Background

Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT.

Methods

Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m2 on days 1, 3, 6, and 11.

Results

Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group (<8 years of age) required an increased mean dose compared to the older group (≥8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%).

Conclusion

Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.

We report a case of primary penile undifferentiated sarcoma. A 16-year-old adolescent man visited Pusan National University Hospital complaining of a painless mass on his penis that was increasing in size. Magnetic resonance images revealed a 5×5-cm mass and pathological examinations revealed small round cell sarcomas with neuroendocrine differentiation. The tumor, which had metastatic pulmonary nodules, was treated by tumorectomy and systemic chemotherapy. Thirty-four months after the initial diagnosis, the patient was still alive without evidence of local recurrence or metastatic disease. This is our second case of an undifferentiated penile sarcoma.

4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a major costimulatory receptor that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. The interaction of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide-induced involution. Four-color flow cytometry showed that 4-1BB and 4-1BBL were present in the normal thymus and were preferentially expressed in the regenerating thymus, mainly in CD4+CD8+ double-positive (DP) thymocytes. Furthermore, the CD4loCD8lo, CD4+CD8lo and CD4loCD8+ thymocyte subsets, representing stages of thymocyte differentiation intermediate between DP and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during thymus regeneration but to a lesser degree. Interestingly, the 4-1BB and 4-1BBL positive cells among the CD4+CD8+ DP thymocytes present during thymus regeneration were TCRhi and CD69+ unlike the corresponding controls. Moreover, the 4-1BB and 4-1BBL positive cells among the intermediate subsets present during thymus regeneration also exhibited TCRhi/int and CD69+/int phenotypes, indicating that 4-1BB and 4-1BBL are predominantly expressed by the positively selected population of the CD4+CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.

Lymphangioma is an abnormal collection of lymphatics that are developmentally isolated from the normal lymphatic system. Lymphangioma rarely presents as a solitary pulmonary lesion. We report a rare case of intrapulmonary cystic lymphangioma involving the upper lobe of the right lung, which presented with dyspnea in a 2-month-old infant. High-resolution computed tomography (HRCT) of the chest demonstrated a well-circumscribed, multiseptate, cystic lesion in the upper lobe of the right lung, mimicking the feature of type I congenital cystic adenomatoid malformation. The tumor was removed by bilobectomy of the upper and middle lobes of the right lung, and its pathologic examination confirmed the diagnosis of an intrapulmonary cystic lymphangioma.

Yarrowia lipolytica is a weakly pathogenic yeast that is rarely isolated from the blood. We observed transient recurrent catheter-related fungemia attributable to this organism in a leukemic patient. The fungemia and accompanying fever subsided spontaneously. The data suggest that it might be possible to withhold specific treatment for Y. lipolytica fungemia even in an immunocompromised patient.

Background

Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years.

Methods

The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study.

Results

The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%).

Conclusion

The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.

Purpose

Natural history and consequences of the novel 2009 influenza A H1N1 (2009 H1N1) infection in immunocompromised pediatric patients are not yet fully understood. In this study, we investigated the clinical features and outcomes of the 2009 H1N1 infection in pediatric patients with hematological and oncological diseases.

Methods

We retrospectively reviewed the medical records of 528 patients who had hematological and oncological diseases and who were treated at 7 referral centers located in the Yeungnam region. Among the 528 patients, 27 with definite diagnosis of 2009 H1N1 infection were the subjects of this study. All patients were divided into the following 3 groups: patients who were receiving chemotherapy (group 1), patients who were immunosuppressed due to a non-malignant hematological disease (group 2), and patients who were off chemotherapy and had undergone their last chemotherapy course within 2 years from the influenza A pandemic (group 3).

Results

All 28 episodes of 2009 H1N1 infection were treated with the antiviral agent oseltamivir (Tamiflu®), and 20 episodes were treated after hospitalization. Group 1 patients had higher frequencies of lower respiratory tract infection and longer durations of fever and hospitalization as compared to those in group 2. Ultimately, all episodes resolved completely with no complications.

Conclusion

These results suggest that early antiviral therapy did not influence the morbidity or mortality of pediatric patients with hematological and oncological diseases in the Yeungnam region of Korea after the 2009 H1N1 infection. However, no definite conclusions can be drawn because of the small sample size.