Naito H

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.

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.

High Susceptibility to Severe Infectious Complications at Reinduction Chemotherapy in Patients Who Relapse After Stem Cell Transplantation

Patients who relapse after stem cell transplantation (SCT) usually appear to be liable to severe infectious complications at reinduction chemotherapy compared to patients at the first induction therapy, though this is not statistically substantiated. The aim of this study was to analyze episodes of infectious complications during reinduction chemotherapy among patients who relapsed after SCT compared with those at the first induction chemotherapy. Between February 1988 and March 2004, 145 children received SCT, and 17 (12 with hematologic malignancies and 5 with solid tumors) were enrolled as eligible subjects for this study. Positive blood cultures (sepsis) were present in six patients exclusively at the reinduction therapy but none at the first induction (P = .009). Three of the six patients progressed to septic shock. Moreover, all patients positive for blood cultures were those with hematologic malignancy (P = .007), and every patient with septic shock had received allogenic transplantation. Our results showed that reinduction chemotherapy needs attention for severe infectious complications, particularly among patients with hematologic malignancies receiving allogenic transplantations. Possible immaturity of the reconstructed systemic immune system and/or insufficient recovery of mucosal protective functions in the patients after SCT are discussed in view of their high susceptibility to severe infectious complications.

Painless and Safe Subcutaneous Catheter for Injection of Various Cytokines in Patients with Hematological Disorders

Various cytokines have been used to treat patients with hematological disorders, eg, recombinant granulocyte colony-stimulating factor (G-CSF),1 recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF),2 and erythropoietin (EPO) are given to patients with aplastic anemia (AA). G-CSF and GM-CSF are also used to treat neutropenia in patients with leukemia, lymphoma, and other solid tumors who receive such treatment as intensive chemotherapy.3 Interferon (IFN)-gamma is used to treat patients with chronic granulomatous disease (CGD).4 Generally these cytokines are administered either intravenously or subcutaneously. However, it is difficult to continue intravenous injection for long periods, especially in children. One of the major problems associated with the subcutaneous route is pain. Recently, teflon catheters have been used for daily painless injections of insulin by subcutaneous inplantation into the abdominal wall of diabetic patients.5