Molecular detection of a late-appearing BCR-ABL gene in a child with T-cell acute lymphoblastic leukemia.

Approximately 2-5% of children with newly diagnosed acute lymphoblastic leukemia (ALL) have a Philadelphia (Ph) chromosome detectable on cytogenetic analysis, which is associated with a poor prognosis. In rare ALL cases the Ph chromosome may appear in leukemic cells during the course of the disease. We report here the case of a 5.5-year-old male patient with T-ALL who was found to have the b2a2 BCR-ABL mRNA transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) at first marrow relapse. At the time of initial diagnosis, no BCR-ABL transcripts had been detected by PCR in the patient's blood and marrow samples. Further studies were performed using a competitive PCR titration assay and the fluorescence in situ hybridization (FISH) method to monitor the leukemic clone. Progression of the disease was associated with a higher BCR-ABL transcript level and an increasing proportion of BCR-ABL-positive cells. Metaphase FISH analysis identified the presence of the BCR-ABL fusion gene on a normal chromosome 22. This study shows that a late-appearing Ph translocation in ALL may be cytogenetically invisible. Quantitative RT-PCR and FISH techniques are appropriate and efficient methods for detecting these rare ALL variants expressing the BCR-ABL fusion gene and for estimating the level of residual disease following treatment.

Kinetics of hematopoietic progenitor cell release induced by G-CSF-alone in children with solid tumors and leukemias.

The kinetics of peripheral blood progenitor cell (PBPC) release induced by G-CSF-alone at 10 microg/kg/day were monitored daily in 42 children with solid tumors and leukemias. Median 16- and 27-fold enrichment of circulating CD34+ cells and granulocyte-macrophage colony-forming units (CFU-GM) was noted with peak values occurring after the 4th or the 5th G-CSF dose. Individual values of PBCD34+ cell levels in patients with solid tumors were not significantly different after the 4th and after the 5th dose. The day-of-collection PBCD34+ cell concentration was related to the harvested CD34+ cell (P = 0.0001) and CFU-GM numbers (P = 0.0001). No correlations were found between PBPC enrichment and either patient age, body weight, diagnosis or pre-mobilization treatment duration. The median numbers of 1.1 x 10(6) CD34+ cells/kg and 28.1 x 10(4) CFU-GM/kg were derived from one patient's blood volume processed. Nineteen patients received G-CSF-alone primed grafts and had successful engraftment. Our data indicate that in 88% of children a single standard leukapheresis is sufficient to obtain a minimum graft (2 x 10(6) CD34+ cell and/or 10 x 10(4) CGU-GM per kg) whether undertaken after the 4th dose of G-CSF or the 5th.

A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study.

Sixteen children with refractory or relapsed ependymoma were entered in a phase-II study of high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of busulfan 150 mg/m2/day for 4 days and thiotepa 300 mg/m2/day for the 3 following days. All patients had previously been treated by surgery and conventional chemotherapy. Eight of them had also received irradiation at doses ranging from 45 to 55 Gy at the tumor site. At the time of transplantation, 9 patients were in first relapse, 5 in second relapse and 2 in third relapse or more; all had measurable disease; 15 patients were evaluable for response. No radiologic response > 50% was observed. Stable disease and progressive disease were documented in 10 and 5 cases, respectively. The duration of response to this treatment, which lasted for a median time of 7 months (range: 5-8 months), was only evaluable in 5 patients who did not receive further treatment after ABMT. To date, there are 3 disease-free survivors at 15, 25 and 27 months all of whom were treated with second complete surgical resection and local radiotherapy (55 Gy). Toxicity was severe, mainly digestive and cutaneous, and 1 toxicity-related death occurred. Unlike medulloblastomas, ependymomas do not appear to be sensitive to this combination therapy. New therapeutic approaches are warranted.

[Malassezia furfur septicemia after bone marrow graft]. / Septicémie à Malassezia furfur au décours d'une greffe de moelle.

BACKGROUND: Systemic Malassezia furfur (Mf) infections are only seen in neonates and immunocompromised patients. CASE REPORT: A 2-year-8-month-old boy was given chemotherapy for mediastinal T cell lymphoma. Meningeal relapse supervened 10 months later, requiring polychemotherapy plus CNS irradiation followed by bone marrow transplantation. Three days after transplantation, fever associated with neutropenia required administration of ceftazidime, amikacin, vancomycin plus acyclovir followed by amphotericin B, cefotaxime plus erythromycin. Blood cultures were negative, but blood swears showed yeasts into polynuclear cells after cytocentrifugation; these yeasts were also present in the central catheter removed after a few days course of amphotericin B, flucytosine plus fluconazole. The patient was then given GM-CSF subcutaneously (5 micrograms/kg/day), followed by progressive correction of aplasia and cure of the Mf infection. CONCLUSION: This is a new case of systemic Mf infection seen in an immunocompromised child receiving parenteral nutrition with lipids.

[Rapid efficacy of preoperative chemotherapy in nephroblastoma involving cardiac cavities]. / Efficacité rapide de la chimiothérapie préopératoire sur un néphroblastome envahissant les cavités cardiaques.

BACKGROUND: Tumors involving the inferior vena cava and cardiac cavities are rare in nephroblastoma. When they do occur, the standard treatment is primary surgery; but this is often technically difficult. CASE REPORT: A 3 year-7-month-old girl was admitted because of an abdominal mass and signs of heart failure. Ultrasonography showed that this mass involved the right renal vein and the inferior vena cava including the right atrium. A CT scan showed no metastases. Echocardiography showed that the mass occupied two thirds of the right atrium and had blocked the tricuspid valve. The patient was given heparin (2 mg/kg/day), vincristine (1.5 mg/m2 on day 1) and actinomycin D (15 micrograms/kg on day 1 to 3). The heart failure disappeared and the abdominal mass decreased in volume. This improvement was confirmed by successive ultrasonographies. Chemotherapy was then completed and the patient was operated on six weeks later: right nephrectomy and removal of the cavoatrial tumoral thrombus. Pathological examination confirmed the nephroblastoma and the patient was given radiotherapy and chemotherapy for 28 weeks. She was also given aspirin for 17 weeks. Pulmonary metastases were detected 1 year after onset and were treated by a combination of surgery and chemotherapy. The patient is well 20 months after the onset of the disease. CONCLUSION: Preoperative chemotherapy seems to be effective in nephroblastoma extending to cardiac cavities; it allows subsequent surgery and facilitates postoperative radiotherapy.