共查询到20条相似文献,搜索用时 15 毫秒
1.
Thomas M. Habermann Izidore S. Lossos Glen Justice Julie M. Vose Peter H. Wiernik Kyle McBride Kenton Wride Annette Ervin-Haynes Kenichi Takeshita Dennis Pietronigro Jerome B. Zeldis Joseph M. Tuscano 《British journal of haematology》2009,145(3):344-349
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis following first relapse. We present a subgroup analysis of an open-label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL. Oral lenalidomide 25 mg was self-administered once daily on days 1–21 every 28 d for up to 52 weeks, according to tolerability or until disease progression. The primary endpoint was overall response rate (ORR) and secondary endpoints were duration of response, progression-free survival (PFS) and safety. Among 15 patients with MCL with a median disease duration of 5·1 years and a median of four prior treatments, the ORR was 53%. Three patients (20%) had a complete response and 5 (33%) had a partial response. The median duration of response was 13·7 months and median PFS was 5·6 months. Four of five patients who relapsed after transplantation and two of five patients who previously received bortezomib responded to lenalidomide. The most common grade 4 adverse event was thrombocytopenia (13%) and the most common grade 3 adverse events were neutropenia (40%), leucopenia (27%) and thrombocytopenia (20%). In conclusion, oral lenalidomide monotherapy is well tolerated and active in relapsed or refractory MCL. 相似文献
2.
Ingram W Devereux S Das-Gupta EP Russell NH Haynes AP Byrne JL Shaw BE McMillan A Gonzalez J Ho A Mufti GJ Pagliuca A 《British journal of haematology》2008,141(2):235-243
The role of haematopoietic stem cell transplantation (HSCT) in relapsed follicular lymphoma remains controversial. This study analysed 126 patients with relapsed, advanced stage follicular lymphoma who received BEAM (BCNU [carmustine], cytarabine, etoposide, melphalan)-alemtuzumab allogeneic HSCT (BEAM-allo) ( n = 44) or BEAM-autologous HSCT (BEAM-auto) ( n = 82). The BEAM-allo group had a younger median age (48 years vs. 56 years, P < 0·001) but received a higher median number of therapies pretransplant ( P = 0·015) compared with the BEAM-auto group. There was a higher non-relapse mortality (NRM) in the BEAM-allo group compared with the BEAM-auto group at 1 year (20% vs. 2%, P = 0·001). Older age and heavily pretreated patients were associated with a higher NRM and poorer survival in the BEAM-allo group. There was, however, a significantly lower relapse rate (20% vs. 43%, P = 0·01) at 3 years with BEAM-alemtuzumab, with no relapses after 2 years, compared with a continued pattern of relapse in the autologous group. No difference in overall survival (OS) ( P = 0·99) or disease-free survival (DFS) ( P = 0·90) was identified at 3 years, whereas a plateau in OS and DFS with crossing of the survival curves in favour of BEAM-allo group was observed. Furthermore, the ability to re-induce remissions with donor leucocytes provides additional benefit in favour of allogeneic HSCT. 相似文献
3.
David A. Jacobsohn William T. Tse Stanley Chaleff Alfred Rademaker Reggie Duerst Marie Olszewski Wei Huang Pauline M. Chou Morris Kletzel 《British journal of haematology》2009,146(6):669-674
WT1 gene expression has been proposed as a useful marker of minimal residual disease in leukaemia. Its utility in paediatric haematopoietic stem cell transplantation (HSCT) has not been studied. We studied the prognostic value of WT1 expression in peripheral blood prior to HSCT in 36 children with acute myeloid leukaemia (AML). Samples were obtained 2 weeks pre-transplant to determine the level of WT1 expression. WT1 expression was normalized using K562 cells as a control and a relative value of 0·5 was chosen as the cut-off point between high and low WT1 expression. The median level of pre-transplant WT1 expression in the 36 patients was 0·09 (range 0·0001–11·0), with 11patients having WT1 ≥ 0·5 and 25, WT1 < 0·5. After HSCT, 76% of patients with high pre-transplant WT1 expression relapsed, in contrast to 0% of the patients with low WT1 expression. Those with high WT1 expression had significantly lower 5-year event-free survival (EFS) (18%, 95% CI 0–40%) as compared to those with low WT1 expression (68%, 95% CI 50–86%, P = 0·007). Multivariate analysis showed that pre-transplant WT1 level is the only significant prognostic factor for the difference in EFS. Our finding suggests that elevated WT1 gene expression before HSCT in paediatric AML predicts relapse and poor long-term EFS. A larger prospective study is warranted to compare the value of high WT1 expression and other markers of minimal residue disease in predicting clinical outcomes after HSCT. 相似文献
4.
Owen A. O'Connor Craig Moskowitz Carol Portlock Paul Hamlin David Straus Otilia Dumitrescu Debra Sarasohn Mithat Gonen John Butos Ellen Neylon Rachel Hamelers Barbara Mac-Gregor Cortelli Susan Blumel rew D. Zelenetz Leo Gordon John J. Wright Julie Vose Brenda Cooper Jane Winter 《British journal of haematology》2009,145(1):34-39
The recent approval of bortezomib for the treatment of mantle cell lymphoma (MCL) by the US Food and Drug Administration is based on the results of the multicentre PINNACLE study with supportive data from a number of single and multicentre Phase 2 studies. This multicentre Phase 2 study enroled 40 patients with heavily pretreated MCL. The overall response rate (ORR) was 47%, including 5 complete remissions and 14 partial remissions. Overall, these remissions are relatively durable. The ORR in relapsed and refractory patients was 50% and 43% respectively ( P = 0·74), while both populations of patients exhibited essentially similar progression-free survival (PFS; 5·6 months vs. 3·9 months, P = 0·81). Responding patients experienced a PFS from bortezomib that was similar to their line of prior therapy (7·8 months vs. 8·4 months, respectively). The data showed similar responses in relapsed and refractory patients as well as remission durations similar to prior therapy, suggesting that there may be little cross-resistance with other conventional cytotoxic agents. Importantly, these data suggest that MCL patients with refractory or poorly responsive disease may still derive meaningful clinical benefit from treatment with bortezomib. 相似文献
5.
Murali S Winton E Waller EK Heffner LT Lonial S Flowers C Kaufman J Arellano M Lechowicz MJ Mann KP Khoury HJ Langston AA 《Bone marrow transplantation》2008,42(8):529-534
Autologous hematopoietic progenitor SCT (HPCT) has been studied both as a consolidative and salvage maneuver in mantle-cell lymphoma (MCL), and may improve failure-free survival rates as well as overall survival. We describe 21 patients with MCL who received autologous HPCT at Emory University Hospital as part of the primary treatment strategy. Sixteen patients were in CR1 and five in PR1 at the time of HPCT. The most commonly used induction chemotherapy was the hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimen with or without rituximab. At the last follow-up, 17 patients were in continuous CR, and there were four relapses. There were no transplant-related deaths. With a median follow-up of 54 months from HPCT, 5-year progression-free survival and overall survival are 73% and 76%, respectively. Our retrospective analysis provides the longest follow-up to date for patients with MCL who received an autologous HPCT as part of primary treatment. This lengthy follow-up helps define the natural course of MCL after autologous transplantation. 相似文献
6.
Yao Liu Jun Rao Jiali Li Qin Wen Sanbin Wang Shifeng Lou Tonghua Yang Bin Li Lei Gao Cheng Zhang Peiyan Kong Li Gao Maihong Wang Lidan Zhu Xixi Xiang Sha Zhou Xue Liu Xiangui Peng Jiangfan Zhong Xi Zhang 《Haematologica》2021,106(1):163
T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and no standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) for adult T-LBL and evaluated prognostic factors affecting survival. A total of 181 newly-diagnosed adult T-LBL patients were enrolled: 89 patients were treated with chemotherapy alone, 46 were allocated to the single auto-HSCT group, 46 were treated with tandem auto-HSCT. Median follow-up time was 37 months; the 3-year progression/relapse rate of the tandem auto- HSCT group was significantly lower than that of the single auto-HSCT and chemotherapy groups (26.5% vs. 53.1% and 54.8%). The 3-year progression- free survival (PFS) and overall survival (OS) rates of the tandem auto- HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplant impacted OS and PFS. Multivariate analysis identified that disease status after the first transplant was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8+CD28+/CD8+CD28– T-cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto- HSCT can be considered an optimal strategy for adult T-LBL patients. (Study registered at: ChiCTR-ONN-16008480). 相似文献
7.
Diana X. Nichols-Vinueza Mark Parta Nirali N. Shah Jennifer M. Cuellar-Rodriguez Thomas R. Bauer Robert R. West Amy P. Hsu Katherine R. Calvo Seth M. Steinberg Luigi D. Notarangelo Steven M. Holland Dennis D. Hickstein 《British journal of haematology》2022,196(1):169-178
GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft-versus-host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event-free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety-six percent of surviving patients had reversal of the hematologic disease phenotype by one-year post-transplant. Incidence of grade III-IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post-transplant cyclophosphamide (PT/Cy), no patient developed grade III-IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III-IV aGVHD. In summary, a busulfan-based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD. 相似文献
8.
Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma 总被引:7,自引:1,他引:7
María J. Calasanz Juan C. Cigudosa MaríA D. Odero JesúS García-Foncillas Julián Marín Mariá T. Ardanaz Eduardo Rocha & Arturo Gullón 《British journal of haematology》1997,98(2):418-425
Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The present series includes 111 newly diagnosed MM patients treated with one of three standard-dose regimens or autologous transplantation over an 8-year time interval. As expected, the presence of an abnormal karyotype (39% of patients) correlated with poor prognosis (progression rate 63% v 47%, P = 0.042), shorter event-free (EFS, P = 0.014) and overall (OS, P = 0.005) survival. Two distinct cytogenetic abnormalities were the most significant variables that influenced EFS and OS in the univariate analysis. The presence of hypodiploid karyotypes or rearrangements of band 22q11 were associated with higher progression rate ( P = 0.001) and shorter EFS ( P < 0.024) and OS ( P < 0.004). The median EFS and OS for patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis showed that absence of hypodiploidy was the most favourable prognostic variable for OS ( P = 0.022) followed by stage ≤IIA, serum calcium ≤2875 μmol/l, and absence of abnormalities 22q. The data suggest that the presence of hypodiploid karyotypes and rearrangements on 22q11 band show a higher progression rate and shorter survival in MM patients. 相似文献
9.
To determine graft-versus-leukemia (GVL) effect after hematopoietic stem cell transplantation (HSCT), we studied the outcome of consecutive children with acute lymphoblastic leukemia (ALL) who received fully matched marrow allografts comparing relapse rate post HSCT between matched sibling donor (MSD) and matched unrelated donor (MUD) recipients. Furthermore, we estimated event-free survival (EFS) on the basis of the occurrence of acute graft-versus-host disease (aGVHD). Between 1998 and 2006 we performed 37 fully MSD and 36 fully MUD HSCTs. All patients received identical conditioning regimens with cyclophosphamide/total body irradiation and dual GVHD prophylaxis with cyclosporine (CSA) and methotrexate (MTX). Three-year cumulative incidence of relapse for the MSD and MUD groups were 55.6+/-12.3 and 22.0+/-8.1%, respectively (P=0.03). Three-year EFS according to aGVHD was 32.7+/-12.2% for no aGVHD, 61.2+/-10.0% for grade I-II aGVHD and 66.7+/-11.1% for grade III-IV aGVHD. Three-year EFS and overall survival (OS) were 40.5+/-11.6, 49.1+/-9.5% for the MSD group, and 60.5+/-8.7, 62.3+/-8.4% for the MUD group. In children with ALL receiving dual GVHD prophylaxis, relapse rate is significantly higher among recipients of MSD compared to MUD transplantation, which may in part be attributed to a better GVL effect with the unrelated graft. 相似文献
10.
Hamlin PA Portlock CS Straus DJ Noy A Singer A Horwitz SM Oconnor OA Yahalom J Zelenetz AD Moskowitz CH 《British journal of haematology》2005,130(5):691-699
Primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)-like therapy, the non-Hodgkin lymphoma (NHL)-15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow-up of 10.9 years, event-free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP-like, NHL-15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP-like regimens had inferior EFS and OS versus NHL-15 or upfront ASCT (P < 0.001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL-15 or upfront ASCT); for OS, only initial therapy with NHL-15. We conclude: (i) dose-dense chemotherapy with NHL-15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age-adjusted IPI did not predict survival in this analysis; (iv) high-dose chemotherapy/ASCT should be reserved for upfront anthracycline-based therapy failure or in clinical trials for high-risk patients. 相似文献
11.
Mars B. van 't Veer Daphne de Jong Marius MacKenzie Hanneke C. Kluin-Nelemans Marinus H. J. van Oers Jose Zijlstra Anton Hagenbeek Wim L. J. van Putten 《British journal of haematology》2009,144(4):524-530
Mantle cell lymphoma (MCL) has a dismal outcome when treated with conventional chemotherapy. This single arm phase 2 study evaluated intensive consolidation treatment of patients with newly diagnosed MCL up to the age of 65 years, responsive to R-CHOP (rituximab, cyclophosphamide, oncovin, adriamycin, prednisolone). Endpoints for evaluation were toxicity, failure-free survival (FFS) and overall survival (OS). Eighty-seven patients were treated with three cycles of R–CHOP. Sixty-six patients responded to R-CHOP with at least a partial response, 62 continued protocol treatment with high-dose cytarabine (Ara-C; 2000 mg/m2 , bid. over 4 d) and 61 patients received rituximab and stem cell harvest, followed by BEAM (carmustine, etoposide, Ara-C, melphalan) and autologous stem cell rescue. Non-haematological toxicity, grades III and IV, was seen in 8% of the patients after R-CHOP, in 22% after high-dose Ara-C and in 55% after BEAM. The overall response rate was 70% (complete response rate 64%, partial response rate 6%), FFS and OS at 4 years were 36 ± 7% and 66 ± 6%, respectively. The FFS and OS at 4 years from the evaluation after BEAM in the 61 R-CHOP responsive patients was 46 ± 9% and 79 ± 7%, respectively. In conclusion, high-dose Ara-C and BEAM with stem cell rescue in newly diagnosed MCL patients responsive to R-CHOP is a manageable treatment with respect to toxicity. This regimen leads to long-term, but probably not durable, remissions. 相似文献
12.
Pineda-Roman M Zangari M Haessler J Anaissie E Tricot G van Rhee F Crowley J Shaughnessy JD Barlogie B 《British journal of haematology》2008,140(6):625-634
Total therapy 3 (TT3), incorporating bortezomib up-front into a tandem transplant regimen for newly diagnosed multiple myeloma (MM), effected 2-year complete response (CR) estimates >90%, which appeared superior to results reported for total therapy 2 (TT2). With median follow-up times of 2 years with TT3 and 5 years with TT2, the clinical outcomes of 303 patients in the former and 668 in the latter trial were compared, including the subset of 607 patients with gene expression profiling (GEP) data. With similar baseline prognostic factors, event-free survival (EFS) ( P = 0·0002) and CR duration ( P = 0·003) were superior with TT3 vs. TT2 with a strong trend noted also for improved overall survival (OS) ( P = 0·16). In the GEP-defined FGFR3 subgroup, TT3 imparted significantly superior OS, EFS and CR duration vis-à-vis TT2. Matching 300 patients each by standard prognostic factors, TT3 yielded superior EFS and CR duration and borderline superior OS. The advantage of TT3 still pertained when the comparison was limited to patients who completed TT2 consolidation rapidly within 24 months. Our data strongly suggest that the addition of bortezomib in TT3 was accountable for its superior performance rather than greater compliance with protocol completion as a result of greater dose-density in TT3 vs. TT2. 相似文献
13.
Miller KB Roberts TF Chan G Schenkein DP Lawrence D Sprague K Gorgun G Relias V Grodman H Mahajan A Foss FM 《Bone marrow transplantation》2004,33(9):881-889
Summary:In all, 55 patients at high risk or ineligible for a conventional allogeneic hematopoietic stem cell transplant (HSCT) received a regimen consisting of extracorporeal photopheresis, pentostatin, and reduced dose total body irradiation. The median age was 49 years (18-70 years); 44 received a sibling and 11 an unrelated HSCT; 44% were over the age of 50 years and 31% had undergone a prior HSCT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Full donor chimerism was documented in 98% by day +100. The 1000-day nonrelapse mortality was 11%. The median follow-up is 502 days (154-1104 days). The 1- and 2-year overall survival (OS) and event-free survival (EFS) are 67, 58 and 55%, and 47%, respectively. Patients who had not received a prior HSCT or had less than three prior chemotherapy regimens had a 71% OS and 67% EFS at 1 year. Greater than grade II aGVHD developed in 9% and chronic GVHD (cGVHD) in 43%, and extensive in 12% and limited in 31%. Of the patients, 86% who engrafted had a disease response, 72% had complete and 14% partial responses. This novel reduced intensity preparative regimen was well tolerated and associated with a low incidence of transplant-related mortality and serious acute and cGVHD. 相似文献
14.
Robert M. Dean Brad Pohlman John W. Sweetenham Ronald M. Sobecks Matt E. Kalaycio Stephen D. Smith Edward A. Copelan Steven Andresen Lisa A. Rybicki Julie Curtis Brian J. Bolwell 《British journal of haematology》2010,148(2):226-234
Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral ( n = 468) or IV ( n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse ( P = 0·01), RFS ( P = 0·002) and OS ( P = 0·001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study. 相似文献
15.
Voravit Ratanatharathorn Brent Logan Dan Wang Mary Horowitz Joseph P. Uberti Olle Ringden Robert Peter Gale Hanna Khoury Mukta Arora Stephen Spellman Corey Cutler Joseph Antin Martin Bornhaüser Gregory Hale Leo Verdonck Mitchell Cairo Vikas Gupta Steven Pavletic for the Center for International Blood Marrow Transplant Research Milwaukee WI USA 《British journal of haematology》2009,145(6):816-824
Prior therapy with rituximab might attenuate disparate histocompatibility antigen presentation by B cells, thus decreased the risk of acute graft-versus-host disease (GVHD) and improved survival. We tested this hypothesis by comparing the outcomes of 435 B-cell lymphoma patients who received allogeneic transplantation from 1999 to 2004 in the Center for International Blood and Marrow Transplant Research database: 179 subjects who received rituximab within 6 months prior to transplantation (RTX cohort) and 256 subjects who did not receive RTX within 6 months prior to transplantation (No-RTX cohort). The RTX cohort had a significantly lower incidence of treatment-related mortality (TRM) [relative risk (RR) = 0·68; 95% confidence interval (CI), 0·47–1·0; P = 0·05], lower acute grade II–IV (RR = 0·72; 95% CI, 0·53–0·97; P = 0·03) and III–IV GVHD (RR = 0·55; 95% CI, 0·34–0·91; P = 0·02). There was no difference in the risk of chronic GVHD, disease progression or relapse. Progression-free survival (PFS) (RR = 0·68; 95% CI 0·50–0·92; P = 0·01) and overall survival (OS) (RR = 0·63; 95% CI, 0·46–0·86; P = 0·004) were significantly better in the RTX cohort. Prior RTX therapy correlated with less acute GVHD, similar chronic GVHD, less TRM, better PFS and OS. 相似文献
16.
John Gerecitano Carol Portlock Craig Moskowitz Paul Hamlin David Straus rew D. Zelenetz Zhigang Zhang Otilia Dumitrescu Debra Sarasohn Dorothy Lin Jennifer Pappanicholaou Barbara M. Cortelli Ellen Neylon Rachel Hamelers John Wright Owen A. O'Connor 《British journal of haematology》2009,146(6):652-655
Twice-weekly bortezomib has proven activity in mantle cell (MCL) and indolent lymphomas. This study explored a weekly schedule of bortezomib in follicular lymphoma (FL) and MCL. Although weekly bortezomib was better tolerated, the overall response rate (ORR) was inferior (18% vs. 50%, P = 0·02) with no complete remissions (CR) (compared with 18% CR for the twice-weekly schedule). Progression-free survival (PFS) was not different. The weekly schedule of bortezomib was less toxic, but yielded fewer and lower quality responses than twice-weekly bortezomib. Given the similar PFS, the weekly schedule may still be appropriate for some patients. 相似文献
17.
Christopher Mitchell Jeanette Payne Rachel Wade Ajay Vora Sally Kinsey Sue Richards Tim Eden 《British journal of haematology》2009,146(4):424-436
The 1997 acute lymphoblastic leukaemia (ALL) trial (ALL97) was a randomised comparison of prednisolone versus dexamethasone and of 6-mercaptopurine versus 6-thioguanine. During the first 2 years of the trial, review of survival data showed the preceding trial, UKALL XI, was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups. The therapy template was therefore altered to an American Children's Cancer Group (CCG) style regimen, including stratification by age, white cell count and early response to therapy by assessment of the bone marrow. This phase of the trial was designated ALL97/99. Comparison of the two phases showed that the event-free survival (EFS) for both ALL97 and ALL97/99 was better than previous UKALL trials, as was overall survival (OS) for ALL97/99. Both EFS and OS were significantly better in ALL97/99 than in ALL97 (at five years, 80·0% vs. 74·0%, P = 0·002; and 88·0% vs. 83·5%, P = 0·005, respectively). Isolated central nervous system (CNS) relapse for patients in ALL97/99 was half that in ALL97 (3·0% vs. 4·9%), P = 0·03) and the overall CNS relapse rate was halved in ALL97/99 (4·4% vs. 9·6%, P < 0·00005). There were no significant differences for non-CNS relapse, induction deaths or deaths in remission between the two phases of the trial. 相似文献
18.
Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen) 总被引:11,自引:4,他引:11
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Gianni AM Magni M Martelli M Di Nicola M Carlo-Stella C Pilotti S Rambaldi A Cortelazzo S Patti C Parvis G Benedetti F Capria S Corradini P Tarella C Barbui T 《Blood》2003,102(2):749-755
Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease. 相似文献
19.
Dita Gratzinger Ranjana Advani Shuchun Zhao Neha Talreja Robert J. Tibshirani Ragini Shyam Sandra Horning Laurie H. Sehn Pedro Farinha Javier Briones Izidore S. Lossos Randy D. Gascoyne Yasodha Natkunam 《British journal of haematology》2010,148(2):235-244
Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co-express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)-like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic Index (IPI) ( P = 0·0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression-free survival (PFS, P = 0·044) and trended toward shorter OS on univariate analysis. VEGFR1 was not predictive of survival on univariate analysis, but it did correlate with better OS on multivariate analysis with VEGF, VEGFR2 and IPI ( P = 0·036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI ( P = 0·01). These results are concordant with our prior finding of an association of VEGFR1 with longer OS in DLBCL treated with chemotherapy alone. We postulate that VEGFR1 may oppose autocrine VEGFR2 signalling in DLBCL by competing for VEGF binding. In contrast to our prior results with chemotherapy alone, microvessel density was not prognostic of PFS or OS with R-CHOP-like therapy. 相似文献
20.
Hosein PJ Pastorini VH Paes FM Eber D Chapman JR Serafini AN Alizadeh AA Lossos IS 《American journal of hematology》2011,86(10):841-845
Positron emission tomography (PET) scans are widely used in patients with lymphoma but little is known about their utility in mantle cell lymphoma (MCL). MCL patients were included from two prospective trials and one observational study at our institution. A total of 276 PET scans were performed among 52 patients. After a median follow-up of 37.5 months, the 3-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI]: 61-85%) and 92% (95% CI 85-100%), respectively. There were 34 pretreatment PET scans, 26 interim, 28 end-of-treatment, 162 surveillance, and 26 scans at relapse or beyond. Pretreatment PETs were positive in 94%. A negative interim or end-of-therapy PET scan was not significantly associated with better EFS or OS, but no deaths were observed in patients who had a negative interim or end-of-therapy PET. Surveillance PET scans had a high false positive rate (35%) and low positive predictive value (8%). PET scans contributed to an earlier diagnosis of relapse in only two out of the 18 patients (11%) who relapsed. PET scans did not meaningfully contribute to staging or surveillance of MCL patients in this study. There was a trend toward improved survival in patients who had a negative end-of-therapy PET scan. 相似文献