Expression of tumor necrosis factor-receptor (TNF-R) was studied using flow cytometry. Both TNF-Rp55 and TNF-Rp75 were expressed on peripheral T cells, B cells and granulocytes. Monocytes expressed TNF-Rp75 alone. Both types of TNF-R were significantly up-regulated on IL-2-activated T cells. TNF-Rp55 and TNF-Rp75 were detected on leukemic cells from 42 of 51 cases and from 32 of 51 cases, respectively. We also demonstrated that TNF-α induced significant inhibition of DNA synthesis in 9 of 12 ALL cases. In contrast, response of ANLL was more variable. Inhibition of DNA synthesis was induced in 9 of 17 ANLL cases, whereas TNF-α enhanced DNA synthesis in 2 ANLL cases. It was suggested that TNF-α could trigger inhibitory signals mainly through TNF-Rp55 because : 1) TNF-α-induced inhibitory effect on DNA synthesis could be observed in leukemic cells, which expressed TNF-Rp55 alone, and 2) blocking antibodies against TNF-Rp75 could not restore the inhibition of DNA synthesis triggered by TNF-α at all.

View full abstract

Cytogenetic studies of alveolar rhabdomyosarcoma (RMS) have demonstrated the presence of unique chromosomal translocations, t (2 ; 13) (q35 ; q14) or t (1 ; 13) (p36 ; q14). More recently, the genes involved in these translocations have been identified. PAX3-FKHR and PAX7-FKHR chimeric transcripts are generated by t (2 ; 13) (q35 ; q14) and t (1 ; 13) (p36 ; q14), respectively. We examined PAX3-FKHR and PAX7-FKHR chimeric transcripts in RMS by reverse transcriptase-polymerase chain reaction (RT-PCR). PAX3-FKHR was detected in two of seven human RMS cell lines (KP-RMS-DH and SCMC-RM2) and two alveolar RMS tumors. In contrast, PAX7-FKHR was not found in all RMS cell lines and tumors investigated. RT-PCR is highly sensitive to detect PAX3-FKHR because its chimeric transcript was detectable in the cell mixture of HL60 and KP-RMS-DH (HL60/KP-RMS-DH=1/10^-7). Thus, RT-PCR assays for chimeric transcripts are a useful method for the rapid diagnosis and identification of residual tumor cells in bone marrow or peripheral blood stem cells.

View full abstract

Acute graft-versus-host-disease (GVHD) remains a major problem, limiting the success of bone marrow transplantation (BMT), particularly so in unrelated BMT. We are currently employing FK506 for prophylaxis of acute GVHD in unrelated BMT. The efficacy and toxicity of FK506 are presented. Twelve patients have undergone unrelated BMT. Among them, ten patients received FK506 as prophylaxis for GVHD. For the first 5 patients, FK506 was begun on the day before BMT as a continuous infusion at a dose of 0.1 mg/ kg/day. However three of the 5 patients had to stop FK506 due to the toxicity (renal dysfunction or convulsions). Thereafter, FK506 was started at a initial dose of 0.05 mg/kg/day, and the dose was adjusted to keep the blood level between 20 and 40 ng/ml for the remaining 5 patients. Three of the 5 patients who received CsA (cyclosporine) or discontinued FK506 developed severe acute GVHD (grade III-IV), but two of the 7 patients who completed FK506 prophylaxis developed severe acute GVHD. All patients treated with FK506 revealed nephrotoxicity, and mostly depended on higher blood level of FK506 at the beginning. Other major side effects were hypertension (6 of 10), hyperglycemia (2 of 10) and convulsion (1 of 10). Recovery of neutrophils was quicker when compared with conventional prophylaxis (CsA+ short course methotrexate). Prophylactic use of FK506 seemed to be effective. Although we need a comparative study before any conclusions can be reached, our preliminary results suggest some advantage of FK506 use in the prevention of acute GVHD. It is important, however, to control the side effects of FK506 such as nephrotoxicity, hypertension and hyperglycemia. Therefore, careful monitoring of the blood level of FK506 is critical.

View full abstract

The chronological changes of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-l (PAI-l) in plasma which play an important role at the early stage of the fibrinolytic system were evaluated in childhood. The plasma levels of tPA showed a wide range in cord blood, were decreased between 3 and 5 days of life and then increased to the adult level at 7-13 days of life. On the other hand, the plasma PAI activity and PAI-l antigen levels were high in the neonatal period. The plasma levels of PAI-l antigen were about twice as high as those of PAI activity in the neonatal period. Hyperfibrinolytic activity was found in a part of the cord plasma and plasma in the early neonates (until 3 days of life). These infants had high levels of plasma tPA and plasmin·α₂-plasmin inhibitor (α₂-PI) complex (PIC). These findings indicate that tPA and PAI-l regulate the dynamic changes of the fibrinolytic system in the early neonatal period.

View full abstract

A 14-year-old girl developed acute abdomen with free air on abdominal X-ray, and was found to have MALT (mucosa-associated lymphoid tissue) lymphoma in the perforated area in the stomach at laparotomy. One-third of the stomach including the pathological lesion was excised at the second operation and a combination chemotherapy for childhood B-lymphoma was administered for 6 months. The patient has been in remission longer than 14 months after the diagnosis. Reports on MALT lymphoma in children are rare, but in adulthood, the prognosis of this lymphoma is reported to be good, which is associated with Helicobacter pylori infection. In the patient described here, no involvement of H. pylori was verified.

View full abstract

We describe a patient with acute promyelocytic leukemia (APL, M3) who obtained a second complete remission (CR) using all-trans retinoic acid (ATRA). The patient was a 16-year-old boy. He obtained his first remission using BH-AC AMP and the 13th-acute nonlymphocytic leukemia protocol of Tokyo Children's Cancer Study Group. Fourteen months later, the first bone marrow relapse occurred. He was treated with BH-AC AMP again, but could not obtain a second CR. We administered ATRA (45 mg/m²) and the second CR was achieved. After 3 months, a second bone marrow relapse occurred, and he was treated with ATRA again.However, a third CR could not be obtained, and he died. Administration of ATRA for APL is worthy of consideration. We must establish the best postremission induction therapy using ATRA. This patient also showed an abnormal increase in blasts and worsening of DIC with G-CSF administration. DNA synthesis stimulation with G-CSF in vitro was positive.

View full abstract

An 11-year-old girl was admitted to our hospital because of high fever and bilateral cervical lymphadenopathy on December 25, 1993. The laboratory data revealed marked leukopenia with mild anemia and thrombocytopenia, and elevated LDH and ferritin levels. The bone marrow aspiration showed hypocellular marrow with an increased number of hemophagocytic histiocytes. She then developed generalized erythematous rash with persistent fever and enlarged cervical lymph nodes. On day 19 of the disease, she was diagnosed as having subacute necrotizing lymphadenitis (SNL) by the lymph node biopsy. She became free from all symptoms in a few days following oral prednisolone therapy. She had two past episodes of SNL at the ages of 3 and4. Recently, there have been increasing reports of SNL cases accompanied with HPS. The pathogenetic relationship between SNL and histiocytosis syndrome is discussed.

View full abstract

The success of unrelated donor bone marrow transplantation (BMT) for severe acquired aplastic anemia depends on the prevention of rejection and control of graft versus host disease (GVHD). We report a 13-year-old girl with severe acquired aplastic anemia who received a BMT from an unrelated donor. The pretransplant conditioning regimen consisted of cyclophosphamide (50 mg/kg×4 days), TBI (5 Gy), TLI (5 Gy), ATG (2.5 mg/kg×4 days). GVHD prophylaxis consisted of short term MTX plus cyclosporine. Acute GVHD (Stage I, skin rash and oral vesicles) appeared but improved with oral prednisolone. Mild thrombocytopenia of unknown origin was observed from about day 50 to day 90. Varicella infection was observed at day 90. The patient has suffered from chronic GVHD from day 110 post-transplant. To control this, we tried to increase the dose of prednisolone and cyclosporine, but the patient's compliance was poor. Only herb medicine was accepted by her for improvement of the chronic GVHD. She is currently followed in the outpatient department without therapy at 19 months after BMT. Although evaluation of unrelated BMT for children with severe aplastic anemia is not established, it can be an effective therapy by a strong conditioning regimen such as cyclophosphamide, TBI, TLI, and ATG.

View full abstract

We report a case of Listeria meningitis which developed after autologous bone marrow transplantation (A-BMT) in a 5-year-old boy diagnosed with stage IV_A neuroblastoma of the left abrenal gland. Seventy days after the A-BMT, the patient was febrile with a temperature of 39°C accompanied by headache and stiffness of the neck. The spinal fluid contained cell counts of 799/μl (M. : P.=495 : 104), protein levels of 138 mg/dl, glucose levels of 21 mg/dl and chloride levels of 121 mEq/l. Listeria monocytogenes was found in the spinal fluid culture. At this time an antibiotics treatment regimen of ABPC 400 mg/kg was started. After the patient received this treatment for 11 days, CRP became negative and the spinal fluid data improved. We continued this treatment for another 3 weeks, and no further neurological symptom appeared. Since L. monocytogenes was also found in the stool culture, this infection might have arisen from the digestive system due to ingestion of cheese. Listeria meningitis is a possible complication that needs to be monitored in children who are immunocompromised after receiving BMT.

View full abstract

We report our experience of induction of immune tolerance by factor VIII in low or intermediate dose carried out on 2 hemophiliacs A with inhibitor. Case 1, an 11-month-old boy, high responder (inhibitor level 48 Bethesda units), had been treated with factor VIII at 500 units (60 units/kg) ×3times/week. In the 10th week of treatment, his inhibitor level was increased to 78 Bethesda units but it was decreased to 11 Bethesda units in the 68th week. Case 2, a 20-year-old man, low responder (inhibitor level 0.9 Bethesda units), suffered from left iliopsoas hematoma. He had been treated with factor VIII at 6, 000 units (74 units/kg) /day×10 days and 3, 000 units/day×14 days. His inhibitor level was increased to 1.8 Bethesda units after treatment, but it had decreased to less than 0.5 Bethesda units 2 years later. We recommend this treatment for hemophiliacs with inhibitors for both cost and safety reasons.

View full abstract