1/5. Donor lymphocyte infusion followed by interferon-alpha plus low dose cyclosporine A for modulation of donor CD3 cells activity with monitoring of minimal residual disease and cellular chimerism in a patient with first hematologic relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation.A 15-year-old girl with Ph-positive chronic myelogenous leukemia in first chronic phase received bone marrow from her human leukocyte antigen matched brother. Twenty three months after bone marrow transplantation hematological relapse occured which was treated with two infusions of donor lymphocytes (DLI) (0.5x10(8) CD3/kg b.w./infusion). To enforce the graft-versus-leukemia effect (GvL), the first DLI was followed by administration of interferon-alpha (INF-alpha) 6x10(6) U/day for 30 days, whereas, after the second infusion INF-alpha was given at the same dose until hematological remission was achieved (80 doses). Minimal residual disease (MRD) was detected by conventional cytogenetics (Ph chromosome), fluorescence in situ hybridization (FISH) cytogenetics (BCR/ABL translocation) and reverse transcriptase-polymerase chain reaction (RT-PCR) Ecotropic virus integration site-1 (EVI-1 gene expression), whereas cellular chimerism was monitored by assessment of microsatellite markers PCR and Y-chromosomal dna content FISH. When hematological remission was achieved the pancytopenia was observed and the cytogenetic and molecular investigations revealed only partial remission and mixed chimerism, however, with predominance of donor origin hematopoiesis. To diminish the myelosupressive effect of donor CD3 cells without switching-off the GvL effect, a low dose of cyclosporine A was given. Further observation revealed significant improvement of hematopoiesis with parallel gradual decline of MRD and increase of donor hematopoiesis up to complete chimerism. Graft-versus-host disease was not observed at any stage of the treatment.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/5. Detection of minimal residual disease in peripheral blood prior to clinical relapse of childhood acute lymphoblastic leukaemia using PCR.Submicroscopic evidence of persistent minimal residual disease (MRD) in first remission bone marrow samples from children with acute lymphoblastic leukaemia (ALL) indicates a high risk of clinical relapse. Since microscopic evidence of leukaemic lymphoblasts is often present in the peripheral blood in the weeks before clinical presentation at diagnosis or relapse, peripheral blood may be used instead of bone marrow to detect MRD in ALL patients. We examined a median of 0.165 microg (from 1.0-2.0x10(4)cells) genomic dna from archived peripheral blood smears collected 8-16 months prior to clinical relapse in eight children with ALL for evidence of MRD. We used the polymerase chain reaction and primers designed to identify clonal antigen receptor gene rearrangements. Among the seven patients with bone marrow relapse, MRD was detected at a median of 1.2 months (0-8 months) prior to clinical relapse, indicating that MRD in the peripheral blood may be a late event in the course of leukaemic relapse. A prospective MRD study in ALL patients analysing larger numbers of peripheral blood cells will be needed to evaluate the utility of peripheral blood over bone marrow for MRD testing in childhood ALL.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/5. Concurrent presence of both patient and donor t(14;18) in a follicular lymphoma patient after undergoing allogeneic BMT: implications for minimal residual disease detection post-transplant.We report the case of a t(14:18)( ) follicular lymphoma (FL) patient in long-term clinical remission after undergoing an allogeneic bone marrow transplantation (allo-BMT) from a human leukocyte antigen (HLA)-identical sibling donor who was the normal healthy carrier of a t(14:18)( ) B cell clone. Using real-time quantitative PCR (RQ-PCR) and gel electrophoresis, we document the temporal disappearance of the patient's t(14:18)( ) clone early post-transplant with the concomitant emergence and long-term persistence of the donor's t(14:18)( ) clone in the patient's peripheral blood. This report indicates that the use of PCR-based techniques to measure minimal residual disease in FL patients post-alloBMT should incorporate pretransplant screening of the donor for t(14;18). Furthermore, it suggests that healthy individuals with t(14:18) need not be excluded as donors for FL patients treated with allo-BMT.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/5. Successful treatment of a patient with subcutaneous panniculitis-like T-cell lymphoma with high-dose chemotherapy and total body irradiation.A 24-yr-old man was referred for fever, right cheek swelling, subcutaneous tumor and liver dysfunction. physical examination showed an elastic hard subcutaneous tumor on the right cheek, left axillary lymph node swelling and multiple small subcutaneous tumors in the trunk. Laboratory examinations showed elevated levels of transaminase, soluble interleukin-2 receptor and ferritin. biopsy of the subcutaneous tumor showed proliferation of medium-sized cells with abundant clear cytoplasm and hyperchromatic nuclei among the subcutaneous fat tissues. These cells showed CD3 , CD4-, CD8 , CD56- and CD20- phenotype and possessed cytotoxic molecules such as granzyme B and T-cell intracellular antigen-1. Bone marrow aspiration showed proliferation of small numbers of abnormal lymphocytes with severe hemophagocytosis. He was thus diagnosed as having subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and treated with dose-escalated CHOP regimen. After three courses of the chemotherapy, he was further treated with high-dose chemotherapy and total body irradiation (TBI) with autologous peripheral blood stem cell rescue. Thereafter, he has been in remission for more than 2 yr. We consider that SPTCL with hemophagocytosis is an extremely aggressive disease, and high-dose chemotherapy and TBI should be included for the choice of the treatment.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/5. Molecular persistence of chronic myeloid leukemia caused by donor T cells specific for lineage-restricted maturation antigens not recognizing immature progenitor-cells.Although donor lymphocyte infusion (DLI) induces complete remissions in 70% of patients with relapsed chronic myeloid leukemia (CML) after allogeneic stem-cell transplantation (SCT), some patients are refractory to DLI by showing disease persistence. In a patient who received DLI for relapsed CML, we observed persisting molecular disease despite a hematological and cytogenetic remission in the absence of graft-versus-host disease (GVHD). To determine the nature of this immune response, we isolated leukemia-reactive donor T-cell clones from the bone marrow (BM) of the patient at the time of clinical response. Four different types of CD8 HLA class I restricted T-cell clones were obtained that were cytotoxic against Ebstein-Barr virus-transformed B-cell lines (EBV-LCL) of the patient, but not the donor, indicating recognition of minor histocompatibility antigens (mHags). By using survival studies with CFSE labelled BM cells populations, a hematopoietic progenitor cell inhibition assay and direct morphological examination we showed that the T-cell clones recognized mature monocytic and myeloid cells, whereas immature BM progenitor cells were insufficiently lysed. This patient's refractoriness for DLI appears to be caused by inadequate lysis of progenitor cells by these cytotoxic T cells. These findings support the hypothesis that for eradication of CML a cytotoxic T-cell response against leukemic progenitor cells is essential.- - - - - - - - - - ranking = 5keywords = antigen (Clic here for more details about this article) |