal fusion surgeries performed on patients with severe hip pathology could cause early PJFs and unexpected decline in activities of daily living. Patients with such risks often do not complain of hip symptoms before spinal correction surgery. Surgeons should routinely evaluate hip joints and be cautious about the indication for spinal fusion which inevitably affects spinal mobility.

Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond-Blackfan anemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond-Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

Cementless Bipolar Hemiarthroplasty for Low-energy Intracapsular Proximal Femoral Fracture in Elderly East-Asian Patients: A Longitudinal 10-year Follow-up Study.

PURPOSE: Short-term outcomes following cemented and cementless hemiarthroplasties (HAs) are reported to be comparable, however, long-term outcomes of cementless HA-especially among Asian patients-is limited. We aimed to assess long-term outcomes in elderly East-Asian patients with intracapsular proximal femoral fractures treated with cementless HA. MATERIALS AND METHODS: We enrolled 135 patients treated with cementless HA who met our inclusion criteria. We documented bone/implant-related complications (e.g., incidences of revision hip surgery, femoral stem subsidence, dislocation, intraoperative and postoperative periprosthetic fractures, contralateral hip fractures). We included those patients who are still alive 10 years after the index surgery in the final functional analysis of the existence of pain, ambulatory status, and residential status. RESULTS: The mean age at injury was 78.3 years (range: 60-85 years). At the 10-year follow-up, 26 of the original patients (19.3%) had survived. During follow-up, revision hip surgery was conducted in two patients (1.5%). We recorded the incidence of intraoperative fractures, postoperative periprosthetic fractures, and contralateral fractures in two (1.5%), eight (5.9%), and six patients (4.4%), respectively. Among the 10-year survivors, six patients (23.1% of the survivors) complained of groin pain, but generally reported the pain to be tolerable. CONCLUSION: Among elderly East-Asian patients, the incidence of revision surgery after cementless HA may be lower than that in their European counterparts, whereas the incidence of periprosthetic fractures can still be considerably higher. For patients undergoing cementless HA, prevention of such secondary fractures is of critical importance.

A case of subacute combined degeneration of the spinal cord due to folic acid and copper deficiency.

Subacute combined degeneration of the spinal cord (SACD) is a rare neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. Herein we present an autopsy case of SACD caused by folic acid and copper deficiency. A 16-year-old male presented with gradually worsening unsteady gait, and bladder and rectal dysfunction. He had a medical history of T-cell acute lymphoblastic leukemia (T-ALL), diagnosed 1.5 years previously. The patient had undergone chemotherapy, including methotrexate, as well as allogeneic bone mallow transplantation. Laboratory tests revealed normal vitamin B12 and methylmalonic acid concentration, but reduced serum copper, ceruloplasmin and folic acid concentrations. Magnetic resonance imaging revealed symmetrical T2 signal hyperintensities in the posterior and lateral spinal cord. The patient was treated with oral copper, oral folate, and intravenous vitamin B12. A month after this treatment, the patient's symptoms were unchanged, and 2 months later he died of acute adrenal insufficiency. The pathological findings of the spinal cord were compatible with SACD. Because SACD is usually reversible with early treatment, it should be suspected in high-risk patients undergoing chemotherapy or those who are malnourished with characteristic symptoms of SACD, even in young patients.

Chronic Kirschsteiniothelia infection superimposed on a pre-existing non-infectious bursitis of the ankle: the first case report of human infection.

BACKGROUND: Kirschsteiniothelia is a saprophytic fungus that is abundantly present in the environment. To date, there have been no reports of human infection caused by this fungus. We report a case of Kirschsteiniothelia infection superimposed on a pre-existing non-infectious bursitis of the ankle. CASE PRESENTATION: An 81-year-old immunocompetent female local farmer noticed the presence of a nodule on her right ankle 5 years before her first visit to our hospital. A cystic mass of approximately 45 mm × 30 mm was present at the tip of the right lateral malleolus. Culture of the aspirated fluid revealed visibly black colonies and characteristic blackish hyphae; nucleotide sequence of the internal transcribed spacer region was determined and compared in a GenBank database. The results indicated Kirschsteiniothelia infection. CONCLUSIONS: We described the first case of Kirschsteiniothelia infection manifested as ankle bursitis. The disease seemed to be localized and systemic antibiotics had not been used in this case. However, continued observation is needed because of the possibility of disease progression with the pathogen.

Neuroblastoma.

Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation. However, the frequency of gene mutations is relatively small and other aberrations, such as epigenetic abnormalities, have also been proposed. The risk-stratified therapy was introduced by the Japan Neuroblastoma Study Group (JNBSG), which is now moving to the Neuroblastoma Committee of Japan Children's Cancer Group (JCCG). Several clinical studies have facilitated the reduction of therapy for children with low-risk neuroblastoma disease and the significant improvement of cure rates for patients with intermediate-risk as well as high-risk disease. Therapy for patients with high-risk disease includes intensive induction chemotherapy and myeloablative chemotherapy, followed by the treatment of minimal residual disease using differentiation therapy and immunotherapy. The JCCG aims for better cures and long-term quality of life for children with cancer by facilitating new approaches targeting novel driver proteins, genetic pathways and the tumor microenvironment.

Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma with Cardiac Metastasis and Arterial Tumor Embolisms during First-Course Chemotherapy.

We described an 11-year-old boy suffering from pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with heart metastasis at diagnosis and arterial tumor embolisms during chemotherapy. Both the heart metastasis and pericardial effusion showed improvement with prednisolone, but numbness and pallor sequentially developed in his lower extremities during the first course of chemotherapy. Contrast-enhanced imaging revealed occlusion of the right anterior tibial artery and left popliteal artery. These symptoms were spontaneously remitted due to the compensation of other arteries. Arterial tumor embolism is a rare but possible complication when a lymphoma shows intracardiac infiltration.

Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of T cells and macrophages with overproduction of cytokines. Familial HLH type 2 (FHL2) is the most common form of primary HLH and is caused by mutations in PRF1. We have recently described a significant increase in the subpopulation of CD8(+) T cells with clonal expansion and CD5 down-regulation in Epstein-Barr virus associated-HLH, which represented a valuable tool for its diagnosis. However, this unusual phenotype of CD8(+) T cells has not been investigated fully in patients with FHL2. We performed immunophenotypic analysis of peripheral blood and measured serum pro-inflammatory cytokines in five patients with FHL2. All patients showed significantly increased subpopulations of activated CD8(+) T cells with down-regulation of CD5, which were negligible among normal controls. Analysis of T-cell receptor Vß repertoire suggested the reactive and oligoclonal expansion of these cells. The proportion of the subset declined after successful treatment concomitant with reduction in the serum levels of cytokines in all patients except one who continued to have a high proportion of the subset and died. These findings suggest that down-regulation of CD5 on activated CD8(+) T cells may serve as a useful marker of dysregulated T cell activation and proliferation in FHL2.

Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.

Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.

The prognostic significance of blastemal predominant histology in initially resected Wilms' tumors: a report from the Study Group for Pediatric Solid Tumors in the Kyushu Area, Japan.

BACKGROUND AND PURPOSE: The strategy used to treat pediatric renal tumors in Japan is based on the Japanese Wilms' Tumor Study (JWiTS) protocol, which was based on the National Wilms' Tumor Study (NWTS)-5 regimen. The regimen is characterized by an initial radical operation, followed by adjuvant chemotherapy and radiotherapy. Concerning the histological classification, a new classification based on the International Society of Pediatric Oncology (SIOP) classification was used beginning in 2008. The main points of revision are that the "blastemal predominant type" was classified as an independent category in the Wilms' tumor subtypes. The purpose of this study was to analyze the biological characteristics from the standpoint of the newly established histological classification. MATERIALS AND METHODS: From 1971 to 2005, 174 cases of Wilms' tumors treated with an initial operation followed by adjuvant therapy were re-evaluated by the new histological classification. Histologically, all these materials showed no secondary changes associated with adjuvant therapy. RESULTS: According to the new classification, Wilms' tumors were classified into four subtypes, including the mixed type (n=112), epithelial type (n=17), mesenchymal type (n=15), and blastemal predominant type (n=26). The 5 year overall survival rates were as follows; mixed type (90.1%), epithelial type (100%), mesenchymal type (93.3%), and blastemal predominant type (65.4%). CONCLUSION: The patients with blastemal predominant tumors demonstrated a significantly worse prognosis compared with those of other subtypes. The treatment strategy of blastemal predominant category should be distinguished from the other favorable subtypes.

Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)± low-dose total body irradiation (TBI 2-4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL (≥120 mg/m(2) )+TBI, or high-dose MEL (180 mg/m(2) ) than for others (83% vs. 25%, p = 0.036). The FLU+MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation.

Partial tandem duplication of MLL gene in acute myeloid leukemia with translocation (11;17)(q23;q12-21).

Translocation 11q23 and MLL gene rearrangements are commonly observed in acute myeloid leukemia (AML) in association with the myelomonocytic or monocytic feature. We describe a case involving a 15-year-old patient with AML characterized by leukemic cells exhibiting translocation (11;17)(q23;q12-21) and MLL gene rearrangement. No fusion partner gene of the MLL gene was identified, including RARalpha(17q12) or AF17 (17q21); however, a partial tandem duplication of the MLL exon 11/exon 10 was detected in leukemic cells via a 3'RACE method for detection of unknown partner genes. The patient has been in remission for more than 2 years without hematopoietic stem cell transplantation.