Neutrophil is a white blood cell which plays an important role in microbial infection and inflammation. CD 11/CD18 on neutrophil membrane is an adhesive molecule binding bacteria opsonized with complement or endothelial cells. Chemotaxis, phagocytosis, or phagolysosome formation are regulated by GTP-induced polymerization of actin-filament. NADPH oxidase is activated with assambly of α- and β-subunit of cytochrome b558 on membrane and at least three kinds of cytosol factors. Congenital neutrophil dysfunctions are reported including leukocyte adhesion deficiency, Chediak-Higashi disease, and chronic granulomatous disease. Their etiology, clinical futures, and treatment were described.

View full abstract

Five children with leukemia lymphoma syndrome (LLS) in complete remission (CR) were received high-dose chemotherapy and/or total body irradiation followed by autologous bone marrow transplantation (ABMT). Autologous bone marrow was harvested at 1st CR in all patients and purged with 4-hydroperoxycyclophosphamide (4HC). Although one patient autografted in 2nd CR died of relapse, the other three patients in 1st CR are alive without relapse at +22m, +20m, + 11m. Especially, the treatment in two of them was finished within nine months from their diagnosis. Adverse effects of ABMT were a few and tolerable by the supportive cares. ABMT purged with 4HC would be effective and useful treatment in children with LLS.

View full abstract

Neutrophil function was assessed in 22 normal term infants, their mothers, and healthy adult controls. Chemotaxis, reactive oxygen generating capacity of neutrophils and serum opsonic activity were measured. Those were significantly low in the cord blood compared to the maternal blood and controls. Therefore, neutrophil function of normal term infants was depressed and such impairment may contribute to the morbidity and mortality observed in serious neonatal infections. Chemotactic function in their mothers was lower than that of the controls, but other functions were similar to that of the controls. The number of neutrophils was increased in maternal blood, which may play a role to protect from bactericidal infections at delivery. Statistically significant correlation was observed between reactive oxygen generating capacity of cord neutrophils and their maternal neutrophils. This study indicates that the bactericidal activity of maternal neutrophils is a factor for inferring the bactericidal activity of their infant neutrophils.

View full abstract

Fourty patients underwent peripheral blood stem cell autografts (PBSCT) without total body irradiation and were evaluated for the infectious complications developed within 4 weeks postgraft. The patients were kept in isolated room with a laminar air flow facility and under their mothers' daily care. Gut sterilizations, systemic prophylactic antibiotics, nonmicrobial diet or skin cleaning were not used. Acyclovir, cytomegalovirus hyperimmune globulin preparations, oral amphotericin B or oral fluconazole were administered prophylactically. Thirty-eight patients developed a total 43 febrile episodes and the diagnoses included mucositis (26), fever of unknown origin (10), pneumonia (5), septicemia (4), perianal abscess (4), fungemia (1), and varicella-zoster infection (2). All infectious episodes were successfully treated and none died of infectious complications. Our conclusion is that PBSCT can be performed safely with a simple and inexpensive patient management protocol without a strict aseptic procedure.

View full abstract

Towards the slated implementation of the self-sufficiency program (the supply of coagulation factor products derived solely from domestic voluntary donation blood), the Blood Coagulation Factor Products Committee of the Blood Products Research Organization and the Japanese Ministry of Health and Welfare conducted a collaborative questionnaire-performance survey with Japanese hemophilia specialists regarding the number of hemophilia patients treated, intended usage per annum of factor products and brandname thereof. In consequence, the hemopholiac population was grasped to be 3, 163 patients with hemophilia A, 564 with hemophilia B, and 456 with von Willebrand (vW) disease. The morbidity rate of hemophilia A plus B per 100, 000 male population amounted to 6.1 overall (nationwide) and the geographic region-specific rate somewhat varied, ranging from 7.9 in Chubu area to 3.6 in Shikoku area. The intended overall annual usage of factor products was roughly estimated to be 100, 20, and 2 million units for Factor VIII, IX, and vW products, respectively. The corresponding usage figure per patient showed some differences among different regions and revaled that those institutions caring for a larger number of hemophiliacs intended to use a smaller amount of factor products. Chronological changes in annual usage of Factor VIII and IX products over these 15 years were compared between Japan and the US, disclosing year-by-year increasing overall usage in both countries and the US usage to be around four times that of Japan regardless of either factor.

View full abstract

The nationwide surveillance of hemolytic disease of the newborn and acquired hemolytic anemia of childhood was conducted by the authors. 801 newborns with hemolytic disease were registered from 98 institutions between January 1986 and December 1990. The largest number of cases -523, or 65.3%-were attributed to ABO incompatibility, followed by 199 (24.9%) assessed as being due to Rh incompatibility. While the incidence of hemolytic disease of the newborn due to Rh (D) incompatibility has been decreasing thanks to the development of and Rh (D) globulin, there has been a relative increase in the number of cases of Rh (E) incompatibility. The revised diagnostic criteria of hemolytic disease caused by ABO incompatibility were also discussed. 236 cases with acquired hemolytic anemia of childhood were registered from 90 institutions within the same period. Among them, the incidence of hemolytic uremic syndrome was highest : 146 cases (61.8%). And 17 cases (12%) had E. coli 0157 : H7 isolated from the stool. The mortality rate was 5.5%. 38 children with autoimmune hemolytic anemia were registered, and 24 cases (63%) were of the acute type.

View full abstract

We have treated three patients with ALL in recurrent and refractory CNS relapse with intraventricular methotrexate (MTX) via an Ommaya reservoir by a low-dose “concentration × time” schedule of 1 mg every 12 hr for 3 days. This method was originally devised by Bleyer et al to maintain minimal cytocidal MTX concentration in CSF for the entire cell cycle time while eliminating the high peak level responsible for neurotoxicity. In spite of the fact that all the patients had been in relapse after repeated intrathecal MTX (12 mg/m²) and/or high dose MTX with abnormal radiological imaging (n=2), neurological deficits (n=2) and/or acute MTX toxicity (n=2), remission was achieved in each patient without neurotoxicity. We have studied the concentration of intraventricular MTX in a total of 60 samples and confirmed that CSF concentration of MTX was maintained at greater than 1 μM in 47 of 60 (78%) injections. Our data suggest that the “C × T” MTX via an Ommaya reservoir is an effective and safe treatment for patients with CNS leukemia.

View full abstract

In the CCLSG-874 protocol for children with low-risk (LR) and intermediate-risk (IR) acute lymphoblastic leukemia (ALL), two regimens with or without cranial irradiation (CI) were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. From 1987 to 1990, 82 and 109 evaluable patients were registered into L874 and I874 protocols for LR and IR patients, respectively. All responders to induction therapy were randomized to treatment with 18Gy of CI plus intrathecal methotrexate (MTX it) or to treatment with high-dose MTX plus MTX it. Patients were then treated with standard maintenance regimens of L874 and 1874. At a median follow-up of 39 months (range 14-58 months) there was no difference in the rate of hematologic relapse between the CI group and MTX group. The rate of CNS relapse in the MTX group seemed to be higher (3 of 39 in L874 and 2 of 54 in 1874) than that in the CI group (1 of 43 in L874 and 0 of 55 in 1874), but these data were not statistically significant. The rates of 4-year event-free survival (EFS) in L874 were 81.1±7.6% (mean±SE) and 75.2±7.9% (ns) for the CI and MTX group, respectively, and the rates of EFS in 1874 were 70.0±13.6% and 70.0±9.0% (ns) for the CI and MTX group, respectively. These data suggest that MTX alone may be as effective as CI to prolong diseasefree survival in LR and IR ALL although further continuous studies are needed. Analysis of serial CCLSG protocols for ALL from 1981 revealed that the rate of EFS of ALL allover including all risk groups has gradually been increasing from 44.2±3.6% for 811 protocol and 53.1±3.5% for 841 to 65.5±3.6% for the present 874 protocol.

View full abstract

Of children with Burkitt's lymphoma treated at our clinic for the past five years, we report here the therapeutic results of those treated in accordance with a modified NCI 77-04 protocol of Magrath et al. They were seven boys and two girls, age ranged 2 to 14 years. The primary site was intestine in five children, neck in two and pharynx in two. Staging at the first examination was Stage I in two cases, Stage II in three, Stage III in three and Stage IV in one. Treatment comprised complete resection by surgery in four cases, partial resection in three and biopsy only in two. Post operatively, treatment in accordance with the protocol was instituted, and radiotherapy was concurrently used in five children. The protocol was completely accomplished in eight of nine children, and all are still alive (2 yrs 10 months-6 yrs 3 months). Recurrence of the tumor was detected in two cases, but in one case remission was achieved by reinduction therapy. The other case in which remission was not attained was in Stage IV ; this child died from infiltration of multiple organs, including the central nervous system. Stomatitis occurred frequently as an adverse reaction of this therapy, but this was reversible. The therapy may thus be considered a modality as it showed and maintained a high rate of remission for Burkitt's lymphoma.

View full abstract

We examined red blood cell volume distribution width (hereinafter referred to as RDW) on healthy children. RDW was as high as 16.6 ±1.6% (mean ± 1 SD) in normal and premature neonates. RDW was the largest at neonatal period and thereafter decreased gradually with age. No significant difference from adults was noted for children ≥6 years, the normal RDW being 13.0 ±1.0%. For iron deficiency anemia, mean corpuscular volume (MCV) was low and RDW was high. After the treatment, RDW became higher with reticulocytosis, with red blood cell histogram being wave-like. With the improvement in anemia, RDW returned to the normal. For hereditary spherocytosis, MCV was normal, RDW being high before splenectomy, and both these were normal after splenectomy. For hemolytic anemia due to pyruvate kinase deficiency, MCV and RDW were remarkably high after splenectomy. Of 13 cases with aplastic anemia, 7 showed high MCV and normal RDW and 6 showed high MCV and RDW ; no correlations were noted between RDW, conditions and anemia. For leukemic children, the marjority of those under long-term remission and withdrawal showed normal RDW, and those under intensive chemotherapy using high-dose cytosine arabinoside mostly showed smaller MCV and RDW, and thereafter had larger or pre-treatment RDW values with reticulocytosis. Generally, RDW was proportional to the peripheral reticulocyte count. RDW and erythrocyte histogram may indicate the state of bone marrow erythropoiesis in the patients with various kinds of hematological disorders.

View full abstract

Variable number of tandem repeats (VNTR) loci are highly polymorphic due to variation in the number of tandemly repeated sequences in different alleles. We analyzed the genotypic typing of VNTR loci (YNZ22 and MCT 118) using polymerase chain reaction after allogeneic bone marrow transplantation (allo-BMT). PCR analysis of VNTR loci was found to be useful for monitoring successful engraftment or hematological chimerism. Compared with conventional methods such as cytogenetic analysis and erythrocyte antigens, PCR analysis showed engraftment or graft rejection during early hypoplastic stages after allo-BMT with no influence from blood transfusion. Interesting cases are presented in the following. In one case, chimerism in PCR analysis preceded the patient's leukemia relapse ; we discuss whether this analysis is capable of the early detection of post allo-BMT relapse. Another case had acute GVHD-like syndrome with no donor-specific fragment in PCR analysis. Thus, PCR analysis of VNTR loci is one of the most useful tools to clarify the engraftment kinetics after allo-BMT.

View full abstract

Plasma antithrombin III (AT III) activity and antigen were examined in newborn infants with or without complication of intracranial hemorrhage (ICH) or respiratory distress syndrome (RES). AT III activity and antigen in cord plasma obtained from 183 full-term newborns were 57.4±13.2% and 58.7±12.9%, respectively, and reached to 69.2±11.3%, 66.9±11.5% on the eighth day. In 120 healthy premature newborns, both AT III activity and antigen were lower than those in full-term newborns; these were furthermore decreased in premature infants with ICH or RDS. Crossed immunoelectrophoresis (CIE) with heparin of newborn plasma showed only the fast anodal peak (IAT III¹). However, when the same level of AT III antigen as that in normal adult plasma was used, three components were detected, but the cathodal components (IAT III² and IAT III³) were still reduced in comparison to adult values, and did not increase to this value during 2-5 years of observation. On CIE with heparin of plasma of premature infants with ICH, the cathodal components were more increased than those in non-complicated premature infants. It is suggested that the increase of the cathodal components in newborns with ICH might be due to formation of AT III-activated coagulation factor complexes.

View full abstract

We report surface marker studies for three cases with primary lymphoma of the bone. These cases were staged at IV, III, and I by the Murphy's classification, respectively. The following were histopathological features of these 3 cases : one case was classified as lymphoblastic type, and the other 2 cases were classified as diffuse medium cell type according to the LSG classification. All cases including lymphoblastic type were originated from non T cell, and two of these were shown to be positive for CD 10 (CALLA). Recently, primary lymphoblastic lymphoma of the bone has been increasingly shown to be positive for CD 10 (CALLA). Studies of surface markers are essential for the accurate diagnosis of cellular origin with primary lymphoma of the bone.

View full abstract

It is rare to observe pancreatic tumor involvement in childhood malignant lymphoma. Here we report a ten-year-old boy with non-Hodgkin's lymphoma (NHL) who had pancreatitis on admission and developed drug-induced recurrence of pancreatitis. He was admitted to our hospital because of a swelling in his left cheek and upper abdominal pain in November 1989. Histological examination of the tumor specimen taken from his maxillary sinus revealed NHL with immunocytochemical evidence of B cell origin. The patient also had pancreatitis due to tumor involvement or oppression. Remission was achieved with induction therapy. However, during maintenance therapy, pancreatitis recurred, induced by L-asparaginase in February 1990. Furthermore, a pancreatic pseudocyst was noted. After surgical treatment, the patient suffered a relapse and died in July 1990. Only nine reported cases of malignant lymphoma have involved pancreatitis at onset. In our case, recurrence of pancreatitis necessitated the termination of maintenance chemotherapy in this patient. This case suggests that L-asparaginase should be used with caution in oncologic patients with pancreatitis.

View full abstract

A 5-year-old boy with the relapse of acute promyelocytic leukemia was successfully treated. by oral administration of the all-trans retinoic acid (ATRA). The leukemic cells in relapse were usually resistant to the chemotherapy. Subsequent to the high dose Ara-C therapy, therefore, ATRA therapy was started at the dose of 60 mg/m²/day. An informed consent was obtained from the parents prior to ATRA therapy. On the 64th day of the administration, a complete remission was achieved. Processes of the differentiation of leukocytes into mature neutrophilic leukocytes, which had been caused by ATRA administration, was observed on the hemograms of the peripheral blood and bone marrow and also on the flowcytometry of peripheral blood cells. A chromosome analysis using bone marrow aspirate disclosed abnormal karyotype with t (15; 17). On the DNA analysis, the rearrangement of the retinoic acid receptor α (RARα) gene was detected. A few side effects noticed in this patient were negligible. ATRA was considered to be useful drug for the induction therapy of acute promyelocytic leukemia in children.

View full abstract

A 7-year-old girl with acute myeloblastic leukemia (AML) complicated by pulmonary alveolar proteinosis was reported. She has suffered from thrombocytopenia from 3 years and 6 months of life. Megaloblastic changes of erythroblasts with multilobulated nucleus in bone marrow specimens and elevated HbF levels have been observed thereafter. She was diagnosed as RAEB at 6 years old and was successfully treated with low-dose Ara-C about one year, until the disease transformed into AML (M2). During induction therepy with multiple drug combination regimens, diffuse pulmonary infiltrations and cardiomegaly were observed in roentgenogram at 9 months after admission. Treatments with antibiotics, antifungal agents and digitalis did not facilitate recovery and she died about 2 months later. The histological findings corresponding to pulmonary aspergillosis with cavity formation were observed at necropsy. Pulmonary alveolar spaces were filled with PASpositive amorphous materials which were partially stained by oil red 0. Numerous multilamellated structures were also observed in electron micrographs. These findings were compatible with pulmonary alveolar proteinosis.

View full abstract

We reported a case of acute megakaryoblastic leukemia refractory to induction chemotherapy, who finally achieved a complete remission with allogeneic bone marrow transplantation. The patient was a seven-month-old boy who had been treated with 4 courses of intensive chemotherapy including daunorubicin, cytosine arabinoside, etoposide, 6-mercaptopurine and mitoxantrone without complete remission. Six months after the diagnosis, he underwent allogeneic bone marrow transplantation from HLA phenotypically identical, mixed lymphocyte culture reaction negative father. Conditioning regimen consisted of busulfan 120 mg/m²/day for 4 days and cyclophosphamide 60 mg/kg/day for 2 days. He has remained in complete remission for 27 months following transplant. For patients with acute leukemia refractory to induction chemotherapy, high dose chemotherapy followed by allogeneic bone marrow transplantation may be effective, if it is performed before the appearance of a resistance to anti-cancer drugs or severe complications due to repeated intensive chemotherapy.

View full abstract

We described a 3-year-old girl with marrow necrosis preceding acute lymphocytic leukemia (ALL). She was diagnosed from appearance of leukemic blasts in bone marrow as T-cell ALL after chemotherapy, though leukemic blasts were not recognized in peripheral blood nor bone marrow blood before chemotherapy. Note that such bone marrow necrosis is often prior to demonstrating any malignant disease involving the marrow although it is an uncommon finding in childhood leukemia.

View full abstract

We described a case of nephrotic syndrome (NS) associated with Hodgkin's disease (HD) in a 4-year-old boy. He was admitted because of left cervical lymphadenopathy and generalized edema. Nodular sclerosing type of HD was diagnosed by the cervical lymphnode biopsy. The clinical staging of HD was stage IA. Although his renal function was normal (Ccr 98.5 ml/min/1.73 m²), he had NS (serum T.P. 4.4 g/dl; serum Alb. 1.8 g/d1; serum T. cho. 331 mg/di; urine protein8.6 g/day). The renal biopsy showed minor glomerular abnormalities. The clinical manifestation of NS improved after lymphnode biopsy, but relapsed soon. Proteinuria disappeared within several days with prednisolone treatment (60 mg/m²) and irradiation to the involved field. HD complicating NS has been classically documented, but their association is particularly rare in childhood. This case showed normal OKT 4/8 ratio (1.91) and normal lymphocyte stimulation test with lectin, although the mechanism of the association is interpreted to be due to lymphocyte dysfunction of HD.

View full abstract

An 8-month-old female infant developed symptoms of Langerhans' cell histiocytosis (LCH) following chicken pox. The clinical course of her chicken pox was uneventful with normal lymphocyte subsets. With tumors at the right clavicula and occipital bone, and skin lesions which were histologicaly proven to be LCH, the patient showed high serum interferon gamma level and markedly reduced CD8+ lymphocytes. The patient responded to etoposide (VP-16) and prednisolone associated with normal serum interferon gamma level and CD8 + lymphocytes. It was suggested that LCH has relevance to altered T cell function and other immunological condition. We considered that chicken pox may have modified the patient's immunological condition which prompted the development of LCH.

View full abstract

We reported a case of intestinal perforation during remission induction therapy in a 3-year-old male with acute myelocytic leukemia. He complained of fever, petechiae and pain of right ear on onset. The patient was diagnosed as having AML (FAB, M2). He was treated with BHAC-AMP therapy, but unremitting high fever and watery diarrhea continued. He died of duodenal and jejunal perforation 40 days later. Autopsy revealed diffuse infiltration of leukemic cells in all laminae of intestine including the perforated lesions.

View full abstract

We report a boy with Down syndrome who had transient abnormal myelopoiesis (TAM) (transient myeloproliferative disorder) during the neonatal period, followed by megakaryoblastic leukemia at 31 months of age. At birth, the peripheral white blood cell count was 28, 600/μl, 1 with 42.8% blast cells, and the bone marrow aspirate with 22.7% blast cells. By 3 months of age, blast cells disappeared without treatment from the peripheral blood. At age 26 months, the blast cells reappeared in peripheral blood. At age 31 months, the white blood cell count was 47, 700/μl, 1 with 93.5% blast cells. The blast cells were positive for both platelet peroxidase and platelet-associated antigens (pl-gp Ib and pl-gp IIb/IIIa). The karyotype of the blast cells was 47, XY, +21, del (20) (q13). The patient was treated with a low-dose cytosine arabinoside, adriamycin and etoposide but no remission was attained, and he died at age 38 months. Sequential Q- and R-banding analysis demonstrated duplication of a paternal chromosome 21 in two of the three chromosome 21.

View full abstract