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1.
Barry W. Hancock Wendi Qian David Linch Jean-Charles Delchier Paul Smith Ira Jakupovic Cathy Burton Robert Souhami rew Wotherspoon Christiane Copie-Bergman Carlo Capella Catherine Traulle Michael Levy Sergio Cortelazzo res J. M. Ferreri Achille Ambrosetti Graziella Pinotti Giovanni Martinelli Umberto Vitolo Franco Cavalli Christian Gisselbrecht Emanuele Zucca 《British journal of haematology》2009,144(3):367-375
Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = −9% to 29%, P = 0·15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0·96, 95% CI = 0·41–2·2, P = 0·91] or overall survival (HR = 1·93, 95% CI = 0·39–9·58, P = 0·42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti -H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas. 相似文献
2.
Tait D. Shanafelt John C. Byrd Betsy LaPlant Clive S. Zent Tim Call Charla Secreto Michael R. Grever Thomas S. Lin Neil E. Kay 《British journal of haematology》2009,146(6):660-664
Serum levels of pro-[vascular endothelial growth factor (VEGF)] and anti-[thrombospondin-1 (TSP)] angiogenic cytokines were prospectively measured in a phase II trial of chemoimmunotherapy (CIT) for chronic lymphocytic leukaemia (CLL) patients ( n = 56). Pretreatment VEGF levels were lower among patients who achieved complete remission (CR) or nodular partial remission (nPR) relative to those with partial remission (PR) or stable/progressive disease (median 122·0 pg/ml vs. 246·8 pg/ml; P = 0·03). VEGF:TSP ratio was lower (anti-angiogenic phenotype) among patients who achieved CR/nPR. The pretreatment VEGF:TSP ratio also correlated with overall survival ( P = 0·008). A pro-angiogenic profile appears associated with diminished response and inferior survival in CLL patients receiving CIT. 相似文献
3.
Objective To confirm the safety and efficacy of 75 IU lutropin alfa with concomitant follitropin alfa in inducing follicular development in women with profound gonadotrophin deficiency.
Design Double-blind, randomized, placebo-controlled trial conducted in 25 medical centres in four countries.
Patients Thirty-nine patients with LH < 1·2 IU/l and FSH < 5·0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa.
Measurements Primary efficacy end-point (intent-to-treat): follicular development defined by (i) at least one follicle ≥ 17 mm; (ii) serum E2 level ≥ 400 pmol/l on day of hCG administration (DhCG); and (iii) mid-luteal phase progesterone level ≥ 25 nmol/l.
Results In the analysis of evaluable patients, 66·7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20·0% (2 of 10) of patients receiving placebo ( P = 0·023). In the intent-to-treat analysis, follicular development was achieved in 65·4% (17 of 26) of patients receiving lutropin alfa and 15·4% (2 of 13) of patients receiving placebo ( P = 0·006). The statistical difference between treatment groups was preserved when over-response leading to cycle cancellation was analysed as a failed response ( P = 0·034). Lutropin alfa was well tolerated.
Conclusion Subcutaneous co-administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency. 相似文献
Design Double-blind, randomized, placebo-controlled trial conducted in 25 medical centres in four countries.
Patients Thirty-nine patients with LH < 1·2 IU/l and FSH < 5·0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa.
Measurements Primary efficacy end-point (intent-to-treat): follicular development defined by (i) at least one follicle ≥ 17 mm; (ii) serum E
Results In the analysis of evaluable patients, 66·7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20·0% (2 of 10) of patients receiving placebo ( P = 0·023). In the intent-to-treat analysis, follicular development was achieved in 65·4% (17 of 26) of patients receiving lutropin alfa and 15·4% (2 of 13) of patients receiving placebo ( P = 0·006). The statistical difference between treatment groups was preserved when over-response leading to cycle cancellation was analysed as a failed response ( P = 0·034). Lutropin alfa was well tolerated.
Conclusion Subcutaneous co-administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency. 相似文献
4.
Nicolaus Kröger Avichai Shimoni Georgia Schilling Rainer Schwerdtfeger Martin Bornhäuser Arnon Nagler Axel R. Zander Marion Heinzelmann Ronald Brand Gösta Gahrton Curly Morris Dietger Niederwieser Theo de Witte 《British journal of haematology》2010,148(2):323-331
From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II–IV acute graft- versus -host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI): 13–37%] and was significantly lower for human leucocyte antigen (HLA)-matched compared to -mismatched SCT (10% vs. 53%, P = 0·001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40–70%). After a median follow up of 43 months, the estimated 5-year progression-free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P = 0·04 and 56% vs. 16%, P = 0·02). We conclude that optimal donor selection is mandatory for a low non-relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post-transplant strategies to upgrade remission status. 相似文献
5.
Carlo Bernasconi E. Paolo Alessandrino Paolo Bernasconi Maurizio Bonfichi Mario Lazzarino Angelo Canevari Guglielmo Castelli Ercole Brusamolino Guido Pagnucco & Carlo Castagnola 《British journal of haematology》1998,102(3):678-683
One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0–3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2 /12 h i.v. for 5 d, Ara-C 120 mg/m2 /12 h i.v. for 5 d (one or two courses). Patients were randomized to receive or not G-CSF (5 μg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT + G-CSF patients had a significantly shorter duration of neutropenia (8 v 16 d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P < 0.05). 40 patients entered CR: 17 with CT and 23 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12 h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4.5 months). Eight responders received an allo-BMT, six are alive in CR 7–57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions. 相似文献
6.
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
7.
Tamara Intermesoli Federica Delaini Sara Acerboni Silvia Salmoiraghi Orietta Spinelli Vittoria Guerini Alessandro M. Vannucchi Silvia Mappa Giuseppe Rossi Valentina Rossi Eros Di Bona Simona Paratore Alessandra Carobbio Alessandro Rambaldi Tiziano Barbui Renato Bassan 《British journal of haematology》2009,147(5):681-685
Although imatinib may be effective in hypereosinophilic syndromes, the exact response kinetics are not known. Imatinib was administered at 100–400 mg/d each week in a 12-week response-oriented schedule, targeting a complete clinical and haematological remission (CR). CR was achieved in 11/23 patients (6/6 with FIP1L1 - PDGRFA rearrangement and 5/17 without, P = 0·006), most after 2 weeks of 100 mg/d imatinib. The maximum imatinib dose had no effect in early unresponsive patients. Low-dose, short-course imatinib may represent a rational choice for identifying responsive cases, both within and outside the pre-defined FIP1L1 rearrangement subset. 相似文献
8.
Rakesh Popat Heather Oakervee Catherine Williams Mark Cook Charles Craddock Supratik Basu Charles Singer Stephen Harding Nicola Foot Simon Hallam Liz Odeh Simon Joel Jamie Cavenagh 《British journal of haematology》2009,144(6):887-894
This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m2 ) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m2 and bortezomib 1·3 mg/m2 . The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD ( n = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD ( P < 0·05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted. 相似文献
9.
Monica Else Claire E. Dearden Estella Matutes Juan Garcia-Talavera Ama Z. S. Rohatiner Steve A. N. Johnson Nigel T. J. O'Connor y Haynes Nnenna Osuji Francesco Forconi Francesco Lauria Daniel Catovsky 《British journal of haematology》2009,145(6):733-740
Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin ( n = 188) or cladribine ( n = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse ( n = 79) or non-response ( n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy ( n = 23), 50% achieved CR and median relapse-free survival was 6·5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 × 109 /l before treatment had the longest relapse-free survival ( P < 0·0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan. 相似文献
10.
Emilia Parodi Elisa Rivetti Giovanni Amendola Gianni Bisogno Roberto Calabrese Piero Farruggia Paola Giordano Sofia Maria Rosaria Matarese Margherita Nardi Bruno Nobili Lucia D. Notarangelo Giovanna Russo Chiara Vimercati Marco Zecca Domenico De Mattia Ugo Ramenghi 《British journal of haematology》2009,144(4):552-558
We report the long-term follow-up (median 39·5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 × 109 /l at a median 20·2 months from treatment. Kaplan–Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders ( P = 0·027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88·9% vs. 56·7%, P = 0·037). Earlier responses (within 20 d from treatment) were significantly associated with both complete ( P = 0·004) and sustained response ( P = 0·002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up. 相似文献
11.
Poor response to intensive chemotherapy in de novo acute myeloid leukaemia with trilineage myelodysplasia 总被引:7,自引:0,他引:7
Kazutaka Kuriyama Masao Tomonaga Tatsuki Matsuo Tohru Kobayashi Hiroshi Miwa Shigeru Shirakawa Mitsune Tanimoto Koichi Adachi Nobuhiko Emi Akira Hiraoka Nobuhiko Tominaga Kuniyuki Imai Norio Asou Kazuo Tsubaki Isao Takahashi Saburoh Minami Minoru Yoshida Hirokazu Murakami Keisuke Minato Toshiteru Oshima Shinpei Furusawa Ryuzo Ohno 《British journal of haematology》1994,86(4):767-773
Summary. The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Group AML-87 protocol. 40 (17%) patients had AML/TMDS. Platelet count was significantly higher ( F =0·006) and bone marrow blasts were fewer ( P =0·01) in the AML/TMDS group than in the AML without TMDS. Abnormal karyotype was shown in 12/30 patients (40%) analysed.
The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63% v 81%) ( P =0·01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS ( P =0·0005). AML/TMDS also showed significantly worse disease-free survival (DFS) ( P =0·0001).
Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR ( P =0·01) and a significant factor in predicting longer DFS ( P =0·04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML. 相似文献
The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63% v 81%) ( P =0·01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS ( P =0·0005). AML/TMDS also showed significantly worse disease-free survival (DFS) ( P =0·0001).
Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR ( P =0·01) and a significant factor in predicting longer DFS ( P =0·04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML. 相似文献
12.
Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study 总被引:2,自引:0,他引:2
Wattel Solary Hecquet Caillot Ifrah Brion MahÉ Milpied Janvier Guerci Rochant Cordonnier Dreyfus Buzyn Hoang-Ngoc Stoppa Gratecos Sadoun Stamatoulas Tilly Brice Maloisel Lioure Desablens Pignon Abgrall Leporrier Dupriez Guyotat Lepelley & Fenaux Groupe Français des Myélodysplasies Groupe Ouest Est des Leucémies Aiguës Myéloïdes 《British journal of haematology》1998,102(4):1015-1024
Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged 65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m2 /d days 2–5 + AraC 1 g/m2 /12 h days 1–5, with (Q+ ) or without (Q− ) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/25 (52%) patients in the Q+ group achieved CR, compared to 3/17 (18%) patients in the Q− group ( P = 0.02) and median Kaplan-Meier survival was 13 months in the Q+ group, and 8 months in the Q− group ( P = 0.01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy. 相似文献
13.
Background and Objectives Evidence supporting the use of platelets and plasma in resuscitation of massive bleedings is questionable. Current consensus guidelines recommend restrictive use. Our aim was to determine the effect of changing the transfusion practice on 30-day survival in massively bleeding patients.
Materials and Methods Consecutive adult patients receiving more than 10 units of red blood cells (RBC) within 24 h 2 years prior to (2002–2003) and 2 years after (2005–2006) a change in transfusion practice were included. In 2004, we implemented Haemostatic Control Resuscitation (HCR) with preemptive use of platelets and plasma, administered in transfusion packages, comprising 5 units of RBCs, 5 units of fresh-frozen plasma and 2 units of platelet concentrates (PC), when massive bleeding occurred or upon arrival at the emergency room and thereafter directed by thrombelastography throughout the peri- and postoperative period.
Results In 2005–2006, the 442 patients received more PCs within 24 h from admission [mean 5·0 (SD 4·2) vs. 1·7 (2·0); P < 0·0001] and had a smaller decrease in platelet count during the bleeding episode [91·5 (81·2) vs. 119·7 (100·8) × 109 /l; P = 0·0025] than the 390 patients treated in 2002–2003. Thirty-day mortality was reduced in 2005–2006 (20·4% vs. 31·5%; P = 0·0002) and at 90-day (22·4% vs. 34·6%; P < 0·0001) as compared to 2002–2003.
Conclusions In patients who experience massive bleeding, HCR with platelets and plasma, as guided by thrombelastography, is associated with improved survival. While confirmation from a randomized controlled trial is urgently needed, HCR may be considered in these patients. 相似文献
Materials and Methods Consecutive adult patients receiving more than 10 units of red blood cells (RBC) within 24 h 2 years prior to (2002–2003) and 2 years after (2005–2006) a change in transfusion practice were included. In 2004, we implemented Haemostatic Control Resuscitation (HCR) with preemptive use of platelets and plasma, administered in transfusion packages, comprising 5 units of RBCs, 5 units of fresh-frozen plasma and 2 units of platelet concentrates (PC), when massive bleeding occurred or upon arrival at the emergency room and thereafter directed by thrombelastography throughout the peri- and postoperative period.
Results In 2005–2006, the 442 patients received more PCs within 24 h from admission [mean 5·0 (SD 4·2) vs. 1·7 (2·0); P < 0·0001] and had a smaller decrease in platelet count during the bleeding episode [91·5 (81·2) vs. 119·7 (100·8) × 10
Conclusions In patients who experience massive bleeding, HCR with platelets and plasma, as guided by thrombelastography, is associated with improved survival. While confirmation from a randomized controlled trial is urgently needed, HCR may be considered in these patients. 相似文献
14.
Thomas Lehrnbecher Marie-Chantal Ethier Theoklis Zaoutis Ursula Creutzig Alan Gamis Dirk Reinhardt Richard Aplenc Lillian Sung 《British journal of haematology》2009,147(1):125-128
This study described infection-related supportive care practices amongst centres participating in two large paediatric acute myeloid leukaemia (AML) cooperative groups, Children's Oncology Group (COG) and Berlin-Frankfurt-Muenster (BFM). We surveyed 216 COG and 55 BFM institutions. The overall survey response rate was 83·8%. Antibacterial prophylaxis was more common among BFM (15/46, 32·6%) compared to COG (24/180, 13·3%, P < 0·0001) institutions. Antifungal prophylaxis also was more common among BFM (42/46, 91·3%) compared to COG (137/178, 77·0%, P = 0·03). There were systematic differences in infection-related supportive care practices. This information may be used to encourage harmonization of supportive care practices and future randomized trials. 相似文献
15.
G. Malcolm Taylor Sue Richards Rachel Wade Adiba Hussain Jill Simpson Frank Hill Chris Mitchell Tim Eden 《British journal of haematology》2009,145(1):87-95
We recently reported that two of six HLA-DP supertypes (DP1–4, 6, 8) were associated with susceptibility (DP2) and resistance (DP1) to childhood acute lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated with childhood ALL prognosis, we compared treatment outcomes in a cohort ( n = 798) of DPB1 -typed ALL cases in the UK Medical Research Council UKALL XI trial. No differences in clinical characteristics and outcome between DPB1 -typed and untyped ( n = 1292) cases suggest no selection bias. Event-free survival (EFS) rates in patients with DP1 and DP3 supertypes were significantly worse than in patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval (CI) = 49–61%; compared with 64% (61–68%), P = 0·006]. Ten-year EFS in DP1/DP3 heterozygous patients [30% (2–58%)] was significantly worse than in patients with DP1, DP3 or neither allele [56% (50–62%); P = 0·02]. Lack of evidence that DP1 or DP3 are associated with known prognostic factors leads us to suggest that these two supertypes exert an independent effect on prognosis. This may involve abrogation of DP1/3-restricted T-cell control of residual disease due to selective effects of chemotherapy. Further studies of HLA supertypes in relation to outcome in recent childhood ALL trials may resolve this question. 相似文献
16.
High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults
Shinsuke Takagi Kazuhiro Masuoka Naoyuki Uchida Kazuya Ishiwata Hideki Araoka Masanori Tsuji Hisashi Yamamoto Daisuke Kato Yoshiko Matsuhashi Eiji Kusumi Yasunori Ota Sachiko Seo Tomoko Matsumura Naofumi Matsuno Atsushi Wake Shigesaburo Miyakoshi Shigeyoshi Makino Kenichi Ohashi Akiko Yoneyama Shuichi Taniguchi 《British journal of haematology》2009,147(4):543-553
Umbilical cord blood transplantation (CBT) is widely accepted, but one critical issue for adult patients is a low engraftment rate, of which one cause is haemophagocytic syndrome (HPS). We aimed to identify the contribution of HPS to engraftment failure after CBT, following preparative regimens containing fludarabine phosphate, in 119 patients (median age, 55 years; range; 17–69 years) with haematological diseases. Graft- versus -host disease prophylaxis comprised continuous infusion of a calcineurin inhibitor with or without mycophenolate mofetil. Of the 119 patients, 20 developed HPS within a median of 15 d (cumulative incidence; 16·8%) and 17 of them did so before engraftment. Donor-dominant chimaerism was confirmed in 16 of 18 evaluable patients with HPS. Despite aggressive interventions including corticosteroid, ciclosporin, high-dose immunoglobulin and/or etoposide, engraftment failed in 14 of 18 patients. Of these 14 patients, four received second rescue transplantation and all resulted in successful engraftment. Overall survival rates significantly differed between patients with and without HPS (15·0% vs. 35·4%; P < 0·01). Univariate and multivariate analysis identified having fewer infused CD34+ cells as a significant risk factor for the development of HPS ( P = 0·01 and 0·006, respectively). We concluded that engraftment failure closely correlated with HPS in our cohort, which negatively impacted overall survival after CBT. 相似文献
17.
JM Ribera O García P Montesinos S Brunet E Abella M Barrios J González-Campos P Bravo ML Amigo JM Hernández-Rivas 《British journal of haematology》2012,159(1):78-81
The main outcomes of the Programa Español para Tratamiento de Hemopatías (PETHEMA)‐acute lymphoblastic leukaemia (ALL)‐Ph‐08 trial were described and compared with those of the historical PETHEMA‐CSTIBES02 trial. The trials differed in imatinib dose (600 vs. 400 mg/d) and amount of chemotherapy (one vs. two consolidation cycles) before stem cell transplantation (SCT). All patients (n = 29) enrolled in the ALL‐Ph‐08 trial achieved complete remission (CR) (vs. 90% in CSTIBES02), and SCT was performed in CR in 90% (vs. 78%). The reduction in early death, relapse before SCT and transplant‐related mortality observed in the ALL‐Ph‐08 trial resulted in an improved 2‐year event‐free survival (63% vs. 37%, P = 0·009). 相似文献
18.
Simpson CD Gao J Fernandez CV Yhap M Price VE Berman JN 《British journal of haematology》2008,141(6):820-826
Bone marrow examination (BME) in paediatric Hodgkin lymphoma (HL) was evaluated, as evidence from adult HL suggests it may be unnecessary. An internet-based survey was used to examine the practice of Canadian paediatric oncologists regarding BME in children and the impact of routine BME was evaluated in patients with HL treated at our institution. Sixteen of 17 paediatric oncology centres were represented. Forty-three percent of eligible doctors completed the survey. Routine BME for stages III and IV disease was consistent nationally. By contrast, 54% and 70% of respondents reported performing routine BME for stages I and II HL respectively. Respondents were more likely to report performing routine BME in low-stage HL if trained outside Canada ( P = 0·04, stage I; P = 0·07, stage II) or practicing at smaller centres ( P = 0·05, stage I; P = 0·03, stage II). At our institution, 62 patients were eligible for analysis. Only four patients (6·5%) had a positive BME. Anaemia was the only significant risk factor ( P = 0·006). No patient with otherwise low stage was found to have marrow involvement. Comparison of staging with and without BME demonstrated no significant difference to final risk classification. BME in paediatric patients with low-stage HL has extremely low yield and may be unnecessary. 相似文献
19.
Deepika Bhatla Robert B. Gerbing Todd A. Alonzo Heather Conner Julie A. Ross Soheil Meshinchi Xiaowen Zhai Tiffany Zamzow Parinda A. Mehta Hartmut Geiger John Perentesis Stella M. Davies 《British journal of haematology》2009,144(3):388-394
Cytosine arabinoside (ara-C) is irreversibly deaminated to a non-toxic metabolite by cytidine deaminase (CDA). A common polymorphism, A79C, in the gene encoding cytidine deaminase ( CDA ) changes a lysine residue to glutamine resulting in decreased enzyme activity. CDA A79C genotypes were determined in 457 children with acute myeloid leukaemia (AML) treated on the Children's Cancer Group (CCG) 2941 and 2961 protocols and analyzed the impact of CDA genotype on therapy outcomes. Postinduction treatment-related mortality (TRM) was significantly elevated in children with the CC genotype (5-year TRM 17 ± 13% CC vs. 7 ± 4% AA, 5 ± 4% AC, P = 0·05). This was more notable in children who received idarubicin, fludarabine, ara-C, and granulocyte colony-stimulating factor (IDA-FLAG; ara-C = 7590 mg/m2 ) (5-year TRM 24 ± 21% CC vs. 6 ± 6% AA, 6 ± 7% AC, P = 0·07) as consolidation therapy compared to idarubicin, dexamethasone, cytarabine, thioguanine, etoposide and daunomycin (IDA-DCTER; ara-C = 800 mg/m2 ) (5-year TRM 15 ± 20% CC vs. 8 ± 6% AA, 4 ± 6% AC; P = 0·29). Relapse-free survival was non-significantly increased in children with the CC genotype treated with IDA-FLAG (76 ± 20% CC vs. 59 ± 12% AA and 55 ± 14% AC; P = 0·40). These data indicate that children with a low activity CDA genotype are at increased risk of TRM with ara-C based therapy for AML. 相似文献
20.
Leandro F. F. Dalmazzo Rafael H. Jácomo ré F. Marinato Lorena L. Figueiredo-Pontes Renato L. G. Cunha Aglair B. Garcia Eduardo M. Rego Roberto P. Falcão 《British journal of haematology》2009,144(2):223-229
Some cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28·5%), which we designated T/NK-ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK-ALL and T-ALL patients. Significant differences were observed regarding age (24·9 vs. 16·4 years in T/NK-ALL and T-ALL, respectively, P = 0·006) and platelet counts (177 × 109 /l vs. 75 × 109 /l in T/NK-ALL and T-ALL, respectively, P = 0·03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK-ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T-ALL patients ( P < 0·05 ) . The mean overall survival (863 vs. 1869 d, P = 0·02) and disease-free survival (855 vs. 2095 d, P = 0·002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK-ALL compared to T-ALL. Perforin, granzyme B and TIA-1 were detected in 12/17, 4/17 and 7/24 T/NK-ALL patients and in 1/20, 0/20 and 1/20 T-ALL respectively ( P < 0·001, P = 0·036 and P = 0·054). Therefore, the presence of CD56/CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts. 相似文献