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  • American Society of Hematology  (9)
  • 2000-2004  (9)
  • 1
    Online Resource
    Online Resource
    A Phase I/II Trial of Xcellerated T Cells™ in Patients with Chronic Lymphocytic Leukemia.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2508-2508
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2508-2508
    Abstract: Background: T cells from CLL subjects can be activated and expanded ex vivo using the XcellerateTM Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 and anti-CD28 antibody-coated magnetic beads (XcyteTM-Dynabeads®). With this process, anergic T cells from CLL subjects can be activated, leading to upregulation of important immune molecules on leukemic B cells and leukemic cell apoptosis (Bonyhadi et al., ASH 2002). This trial was initiated to evaluate the safety and efficacy of autologous Xcellerated T Cells in CLL subjects. Methods: Subjects had high risk or symptomatic/progressive intermediate-risk disease and ECOG PS 0–2. PBMC were collected by leukapheresis for the Xcellerate Process, and subjects subsequently received an infusion of Xcellerated T Cells. Cohorts of 3 subjects each were treated with increasing cell doses: 10 x 109, 30 x 109 and 60–100 x 109. Additional subjects were treated at the highest dose level. Results: 17 subjects have been treated to date. Data are available for 14 subjects, with a median follow-up of 12 weeks (range 8–12). Baseline characteristics [median (range)] were: age=57 (39–68), years from diagnosis=3.9 (1.8–8.7), WBC =56 x 103/mm3 (6–274). Prior treatments included chemotherapy ± monoclonal antibody treatment (n=8), investigational vaccine (n=3), and no prior therapy (n=3). After the first cohort, a WaveBioreactor-based Xcellerate III Process (Hami et al., Bioprocessing Journal 2003) was instituted, which yielded 137 ± 35 x 109 cells with 98.4 ± 1.1% T cell purity (n= 13; mean ± SD). To date there has been one serious adverse event of atrial fibrillation, which was unlikely related to Xcellerated T Cells. Following treatment, T cell counts increased in a dose dependent manner and were sustained over the 12 week f/u period, with peak mean increase of 118% in the highest dose cohort. Increases in neutrophil, platelet, hemoglobin and NK counts were observed, with peak mean increases of 118%, 26%, 9% and 66%, respectively. A ≥ 50% reduction in lymph node area was observed in 11 of 14 evaluable subjects. Median (range) spleen measurement in cm below left costal margin decreased from 3 (0–10) prior to treatment to 〈 1 (0–4), a 50% or greater decrease in 10 of 12 subjects with enlarged spleens. Treatment effects were observed at all dose levels of Xcellerated T Cells administered. Decreases in peripheral leukemic cell counts have not been observed to date. Six subjects have received a second infusion of Xcellerated T Cells (median dose 77.1 x 109; range 68.7–96.4 x 109) a median of 10.3 months (range 5.8–11.0) following the first infusion. The second infusions were well-tolerated, with no serious adverse events reported; clinical efficacy data are pending. Conclusions: Xcellerated T Cells were reproducibly manufactured for CLL subjects and were well tolerated in doses of up to 100 x 109 cells. Treatment led to significant increases in T cell counts, increases in neutrophil, platelet and hemoglobin counts, and significant decreases in lymphadenopathy and splenomegaly. Data on subjects receiving a second treatment will be reported. Clinical trials of Xcellerated T Cells following cytoreductive therapy are planned.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2508.2508
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
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    Online Resource
    Campath-1H-Based Reduced-Intensity Conditioning Followed by Allogeneic Blood Stem-Cell Transplantation and Preemptive CD8-Depleted Donor Lymphocyte Infusions.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 5069-5069
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5069-5069
    Abstract: Recent reports have demonstrated the feasibility of using the anti-CD52 antibody Campath-1H for in vivo T-cell depletion (TCD) in the context of a fludarabine/melphalan-based reduced-intensity conditioning regimen (Kottaridis et al. Blood 2000, 96:2419). Major disadvantage of this protocol is the severe immunosuppression which results in an increased rate of opportunistic infections and disease relapses. Donor lymphocyte infusions (DLI) are frequently used to overcome this limitation. The application of DLI, however, is associated with a profound risk of GvHD. Depletion of CD8+ lymphocytes from either the allotransplant or from DLI has proven feasible to reduce the incidence of GvHD (Nimer et al. Transplantation 1994, 57:82; Giralt et al. Blood 1995, 86:4337). We set up a phase-I allotransplantation study which combines the Campath-1H (100mg)/fludarabine (150mg/m2)/melphalan (140mg/m2) preparative regimen with the preemptive administration of CD8-depleted DLI in patients with hematological malignancies not eligible for myeloablative conditioning. After early withdrawal of CsA immunosuppression, CD8-depleted DLI are scheduled in a dose-escalating regimen starting on day +60 after HLA-identical sibling transplantation and on day +120 after unrelated donor transplantation, respectively. For CD8-depletion of donor leukaphereses a new CliniMACS-based protocol using clinical grade CD8 Microbeads is used. Our data show that this procedure is efficient in reducing the content of CD8+ T-cells by at least 2.5 to 3.5 logs, while CD4+ cells remain largely unchanged. In this ongoing study, 8 patients (4 myeloma, 2 CMPD, 1 ALL, 1 NHL) were included and received peripheral blood stem cells (PBSC) from HLA-identical sibling (1), HLA-matched (5) or DRB1-mismatched unrelated donors (2), according to high-resolution HLA typing. Chimerism analyses on total bone marrow-derived cells as well as on purified CD4, CD8, CD19, CD14 and CD15-positive peripheral blood cells showed durable complete donor chimerism in all but one patient (see below). After successful withdrawal of CsA, 2 patients already received CD8-depleted DLI without any acute toxicity. In the first patient (UPN 3), who was transplanted from an HLA-identical sibling, DLI were given on days 60 and 120 (1 and 5 x 106 CD4+ T cells, respectively). The second patient (UPN 4), who was transplanted from a matched unrelated donor, received the first dose of 1 x106 CD8-depleted DLI on day 120. DLI were regularly followed by a more than 2-fold increase of CD4+ cells during the first two weeks after application, while CD8+ cells remained unchanged. After the second DLI, patient UPN 3 developed a grade 2 GvHD of the skin (d+22 after DLI). Both patients were at high risk for CMV reactivation (donor: CMV negative, host: CMV positive) and repeatedly received preemptive treatment. Immediately prior to the second DLI, the CD8+ cell count in patient UPN 3 increased during an ongoing CMV reactivation. Line-specific chimerism analysis revealed that more than 50% of these CD8+ cells were of host origin. As expected, transfer of CD8-depleted DLI from CMV-negative donors was unable to entirely prevent CMV reactivation in seropositive patients. Nevertheless, our preliminary data suggest that the preemptive transfer of CD8-depleted DLI is able to accelerate immune reconstitution after reduced intensity TCD allogeneic PBSCT without rapid increase of CD8+ donor cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.5069.5069
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
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    Online Resource
    A Randomized Phase II Study of Xcellerated T Cells™ with or without Prior Fludarabine Therapy in Patients with Relapsed or Refractory Multiple Myeloma.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2410-2410
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2410-2410
    Abstract: Background: T cells from myeloma subjects can be activated and expanded ex vivo using the Xcellerate™ Process, in which peripheral blood mononuclear cells are incubated with anti-CD3 and anti-CD28 antibody-coated magnetic beads (Xcyte™-Dynabeads®). In a previous study (Borrello et al., ASCO 2004), Xcellerated T Cells administered to myeloma subjects following high dose chemotherapy and autologous stem cell transplantation led to accelerated lymphocyte recovery and restoration of the T cell receptor repertoire. In the current study, subjects with relapsed or refractory myeloma were randomized to Xcellerated T Cells with or without one cycle of fludarabine prior to Xcellerated T Cells. Fludarabine is being used to assess the influence of lymphoablation on the anti-tumor and immune reconstitution effects of T cell therapy; it has previously been reported to have no significant activty in myeloma (Kraut et al., Invest. New Drugs, 1990). Methods: Approximately 30 subjects are planned to receive treatment. Each receives a single dose of 60–100 x 109 Xcellerated T Cells. Subjects on the fludarabine arm receive a single cycle (5 days at 25 mg/m2), completed 4 days prior to the Xcellerated T Cell infusion. Results: 17 subjects have been enrolled and 13 treated to date, with median last f/u visit of 28 days (range 0–140). Xcellerated T Cells were successfully manufactured in all subjects, with T cell expansion 136 ± 61 fold (mean ± SD), with 79.2 ± 13.8 x 109 cells infused, and final product 98.0 ± 2.0% T cells (n=13). There have been no reported serious adverse events related to Xcellerated T Cells. In the fludarabine arm, lymphocytes decreased from 1,228 ± 290/mm3 (mean ± SEM) to 402 ± 164 following fludarabine, and then increased to 1,772 ± 278 on Day 14 following T cell infusion (n=7). In the non-fludarabine arm, lymphocyte counts increased from 1,186 ± 252 to 3,204 ± 545 on Day 14 (n=4). Lymphocytes were comprised of both CD4+ and CD8+ T cells. Increases were observed in NK cells from 77 ± 26 to 121 ± 25, monocytes from 166 ± 44 to 220 ± 30 and platelets from 218 ± 16 to 235 ± 24 by Day 14 (n=11). In the non-fludarabine arm, neutrophils increased from 3.6 ± 0.9 to 4.8 ± 0.6 on Day 1. On the fludarabine arm, 3 of 6 subjects developed Grade 4 neutropenia and one developed Grade 3 thrombocytopenia. Seven subjects were evaluable for serum M-protein measurements to Day 28. One of three fludarabine treated subjects had an M-protein decrease of 38%. Conclusions: Xcellerated T Cells were well-tolerated and led to increased lymphocytes, including T cells and NK cells. Increases in other hematologic parameters, including neutrophils and platelets were also observed. In this patient population, fludarabine is lymphoablative and also can cause neutropenia and thrombocytopenia. The fludarabine schedule has been decreased from 5 to 3 days. A decrease in M-protein has been observed in one of three fludarabine-treated subjects; data on additional subjects will be presented.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2410.2410
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
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    Online Resource
    Inv (16) Suppresses CEBPA in Acute Myeloid Leukemia by Activation of Calreticulin.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 3388-3388
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 3388-3388
    Abstract: Inversion of chromosome 16 (inv(16)) results in the reciprocal chromosomal rearrangement of the CBFB and MYH11 genes and it is the hallmark of malignant cells observed in patients with acute myeloid leukemia (AML) subtype M4Eo. Alterations of structure or expression of CEBPA - a key myeloid transcription factor - have been implicated in particular subtypes of AML. To investigate the effects of inv(16) on CEBPA we conditionally expressed inv(16) in U937 cells and found that CEBPA mRNA levels remained unchanged. However, CEBPA protein and binding activity were suppressed by 100% and 71%, respectively. In parallel, analysis of patients with inv(16) (n=12) as compared to normal karyotype AML M4 patients (n=6) showed that CEBPA protein and binding activity were significantly reduced (100% and 71.6%, respectively) whereas CEBPA mRNA levels remained similar. Calreticulin, an inhibitor of CEBPA translation, was induced on mRNA and on protein level in inv(16) AML patients as well as after conditional expression of inv(16) in a U937 cell system. Furthermore, inhibition of Calreticulin by siRNA powerfully restored CEBPA levels. Our results identify CEBPA as a key target gene of the leukemic fusion protein inv(16) and suggest that suppression of CEBPA by Calreticulin contributes to the differentiation block in AML with inv(16).
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.3388.3388
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
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    Online Resource
    PKC412 Inhibits the ZNF198-FGFR1 Fusion Tyrosine Kinase and Is Efficacious in Treatment of t(8;13)(p11;q12) Associated Stem Cell Myeloproliferative Disease.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2549-2549
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2549-2549
    Abstract: Human stem cell leukemia-lymphoma syndrome usually presents as a myeloproliferative disease (MPD) that evolves to acute myeloid leukemia and/or lymphoma. The syndrome associated with t(8;13)(p11;q12) results in expression of the ZNF198-FGFR1 fusion tyrosine kinase. Current empirically-derived cytotoxic chemotherapy is inadequate treatment of this disease. We hypothesized that small molecule inhibitors of the ZNF198-FGFR1 fusion would have therapeutic efficacy. We characterized the transforming activity of ZNF198-FGFR1 in hematopoietic cells in vitro and in vivo. Expression of ZNF198-FGFR1 in primary murine hematopoietic cells caused a myeloproliferative syndrome in mice that recapitulated the human MPD phenotype. Transformation in these assays, and activation of the downstream effector molecules PLCγ, STAT5 and PI3K/AKT, required the proline-rich, but not the zinc-finger domains of ZNF198. A small molecule tyrosine kinase inhibitor, PKC412 (N-benzoyl-staurosporine) effectively inhibited ZNF198-FGFR1 tyrosine kinase activity and activation of downstream effector pathways, and inhibited proliferation of ZNF198-FGFR1 transformed Ba/F3 cells. Furthermore, treatment with PKC412 resulted in statistically significant prolongation of survival in the murine model of ZNF198-FGFR1 induced myeloproliferative disease. Based in part on these data, PKC412 was administered to a patient with t(8;13)(p11;q12) and was efficacious in treatment of progressive myeloproliferative disease with organomegaly. Therefore, PKC412 may be a useful therapy for treatment of human stem cell leukemia-lymphoma syndrome.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2549.2549
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
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    Online Resource
    Defensins are dominant HLA-DR-associated self-peptides from CD34− peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia)
    American Society of Hematology ; 2000
    In:  Blood Vol. 95, No. 9 ( 2000-05-01), p. 2890-2896
    Details
    In: Blood, American Society of Hematology, Vol. 95, No. 9 ( 2000-05-01), p. 2890-2896
    Abstract: The HLA-DR-associated peptides from peripheral blood mononuclear cells of 2 patients with plasmacytoma and 1 with chronic myeloid leukemia were isolated, identified, and compared. Several were identified as derivatives of the defensin family. Defensins (or human neutrophil peptides [HNP]) are antimicrobial, cationic peptides of 29 to 35 amino acids in length and are the major constituents of the azurophilic granules of human neutrophils. Using peripheral blood cells from leukapheresis, containing about 90% of polymorphonuclear cells, we could identify HNP-1, -2, and -4 and propeptides of up to 49 amino acids in length, eluted from HLA class II molecules. Binding of isolated and synthetic defensin peptides to various HLA-DR alleles using an in vitro binding/competition assay based on size exclusion chromatography revealed that defensin may bind into the peptide-binding groove. In a T-cell competition assay, defensins were able to reduce the proliferation of an HLA-DR-restricted T-cell line after preincubation of stimulating cells (CHO-DRB1*0401 transfectants) with defensin. Therefore, binding of defensins might prevent T-cell recognition of HLA class II molecules expressed on different blood precursor cells (all of which are “nonprofessional” antigen-presenting cells) by blocking the HLA peptide-binding groove or, alternatively, might protect defensin-expressing cells from self-destruction.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V95.9.2890.009k09_2890_2896
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2000
    detail.hit.zdb_id: 1468538-3
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  • 7
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    Characterization of Renal-Cell Carcinoma (RCC)-Reactive Cytotoxic T-Lymphocyte Responses Generated from Peripheral Blood of HLA-Matched Sibling and Unrelated Healthy Individuals in Vitro.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 4971-4971
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4971-4971
    Abstract: Although current allo-transplantation therapy can induce considerable graft-versus-tumor (GvT) effects in RCC patients, it is also accompanied by severe, even life-threatening side effects, mainly due to graft-versus-host disease (GvHD). Efforts aiming to improve the specificity and efficiency of allogeneic cell therapy in this disease (e.g. specific donor lymphocyte infusion or vaccination) will certainly benefit from the identification of potential anti-tumor effector mechanisms and their corresponding target structures. We recently demonstrated that RCC-reactive cytotoxic T-lymphocyte (CTL) clones can be isolated from peripheral blood of healthy donors matched with the RCC stimulators for HLA-class I. These CTL were found to recognize a broad panel of RCC antigens with restricted or ubiquitous tissue expression (Doerrschuck A, et al., Blood July 1, 2004, Epub). We now extended our analyses on peripheral blood mononuclear cells (PBMC) of further HLA-matched healthy sibling (1) and unrelated individuals (4) and compared these results with available autologous patient PBMC. While mixed lymphocyte/tumor-cell culture (MLTC) responders derived from allogeneic donors showed a robust antigen-dependent proliferation over several weeks, a weak if any proliferative response was seen with autologous MLTC populations. By analysing the fine specificity of MLTC-derived clonal CTL the majority of allogeneic effectors recognized exclusively their RCC stimulators, but not corresponding lymphoblastoid-cell lines or natural killer target K562. These CTL were restricted by various HLA-A, -B or -C molecules. We further isolated CTL clones that exhibit an extraordinary strong recognition of RCC and various epithelial tumor-cell lines. Antibody blocking experiments provided clear evidence that these CTL are restricted by a not yet defined HLA-Ib molecule and, simultaneously, by a NKG2D-dependent mechanism. Other rapidly proliferating CD3+ CD8+ CTL clones were obtained that showed a non-HLA-restricted reactivity against RCC and a minor but consistent reactivity against targets with low or absent HLA-class I expression (e.g. K562). In conclusion, our results demonstrate that a heterogeneous panel of RCC-reactive HLA-Ia/Ib-restricted CTL can be isolated from PBMC of HLA-class I-matched healthy individuals. Alternatively, CTL recognizing RCC in a non-HLA restricted manner can be obtained. Our observations might reflect the superior ability to activate and expand RCC-directed T cells from PBMC of allogeneic healthy donors compared to the autologous setting. At this point, we cannot conclude whether these various CTL populations contribute to effective anti-RCC immune responses occurring in vivo. Answering this question will certainly require to identify further CTL-defined target structures at the molecular level. This would allow us to analyse the expression of candidate antigens and the frequency of specific CTL in RCC patients after allogeneic blood stem-cell transplantation, and to correlate these findings with clinical GvT and GvH events.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.4971.4971
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
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    Is ARAC Required in the Treatment of Newly Diagnosed APL? Results of a Randomized Trial (APL 2000).
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 391-391
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 391-391
    Abstract: The combination of ATRA and anthracycline based chemotherapy (CT) is established as the reference treatment of newly diagnosed APL. For CT, recent reports have suggested than an anthracycline alone may be as effective as anthracycline-AraC combinations, while being less myelosuppressive. We tried to confirm this hypothesis in a randomized trial. Patients and methods: In APL 2000 trial (started in July 2000) newly diagnosed APL patients (pts) 〈 60 years with WBC 〈 10,000/mm3 were randomized between a standard group A (induction : ATRA 45mg/m2/d until CR with DNR 60 mg/m2/dx3 and AraC 200mg/m2/dx7 started on day 3 ; first consolidation with the same CT course, second consolidation with DNR 45 mg/m2/dx3 and AraC 1g/m2/12h x4d ; maintenance : intermittent ATRA 15d every 3 months and continuous 6 MP + MTX, during two years) and Group B (same treatment as group A, but without AraC). Other pts were not randomized: pts aged 〈 60 with WBC 〉 10,000/mm3 (Group C) received the same treatment as Group A, but with AraC 2 g/m2/12h x4d during the second consolidation course. Pts aged 〉 60 with WBC 〈 10,000 (Group D) and 〉 10,000/mm3 (Group E) received the same treatment as Group B and Group A, respectively. All pts with WBC 〉 10,000/mm3 received intrathecal MTX +AraC for CNS prophylaxis. Results: the first interim analysis was made at the reference date of September 1st 2003, after inclusion of 300 patients. Overall 289 (96.3 %) patients achieved CR, 9 (3 %) had early death (ED) and 2 had resistant leukemia. 19 patients relapsed, including 15 hematological relapses (Hem Rel) and 4 purely molecular relapses (Mol Rel) (ie treated before Hem rel). The randomized groups (pts 〈 60 years, WBC 〈 10,000) i.e. Group A (AraC +, 80 pts) and Group B (AraC -, 87 pts) were well balanced for all pretreatment characteristics. In Group A, 79 patients (98 %) achieved CR and one had early death (ED), as compared to 82 (94 %) CR, 3 ED, and 2 resistant leukemias in Group B (p = NS). The 2 year incidence of relapse, event free survival and survival was 3.8% vs. 11.9% (p = 0.021), 93.6% vs. 83.4% (p = 0.019), and 97.4% vs. 89.9% (p = 0.085) in Group A and B, respectively. Of the 11 relapses in group B, 9 were Hem Rel and 2 were Mol Rel, as compared to 1 and 1, respectively, for the 2 relapses in group A. For non randomized groups, the CR rate, 2 year relapse rate, EFS and survival were 97 %, 2.6%, 88.4%, and 91% for Group C ( 〈 60 years, 〉 10 000 WBC, n = 70), 98 %, 11%, 79.4%, and 90.3% for Group D ( 〉 60 years 〈 10 000 WBC, n = 47) and 87 %, 0%, 78.3%, and 78.3% for Group E ( 〉 60 years, 〉 10 000 WBC, n = 16). Conclusion: Our results strongly support that, at least with the anthracycline used (DNR at a cumulative dose of 495mg/m2) AraC should not be omitted in consolidation chemotherapy of newly diagnosed APL, even in patients with WBC 〈 10,000/mm3. The low relapse rate in patients with WBC 〉 10 000/mm3 supports a role for high dose AraC (1 to 2 g/m2/12h) in this population at higher risk of relapse. Following this first interim analysis, Groups B and D (ie groups without AraC) were closed for inclusion. Updated results will be presented.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.391.391
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
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    Analyzing the MLL Recombinome.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 4267-4267
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4267-4267
    Abstract: Acute leukemias are frequently associated with specific chromosomal translocations of the human MLL gene. In general, MLL translocations define a distinct disease entity that needs to be diagnosed with precision to facilitate rapid clinical decisions. Here we present data about a new PCR based method that uses patient genomic DNA to identify any MLL fusion. Fourty different MLL translocations were successfully analyzed. We will present three novel MLL translocation partner genes and a new MLL deletion. The benefits of this novel technique for diagnosis and MRD analyses will be discussed. Supported by grant 2001.061.1 from the Wilhelm Sander foundation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.4267.4267
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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