Takaaki Shikano

Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction

To facilitate the diagnosis of bone marrow metastasis in neuroblastoma, we have developed a method of amplifying and detecting the tyrosine hydroxylase (TH) mRNA sequence in bone marrow cells using a combination of reverse transcription and the polymerase chain reaction (RT/PCR). By this method, the sequence of TH was detected clearly in the neuroblastoma tissues of all 6 patients and not detected in the bone marrow cells of any of the 9 negative control children. In a reconstitution experiment, 1 neuroblastoma cell per 100,000 normal bone marrow cells could be detected, thus indicating the great sensitivity of this method. Based on these results, this technique may be of value in the diagnosis and treatment follow-up of bone marrow metastasis of neuroblastoma.

Neurological complications after stem cell transplantation in childhood

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.

Balanced and unbalanced 1;19 translocation‐associated acute lymphoblastic leukemias

The authors studied clinical and immunologic characteristics of six children with 1;19 translocation‐ associated acute lymphoblastic leukemia (ALL); two of the six had the balanced type, t(l;19)(q23;p13), three had the unbalanced type, ‐19,+der(19)t(l;19)(q23;p13) with a resultant partial 1q trisomy, and the other had a mosaicism of cells with the balanced type and those with the unbalanced one, t(l;19)/ ‐19,+der(19)t(l;19). Leukemic cells of all three patients, in which intracytoplasmic immunoglobulin was determined, were proved to show pre‐B phenotype. Of the six patients, three had an initial leukocyte count of >50 × 109/1, and were classified in the high‐risk group. Three patients relapsed after a brief remission and died. The mosaicism observed suggested that at least in some patients the leukemic cells with ‐19,+der(19)t(l;19) might derive from those with t(1;19) as a step in the course of clonal evolution. Our data and a review of the literature indicate that there may be no differences in the clinical and immunologic characteristics between the patients with the balanced translocation and those with the unbalanced one, and that the leukemia with the 1;19 translocation may join with other translocation‐ associated ALLs, with which the patients are known to have poor prognosis.

Electroencephalogram abnormality and high-dose busulfan in conditioning regimens for stem cell transplantation

High-dose busulfan (BU) is widely used in combined chemotherapy before allogeneic or autologous bone marrow transplantation. Convulsions are reported as a side-effect of high-dose BU. We recorded electroencephalograms (EEGs) before and on the third day of BU administration in 22 patients. Abnormal EEGs were observed on the third day in 13 cases (59%). These patients were older (P < 0.05) and had had larger doses of bu (P < 0.025) than the nine patients with normal eegs. convulsions occurred in two of the 22 patients, one of whom was receiving prophylaxis with phenytoin. gamma aminobutyric acid (gaba), a natural mediator of defense against epileptic activity, concentrations in cerebrospinal fluid measured before and after administration of bu showed no definite changes.

Clinical and Genetic Characteristics of Japanese Burkitt Lymphomas with or without Leukemic Presentation

To clarify the clinical and genetic features of Burkitt lymphoma with or without leukemic presentation, we have conducted clinical, cytogenetic, and genetic studies. Of 40 Japanese patients with Burkitt lymphoma examined by cytogenetic and/or fluorescence in situ hybridization analysis or Southern blot analysis usingMYC probes, 35 patients had t(8;14) translocations, and 5 had t(8;22). Breakpoints were located far upstream ofMYC in 4 (12%) of 33 tumors with t(8;14), and Epstein-Barr virus infection was found in 3 (8%) of 40 tumors. These findings are similar to those reported for non-Japanese patients with the sporadic form of Burkitt lymphoma. Clinical and genetic characteristic were compared for 30 patients presenting with lymphoma and 10 presenting with leukemia. The overall survival was shorter in aggressively treated leukemia patients than in aggressively treated lymphoma patients(P =.003); however, the incidence rates ofTP53 mutation,p16INK4a deletion, andp15INK4b deletion that were found in 6 (15%) of 40,3 (9%) of 35, and 2 (6%) of 35 tumors, respectively, were similar between the 2 subtypes. Thus, the present study has shown the different prognoses for the 2 subtypes of Burkitt lymphoma but has failed to clarify the genetic backgrounds that may explain the different outcomes.Int J Hematol. 2003;77:490-498.

Myelodysplastic syndrome with partial deletion of the long arm of chromosome 5: first report of a case in a child.

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q‐) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 × 103/l with 3% atypical lymphocytes, and platelet count 17.7 × 104/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q‐ in 100% of the metaphases.

Ph1‐positive and Ph1‐negative abnormal cell lines in a child with lymphoblastic lymphoma

Summary. A 7‐year‐old Japanese boy with Ph1‐positive‐lymphoblastic lymphoma is described. The diagnosis was based on biopsied tonsils which were enlarged at the time of admission. On the eighth day after admission an enlarged mediastimal mass was detected on a chest X‐ray film. The lymphoblasts which appeared in the peripheral blood and bone marrow proved to be T‐cells. Chromosome studies on the bone marrow cells revealed two abnormal cell lines; one had a 7; 11 translocation and the other a 7;11 translocation and a 9;22 translocation, forming the Ph1‐chromosome. The latter line with the Ph1 chromosome was considered to have been derived from the former line without the Ph1. Our findings show that the Prochromosome may be a secondary change in the course of karyotypic evolution.

Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia with T(1; 19)

To clarify the incidence of leukoencephalopathy in patients with t(1;19) and their clinical characteristics, we studied 239 acute lymphoblastic leukemia (ALL) cases. The 1;19 translocation was found in 20 (8.5%) of the 239 children with ALL. Leukoencephalopathy occurred in 2 (10%) patients with t(1;19) during the early first remission and in one case with t(1;19) at the time of central nervous system (CNS) relapse. Leukoencephalopathy was not found during the early first remission in patients lacking t(1;19), but did develop in 4 patients lacking t(1;19) at the time of CNS relapse. There were no differences in age, sex, leukocyte count, platelet count or serum lactate dehydrogenase level between t(1;19) patients with and without leukoencephalopathy. Our results suggest the incidence of leukoencephalopathy in patients with t(1;19) during the early first remission to be 10%, but we can not predict which patients will develop leukoencephalopathy.

A Case of Yersinia pseudotuberculosis Septicemia Accompanied by a Large Abdominal Tumor

A 2-year-old girl with Yersinia pseudotuberculosis septicemia had a large abdominal mass that had to be differentiated from malignant tumor. The mass disappeared rapidly with antibiotic therapy and was defined to be a cluster of enlarged ileocecal lymph nodes by the clinical course and the findings at ultrasonic examination and Gallium scintigraphy.

A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia

A 2-year-old girl with a very rare form of acute megakaryoblastic leukemia (AMKL), having the 11p13;14q11 translocation specific for T-cell malignancies, is reported. She was diagnosed as having AMKL on the basis of her bone marrow, which contained 30% megakaryoblasts identified by characteristic morphology on May-Giemsa stain, positive for platelet peroxidase activity and for the surface marker of platelet glycoprotein IIb/IIIa, CD41. Cytogenetic studies of marrow cells revealed 47,XX,i(7q), +der(11)t(11;14)(p13;q11), -14, +21. She achieved hematologic remission after two courses of chemotherapy including behenoyl cytarabine, acracinorubicin, 6 mercaptopurine, and prednisolone, but soon relapsed and died 11 months after admission. This case suggests that adequate diagnostic assessments of morphology, surface markers, and cytogenetics are necessary for proper diagnosis in leukemia and lymphoma, and that an important, though as-yet unidentified, gene in megakaryopoiesis may reside in the 14q11 chromosomal region.