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  • American Society of Hematology  (90)
  • 1
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    The Effects of Induction Chemotherapy and High-Dose Melphalan with Tandem Autologous Transplantation in Multiple Myeloma: The Prospective Randomized DSMM 2 Study.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 446-446
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 446-446
    Abstract: The concept of the DSMM 2 study was to give age-adjusted high-dose treatment to elderly myeloma patients in order to balance efficacy and toxicity. The value of conventional induction chemotherapy before high-dose melphalan and autologous stem cell transplantation and the durability of unmaintaned remissions afterwards was addressed. Between September 2001 and September 2006, 434 multiple myeloma patients 60–70 years of age with 0–1 cycle of pretreatment were recruited from 45 centers. The median age was 65 years. The patients were randomized to receive 4 cycles of conventional induction chemotherapy [A1] (n=216; VAD or idarubicin/Dex in 88%) or no induction chemotherapy [A2] (n=218). Instead of induction chemotherapy, patients in [A2] received only one short course of dexamethasone 40 mg orally (days 1–4 and 8–11). Subsequently, stem cells were mobilized after combination chemotherapy with ifosfamide, epirubicin and etoposide (IEV) followed by G-CSF; stem cells could be collected in 97% of the patients. Then the patients proceeded to tandem MEL140 (melphalan 140 mg/m2) and autologous peripheral blood stem cell transplantation with a time interval between high-dose cycles of 2 months. No consolidation or maintenance treatment was scheduled. Analyses were performed in an intent-to-treat approach. 87% of patients completed the first transplant, 74% the second. Overall, the treatment was well tolerated and grade 3/4 infections and stomatitis after high-dose melphalan occurred in 37% and 9% of patients, respectively. The overall mortality (tumor and/or toxicity) during treatment was 7.1%: 4.5% during the induction phase (6.1% in [A1] versus 2.9% in [A2]), 1.5% after mobilization and 1.1% after high-dose therapy. Notably, the best response (EBMT criteria) at the end of treatment in patients randomized to [A1] (16% CR, 64% PR) or [A2] (18% CR, 69% PR) was not different. An early loss of tumor control with disease progression occurred in 6% in [A1] versus 1% in [A2]. With a median follow-up time of 20 months, there was no significant difference in the median event-free survival (EFS) (22 months in [A1] versus 20 months in [A2]) and not in the overall survival (OS) at 4 years (63% in [A1] versus 65% in [A2]). In ≥ 50% of patients, the time between last treatment and progression was 〉 16 months. The EFS of patients 60–64 years of age and 65–70 years of age was the same. In conclusion, there was no benefit of conventional induction chemotherapy with VAD- or VAD-like regimens in patients receiving tandem MEL140 with autologous transplantation. This induction treatment therefore may be avoided. Tandem-MEL140 is feasible and well tolerated in the majority of elderly patients with symptomatic myeloma. Its profound and durable anti-tumor effect was demonstrated by prolonged unmaintained remissions. The addition of new agents given as consolidation or maintenance probably will further improve treatment results.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.446.446
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 2
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    The Efficacy and Safety of RAD (Lenalidomide, Adriamycin and Dexamethasone) In Newly Diagnosed Multiple Myeloma – First Results of a Phase II Trial by the German DSMM Group
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 1945-1945
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1945-1945
    Abstract: Abstract 1945 Background Prognosis of patients with multiple myeloma (MM) has significantly improved by the introduction of autologous (auto) stem cell transplantation (SCT). The “novel drugs” which have shown activity in relapsed MM are increasingly used in first-line therapy aiming at maximized response prior to SCT. Whether allogeneic (allo) SCT adds to further disease control remains a matter of debate. Our group has shown the RAD regimen (lenalidomide, adriamycin and dexamethasone) to be highly effective and relatively well tolerated in relapsed and refractory MM. Therefore, we decided to explore RAD in the up-front management. Patients and Methods The current phase-II trial (DSMM XII) was designed to include patients (pts) up to the age of 65 years with newly diagnosed MM requiring treatment. We chose four cycles of RAD (lenalidomide 25 mg d-21; infusional adriamycin 9 mg/m2 per day d1-4; dexamethasone 40 mg d1-4 and 17–20; pegfilgrastim 6 mg d 6) every 4 weeks for induction followed by chemomobilization of peripheral blood stem cells. Low molecular weight heparin is mandatory during RAD treatment for thromboprophylaxis. All pts are to undergo one cycle of melphalan 200 mg/m2 followed by auto SCT. A subsequent allo SCT after reduced intensity conditioning (treosulfan/fludarabin) is scheduled for pts featuring at least one previously identified (cytogenetic or serologic) risk factor. Those with very favourable risk are to proceed to a second auto SCT. All patients will receive 12 months of lenalidomide maintenance (10 mg per day) on a continuous basis. Here, we present results of a planned safety analysis. Results 75 pts with a median age of 57 (range, 35–66) years have been enrolled by 11 German centers between 9/2009 and 7/2010. Currently, 51 pts are evaluable for toxicity during RAD induction: In all, 25 severe adverse events (SAEs) were reported for 16 subjects (31%). 68% of SAEs were assessed to be drug-related. Most frequent events were venous thrombosis (VTE; n=4), pyrexia (n=3) and syncope (n=2). Neutropenia, extravasation, pleural effusion, and allergic dermatitis accounted for one SAE each. 17 patients, 10 of whom (59%) had ISS stage II/III disease, are evaluable for post-induction response. Ten subjects (59%) achieved VGPR or better: 6 pts had VGPR and 2 patients each CR and stringent CR as assessed by the investigator. Conclusions Our preliminary results suggest RAD to be a well tolerated and effective novel induction protocol in up-front treatment of MM. Notably, incidence of severe hematotoxicity observed so far is significantly lower than was in our previous study in relapsed/refractory pts. Incidence of VTE was acceptable while no neurotoxicity occurred. Updated results will be presented. Disclosures: Knop: Celgene Germany: Consultancy, Honoraria. Off Label Use: Lenalidomide in combination with doxorubicin in myeloma first-line therapy. Reichle:Celgene Germany: Research Funding. Einsele:Celgene Germany: Consultancy, Honoraria. Bargou:Celgene Germany: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.1945.1945
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 3
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    Blinatumomab Monotherapy Shows Efficacy in Patients with Relapsed Diffuse Large B Cell Lymphoma
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 1637-1637
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1637-1637
    Abstract: Abstract 1637 Blinatumomab (MT103) is a single-chain bispecific antibody construct with specificity for CD19 and CD3 belonging to the class of bispecific T cell engager (BiTE®). A phase I trial with indolent and mantle cell lymphoma patients established a maximal tolerable dose (MTD) at 60 μg/m2/d. The trial was subsequently amended to evaluate blinatumomab in patients with diffuse large B cell lymphoma (DLBCL). Patients were treated by 4–8-week continuous i.v. administration with the following dosing regimen: first week at 5 μg/m2/d, second week at 15 μg/m2/d and for the remaining treatment period at 60 μg/m2/d. Two cohorts each with 6 DLBCL patients were enrolled. The two cohorts solely differed by the dose and schedule of corticosteroid medication administered at the beginning of blinatumomab infusion for mitigation of adverse events. In the first cohort 100 mg prednisolone was applied 1 hour prior to start; and in the second cohort patients received dexamethasone on days 1, 2, and 3. Three sequential patients received dexamethasone also 6–12 hours prior to start of infusion. Out of the twelve patients, 5 were male and 7 female. The median age was 57 years (range from 26 to 78 years). Patients had received a median of 4 prior regimens (range from 2–6). All patients had been exposed to rituximab. Eight of the 12 patients had undergone autologous stem cell transplantation (ASCT). International prognostic index (IPI) at screening ranged from 1 to 3 with a median of 2. The most common clinical adverse events (AEs) regardless of causality ( 〉 30%) were pyrexia (81.8%), fatigue (54.5%), constipation (36.4%), headache (36.4%), tremor (36.4%) and weight increase (36.4%). The most frequent laboratory AEs regardless of causality ( 〉 30%) were hyperglycemia (63.6%), lymphopenia (54.5%), C-reactive protein increase (45.5%), gamma-glutamyltransferase increase (45.5%) and thrombocytopenia (36.4%). Most AEs occurred early and were reversible. Four of 12 patients discontinued infusion due to fully reversible CNS events, 2 of which qualified as dose limiting toxicities (DLTs). Although just one DLT (reversible CNS event grade 3) occurred in the prednisolone cohort, a further cohort applying prophylactic dexamethasone was opened to optimize management of CNS events. A further refinement of the dexamethasone schedule, starting longer time prior to start of blinatumomab, was introduced after one early patient in the cohort receiving dexamethasone had experienced a reversible CNS event leading to discontinuation. All three patients treated in this manner completed the first blinatumomab cycle without discontinuations. Only one showed a grade 1 tremor, and no other CNS AEs were reported in these three patients. Two of 12 patients were not exposed to 60 μg/m2/d due to early discontinuations and 1 patient is too early in treatment for response evaluation. Five out of the remaining 9 evaluable patients (56%) showed objective clinical responses (4 CR/CRu; 1 PR). Three out of the 5 patients with CR/CRu or PR had prior ASCT. Two patients achieved objective responses (1 CR, 1 PR) despite of discontinuation at 60 μg/m2/d. The median response duration is +182 days (longest current duration +428 days), with 4 out of 5 responses still ongoing. Further evaluation of the last cohort will refine the recommended phase II dose, and the intensity and timing of dexamethasone comedication. The observation of lasting CRs after blinatumomab monotherapy in DLBCL patients is promising and warrants further exploration in a phase II study. Disclosures: Krause: Micromet: Research Funding. Mackensen:Micromet Inc.: Research Funding. Topp:Micromet: Consultancy, Honoraria. Scheele:Micromet Inc.: Employment, Equity Ownership, Patents & Royalties. Nagorsen:Micromet Inc.: Employment, Equity Ownership, Patents & Royalties. Zugmaier:Micromet: Employment. Degenhard:Micromet Inc: Employment. Schmidt:Micromet AG: Employment. Kufer:Micromet Inc: Employment, Equity Ownership. Libicher:Micromet Inc.: Consultancy, Honoraria. Bargou:Micromet: Consultancy, Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.1637.1637
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 4
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    Parallel Evolution of Multiple PSMB5 mutations in a Myeloma Patient Treated with Bortezomib
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 3282-3282
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3282-3282
    Abstract: Introduction: Proteasome inhibition is the backbone of various Multiple Myeloma (MM) treatment regimens, leading to durable responses and high quality remissions. However, under prolonged therapy patients eventually develop drug resistance and the underlying mechanisms have been poorly understood. Proteasome inhibitor resistant cell lines were generated by continuous exposure to proteasome inhibiting drugs. In these cell line models a number of variants within the PSMB5 gene were observed. This includes single point mutations, leading to conformational changes of the _5 subunit within the 20S proteolytic core of the proteasome, impairing its chymotryptic catalytic function and the binding of inhibitory drugs. However, no PSMB5 mutations could, so far, be identified in human disease, leaving the functional relevance of such mutations to be determined. Methods: We applied the MM Mutation Panel (M3P) and used the Personal Genome Machine (Life Technologies) to sequence CD138+ purified bone marrow plasma cells and peripheral blood germ line control from a MM patient in third relapse that had been previously treated by various proteasome inhibitor containing therapies (VTD-PACE, VCD, PAD-Rev). This patient was subsequently treated with a pomalidomide, bortezomib, adriamycin and dexamethasone combination therapy (Pom-PAD) and achieved a partial remission after 4 cycles of therapy. When being exposed to VCD at earlier relapse a complete remission was induced within 6 cycles of therapy, demonstrating excellent response to proteasome inhibition at this earlier disease stage. Results: We identified clonal missense mutations in this patient at known NRAS hotspot location (p.Gln61Arg) and in MAX (p.Arg35His). Most notably we found and validated four subclonal single point mutations in PSMB5, each of them in subclonal frequencies with variant reads (VR) ranging from 1.9%- 5.9% (average read depth 750X). All PSMB5 mutations occurred in a highly conserved region in exon 2 of the gene (p.Cys122Tyr, p.Met104Ile, p.Ala86Pro, p.Ala79Thr), with three of them being located within the proteasome inhibitor drug binding site. Our 400bp amplicon design allowed us to observe that each mutation identified in PSMB5 is exclusively present on a different sequencing read and no reads are shared between the mutations. This implies that the mutations are present on different subclones of the tumor, which means that, despite low VR frequencies of the single mutation, in sum more than a quarter of the whole tumor might be affected by mutated PSMB5. At a disease stage when the patient was well responsive to proteasome inhibitor treatment (at diagnosis and at first relapse), of note, none of the mutations in PSMB5 is detectable. Conclusion: Here we report the first in human PSMB5 mutation in a MM patient. These mutations evolved in parallel within different subclones of the disease under the selective pressure of bortezomib- containing treatment regimens, representing branching evolution. It is to speculate whether previous investigations negating the existence of PSMB5 mutations in proteasome inhibitor treated patients might not have sequenced deep enough or did set up a sensitivity cut-off too rigid to detect such subclonal mutations. Our finding suggests that the mutations identified may contribute to the development of proteasome inhibitor resistance, emphasizing the need for more detailed genomic characterization of tumors, including minor subclonal mutation detection. Functional analysis of the mutations is ongoing and results will be presented at the meeting. Figure Figure. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.3282.3282
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 5
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    BPI A645G SNP but Not NOD2 Genotype Predicts for Acute Lung Injury After Allogeneic Stem Cell Transplantation
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 2324-2324
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2324-2324
    Abstract: Abstract 2324 Introduction: Infectious as well as non-infectious pulmonary complications are key determinants of non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Single nucleotide polymorphisms (SNP) in two genes coding for nucleotide-binding oligomerization domain containing 2 (NOD2) and bactericidal/permeability-increasing protein (BPI) have been shown to predict for the occurrence of GvHD and chronic pulmonary complications after allo-HSCT. We aimed at determining the effect of SNPs in these genes on the occurrence of acute lung injury (ALI) after allo-HSCT. Patients and Methods: We retrospectively analyzed a cohort of 272 patients undergoing allo-HSCT and their respective related and unrelated donors. ALI was functionally defined as a drop of the oxygenation index (OI = partial pressure of oxygen in arterialized capillary blood/inhaled oxygen concentration) below 300. Genotyping for NOD2 SNP 8, 12 and 13 and BPI SNP A645G was done using Real Time-PCR. The incidence of ALI was assessed by univariate competing events statistics and by a multivariate model according to Fine and Gray. Results: Overall, 115 of 272 (42.3%) patients suffered from ALI at least once during the first 100 days post allo-HSCT. Median time to onset was 11 days. Neither NOD2 polymorphisms in the donor nor in the recipient correlated with the occurrence of ALI. Further, BPI recipient genotype was not associated with an increased incidence of this complication. On the other hand, ALI was more frequent in patients receiving a transplant from a donor homozygous for the G allele of the BPI A645G SNP (Figure 1). This association was confirmed in multivariate analysis (OR 1.46, p = 0.048). Other independent risk factors for the occurrence of ALI were age (as continuous variable, OR 1.03, p = 0.002) and transplantation from an unrelated vs. related donor (OR 1.66, p = 0.018) whereas the use of intensive conditioning was a risk factor of borderline significance (OR 1.59, p = 0.077). In spite of its association with ALI, BPI donor genotype did not correlate with cumulative incidence of NRM at 100 days (G/G: 6.7%, 95% CI: 1.0 – 12.4% vs. A/A or A/G: 10.2%, 95% CI: 6.0 – 14.4%; p = 0.380) or overall survival. Conclusion: In contrast to other investigators we found no correlation between NOD2 genotype and the occurrence of acute pulmonary complications after allo-HSCT. On the other hand, BPI A645G SNP in the donor was identified as an independent risk factor for ALI in these patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.2324.2324
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
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    Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes
    American Society of Hematology ; 2020
    In:  Blood Vol. 136, No. 12 ( 2020-09-17), p. 1419-1432
    Details
    In: Blood, American Society of Hematology, Vol. 136, No. 12 ( 2020-09-17), p. 1419-1432
    Abstract: Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used whole-genome (n = 61) and exome (n = 21) sequencing (74% cMCL, 26% nnMCL) combined with transcriptome and DNA methylation profiles in the context of 5 MCL reference epigenomes. We identified that open and active chromatin at the major translocation cluster locus might facilitate the t(11;14)(q13;32), which modifies the 3-dimensional structure of the involved regions. This translocation is mainly acquired in precursor B cells mediated by recombination-activating genes in both MCL subtypes, whereas in 8% of cases the translocation occurs in mature B cells mediated by activation-induced cytidine deaminase. We identified novel recurrent MCL drivers, including CDKN1B, SAMHD1, BCOR, SYNE1, HNRNPH1, SMARCB1, and DAZAP1. Complex structural alterations emerge as a relevant early oncogenic mechanism in MCL, targeting key driver genes. Breakage-fusion-bridge cycles and translocations activated oncogenes (BMI1, MIR17HG, TERT, MYC, and MYCN), generating gene amplifications and remodeling regulatory regions. cMCL carried significant higher numbers of structural variants, copy number alterations, and driver changes than nnMCL, with exclusive alterations of ATM in cMCL, whereas TP53 and TERT alterations were slightly enriched in nnMCL. Several drivers had prognostic impact, but only TP53 and MYC aberrations added value independently of genomic complexity. An increasing genomic complexity, together with the presence of breakage-fusion-bridge cycles and high DNA methylation changes related to the proliferative cell history, defines patients with different clinical evolution.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.2020005289
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 7
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    Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed/refractory AML
    American Society of Hematology ; 2021
    In:  Blood Vol. 137, No. 22 ( 2021-06-3), p. 3145-3148
    Details
    In: Blood, American Society of Hematology, Vol. 137, No. 22 ( 2021-06-3), p. 3145-3148
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.2020009759
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
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    Allogeneic Stem Cell Transplantation for Hodgkin's Disease From Sibling and Unrelated Donors: The German Cooperative Transplantation Study Group Experience.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2293-2293
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2293-2293
    Abstract: Abstract 2293 Poster Board II-270 Introduction: Although modern chemotherapy regimens achieve a high cure rate in primary Hodgkin's disease and relapsed patients can be salvaged by high dose chemotherapy with autologous stem cell transplantation there remains a subgroup of patients with early relapse despite high dose chemotherapy. The prognosis of these patients is dismal with further chemotherapy. Allogeneic transplantation has the potential to exert an alloimmune response against lymphoma cells and has therefor been offered to patients with relapsed or refractory Hodgkin's disease, in particular when a matched sibling donor was available. However only limited information on the feasability of allogeneic transplantion from an unrelated donor is available. Methods: We performed a retrospective analysis of allogeneic transplants for Hodgkins disease within the German Cooperative Transplantation Study Group. 18 centres have provided data on patient and donor characteristics, transplant procedure and outcome. Survival data were analysed by Kaplan-Meier and tested for differences by log rank test. Cumulative incidences for relapse, non-relapse mortality and graft-versus-host-disease were calculated in a competing risk model. Results: 79 patients with a median age of 30 years (range 14-59) were included. 65 (82%) patients had failed a previous autologous transplantation 582 days (median) before allotransplantation. Disease status at transplantation was CR in 17.6%, PR in 54.0%, stable disease in 9.5%, PD in 12.2%, and untreated relapse in 6.8%. Donors were matched related in 33%, mismatched related in 5%, matched unrelated in 42% and mismatched unrelated in 20%. With a median follow up of 19 months for surviving patients the median overall survival (OS) after allotransplant was 42 months with a 2 year survival of 51%. Non-relapse mortality was 21.1% after 12 and 24 months. The median progression-free survival was 14.6 months with a 2 year PFS of 42.0%. Patients relapsing after an autologous transplantation had a significantly better OS (median 53.7 vs 8.4 months, p=0.029) and PFS (22.0 vs 7.5 months, p=0.039) than patients without a prior autograft. No significant difference was seen for OS or PFS regarding the use of related or unrelated donors or disease status at transplant. Conclusions: Allogenic transplantation is a feasible option for high-risk patients with relapsed or refractory Hodgkins disease in particular after failing an autograft. Non-relapse mortality appears to be acceptable in view of the intensive prior treatment. Probabilities for overall survival and progression-free survival were similar after transplantation from a related or unrelated donor. Further optimisation strategies have to focus on on efforts to reduce the high relapse-rate after transplantation, thereby potentially increasing overall and progression free survival. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2293.2293
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 9
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    Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets
    American Society of Hematology ; 2019
    In:  Blood Advances Vol. 3, No. 20 ( 2019-10-22), p. 3143-3156
    Details
    In: Blood Advances, American Society of Hematology, Vol. 3, No. 20 ( 2019-10-22), p. 3143-3156
    Abstract: Pediatric ALL relapses after allogeneic stem cell transplantation display highly diverse, dynamic and patient-individual genetic lesions. Nine of 10 relapsing pediatric transplant recipients present with genetic alterations for which novel targeted therapies are available.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2019000051
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 10
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    Treatment of Indolent Non-Hodgkin’s Lymphoma in Germany - Results of a Representative Population-Based Survey.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1353-1353
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1353-1353
    Abstract: In advanced stage indolent lymphoma, therapeutic approaches may vary from watch and wait, antibody monotherapy, conventional chemotherapy or dose-intensified consolidation up to allogeneic strategies. In this nation-wide survey, representative hematological/oncological centers monitored current treatment strategies under routine conditions. 495 centers involved in the treatment of indolent lymphoma including university hospitals (UH), community hospitals (CH), and office-based hematologists (OBH) were contacted. 13% of identified centers provided information on 741 patients corresponding to 10% of the expected national prevalence. Detailed data on 576 unselected patients (median age 67 years, range 17 to 95) with treatment decision in the second and third quarter of 2006 (start, change or end of therapy) of 46 representative centers (2 UH, 25 CH, and 19 OBH) were included in this analysis. Data were verified by monitoring anonymized patients source data. Median age was 67 with hypertension (28%), coronary heart disease (14%), diabetes (11%), heart failure (8%), cardiac arrhythmia (7%) and renal impairment (7%) being the most frequent concomitant diseases at time of diagnosis. Histology included 39% follicular lymphoma, 26% chronic lymphocytic leukemia (CLL), 10% marginal zone, 9% mantle cell lymphoma, and 16% other histologies. Aim of initial therapy was curative in 35%, aiming at improved survival in 62% and palliation in 54% of patients. Radiation (10%), antibody monotherapy (4%), chemotherapy (33%) and combined immuno-chemotherapy (31%) were the most frequent approaches. Applied chemotherapies included CHOP (46%), fludarabine combinations (F/FC/FCM: 15%), chlorambucil (14%), CVP/COP (9%), Bendamustin (4%), with maintenance (12%) and autologous/allogeneic stem cell consolidation both in 3% of patients. In first relapse, complex regimen including immuno-chemotherapy (49%), maintenance therapy (16%), and autologous/allogeneic transplantation (14%/4%) were more frequently planned. As expected, significant differences were observed between follicular, mantle cell lymphoma and CLL. Interestingly, supportive measures including antibiotics (34%), erythrocyte transfusions (32%), G-CSF (22%), immunoglobulins (19%), antifungal drugs (13%), and erythropoietin (10%) were frequently applied already in first line therapy. Overall response was 83% (FL: 97%, MCL: 95%, CLL: 74%) with a 39% CR rate. Only 10% of first line patients were treated within studies (UH: 19%, CH: 5%, OBH: 13%). In this population-based survey, patient characteristics differed significantly from published study cohorts as did clinical strategies and therapeutic approaches. Thus, clinical studies more relevant to the treatment of medically compromised patients are urgently warranted.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1353.1353
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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