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  • 1
    Online Resource
    Online Resource
    Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 6 ( 2020-06-01), p. 1670-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 6 ( 2020-06-01), p. 1670-
    Abstract: During the phase of proliferation needed for hematopoietic reconstitution following transplantation, hematopoietic stem/progenitor cells (HSPC) must express genes involved in stem cell self-renewal. We investigated the expression of genes relevant for self-renewal and expansion of HSPC (operationally defined as CD34+ cells) in steady state and after transplantation. Specifically, we evaluated the expression of ninety-one genes that were analyzed by real-time PCR in CD34+ cells isolated from (i) 12 samples from umbilical cord blood (UCB); (ii) 15 samples from bone marrow healthy donors; (iii) 13 samples from bone marrow after umbilical cord blood transplant (UCBT); and (iv) 29 samples from patients after transplantation with adult hematopoietic cells. The results show that transplanted CD34+ cells from adult cells acquire an asset very different from transplanted CD34+ cells from cord blood. Multivariate machine learning analysis (MMLA) showed that four specific gene signatures can be obtained by comparing the four types of CD34+ cells. In several, but not all cases, transplanted HSPC from UCB overexpress reprogramming genes. However, these remarkable changes do not alter the commitment to hematopoietic lineage. Overall, these results reveal undisclosed aspects of transplantation biology.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9061670
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy
    Springer Science and Business Media LLC ; 2015
    In:  Bone Marrow Transplantation Vol. 50, No. 2 ( 2015-02), p. 282-288
    Details
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 50, No. 2 ( 2015-02), p. 282-288
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
    URL: Article
    DOI: 10.1038/bmt.2014.231
    RVK:
    XA 10000
    RVK:
    XA 33180
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2004030-1
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  • 3
    Online Resource
    Online Resource
    Early Detection of Relapse by Prospective Reverse Transcriptase-Polymerase Chain Reaction Analysis of the PML/RARα Fusion Gene in Patients With Acute Promyelocytic Leukemia Enrolled in the GIMEMA-AIEOP Multicenter “AIDA” Trial
    American Society of Hematology ; 1998
    In:  Blood Vol. 92, No. 3 ( 1998-08-01), p. 784-789
    Details
    In: Blood, American Society of Hematology, Vol. 92, No. 3 ( 1998-08-01), p. 784-789
    Abstract: Although the majority of patients with acute promyelocytic leukemia (APL) are potentially cured by treatments combining all-trans retinoic acid (ATRA) and chemotherapy (CHT), a sizable proportion (around 30%) will relapse during follow-up. Retrospective molecular monitoring studies using reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific PML/RARα fusion gene, have shown that a positive test usually precedes the occurrence of hematologic relapse. Prospective RT-PCR analyses were performed since 1993 at diagnosis and at preestablished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RARα+ APL enrolled in the multicenter Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin). Treatment consisted of ATRA and idarubicin for induction followed by three polychemotherapy courses as consolidation. The sensitivity level of the RT-PCR assay for PML/RARα, as assessed by serial dilution experiments, was 10−4. All patients were in hematologic remission and tested PCR− at the end of consolidation. Of 21 who converted to PCR-positive thereafter, 20 underwent hematologic relapse at a median time of 3 months (range, 1 to 14) from the first PCR+ result. Seventeen of these 21 (81%) PCR+ conversions were recorded within the first 6 months postconsolidation. Of 142 who tested persistently PCR− in ≥2 tests after consolidation, 8 had hematologic relapse and 134 remained in complete remission (CR) after a median follow-up of 18 months (range, 6 to 38) postconsolidation. Using a time-dependent Cox model, the relative risk of hematologic relapse of patients who converted to PCR+ was 31.8 (confidence limits 95%, 12.9 to 78.3). Our results indicate that conversion to PCR positivity for PML/RARα during remission is highly predictive of subsequent hematologic relapse and highlight the prognostic value of stringent molecular monitoring during the early postconsolidation phase in APL. As a result of the present study, salvage treatment in patients enrolled in the GIMEMA trial AIDA is now anticipated at the time of molecular relapse, defined as the conversion to PCR positivity in two successive BM samplings during follow-up. © 1998 by The American Society of Hematology.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V92.3.784.415k06_784_789
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1998
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    One Year of Intermittent Imatinib (IM) Treatment (InterIM) Maintains the Complete Cytogenetic Response (CCgR) Previously Achieved with Standard IM Therapy In Elderly (≥ 65 years) Ph+ CML Patients – EudraCT Number 2007–005102-42, ClinicalTrials.Gov NCT 00858806.
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 3412-3412
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3412-3412
    Abstract: Abstract 3412 The phase II explorative study of intermittent Imatinib (IM) treatment (InterIM) in elderly patients with Ph + chronic myeloid Leukemia (CML) who achieved a stable complete cytogenetic response (CCgR) after at least 2-years standard IM therapy (any dose between 300 and 800 mg/day) was started in April 2008 and closed for the enrollment in August 2009, since more than 78 patients required by statistics were included into the study. The main objective of the study was to investigate if after 12 months (trial time) the CCgR achieved with standard (daily administration) IM therapy could be maintained with InterIM. For this purpose, the CgR status was assessed by Interphase Fluorescence In Situ Hybridization (I-FISH) on peripheral blood (≥ 200 cells counted) every 3 months. When I-FISH (% Ph + nuclei) increased more then 1%, chromosome banding analysis (CBA) on bone marrow was performed to confirm the loss of CCgR and to check for additional cytogenetic abnormalities (ACA). At the present time, out of the 95 patients who were enrolled, 82 patients were evaluable and out of them 77 (94%), 73 (89%), 71 (87%) and 70 (85%) completed 3, 6, 9 and 12 months of the treatment program, respectively. Therefore, the great majority of patients completed the study core and at the end of 2010 all the patients are expected to complete the trial time (12 mo). During the first 12 months of InterIM, 1% to 11% of the evaluable patients at 3, 6, 9 and 12 months showed an I-FISH 〉 1% Ph+ nuclei (Figure 1). Figure 1 Distribution of patients according to I-FISH Figure 1. Distribution of patients according to I-FISH Totally, eleven (13%) out of 82 patients treated with InterIM showed an I-FISH 〉 1% and they were checked by CBA on bone marrow (Figure 2). Out of them only 3 cases, that means 4% of the 82 evaluable patients, lost the CCgR and resumed standard IM therapy (daily administration), but none completed 3 months of therapy. All the patients lost the MMR and increased several folds the BCR-ABL transcript levels. Two pts had a low risk Sokal and one a high risk; age was 66, 69, 77 years; time from diagnosis was 29, 91 and 100 months; duration of IM therapy was 29, 83 and 84 months; the IM dose was 400mg in all cases. Figure 2 Cytogenetic and molecular response in 11 cases who showed I-FISH 〉 1% + nuclei and who were checked by CBA on bone marrow. Black boxes shows the 3 cases who lost the CCgR Figure 2. Cytogenetic and molecular response in 11 cases who showed I-FISH 〉 1% + nuclei and who were checked by CBA on bone marrow. Black boxes shows the 3 cases who lost the CCgR As concern as molecular response, 99% of the patients had a major molecular response (MMR= 〈 0.001-0.1 BCR-ABL/ABLISX 100) at the baseline. The proportion of the patients who maintained the MMR after 3, 6, 9 and 12 months of InterIM was 95%, 92%, 91%, 84%, respectively. Interestingly, we found a weak but significant correlation between the % of BCR-ABL + nuclei and the BCR-ABL transcript levels in the patients who completed the trial time (12 mo) (r=0.27; p=0.001). In conclusion, the results of the InterIM study core (12 months), clearly show that Intermittent Imatinib (IM) treatment (InterIM) is sufficient to maintain the complete cytogenetic response (CCgR) previously achieved with standard IM therapy in elderly (≥ 65 years) Ph+ CML patients. The risk to loose the CCgR has been very low (4%), while the benefit either in terms of reduction of IM dose and of costs of therapy or in terms of compliance (data not shown) was very high. Acknowledgments: This work was supported in part by CML-Leukemia Net and Progetto Regione Lombardia. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.3412.3412
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Health-Related Quality of Life In Patients with Chronic Myeloid Leukemia Undergoing First Line Treatment with Imatinib for at Least Three Years Compared with the General Population. A Multicenter Study Including 448 Patients
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 2273-2273
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2273-2273
    Abstract: Abstract 2273 Background: While Imatinib (IM) has revolutionized treatment for chronic myeloid leukemia (CML), demonstrating outstanding survival figures, currently no data exist on mid to long term impact of disease burden and therapy from the patients’ perspective. Aim: The main objective of this study is to identify specific limitations of quality of life (QoL) in CML survivors who are undergoing first line treatment with IM in comparison with controls from the general population. Patient-reported symptom prevalence was also investigated. Patients and methods: Patients were recruited in 26 centers, randomly selected to geographically represent the whole study country. Patients selection criteria included: being in treatment with IM for at least three years and being in complete cytogenetic response at the time of study entry. All patients were invited by their treating physicians in the hospital to participate and all consenting patients were requested to complete a Health Survey Packet at home. Pre-paid reply envelopes were also provided with the request to send back completed Surveys to an independent National coordinating Data Center. Generic QoL was assessed with the SF-36 that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. A previously devised patient-reported CML Symptom Checklist was used to investigate 9 symptoms of possible major concern in these patients. Mean SF-36 scores were compared to available national general population reference values and all analyses were adjusted for age and gender. Statistical comparisons were all adjusted for multiple testing. Differences in mean scores were expressed in Cohen effect sizes (ES; with 0.2, 0.5, and 0.8 indicating small, medium, and large ES, respectively) and clinical significance. Results: Between March and December 2009, 448 patients were recruited in a large national-based survivorship project. Patients’ compliance was optimal with 94% of patients (N=421) returning a valid Health Survey Packet to the National coordinating Data center. At study participation, mean age of patients was 56 years (59% male and 41% female) and median time of IM therapy was 5 years. Seventy-seven percent of patients were receiving standard dose of 400 mg and 43% had at least one comorbidity. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P 〈 .001; ES=0.3), GH (P 〈 .001; ES=0.4) and RE (P=.01; ES=0.2). The largest clinically meaningful difference (Δ=12.3 points) was found for the RP domain with mean scores of 61.4 vs. 73.7 respectively for the CML and the general population. Age specific comparisons, adjusted by gender, (55-64; 65–74 and 〉 75 years) suggested an almost uniform pattern in all scales with worse outcomes between CML patients and population controls among the youngest groups. GH was significantly worse in younger patients (55-64) (P=.03; ES=0.4) and no differences were found in the older age groups compared with population norms. Prevalence of reported symptoms (with any level of concern) was: fatigue (82%); problems with muscular cramps (78%); problems with musculoskeletal pain (72%); problems with edema (70%); skin problems (47%); diarrhea (43%); headache (39%); abdominal discomfort and nausea (28%). Conclusion: This study suggests that while still being on treatment with IM for years, CML patients might expect to have a QoL profile broadly similar to that of general population in many areas. However, role limitations (i.e., in work or other regular daily activities) due to physical health seem the major constraint faced by these patients; there is also an indication that younger patients might be those experiencing major limitations. Additional analyses will be undertaken to ascertain the impact of symptoms and other laboratory and clinical data on specific QoL domains. Such unique patient-reported data supplements conventional information on clinical efficacy of IM and may support both clinicians and patients in making more informed treatment decisions in this area. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol M. Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.2273.2273
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    Phase II Multicentric Explorative Study of Intermittent Imatinib (IM) Treatment (INTERIM) in Elderly Patients with Ph+ Chronic Myeloid Leukemia (CML) Who Achieved a Stable Complete Cytogenetic Response (CCgR) with Standard IM Therapy.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 860-860
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 860-860
    Abstract: Abstract 860 Background: Elderly CML patients treated with Imatinib (IM) in early chronic phase (CP) have similar cytogenetic response and survival compared with younger patients, but they show a lower compliance to standard IM therapy (400 mg/day). Aims: The aim of the study is to investigate if CCgR that has been achieved with standard (daily administration) IM therapy can be maintained with the same dose of IM given intermittently (INTERIM). Methods: The study population is represented by elderly patients (≥ 65 years old) with Ph+ CML and with stable CCgR after at least 2 years of standard IM therapy (daily administration). IM is given at the same dose that was given at the time of enrollment by the following intermittent schedule: 1 week on / 1 week off for the 1st month; 2 weeks on / 2 weeks off for the 2nd and 3rd month; 1 month on / 1 month off from the 4th month thereafter. In cases of loss of CCgR INTERIM was stopped and standard therapy (daily administration) was resumed. After 12 months, the patients who are in continuous CCgR are advised to continue the intermittent study schedule and to be followed indefinitely. The CgR status was evaluated at baseline (by conventional cytogenetics on bone marrow and FISH on peripheral-blood) and every 3 months during the study (only by FISH on peripheral-blood). If FISH (% of Ph+ cells) increased more than 1% in two consecutive examinations, evaluation of marrow cells metaphases was performed to confirm the loss of CCgR and to check for additional cytogenetic abnormalities. Quantitative molecular assessment of BCR-ABL transcript by RQ-PCR on peripheral blood was due at baseline and every 3 months during the study and mutational analysis of ABL was performed in case of loss of CCgR. Results: One-hundred and fourteen patients have been considered eligible, but 17 (15%) refused to enter into the protocol. Out of 97 enrolled patients, 87 started INTERIM, 5 patients (5%) went off the study for major protocol violation before the 3rd month and, at present, 82 patients are ongoing. Of these 82 patients, 52, 30 and 11 completed the 3rd, 6th and 9th month, respectively. The preliminary results of the first 6 months are here reported. The distribution of patients according to FISH results is shown in Fig. 1. Only 1/68 pts (at 6th month) showed an increased 〉 1% in Ph+ cells by FISH but he maintained a CCgR when checked by conventional cytogenetic. As showed in Fig. 2, 96 to 87% of patients maintained a major molecular response MMR (≤0,1) according to International Scale (IS). Conclusions: This study is trying to test the minimum effective dose of Imatinib to maintain the CCgR in elderly CML patients with stable CCgR. The preliminary results at 6 months do not show negative trends both for cytogenetic and molecular response. Therefore, the study is ongoing and all patients are expected to complete the trial time (12 months). Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.860.860
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph+-CML
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 1794-1794
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1794-1794
    Abstract: BACKGROUND: The INTERIM study (ClinicalTrials.gov NCT 00858806) showed that in elderly ( 〉 65 years) Ph+ CML patients selected for a stable complete cytogenetic response (CCgR) lasting 〉 2 years, the policy of intermittent imatinib treatment (one month on/one month off) may affect the markers of residual disease (CCgR and major molecular response, MMR or MR3.0), but not the clinical outcomes (overall survival and progression-free survival) (Russo D et al, Blood 2013; 121(26):5138-44). AIMS: To update the results of the INTERIM Study, with a follow up ≥ 5 years. METHODS: After 4 years of follow up, patients continouing INTERIM treatment were monitored with peripheral blood RT-Q-PCR every 3 months according to the ELN-2013 guidelines. RESULTS: At 48thmonth, out of 76 patients enrolled in the INTERIM study, 13 (17%) had lost CCgR and MMR, 14 (18%) had lost MMR only and 50 patients (75%) continued INTERIM. The patients who had lost CCgR and/or MMR resumed imatinib continuously and all of them regained the CCgR and the MMR, within 3 to 12 months. No patient progressed to accelerated or blastic phase, or developed clonal chromosomal abnormalities in Ph+ cells, or BCR-ABL mutations. No patient complained of new or more severe side effects during the months “on”. After a follow up ≥ 5 years, 45/76 (59%) enrolled patients are on INTERIM, with a probability of maintaining intermittent administration of 59% (95% CI: 46-69). No patient lost the CCgR and only 9 additional patients lost the MMR while on intermittent treatment. All these patients resumed continuous imatinib treatment and regained the MMR. Thus, at ≥ 5 years, the probability of maintaing CCgR is 80% (95% CI 68-87) and the probability of maintaining the MMR is 61% (95% CI: 48-71). From start of INTERIM, 6 patients died but no deaths were related to CML progression (3 cases of other non haematological neoplasms, 1 stroke, 1 myocardial infarction, 1 chronic obstructive pulmonary disease).The PFS at ≥ 5 years is 94% (95% CI: 89-100) CONCLUSIONS: In summary, with a follow up ≥ 5 years, intermittent imatinib administration (INTERIM) confirmed to be safe, to produce a reversible increase of residual molecular disease in about one third of patients, but not to affect the long-term outcome. Aknowledgments: This work was supported in part by EuropeanLeukemiaNet (contract LSHC-CT-2004-503216) through the European Treatment and Outcome Study (EUTOS), supported by Novartis Oncology Europe, and COFIN 2009 Disclosures Russo: Celgene: Research Funding; Gilead: Research Funding; Novartis: Consultancy. Martinelli:Novartis: Speakers Bureau; Bristol-Meyers and Squibb: Speakers Bureau; Pfizer: Speakers Bureau. Soverini:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria; Ariad: Consultancy, Speakers Bureau. Turri:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Castagnetti:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Breccia:novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Abruzzese:Novartis: Consultancy. Tiribelli:Novartis: Consultancy, Honoraria; Bristol-Meyers and Squibb: Consultancy, Honoraria. Rosti:Consultant: Consultancy, Speakers Bureau; Bristol-Meiers Squibb: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.1794.1794
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    Early Detection of Relapse by Prospective Reverse Transcriptase-Polymerase Chain Reaction Analysis of the PML/RARα Fusion Gene in Patients With Acute Promyelocytic Leukemia Enrolled in the GIMEMA-AIEOP Multicenter “AIDA” Trial
    American Society of Hematology ; 1998
    In:  Blood Vol. 92, No. 3 ( 1998-08-01), p. 784-789
    Details
    In: Blood, American Society of Hematology, Vol. 92, No. 3 ( 1998-08-01), p. 784-789
    Abstract: Although the majority of patients with acute promyelocytic leukemia (APL) are potentially cured by treatments combining all-trans retinoic acid (ATRA) and chemotherapy (CHT), a sizable proportion (around 30%) will relapse during follow-up. Retrospective molecular monitoring studies using reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific PML/RARα fusion gene, have shown that a positive test usually precedes the occurrence of hematologic relapse. Prospective RT-PCR analyses were performed since 1993 at diagnosis and at preestablished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RARα+ APL enrolled in the multicenter Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin). Treatment consisted of ATRA and idarubicin for induction followed by three polychemotherapy courses as consolidation. The sensitivity level of the RT-PCR assay for PML/RARα, as assessed by serial dilution experiments, was 10−4. All patients were in hematologic remission and tested PCR− at the end of consolidation. Of 21 who converted to PCR-positive thereafter, 20 underwent hematologic relapse at a median time of 3 months (range, 1 to 14) from the first PCR+ result. Seventeen of these 21 (81%) PCR+ conversions were recorded within the first 6 months postconsolidation. Of 142 who tested persistently PCR− in ≥2 tests after consolidation, 8 had hematologic relapse and 134 remained in complete remission (CR) after a median follow-up of 18 months (range, 6 to 38) postconsolidation. Using a time-dependent Cox model, the relative risk of hematologic relapse of patients who converted to PCR+ was 31.8 (confidence limits 95%, 12.9 to 78.3). Our results indicate that conversion to PCR positivity for PML/RARα during remission is highly predictive of subsequent hematologic relapse and highlight the prognostic value of stringent molecular monitoring during the early postconsolidation phase in APL. As a result of the present study, salvage treatment in patients enrolled in the GIMEMA trial AIDA is now anticipated at the time of molecular relapse, defined as the conversion to PCR positivity in two successive BM samplings during follow-up. © 1998 by The American Society of Hematology.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V92.3.784
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1998
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
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    Online Resource
    Distribution ofTP53 mutations among acute leukemias withMLL rearrangements
    Wiley ; 1996
    In:  Genes, Chromosomes and Cancer Vol. 15, No. 1 ( 1996-01), p. 48-53
    Details
    In: Genes, Chromosomes and Cancer, Wiley, Vol. 15, No. 1 ( 1996-01), p. 48-53
    Type of Medium: Online Resource
    ISSN: 1045-2257 , 1098-2264
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.1002/(SICI)1098-2264(199601)15:1〈〉1.0.CO;2-9
    DOI: 10.1002/(ISSN)1098-2264
    DOI: 10.1002/(SICI)1098-2264(199601)15:1〈48::AID-GCC7〉3.0.CO;2-4
    Language: English
    Publisher: Wiley
    Publication Date: 1996
    detail.hit.zdb_id: 1018988-9
    detail.hit.zdb_id: 1492641-6
    SSG: 12
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  • 10
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    Online Resource
    Intermittent Imatinib (INTERIM) Treatment of Patients with Ph+ Chronic Myeloid Leukemia in Complete Cytogenetic Response: Cytogenetic and Molecular Data At One Year
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 1682-1682
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1682-1682
    Abstract: Abstract 1682 Background: The introduction of Imatinib has significantly improved the outcome for patients with Ph+ CML. The complete cytogenetic response (CCgR) is a strong and confirmed predictor of improved long-term outcome. According to current recommendations, Imatinib (IM) should be continued indefinitely. However, optimal responders can be eligible for investigational trials of treatment discontinuation. AIMS: This study (ClinicalTrials.gov NCT 00858806) describes the effects of a policy of intermittent Imatinib (INTERIM) treatment (one month on/one month off) on cytogenetic and molecular responses in a selected population of patients ≥ 65 years old who were receiving treatment with Imatinib for 〉 2 years and were in stable complete cytogenetic response (CCgR). The primary endpoint of the study was the proportion of patients who maintained CCgR after 1 year of INTERIM. The secondary endpoint was the level of BCR-ABL transcripts during INTERIM METHODS: Cytogenetic and molecular responses were monitored by FISH and RT-Q-PCR every 3 months. The definition of CCgR, and of CCgR loss was based on CBA of marrow metaphases which was performed at baseline and in all the patients who became FISH positive (BCR-ABL–positive nuclei 〉 1%). Major molecular response (MMR), corresponding to a 3-log reduction in BCR-ABL transcript level from the standardized baseline, was defined as BCR-ABL ≤0.1%IS and was indicated as MR3.0. For the purposes of this study, complete molecular response (CMR) was defined as a 4-log reduction in BCR-ABL transcript level ( 〈 0.01%IS), with a sensitivity of at least 10,000 ABL copies, and is indicated as MR4.0. In case of loss of CCgR or MMR, Ph+ additional cytogenetic abnormalities (ACA) and BCR-ABL kinase domain (KD) point mutation analysis were also performed. RESULTS: Seventy-six patients have been enrolled. Six patients (8%) lost CCgR (CBA positive), and 3 other patients became FISH positive while remaining CBA negative. At 12 months, the probability of maintaining CBA negativity was 92% (95% CI 86–98%), while the probability of maintaining FISH negativity was 87% (95% CI 79–94%). None of the factors that were examined by univariate and multivariate analysis were found to be associated with an higher probability of either loosing the CCgR (CBA) or showing a FISH positivity ( 〉 1%), with the exception of the duration of imatinib therapy (HR = 0.23, 95% CI 0.008–0.73, P =.01). Among patients with prior Imatinib treatment longer or shorter than 48 months, the probability of maintaining FISH negativity was 94% (95% CI 88–100%) vs 71% (95% CI 53–89%), respectively, HR = 0.23 (P =.007). All the 6 patients who lost CCgR regained the CCgR with daily Imatinib, at the same dose, defined by FISH negativity after 3 to 9 months (4/6 also CBA negative, 2 patients refused bone marrow aspiration). At baseline, all but one patient (99%) were in MMR (MR3.0, BCR-ABL ≤0.1%IS), and 63 patients (83%) were in MR4.0 ( 〈 0.01%IS). After one year of intermittent Imatinib, 18/76 patients (24%) lost MR3.0 and 25/63 (39%) patients lost MR4.0. No patient lost complete hematologic response, progressed to accelerated or blastic phase, developed ACA in Ph+ cells, or developed BCR-ABL mutations. After one year, the remaining 70 patients were allowed to go back to continuous treatment, or to continue the intermittent treatment. During the first six months of follow-up (month 13 to 18), 1 of 70 discontinued Imatinib for atrial fibrillation and 9 of 70 went back to continuous treatment because FISH negativity loss (1 patient) or MMR (MR3.0) loss (8 patients). All the patients continue to be regularly observed and monitored and the first twelve months of follow-up will be presented. CONCLUSIONS: The intermittent use of imatinib in older patients in stable CCgR after continuous imatinib treatment results in the transient loss of the CCgR in a minority (8%) of the patients. However, the disease burden at the molecular level significantly increased. A policy of intermittent treatment may be an alternative both to chronic continuous treatment and to treatment discontinuation, particularly in the elderly. However, a longer follow up is required before drawing final conclusions. Acknowledgments: This work was supported in part by EuropeanLeukemiaNet through the European Treatment and Outcome Study (EUTOS) and by Cofin 2009. Disclosures: Baccarani: Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Castagnetti:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Di Raimondo:celgene: Honoraria. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.1682.1682
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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