Sumio Miyazaki

High doses of gamma globulin and methylprednisolone therapy for idiopathic thrombocytopenic purpura in children

In four children with chronic idiopathic thrombocytopenic purpura (ITP), high doses of gamma globulin or methylprednisolone were effective in increasing platelet counts transiently, yet there was no quantitative relationship between the platelet responses to these two therapies. This finding suggests a qualitative difference in the mechanisms of increasing platelets by the two drugs. High doses of gamma globulin and methylprednisolone showed a synergistic effect on the initial and maximal platelet responses, suggesting an intensification of the effect of gamma globulin by methylprednisolone. This combination therapy should be clinically useful, particularly in the control of acute haemorrhage or in preparations for emergency surgery.

Avascular necrosis of bone in neuroblastoma treated with combination chemotherapy.

We treated two children with neuroblastoma and during the course of chemotherapy, avascular necrosis of the femoral head occurred. The main pathogenetic factor of this necrosis may be the toxic effect of cyclophosphamide.

Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: A new diagnostic test

Reduction of exogenous cytochrome c was induced by the treatment of human polymorphonuclear leucocytes with cytochalasin E. The reduction was completely inhibited by superoxide, dismutase, indicating that superoxide anions were released from the cells. The leucocytes from two patients with chronic granulomatous disease did not show the release reaction that should have been brought on by the treatment. The cytochalasin-induced reduction of exogenous cytochrome c by polymorphonuclear leucocytes is so specific and sensitive that it seems to be useful for diagnosis of chronic granulomatous disease.

Relation between Delayed Skin Reactivity and Macrophage Migration Inhibition or Lymphocyte Transformation in Tuberculin‐Type Hypersensitivity and Jones‐Mote Hypersensitivity

Precise time‐course studies on delayed skin reaction, lymphocyte transformation and macrophage migration inhibition were carried out from day 3 to 270 and from day 3 to 120, respectively, in guinea pigs immunized with bovine gamma‐globulin (BGG) in complete Freunds adjuvant (CFA) and those immunized with BGG in incomplete Freunds adjuvant (IFA). a) Delayed skin reactions could be elicited for a long period of time after immunization with BGG in CFA in the presence of prominent antibody production and were accompanied by induration. b) Delayed reactions could be elicited transiently after immunization with BGG in IFA and were not accompanied by induration. c) At the peak of hypersensitivity, infiltrating cells at the reaction sites were composed largely of mononuclear cells and basophils, respectively, in the animals immunized with BGG in CFA and those immunized with BGG in IFA. d) Uptake of 3H‐thymidine by lymphocytes was increased remarkably in the presence of BGG when cells were obtained at early stages after immunization by both methods. e) Macrophage migration inhibition was strongly positive in animals immunized with BGG in CFA but weakly positive in those immunized with BGG in IFA. Increased lymphocyte transformation preceded the appearance of a positive migration inhibition. f) After immunization with BGG in CFA, Jones‐Mote hypersensitivity appeared to precede the development of tuberculin‐type hypersensitivity.

TREATMENT OF STANDARD-RISK ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: The Results of Protocol AL841 from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 +/- 5.0% and overall survival was 88.7 +/- 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 +/- 6.2%) was superior to that without l-Asp (75.9 +/- 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.

Experimental Models for Prevention of Graft-versus-Host Reaction in Bone Marrow Transfusion

Splenomegaly was strong in the degree and continued for a long period of time in adult F1 hybrids between AKR (H-2k) and C3H/He (H-2k) mice after transfer of spleen cells from normal C3H/He mice. In spleen cells of such F1 recipients, cytotoxicity was detected by an in vivo neutralization test using methylcholanthrene-induced sarcoma or AKR origin as target cells. All of newborn F1 recipients died within 17 days after cell transfer. Induction of splenomegaly and cytotoxicity was not prevented by repeated pretreatments of donors with sonicated AKR spleen cells in saline, which suppressed completely such phenomena of graft-versus-host reaction in an H-2 nonidentical combination. Induction of cytotoxicity in the spleen of F1 recipients was not prevented by a pretreatment of donors with AKR spleen cells in complete Freunds adjuvant, which suppressed the induction of cytotoxicity in an H-2 nonidentical combination. Graft-versus-host reaction appears to be stronger in a combination between parental strains of which major histocompatibility antigens were identical.When lymphoid cells were obtained from AKR donors 12 h after a treatment with C57BL/L cells in complete Freunds adjuvant and transferred to (AKR X C57BL/6) F1 mice, splenomegaly in F1 recipients was augmented but cytotoxicity was suppressed. The suppression of cytotoxicity was antigen-specific. When cell transfer was carried out at stages as early as 3 or 6 h after the treatment of donors, cytotoxicity was enhanced but splenomegaly was suppressed. Irreversible deviation of immune response from the generation of cytotoxicity to the development of splenomegaly appears to occur within 12 h after such a treatment of donors.

Combination Chemotherapy with N4-behenoyl-l-β-D-arabinofuranosylcytosine (BH-AC) in Childhood Leukemia

N4 -behenoyl-1 -0-D-arabinofuranosylcytosine (BH-AC) is a newly synthesized derivative of 1 -0-D-arabinofuranosylcytosine (AraC). It has various kinds of features such as lipophilicity, schedule independence and resistance to cytidine deaminase compared with AraC. Recently in several studies, this regimen showed good results in the treatment of acute nonlymphocytic leukemia in adults. Now we studied combination chemotherapy with BH-AC, aclacinomycin A, 6-mercatopurine and prednisolone for seven patients with childhood leukemia. They included two cases with acute lymphocytic leukemia *(ALL), three cases with acute nonlymphocytic leukemias (ANLL), and two cases with blast crisis of adult and juvenile chronic myelogenous leukemia (ACML, JCML). The dosage schedule of BH-AC was 170 mg/MZ /day for two to nine days. Two out of three ANLL patients achieved complete remission, and one ANLL and one acute crisis of ACML achieved partial remission. Several side effects such as myelosuppression, gastrointestinal symptoms were noted but very mild. This regimen was effective in the treatment of acute nonlymphocytic leukemia in children as well as in adults and we are planning further study on this combination chemotherapy for childhood leukemia.