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In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 87-87

Abstract: Background: Clinical superiority of R-MCP (rituximab, mitoxantrone, chlorambucil, prednisolone) vs. MCP alone in patients with advanced stage indolent Non-Hodgkin’s-Lymphoma was demonstrated in a prospective, randomized, controlled, multicenter clinical trial (n=358). Data on resource utilization were collected alongside this clinical trial. Objective: To evaluate the health economic consequences, i.e. total cost and cost-consequences, of R-MCP vs. MCP from the perspective of a German payer (statutory sickness fund). Methods: Resource utilization data on 329 patients were collected and analyzed for the treatment phase (8 month). In addition, an interim analysis of the first 3 years of the subsequent observation period (planned: 7 years) was conducted. Data on resource utilization for initial chemotherapy, chemotherapy administration, treatment of adverse events, treatment of complications/progressive disease, subsequent chemotherapies and treatment for other reasons were collected. Several sensitivity analyses were performed to address different cost environments (e.g. treatment at university hospital vs. municipal hospital vs. private practice) and discounting scenarios. Results: Mean cost of the treatment phase in the base case analysis was EUR 35,890 for R-MCP (95%CI: EUR 33,178 – 38,602 and EUR 21,508 MCP per patient (95%CI: EUR 17,703 – 25,314). More treatment cycles were administered in the R-MCP arm (1,026 MCP, 1,237 R-MCP). Mean cost per active treatment cycle was EUR 4,932 for R-MCP (95%CI: EUR 4,512 – 5,353) and EUR 3,270 for MCP (95%CI: EUR 2,619 – 3,922). Mean (undiscounted) cost per patient in the observation period amounted to EUR 9,973 for R-MCP (95%CI: EUR 6,015 – 13,931) and EUR 15,896 for MCP (95%CI: 13,407 – 18,385). Mean observation time, after end of active treatment, was similar in both arms, 28.5 months for R-MCP, 27.5 months for MCP. Costs for treatment of adverse events, new chemotherapies and other reasons were reduced by 23%–39%, cost for treatment of progressive disease by 76% in the R-MCP arm compared to MCP alone. Extrapolating data to a full 3-year observation period results in savings of EUR 8,214 per patient with R-MCP compared to MCP alone. This compensates approx. 60% of the higher costs from the treatment phase. Clinically, R-MCP resulted in an objective response rate of 85.6% vs. 65.5% with MCP. After two years, based on Kaplan Maier estimate, event free survival for R-MCP was 69% vs. 44% for MCP alone (p 〈 0.001) (For more detailed clinical results see abstract by Herold et al.) Conclusion: Initial treatment costs with R-MCP were EUR 14,382 higher compared to MCP alone. However, approx. 60% of additional costs are regained during the first three years after therapy due to savings for subsequent treatments, particularly for progressive disease. Combined with the clinical superiority of R-MCP, a favorable cost-effectiveness ratio may be expected when more mature data are available.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V104.11.87.87

Language: English

Publisher: American Society of Hematology

Publication Date: 2004

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 584-584

Abstract: Rituximab proved to be effective in relapsed and refractory indolent NHL as a single agent and generated impressive results in phase II studies in combination with chemotherapy. In a prospective randomized trial we compared the efficacy and toxicity of rituximab (375 mg/m² d 1) plus MCP-chemotherapy ( mitoxantrone 8 mg/m² d 3 + 4, chlorambucile 3 x 3 mg/m² d 3 – 7, prednisolone 25 mg/m² d 3 – 7 ) given every 28 days for a total of 8 cycles versus MCP (d 1 – 5) x 8 cycles alone in advanced indolent NHL and MCL. Efficacy endpoints included overall and complete response rates, event free survival, progression free survival, overall survival and toxicity. For response assessment classical definitions have been used. Between 10/98 and 09/03 we randomized 358 patients (pts) with advanced stage follicular lymphoma (FL) (grade 1 + 2), lymphoplasmacytic lymphoma and MCL to either R-MCP or MCP. The study arms are well balanced for all demographic factors. 201/358 pts (56%) had FL. Both regimens were well tolerated with a low incidence of serious adverse events. The overall response rate (RR) and the complete response rate (CR) for all pts was 85,5% and 42% in the R-MCP arm versus 65,5% and 20% in the MCP arm (p 〈 0,0001). Results were even more impressive in the subgroup of FL pts (n=201) with an overall RR of 92,4% and a CR rate of 49,5% for R-MCP versus 75% and 25% for MCP alone respectively (p 〈 0,0001). In the overall group event free survival (EFS) was significantly prolonged for pts receiving R-MCP vs MCP alone (p 〈 0,001). Median EFS for MCP was 19 months, at this time point EFS for R-MCP was 73%. In FL pts the median EFS for MCP is 19 months too and EFS was 86% for R-MCP at this point. 2-year EFS for all pts was 69% for R-MCP versus 44% for MCP; for FL pts the respective 2-year EFS was 83% for R-MCP and 43% for MCP (p’s 〈 0,0001) (Kaplan Maier estimates). These results compare favourably with the recntly published data of immunochemotherapy for treatment of NHL or MCL. The results from our study confirm the superiority of a combination of rituximab and chemotherapy in the first- line treatment of indolent NHL, primarily follicular lymphoma. The CR rates achieved with the R-MCP regimen are impressive, especially since stricter response criteria were used. In summary we conclude, that the addition of rituximab to MCP chemotherapy improves significantly the outcome of pts with indiolent NHL and MCL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V104.11.584.584

Language: English

Publisher: American Society of Hematology

Publication Date: 2004

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. 5 ( 2018-08-02), p. 469-483

Abstract: Mutations in a VHL cryptic exon may be found in patients with familial erythrocytosis or VHL disease. Synonymous mutations in VHL exon 2 may induce exon skipping and cause familial erythrocytosis or VHL disease.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-03-838235

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 111, No. 9 ( 2008-05-01), p. 4511-4522

Abstract: Erythropoiesis requires erythropoietin (Epo) and stem cell factor (SCF) signaling via their receptors EpoR and c-Kit. EpoR, like many other receptors involved in hematopoiesis, acts via the kinase Jak2. Deletion of EpoR or Janus kinase 2 (Jak2) causes embryonic lethality as a result of defective erythropoiesis. The contribution of distinct EpoR/Jak2-induced signaling pathways (mitogen-activated protein kinase, phosphatidylinositol 3-kinase, signal transducer and activator of transcription 5 [Stat5]) to functional erythropoiesis is incompletely understood. Here we demonstrate that expression of a constitutively activated Stat5a mutant (cS5) was sufficient to relieve the proliferation defect of Jak2−/− and EpoR−/− cells in an Epo-independent manner. In addition, tamoxifen-induced DNA binding of a Stat5a–estrogen receptor (ER)* fusion construct enabled erythropoiesis in the absence of Epo. Furthermore, c-Kit was able to enhance signaling through the Jak2-Stat5 axis, particularly in lymphoid and myeloid progenitors. Although abundance of hematopoietic stem cells was 2.5-fold reduced in Jak2−/− fetal livers, transplantation of Jak2−/−-cS5 fetal liver cells into irradiated mice gave rise to mature erythroid and myeloid cells of donor origin up to 6 months after transplantation. Cytokine- and c-Kit pathways do not function independently of each other in hematopoiesis but cooperate to attain full Jak2/Stat5 activation. In conclusion, activated Stat5 is a critical downstream effector of Jak2 in erythropoiesis/myelopoiesis, and Jak2 functionally links cytokine- with c-Kit-receptor tyrosine kinase signaling.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2007-07-102848

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 12-13

Abstract: Introduction: Acute lymphoblastic leukemia (ALL) represents around 5% of all newly diagnosed leukemia in patients between 55 and 70 years of age. Despite recent advances especially in younger patients, the prognosis of older patients with ALL remains dismal, even after moderately intensive chemotherapy. Due to increasing toxicity and infection rates in older patients, dose intensification of induction treatment often is no justifiable option. Consequently, new treatment options are needed to improve the survival of older ALL patients. Methods: This open label phase II study of the German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) is currently activated in 14 centers in Germany. Patients aged & gt;55 years with newly diagnosed acute B lymphoblastic leukemia, with the exception of Philadelphia-chromosome or BCR-ABL positive ALL or Burkitt's or mixed phenotype acute leukemia, are eligible. Leukemic blasts must have CD22 surface expression of at least 20%. No previous ALL-specific treatment, with the exception of corticosteroids and/or single dose vincristine and/or up to 3 doses of cyclophosphamide (cycloph.) plus standard prephase treatment are allowed. The 1st induction cycle consists of inotuzumab ozogamicin (InO) 0.8 mg/m2 on day1 and 0.5 mg/m2 on days 8 and 15 together with dexamethasone 10 mg/m2 (days 7-8, days 14-17) and 1 intrathecal injection of methotrexate (MTX), cytarabine (AraC) and dexamethasone (Dexa). The 2nd and 3rd induction cycle consist of InO 0.5 mg/m2 on days 1, 8 and 15 plus intrathecal injection of MTX/AraC/Dexa. Response evaluation is scheduled after each cycle. Patients achieving a complete remission are offered to receive 5 conventional consolidation therapies (3 x ID-MTX/asparaginase; 2 x ID-AraC) and one reinduction therapy (idarubicine/AraC/cycloph./Dexa) in combination with rituximab (for CD20+ ALL), followed by a maintenance therapy with 6-mercaptopurine/MTX. The primary endpoint is is event free survival (EFS) at 12-months follow-up. An event is any of the following: persisting bone marrow blasts after 2 cycles of InO, relapse or death. An event rate of ≤40% at 12 months follow-up is considered to qualify the experimental treatment as very promising for additional testing. Under the assumption of one-sided type I error of 5% and 80% power, 42 evaluable patients were needed for primary endpoint analysis. The INITIAL-1 trial is registered with ClinicalTrials.gov, identifier: NCT03460522. Results: As of July 2020, 31 patients have been included, with induction results available for 29 patients. Median age at initial diagnosis was 64 years (range 56-80 years). Twenty-five patients were diagnosed with a common- and 4 with a pro-B lymphoblastic leukemia. Median CD22 expression on leukemic blasts was 70% (range 21-99%). Due to suspected therapy related liver toxicities, 1 patient received 1 induction cycle and 1 patient 2 induction cycles (both were in remission after the 1st induction). All other patients completed induction therapy and achieved complete remission (CR/CRi) mainly after the 1st induction. Results of minimal residual disease (MRD) measured by PCR are available for 23 patients, with 17 being MRD-negative after induction. So far, 4 events have been reported (2 deaths in remission and 1 relapsed ALL in the 1st year of treatment; one relapsed disease in the 2nd year). With a median follow-up of 242 days, the probability of OS at 1 year is 82.4 %. Two patients received an allogeneic stem cell transplantation in ongoing 1st remission. With regard to adverse events (AEs) during induction therapy 1, 2 and 3, most common AEs ≥CTC 3 reported were leukocytopenia (in 64%, 33% and 13% of all cases, respectively), anemia (54%, 28%, 13%), thrombocytopenia (68%, 17%, 26%) and elevation of liver enzymes (31%, 22%, 20%). Conclusion: Replacement of conventional induction chemotherapy by InO is feasible, results in promising remission rates, and may reduce the risk of early morbidity and lethality, particular in older patients with acute B lymphoblastic leukemia. Disclosures Stelljes: Amgen: Consultancy, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau. Wäsch:Pfizer: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Haenel:Amgen, Novartis, Roche, Celgene, Takeda, Bayer: Honoraria. Lenz:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios: Research Funding; AQUINOX: Research Funding; Novartis: Consultancy; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Verastem: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding. Brüggemann:Affimed: Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Roche: Consultancy; Incyte: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Goekbuget:Gilead: Consultancy; Kite: Consultancy; Servier: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Erytech: Consultancy; Amgen: Consultancy, Research Funding. Alakel:Pfizer: Consultancy. OffLabel Disclosure: Inotuzumab ozogamicin for induction therapy (1st line therapy)

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136920

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 5-5

Abstract: Abstract 5 Wiskott Aldrich Syndrome is a life-threatening immune-disorder characterized by bleeding secondary to microthrombocytopenia, immunodeficiency, autoimmunity, and susceptibility to lymphoma. A clinical gene therapy protocol using a GALV pseudotyped MLV-derived retroviral vector was developed at Hannover Medical School. We here present an analysis of ten patients treated in this trial between 2006 and 2009. All patients had evidence of engraftment of WASP-positive hematopoietic progenitor cells except for one patient in whom an insufficient number of CD34+ cells could be harvested. WASP expression was determined in myeloid and lymphoid cells as well as in CD34+ hematopoietic progenitor cells using Western Blot and FACS analysis, respectively. While the percentage of WASP-positive myeloid cells was relatively stable over time (range 10 to 60%), a marked increase over time in the percentage of WASP-positive T lymphocytes and NK cells was observed, resulting in more than 80% of WASP-positive lymphoid cells 12 months after gene therapy. Early after gene therapy, an increase in thrombocyte counts was observed in all patients. Furthermore, the majority of peripheral thrombocytes showed evidence of WASP expression, detectable as early as 3 months after gene therapy. Functional immune reconstitution was documented in dendritic cells (podosome formation), T cells (proliferation in response to CD3-signaling), and NK cells (formation of immunological synapse and NK cell killing activity). TCR Vb spectratyping analyses showed in improvement of receptor skewing upon gene therapy in some patients. A clinical benefit was notable in all patients with the exception of the patients with insufficient engraftment of genetically corrected progenitor cells: eczema, bleeding diathesis and immunodeficiency resolved. Strikingly, the various autoimmune phenomena which the patients in this trial had shown prior to gene therapy resolved when the majority of T lymphocytes were positive for WASP expression, and a particular advantage of WASP-positive regulatory T lymphocytes (Tregs) could be observed at this point, suggesting a crucial role in WASP reconstitution in Tregs for autoimmnity resolution. Repetitive bone marrow examinations did not reveal morphological or cytogenetic alterations. Comprehensive insertion site analysis using 454 pyrosequencing demonstrated vector integration that targeted multiple genes controlling growth, development and immunological responses in a persistently polyclonal hematopoiesis. In sum, hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome is feasible and effective at correcting the various cellular defects implicated in this disease. Our trial provides the first proof-of-principle for gene therapy in Wiskott-Aldrich syndrome and provides evidence that gene therapy may be effective at correcting disorders involving autoimmunity and/or platelets. Prospective monitoring is used in this trial to determine the long-term efficacy and safety profile of this experimental therapeutic approach in Wiskott-Aldrich syndrome. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.5.5

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 123, No. 4 ( 2014-01-23), p. 520-529

Abstract: Jak2 activation-loop–defective mutation results in partial interferon γ signaling, but Jak2 mutant mice die due to abolished EpoR signaling. Jak2 scaffold function mediates IFNGR complex integrity, activity, and physiological Jak1 localization.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2013-03-492157

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 824-824

Abstract: Abstract 824 In multiple myeloma (MM), the second most common hematological malignancy, high-dose therapy followed by autologous CD34+ stem cell transplantation (ABSCT) is therapy of choice for younger patients. Standard treatment to mobilize hematopoietic stem cells (HSC) is either G-CSF alone or combined with chemotherapy. In the last years the antagonism of the CXCR4 receptor has been identified as a potent mechanism of HSC release from the bone marrow compartment. This mobilization by CXCR4 antagonists is more direct and more rapid than by G-CSF given over 4 to 6 days, and the combination of G-CSF plus a CXCR4 antagonist is superior to G-CSF alone. Furthermore, HSC mobilized using G-CSF and a CXCR4 antagonist have been shown to result in a rapid and sustained engraftment post-transplantation. POL6326 is a novel, potent and selective CXCR4 antagonist based on the PEM (Protein Epitope Mimetics) technology for intravenous application. In a previous Phase I study in 52 healthy volunteers POL6326 has been demonstrated to effectively mobilize CD34+ stem cells and was very well tolerated. The goal of the Phase II study in newly diagnosed myeloma patients reported here was to test to what extent POL6326 can be used as monotherapy, infused over 1 or 2h, to mobilize sufficient HSC for subsequent autologous transplantation. In our study the minimum number of HSC required for ABSCT was 2 × 106 CD34+ cells/kg body weight (BW). All patients also received CAD/G-CSF (cyclophosphamide, doxorubicin and dexamethasone) about 10 days after POL6326 and leukapheresis. The second goal was to determine tumour cell mobilization by polymerase chain-reaction after POL6326 or CAD/G-CSF respectively. Here we report the first data of this ongoing study. In all doses tested, up to 1200 μg/kg BW over 2h, POL6326 was safe and very well tolerated. During a total number of 38 infusions the only minor adverse event possibly related to study drug was a discrete pruritus of CTC grade 1 at the infusion site during POL6326 administration on two consecutive days. It resolved spontaneously and did not require any medication. This excellent safety and tolerability profile warrants further dose escalation in the ongoing trial. After first diagnosis, patients received 3 cycles of induction chemotherapy with bortezomib (or thalidomide respectively in one single subject) plus doxorubicin and dexamethasone. 3 weeks after the last injection of induction treatment HSC were mobilized with POL6326 given as a 1 or 2h infusion on up to 4 consecutive days according to an intra-individual dose escalation scheme (from 600 to 1200 μg/kg) with consecutive leukapheresis 30 min after end of infusion. In all patients (n=16) we observed an elevation of leukocytes and HSC compared to baseline. In 66% of patients sufficient stem cells were mobilized with POL6326 for ABSCT (with a mean of 2.5 × 106 CD34+ cells/kg BW). In 75 % of these subjects 2 leukapheresis cycles were sufficient to reach the minimum number of HSC. In all patients undergoing ABSCT with HSC mobilized by POL6326, the engraftment was successful. The time to reconstitution ranged from 10 to 19 days (mean 14 days) and was comparable to ABSCT with CAD/G-CSF-mobilized HSC (historical mean of 14 days and a range from 6 to 31 days). Five patients were evaluated for the presence of tumour cells in peripheral blood before mobilization and in leukapheresis products after treatment with POL6326 and CAD/G-CSF. In 2 of these patients we could not detect any tumour cells, neither in all leukapheresis products nor in all peripheral blood samples. In 2 patients a minor contamination with less than 0.0001% of tumour cells was detected both in the peripheral blood before POL6326 and in the leukapheresis products. Finally, 1 patient showed a similarly minor ( 〈 0.0001%) percentage of tumour cells only in the apheresis product after POL6326 treatment. However, a significant mobilization of tumour cells (0.001%) was detected after CAD plus G-CSF in this patient. Due to the excellent safety and tolerability profile observed for POL6326 in this study the next steps include further dose escalation. These initial data with low doses of POL6326 indicate that this novel CXCR4 antagonist holds the promise to be eventually used as a stand alone therapy not requiring the application of G-CSF. The preliminary findings of the absence or very low counts of tumour cells in the leukapheresis product generated with POL6326 warrant further investigation. Disclosures: Off Label Use: POL6326 as new CXCR4 antagonist for experimental CD34+ hematopoietic stem cell mobilization. Dembowsky:Polyphor Ltd: Employment. Braun:Cytonet Heidelberg GmbH: Employment. Ludin:Polyphor Ltd: Employment.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.824.824

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. 7 ( 2018-08-16), p. 694-706

Abstract: Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1−/− mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify individuals at risk.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2017-10-810739

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 920-920

Abstract: Preceding studies have shown that Rituximab prolongs the time to treatment failure (TTF) and response duration (RD) in follicular lymphoma (FL) when given either together with chemotherapy or as maintenance after a no R containing therapy. In the current study the impact of R maintenance on RD was evaluated after remission induction by an R-chemo combination. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized a first randomization between 4 courses of chemotherapy with Fludarabine (25mg/m2/d days 1–3), Cyclophosphamide (200mg/m2/d days 1–3) and Mitoxantrone (8mg/m2/d day 1) (FCM) versus FCM plus Rituximab (375mg/m2/d on day 0) (R-FCM). Patients entering a complete (CR) or partial remission (PR) underwent a second randomzation for observation only versus R maintenance with 4 weekly doses of R (375mg/m2/d) to be given at three and nine month after end of therapy. Both randomizations were stratified for histology and preceding therapy. The first randomization was stopped after 147 patients demonstrating a significant improvement for the R-FCM therapy in initial response, progression free survival and even overall survival (OS). So all subsequent patients received R-FCM. 174 cases are currently evaluable for the second randomization, 136 of whom had received R-FCM for remission induction. In these patients the median RD has not been reached in the R-maintenance arm whereas it is 17 months in patients with no further treatment after R-FCM (p=0.0024). This improvement was seen both in FL and MCL. This study demonstrates that R maintenance after R-FCM salvage therapy is highly effective and improves the outcome of patients with relapsed FL and MCL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V106.11.920.920

Language: English

Publisher: American Society of Hematology

Publication Date: 2005

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7