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  • 1
    In: European Journal of Haematology, Wiley, Vol. 106, No. 5 ( 2021-05), p. 708-715
    Abstract: In autologous stem cell transplant (ASCT)‐eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. Method We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib‐based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). Results The length of induction treatment required to achieve a Good response did not affect PFS ( P  = .65) or OS ( P  = .61) post‐ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months ( P  = .31), and median OS 81.7, 92.7, and 77.4 months, respectively ( P  = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P ‐value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post‐transplant. Conclusion The kinetics of response did not affect outcomes.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 2
    In: Transplantation Proceedings, Elsevier BV, Vol. 55, No. 1 ( 2023-01), p. 242-248
    Type of Medium: Online Resource
    ISSN: 0041-1345
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1500785-6
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  • 3
    In: Cancer, Wiley, Vol. 104, No. 10 ( 2005-11-15), p. 2099-2103
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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  • 4
    In: American Journal of Hematology, Wiley, Vol. 96, No. 10 ( 2021-10), p. 1186-1194
    Abstract: Allogeneic hematopoietic cell transplantation (allo‐HCT) is increasingly used in older myelofibrosis (MF) patients, but its risk/benefit ratio compared to non‐transplant approaches has not been evaluated in this population. We analyzed the outcomes of allo‐HCT in 556 MF patients aged ≥65 years from the EBMT registry, and determined the excess mortality over the matched general population of MF patients ≥65 years managed with allo‐HCT (n = 556) or conventional drug treatment (n = 176). The non‐transplant cohort included patients with intermediate‐2 or high risk DIPSS from the Spanish Myelofibrosis Registry. After a median follow‐up of 3.4 years, the estimated 5‐year survival rate, non‐relapse mortality (NRM), and relapse incidence after transplantation was 40%, 37%, and 25%, respectively. Busulfan‐based conditioning was associated with decreased mortality (HR: 0.7, 95% CI: 0.5–0.9) whereas the recipient CMV+/donor CMV‐ combination (HR: 1.7, 95% CI: 1.2–2.4) and the JAK2 mutated genotype (HR: 1.9, 95% CI: 1.1–3.5) predicted higher mortality. Busulfan‐based conditioning correlated with improved survival due to less NRM, despite its higher relapse rate when compared with melphalan‐based regimens. Excess mortality was higher in transplanted patients than in the non‐HCT cohort in the first year of follow‐up (ratio: 1.93, 95% CI: 1.13–2.80), whereas the opposite occurred between the fourth and eighth follow‐up years (ratio: 0.31, 95% CI: 0.18–0.53). Comparing the excess mortality of the two treatments, male patients seemed to benefit more than females from allo‐HCT, mainly due to their worse prognosis with non‐transplant approaches. These findings could potentially enhance counseling and treatment decision‐making in elderly transplant‐eligible MF patients.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 5
    In: American Journal of Hematology, Wiley, Vol. 98, No. 1 ( 2023-01), p. 112-121
    Abstract: Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo‐HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo‐HCT for CP CML in 904 patients. A total of 323‐, 371‐, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib ( n  = 778), dasatinib ( n  = 508), nilotinib ( n  = 353), bosutinib ( n  = 12), and ponatinib ( n  = 44). The majority had imatinib as first TKI ( n  = 747, 96%). Transplants were performed in CP1, n  = 549, CP2, n  = 306, and CP3, n  = 49. With a median follow‐up of 52 months, 5‐year OS for the entire population was 64.4% (95% CI 60.9–67.9%), PFS 50% (95% CI 46.3–53.7%), RI 28.7% (95% CI 25.4–32.0%), and NRM 21.3% (95% CI 18.3–24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo‐HCT or to the type of TKI ( p  = ns). Significant factors influencing OS and PFS were  〉  CP1 versus CP1 and Karnofsky performance (KPS) score  〉  80 versus ≤80, highlighting CP1 patients undergoing allo‐HCT have improved survival compared to 〉 CP1 and the importance of careful allo‐HCT candidate selection.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 6
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 108, No. 10 ( 2023-10-01)
    Abstract: We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; P
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2023
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  • 7
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 108, No. 4 ( 2022-06-30), p. 1105-1114
    Abstract: Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR] =0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2022
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  • 8
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3425-3425
    Abstract: Introduction Primary Plasma Cell Leukaemia (pPCL) is a rare disorder and considered the most aggressive plasma cell dyscrasia. Autologous stem cell transplantation (auto) has been shown to improve outcomes, however the role of allogeneic transplantation (allo) is uncertain. The CIBMTR compared outcomes of 147 patients undergoing auto and allo transplant and demonstrated that while allo patients had significantly lower relapse rates their non-relapse mortality was significantly higher. Further evidence is needed to guide clinicians in choosing between auto versus allo in transplant eligible patients. This study examines the largest cohort of patients with pPCL undergoing auto and allo transplantation. Materials and Methods A retrospective analysis was undertaken of the European Group for Bone Marrow Transplantation (EBMT) experience of patients with pPCL undergoing transplantation between 1998 and 2014. Only patients who had achieved Complete Response (CR), Partial Response (PR) or Stable Disease (SD) prior to transplantation were included. The primary end point was Overall Survival (OS). We further analysed Progression-Free Survival (PFS), Cumulative Incidence of Relapse (CIR) and Non-Relapse Mortality (NRM). As this is a retrospective study single- and tandem- transplant groups were compared by landmark analysis (4 months post first auto) and dynamic prediction to avoid time bias. We defined tandem transplants (auto-auto or auto-allo) given within 9 months in absence of progression. Dynamic prediction was used to predict long-term outcomes in all patients according to the treatment actually received and without loss of information as in the traditional landmark analysis. Results A total of 751 patients were included in the analysis. 70 patients received an allo as first transplant. 681 patients received an auto as first transplant; 239 of these patients went on to receive an elective tandem transplant. 122 had a tandem allo and 117 had a tandem auto. Patients having first allo were younger (median age 47.2 years versus 57.7 years for first auto), had a longer time from diagnosis to transplant (first allo 84.3% transplanted in 〈 12 months versus 93.5% in first auto) and had higher proportion of patients both in CR and SD (CR allo 37.1% versus 32.5% first auto, SD 15.7% allo versus 4.8% in first auto). For patients receiving a tandem allo there was a higher proportion of matched unrelated donor transplants (50% versus 28.6% in first allo) and reduced intensity conditioning (80.3% versus 27.1% in first allo). The median OS was 17.5 months for first allo versus 33.5 months for first auto, while median PFS was 11.7 months for first allo and 14.3 months for first auto. As demonstrated by Figure 1 the OS and PFS curves do cross, therefore LogRank test was not appropriate. At 36 months NRM was 27% for allo versus 7.3% for first auto (p 〈 0.0001) which likely accounts for the differences in OS. Figure 1. OS, PFS, CIR and NRM Landmark analysis at 4 months resulted in a reduction in the number of second transplants analysed to 160 patients. The landmark analysis revealed that there is no significant difference in OS or PFS between the transplant groups, and lower CIR (p=0.07) and only a limited early increase of NRM (p=0.24) in the auto-allo group. These results were substantially confirmed when adjusting for covariates, however the landmark analysis is limited by reduced sample size and non-constant relative risks. Dynamic prediction was made with a horizon time of 3 years for OS and 1 year for PFS. Age and disease status at transplant were included and all transplant strategies were compared to single auto as baseline. This revealed that tandem auto allo had a significant improvement in 1 year PFS with a 44% reduction in risk compared to single auto (HR 0.56, p=0.003). The 3 year predicted OS reveals a trend towards superiority for tandem auto allo versus single auto but it did not reach significance (HR 0.78, p=0.20). Conclusion This is largest retrospective study examining transplantation in pPCL. Direct comparison of first allo versus first auto shows that in the short term allo upfront has worse outcome, largely due to significant NRM. Landmark analysis and especially dynamic prediction models reveal for the first time that auto-allo has an acceptable NRM and could be preferred to single auto due to lower relapse rates translating into a better PFS and even a trend for OS in the long term. Figure 1. Figure 1. Disclosures Lawless: Celegene: Honoraria, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees. Foà:AMGEN: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau. Garderet:Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 924-924
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 924-924
    Abstract: Introduction: Intensive therapy (IT) including autologous stem cell transplantation (ASCT) is considered superior to conventional therapy in newly diagnosed myeloma pts 〈 60 yrs. For older pts the benefit of IT is less clear. In 1998 the NMSG started a population-based, prospective trial (#7/98) aiming to study the impact of age on event-free survival (EFS) and survival after IT, and to compare survival to a conventionally treated historic control group. Patients: Newly diagnosed symptomatic pts 〈 65 yrs were included into a protocol with four phases; I) VAD x 3–4; II) cyclophosphamide 2g/sqm, G-CSF (filgrastim) and stem cell harvest; III) melphalan 200 mg/sqm, stem cell infusion and G-CSF; IV) interferon maintenance. Double ASCT was optional. From Jan 1998 to June 2000, 452 pts were registered and 414 (92%) of these were included into the IT protocol (=Intensive Therapy Group (ITG)). 294 were 〈 60 yrs (=ITG-60) and 120 were 60–64 yrs (=ITG-65). The historic control group was derived from a previous population-based, randomized NMSG study (#4/90) where melphalan and prednisone +/− interferon was given as initial therapy. Of the 281 pts 〈 65 yrs registered in this trial, 243 (86%) fulfilled the eligibility criteria for IT stated in the #7/98 protocol and constituted the Control Group (CG). 146 were 〈 60 yrs (=CG-60) and 97 were 60–64 years (=CG-65). Results: In the ITG-60, 261 pts (89%) were actually transplanted (80% single ASCT, 18% double ASCT and 2% allogeneic SCT). In the ITG-65, 98 pts (82%) were transplanted (84% single and 16% double ASCT). Median follow-up is 50 months. Major response rate (CR+PR) was 88% in the ITG-60 and 81% in the ITG-65. EFS at 4 yrs for the ITG-60 was 37% and median EFS 36 months, while the corresponding figures for the ITG-65 were 19% and 24 months (P=.005). Survival at 4 yrs for the ITG-60 was 67% and median survival 67 months, while the corresponding figures for the ITG-65 was 50% and 48 months (P=.004). In a multivariate analysis of the entire ITG, two variables were significantly associated with EFS and survival; beta-2-microglobulin at diagnosis and age 〈 or ≥ 60 yrs. The survival in the ITG-60 was prolonged compared to the CG-60 with a risk ratio (RR) of 0.50 (95%CI 0.38–0.67; p 〈 .0001). Survival at 4 yrs was 67% in the ITG-60 and 44% in the CG-60, with a median survival of 67 and 43 months, respectively. The survival advantage persisted (RR 0.57, 95%CI 0.42–0.78; p=.0004) after statistical analysis of prognostic factors and correction for differences between the groups. Also for patients 60–64 yrs old survival was prolonged in the ITG compared to the CG with a RR of 0.65 (95%CI 0.42–0.92; p=.02). Survival at 4 yrs was 50% in the ITG-65 and 40% in the CG-65 with a median survival of 48 and 28 months, respectively. However, after correction for the difference in prognostic factors between the groups there was no significant difference in survival (RR 0.80, 95%CI 0.55–1.16; p=.23). Conclusions: In this population-based study older age was found to have a negative influence on outcome after IT. Our results indicate that there is an upper age limit that remains to be defined for superiority of IT over conventional chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 10
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4403-4403
    Abstract: Introduction: The EBMT Lymphoma Working Party has previously reported on the long-term outcome of allogeneic HCT for patients with advanced MF/SS [J Clin Oncol 2014; 32: 3347-8 ]. Among a number of disease and transplant factors influencing patient outcome, the use of UD showed to be the strongest independent factor influencing overall survival (OS). The main shortcoming of the original reports was a limited number of 60 cases in the series, of which only 15 received allogeneic HCT from UD. As UD have been increasingly used during recent years, we sought to extend our previous analysis (1997-2007) to include patients with MF/SS allografted between 2008-2011. Patient and Methods: Endpoints were OS, progression-free survival (PFS), non-relapse mortality (NRM) and incidence of disease relapse/progression (DRP). Eligible were patients 〉 = 18 years who were registered with the EBMT and had received an allogeneic HCT for MF/SS between 1997-2011. Centers with eligible patients were contacted to provide additional treatment and follow-up information including a written diagnostic report. Data were collected from the EBMT Registry (closed in July 2014), and endpoints were defined and analyses performed according to EBMT statistical guidelines (www.ebmt.org). Results: Eligible for final analysis were a total of 113 patients, including our original 60 cases (1997-2007) and 53 new cases (2008-2011): 71 men and 42 women, median age at HCT 48 years (21-72), 77 MF (68%) and 36 SS (32%), with 7 EORTC/ISCL stage IIB, 17 stage III, 46 stage IV-A and 26 stage IV-B (17 missing). Demographics of both time periods were comparable, except for a marked increase in the use of UD (15/60, 25% vs 29/53, 55%; p=0.001) and a reduction in the use of TBI for conditioning (30/60, 50% vs 15/53, 28%; p=0.031) in recent years. At HCT, 52 patients (46%) were refractory or in relapse/progression and 61 (54%) in complete or partial remission. Eighty-six patients (76%) received reduced-intensity (RIC) and 27 (24%) myeloablative (MAC) conditioning regimens, including TBI in 45 cases (40%). With a median follow up in survivors of 72 months (IQR: 39-97), allogeneic HCT for MF/SS offers an estimated OS of 56% at 1 year, 44% at 3 years and 38% at 5 years, and PFS of 34% at 1 year, 28% at 3 years and 25% at 5 years. NRM was 26% at 1 year and 28% at 3 years and thereafter. DRP was the main cause of treatment failure, with a probability of 40% at 1 year, 44% at 3 years and 47% at 5 years, and a mortality rate after DRP of 70% (35/50). It is worth noting that 15 patients (30%) remain alive at last follow up despite DRP, suggesting that some of these patients can be successfully rescued with donor lymphocyte infusions and other therapeutic interventions. The cumulative incidence of acute GVHD was 47% at day 100, and chronic GVHD 35% at 1 year, 45% at 3 years and 48% at 5 years. Interestingly, the univariate analysis showed a statistical trend towards a poorer OS in the cohort of new cases registered from 2008 (p=0.106). However, transplant period had no significant impact when included as a covariate in multivariate analysis, and appears to associate with the higher percentage of UD transplants in the new cohort. The use UD remained the main negative independent factor for OS (HR: 0.490; 95CI: 0.283-0.848; p=0.011) and PFS (HR: 0.468; 95CI: 0.259-0.843; p=0.011) in the multivariate models unstratified and stratified by inclusion period. The use of TBI in conditioning appears to have an independent effect to reduce the risk of DRP in the multivariate analysis (HR: 0.427; 95CI: 0.199-0.917; p=0.029), but does not translate into OS or PFS. Conclusions: This extended series confirms the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS, permitting long-term disease control in a substantial proportion of high-risk patients. Follow-up studies need to address the still significant adverse effect of UD and the role of TBI conditioning in order to improve HCT results in these otherwise fatal disorders. Disclosures Mufti: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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    detail.hit.zdb_id: 80069-7
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