Increased interest in the therapeutic use of human stem cells has emerged following significant progress in ongoing stem cell biology research. Although it is at present not possible to predict which types of stem cells will be best suitable for various therapeutic situations, the isolation of human embryonic stem cells and the discovery of adult stem cells taken together give substance to hopes that novel principles of treatment may be developed for a variety of disorders. To achieve this, however, we must solve several technical and ethical problems.

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Because of great improvements in the treatment of childhood cancer in the past 30 years, the survival rate of patients is now 70%. The ultimate goal of childhood cancer treatment is to enable patients to enjoy a good quality of life as they reach adulthood. During the treatment process-diagnosis, treatment, off-treatment, and long-term follow-up-it is important that the physician is aware of the various problems that arise at each stage and makes every effort to support and involve the patient and the patient's family in dealing with them. It is very difficult in Japan to achieve this goal because of a chronic lack of suitably trained personnel. Most hospitals depend solely on overworked doctors and nurses and receive very little support from professional psychosocial personnel. There is a need to involve a variety of trained professionals in the treatment process and for physicians to undergo training in medical communication skills. Furthermore, it is important that patients are truthfully and fully informed of their condition as early as possible with regard to their age and development. Truth-telling ensures the best possible level of communication between the physician and the patient and promotes the patient's involvement and cooperation in treatment, ultimately enhancing his or her emotional and social development.

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The causes of production of a granulocyte-specific allo-antibody cannot be identified in most cases of alloimmune neutropenia. We report here a case of a neonate presenting with anemia (Hb 8.2 g/dl) and neutropenia (neutrophil counts 240/, ul). Her anemia was normocytic and normochromic with a high reticulocyte count, requiring blood transfusion. Her neutropenia responded to G-CSF treatment, and spontaneous increase was noted after 2 months. We diagnosed the neonate as having fetomaternal transfusion syndrome, because of elevated maternal alfa-fetoprotein levels, and also alloimmune neutropenia, because of the presence of an anti-NA2 antibody in the serum of her mother. This is the first case suggesting that fetomaternal transmission via the placenta could cause alloimmune neutropenia by neutrophil-specific antigen sensitization.

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A four-month-old male infant with life-threatening intracranial hemorrhage was admitted to the Kanagawa Children's Medical Center and diagnosed with severe hemophilia A (FVIII : C<1%). His intracerebral hematoma was removed immediately under the replacement with recombinant factor VIII (rFVIII), and complete hemostasis was attained. After a month's use of rFVIII concentrate, he acquired the inhibitor to factor VIII exactly when he took cranioplasty. This was followed by serious epidural hematoma. We first tried to overcome the low titer of inhibitor with the use of high-dose rFVIII concentrate. Because his inhibitor became greater than 10 BU/ml, replacement therapy was ineffective. The emergent use of recombinant activated factor VII (rFVIIa, NovoSeven®) led to hemostasis. The adequate dose (90-120μg/kg body weight) of rFVIIa was injected every 2-3 hours ; the flow of bleeding from drainage then stopped completely. The total administration of rFVIIa is 138 mg/body, corresponding to 6.7 mg/kg. One-and-a-half years after the onset, he is not subjected to neurological abnormality related CNS bleeding. We find a strong negative correlation coefficient between FVII activity and PT (prothrombin time) under the continuous use of rFVIIa. There was no adverse event related to rFVIIa therapy containing DIC and thrombosis.

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We encountered a case in which octreotide was considered effective against pancreatitis caused by L-asparaginase (L-asp) in a 16-year-old boy. Upper abdominal pain and vomiting occurred one day after he was administered L-asp (6, 000 IU/m² : 9, 000 IU) i.m. during maintenance treatment for acute lymphocytic leukemia. The serum amylase level at the time was 112 IU/l, but a CT examination of the abdomen revealed pancreatic swelling, and acute pancreatitis was diagnosed. Treatment with FOY, ulinastatin, and antibiotics was initiated. The next day, since the serum amylase had risen to 1, 027 IU/l and the abdominal pain had become aggravated, octreotide treatment was commenced. From the third day of disease, the serum amylase level began to fall, and by the sixth day it was almost normal, at 136 IU/l. During these events, the formation of a pancreatic pseudocyst was not observed. The administration of octreotide, which acts to inhibit pancreatic exocrine secretion, has been reported to significantly improve the rate of complications and the mortality in cases of pancreatitis. It is therefore a treatment that should be considered for acute pancreatitis caused by L-asp.

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We report a one-year-old female infant with acute idiopathic thrombocytopenic purpura (ITP) following rubella vaccination. She was admitted to our hospital because of purpura on the whole body accompanied by epistaxis 15 days after vaccination. Laboratory findings on admission showed 2×10³/μl of platelet counts in peripheral blood and 174/μl of megakaryocytes in bone marrow. We diagnosed her as having ITP and twice administered high-dose immunoglobulin (1 g/kg). Thereafter the platelet count gradually recovered and reached the normal range 80 days after the onset. The acute ITP was diagnosed at 6 months. A causal relationship between ITP and rubella vaccine was based on the temporal interval and biological plausibility of live attenuated vaccine. There have been a few cases describing ITP after an administration of monovalent rubella vaccine. However, these patients may be reported less frequently than expected from the epidemiological studies about ITP after measles/mumps/rubella vaccine in the United Kingdom. A nationwide surveillance to assess the risk of ITP attributable to rubella vaccination is warranted.

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We report a 13-year-old boy with dic (9 ; 12) -positive acute lymphoblastic leukemia (ALL) who had a 2-week history of fever and jaundice. Physical examination demonstrated an enlargement of the liver and the spleen ; peripheral blood tests showed a white blood cell count of 1, 600/μl with 12%blasts and a platelet count of 6.9×10⁴/μl. Serum biochemical tests indicated abnormal findings for AST (630 U/l), ALT (619U/l), and direct bilirubin (3.2mg/dl). Leukemic cells showed morphological characteristics of FAB L1 and were positive for CD 10, CD 19, and CD20 on surface marker analysis. Cytogenetic analysis demonstrated a karyotype of 45, XY, inv (1) (p22q44), der (12), and dic (9 ; 12) (p11 ; p12). Our patient showed good response to chemotherapy, as much like that reported in previous cases. We could find no reports of Japanese patients complicated by jaundice.

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We report a case of a 7-year-old girl with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) retinitis during maintenance chemotherapy. She complained of blurred vision in her left eye.Ophthalmoscopic examination of the fundus revealed the “cheese-and-ketchup” pattern characteristic of CMV retinitis. CMV was detected in anterior chamber fluid by polymerase chain reaction, and in blood by antigenemia assay. The patient's blurred vision disappeared, and the ophthalmoscopic findings were resolved after stopping maintenance chemotherapy and treatment with gancyclovir. The patient had lymphocytopenia and a decreased number of CD4-positive lymphocytes for a year. These data suggested that cellular immunodeficiency was critical in the development of retinitis. We propose that when CD4-positive lymphocyte counts are low during maintenance chemotherapy, immediate ophthalmologic examination and CMV testing is warranted in cases with disturbances of visual acuity.

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Protein C (PC) is a precursor of a vitamin K-dependent serine protease that is activated by thrombin-thrombomodulin complex. In the absence of activated PC (APC), the inactivation of activated factors V and VIII is impaired, and the fibrinolytic capacity of the circulating blood is reduced. We report a newborn female infant who developed purpura fulminans, disseminated intravascular coagulation, and intracranial and vitreous hemorrhaging. She had undetectable levels of PC activity and antigen, and decreased levels of PC activity and antigen were observed in her parents. The patient was clinically diagnosed with complete PC deficiency and treated with APC concentrates, fresh-frozen plasma (FFP) and warfarin. During hospitalization, she underwent ophthalmic and neurosurgical operations with the use of APC concentrates. In general, the major clinical signs and symptoms of severe PC deficiency have been purpura fulminans on the extremities and scalp, and the major complications have been ophthalmic and neurological with resultant vitreous and intracranial hemorrhaging. At the onset of these signs and symptoms, the measurement of PC activity and antigen and the administration of the initial treatment are both required immediately. Although APC, FFP, warfarin, and prothrombin complex concentrate have been used successfully to treat severe PC deficiency, all have substantial drawbacks and limitations. Ultimately, other methods of treatment, such as liver transplantation or gene therapy, will need to be pursued in the future.

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