Masanori Yanai

Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811)

From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard‐risk group were entered to the protocol JCCLSG‐S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6‐mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6MP (50 mg/m2/day by mouth) plus MTX (20 mg/m2/ week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high‐dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% ± 5.8% (mean ± 1 SE) and 49.7% ± 7.3% (P < 0.01) at 4 years, and 72.1% ± 6.3% and 49.7% ± 7.3% (P < 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.

Histological and fine structural studies on pigmented neuroectodermal tumor of infancy.

Pigmented neuroectodermal tumor of infancy originating from the anterior maxilla in a two‐month‐old male has been studied by light and electron microscopy. The tumor is characterized histologically by two types of neoplastic cells embedded in considerable amounts of fibrous stromal tissue. The first type of cell is cuboidal to columnar in shape with an epithelial appearance having abundant cytoplasm; either scanty or a heavy accumulation of melanin pigment is observed in the cytoplasm. These cells are aligned along the cleft‐like space or arranged in small ductal structures. Electron microscopy shows the characteristic features of melanocytic cells having a varying degree of asynchronous maturation of melanosomes. The second type of cells is small and round in shape and has a hyperchromatic nucleus and scanty cytoplasm, resembling neuroblastic cells or lymphocytes. Electron microscopy reveals cytoplasmic processes resembling immature neurits which protrude into the intracellular space; a small number of secretory granules having a central core surrounded by a single limiting membrane are observed in the cytoplasm and cytoplasmic processes.

Pernicious Anemia in a Patient with Hypogammaglobulinemia

A 19‐year‐old male with pernicious anemia and hypogammaglobulinemia (common variable immunodeficiency: CVID) is reported in comparison with classical pernicious anemia. This case was characterized by an earlier onset of anemia, the absence of autoantibodies to intrinsic factor or gastric parietal cells and involvement of the pyloric antrum as well as the gastric corpus. It is suggested that dysregulation of cellular immunity produces the autoimmune lesion in the gastric mucosa, including the pyloric antrum, in a patient with CVID, and that some of such cases develop pernicious anemia.

Treatment of Acute Nonlymphoblastic Leukemia in the Children’s Cancer and Leukemia Study Group

A total of 114 evaluable children with acute nonlymphoblastic leukemia (FAB categories: Ml, M2, M4, M5) entered into this study for 8 years. Of the 114 patients, 82 (71.9%) achieved complete remission (CR). There was no difference in the CR rate among five different protocols proposed by CCLSG. The rates of continuous complete remission (COR.) at 20 months were 43.0 ± 10.7% (mean ± SE), 23.4 ± 11.0%, and 65.8 ± 10.6% in Regimen I, Regimen II, and ANLL-861, respectively. The curves of CCR showed a plateau after 20 months, so that few cases of long-term remitters might relapse after 2 years. The primary CNS involvement did not affect the CCR duration. Sixteen patients have completed the chemotherapy, and 15 of them have remained in remission for 33–104 months after diagnosis. The incidence of CNS involvement was 9.6% (11/114). CNS involvement frequently occurred in patients with M4 and M5. The CCR duration in patients with monocytic leukemia (M5) was significantly shorter (p <0.01) than in patients with Ml or M2. Further strategy for the patients, including bone marrow transplantation, should be changed according to the ANLL subtype.

Penetration of Antimicrobial Agents into Phagocytic Cells Using Polymorphonuclear Leukocytes of Chronic Granulomatous Disease

Polymorphonuclear leukocytes (PMNs) obtained from a chronic granulomatous disease (CGD) patient, pooled serum and bacteria were preincubated. CGD PMNs containing viable bacteria were then incubated for 60 minutes with either DL‐8280, SMX, TMP, ABPC, or GM.

Opsonic activity of serum, acites fluid, and cerebrospinal fluid in various disease

Polymorphonuclear leucocytes (PMN) dysfunction, such a that found in chronic granulomatous dise sse, is known to be a contributory factor in severe infections. Because opsonins, in-cluding immunoglobulins and complement, are required for PMN phagocytosis, a dysfunction in opsonins may also lead to severe infections.In this study, the opsonic activity of serum, ascites fluid, or cerebrospinal fluid (CSF) obtained from patients with various disease was examined in an assay employing E. coli (ON 2) and Staph. aureus (502 A) .In a case of congenital dysfunction of complement, diminished opsonic activity was observed against both E. coli and Staph, aureus.In three cases of hypogammaglobulinemia, the activity against E. coli depended upon the amount of IgM in the serum, while activity against Staph, aureus was in the normal range.Diminished opsonic activity against both E. coli and Staph. aureus was also observed in a patient at an acute stage of systemic lupus erytematosus, and in patients with prolonged EB virus infections. Premature infants, neonates, and children with measles showed a decreased activity against E. coli only.Normal opsonic activity was found in the ascites of a renal failure patient, in a milky ascites, and in the pleural effusion of an osteosarcoma patient. CSF from a suppurative meningites patient showed a higher activity than normal CSF.