Biomedical subjects

J Vormoor

Publications and source records attributed to J Vormoor.

41 records · Page 3Linked to original sources

PubMedDate not supplied

Treatment of refractory CMV-infection following hematopoietic stem cell transplantation with the combination of foscarnet and leflunomide.

BACKGROUND: Treatment of cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is limited by toxicities of current antiviral drugs and the occurrence of drug resistant strains. Leflunomide, an immunosuppressive agent used for treatment of rheumatoid arthritis, also has activity against CMV by impairing viral assembly. Here we report the control of refractory CMV disease by the combined use of foscarnet and leflunomide. PATIENTS AND RESULTS: A 1S-year-old boy with juvenile myelo-monocytic leukemia (JMML) received an allogeneic HSCT with bone marrow stem cells from a mismatched, unrelated donor (MMUD, recipient and donor CMV-positive). CMV-reactivation two months post transplantation (Tx) could only be controlled by the use of cidofovir. Because of secondary graft failure, the boy received a second HSCT with peripheral blood stem cells (PBSC) of the same donor after overall 6 months. CMV-infection was noticed three weeks later, associated with a considerable rise of both CMV-copy number and pp65-antigen. Since reinduction with cidofovir was ineffective and ganciclovir not warranted due to the history of graft failure, the child then received a combination of foscarnet/leflunomide, leading to a rapid decline of his CMV-copy number and to an afebrile state. Hematological, hepatic or renal toxicities were not observed. CONCLUSION: This case report suggests that leflunomide may be of use in the management of transplant recipients with CMV-infection refractory or intolerant to conventional antiviral therapy.

Antiviral Agents↗

PubMedDate not supplied

[Incidence and prognostic significance of Auer rods in children with acute myeloid leukemia in the studies AML-BFM-78 and -83].

The prognostic significance of Auer rods in children with AML was investigated in 129 patients of the study AML-BFM-78 and 154 patients of the study AML-BFM-83. Auer rods were found in 68 patients (53%) in the study AML-BFM-78 and 69 patients (45%) in the study AML-BFM-83. The incidence was higher in the subtypes FAB M1 (61%) and M2 (75%) compared to the subtypes FAB M4 (44%) and M5 (5%). In both studies the remission rate was higher in Auer rod-positive patients. Moreover, in the study AML-BFM-83 patients with Auer rods had a significant longer remission duration: the probability of an event-free interval (EFI) of 5 years was 77% (SD 6%) in Auer rod-positive patients compared with 44% (SD 7%) in Auer rod-negative patients (p less than 0.01). In the study AML-BFM-78 no differences regarding remission duration between both groups were detected. Analysis of the individual FAB subtypes revealed a significant higher event-free survival rate (EFS) after 5 years in Auer rod-positive compared with 18% (SD 12%) in Auer rod-negative patients (p less than 0.0001). No prognostic significance of Auer rods in other subtypes could be detected. In the overall group of all patients absence of Auer rods was associated with the unfavourable parameters hyperleucocytosis (greater than or equal to 100 x 10(3)/microliters) and acute monocytic leukemia (FAB M5) (p less than 0.01, p less than 0.001, respectively). The multivariate analysis in the study AML-BFM-83 showed that Auer rods were of prognostic significance independent from the initial leukocyte count and the FAB type M5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

[Transient myeloproliferation and acute myeloid leukemia in infants with Down's syndrome].

Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.

Antigens, CD↗

PubMedDate not supplied

Good engraftment of B-cell precursor ALL in NOD-SCID mice.

BACKGROUND: In vivo models for human B cell precursor ALL have been established by transplanting human leukemic cells onto immune-deficient SCID mice. High risk and relapsed leukemias engraft very well in these mice, however, good prognosis pediatric ALL often grow poorly if at all. Recently a new, even more immune-deficient mouse strain has been bred by crossing the scid mutation onto the NOD mouse background. As these NOD-SCID mice have been shown to be better recipients for human myeloid cells the goal of this study was to test these mice as hosts for human acute lymphoblastic leukemia cells. PATIENTS AND METHODS: Bone marrow or peripheral blood cells from/pediatric and one adult patient with B-cell precursor ALL were transplanted onto immune-deficient NOD-SCID mice according to established protocols. MAIN RESULTS: ALL cells from 6 out of the 8 patients (75%) successfully engrafted the NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltration in the murine marrow (> 10%). High level human cell engraftment could be demonstrated by flow cytometry, Southern blot analysis and cytology. By cytology and immunophenotype the leukemia in the mice was indistinguishable from the original leukemia in the patients. The presence of few human eosinophils in the marrow of highly engrafted mice indicates minimal coengraftment of residual normal cells. Development of overt leukemia in the mice after transplantation of cells from different patients varied between 1.5 and 7 months. Interestingly and in contrast to myeloid cells, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. Limiting dilution experiments with leukemic blasts from one patient showed that as few as 10000 cells were sufficient to transfer the leukemia onto NOD-SCID mice. CONCLUSIONS: NOD-SCID mice are sensitive recipients for human ALL xenografts.

Adult↗

PubMedDate not supplied

[Flow cytometric characterization of maturation processes and primitive stem cell population in pre-B-cell ALL in childhood].

Bone marrow and peripheral blood from children with acute lymphoblastic leukemia was analyzed by flow cytometry to assess leukemic cell differentiation and to characterize the profile of cell surface marker expression on rare CD34+ cell populations. The goal of this study was to determine if patterns of cell surface antigens could be identified on CD34+ subpopulations which may allow distinction between normal and leukemic stem cells. Expression of the progenitor cell antigen CD34 on leukemic blasts was very heterogeneous and varied between 0.5 and 100% in 20 patients analyzed in this study. In cALL and pre-B-ALL, a variable percentage of the leukemic cells coexpressed CD20 in addition to CD10. Only in one case, differentiation characteristic for normal B cell development with coordinated downregulation of CD10 with increasing expression of CD20 was observed. By analysing 5 x 10(6)-1 x 10(6) cells, a CD34+ cell population could be identified in 8 out of 8 patients which did not express CD19 and comprised less than 0.1% of all bone marrow or peripheral blood cells. Within this population, there was differentiation from primitive CD34-CD38- to more mature CD34+CD38+ cells. In 4 of these patients, an additional CD34+ population with low expression of CD19 (CD34+CD19lo) was detected. The lack of CD45 expression on the leukemic cells of 2 patients was used as a marker for the leukemic cell clone. In both patients, the CD34+CD19- cells did express CD45 while CD34+CD19lo/+ cells were CD45 negative. This suggests that the CD34+CD19lo cells were part of the leukemic clone and that the CD34+CD38-CD19- cells may represent residual normal primitive hematopoietic cells. In conclusion, flow cytometry allowed identification of primitive CD34+ cell populations in children with ALL, which can now be functionally characterized by transplantation onto immune-deficient mice.

Animals↗