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1.
Toshihiko Imamura Shotaro Iwamoto Rie Kanai Akira Shimada Kiminori Terui Yuko Osugi Ryoji Kobayashi Akio Tawa Yoshiyuki Kosaka Koji Kato Hiroki Hori Keizo Horibe Megumi Oda Souichi Adachi The Japan Association of Childhood Leukaemia Study 《British journal of haematology》2012,159(2):204-210
The acute myeloid leukaemia (AML) 99 trial conducted previously in Japan for the treatment of de novo paediatric AML showed excellent results, with a 5‐year overall survival (OS) and event‐free survival (EFS) of 75·6% and 61·6%, respectively. To examine reproducibility of these results in another cohort, the outcome of 146 newly diagnosed AML paediatric patients prospectively registered in the Japan Association of Childhood Leukaemia Study (JACLS) from 2003 to 2006 was compared to that of 240 patients in the original AML 99 clinical trial. The 5‐year EFS and OS achieved in the new cohort was 66·7 ± 4·0% and 77·7 ± 8·0% respectively, which were comparable to those obtained in the original AML 99 clinical trial, although less frequent core‐binding factor (CBF) AML (29·5% vs. 37%) and an almost equal frequency of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) during first complete remission (16·5% vs. 19%) were observed. The 5‐year EFS in patients with a normal karyotype (NK) (n = 35, 54·9 ± 15·1%) was inferior in the present cohort when compared to the original AML99 trial. This study confirmed the excellent outcome of the original AML99 protocol. 相似文献
2.
Jae Wook Lee Pil‐Sang Jang Nack‐Gyun Chung Bin Cho Hack‐Ki Kim 《British journal of haematology》2013,160(1):80-86
Despite improvements in diagnosis and treatment, 30–40% of children with acute myeloid leukaemia (AML) experience relapse. For those who relapse after allogeneic haematopoietic stem cell transplantation (allo‐HSCT), the prognosis is particularly poor, with limited reported literature on these patients. We reviewed the clinical course of 49 children with AML (28 males, 21 females) who received allo‐HSCT between 1993 and 2011, and who had subsequently relapsed. Study endpoints included (i) complete remission (CR) rate after intensive chemotherapy, and prognostic factors for CR, (ii) disease‐free survival (DFS) and overall survival (OS) for patients who achieved CR and (iii) OS for recipients of intensive chemotherapy and prognostic factors for OS . Of the 36 patients who received intensive chemotherapy after post‐HSCT relapse, 26 (72%) achieved CR. For patients who achieved CR, 5‐year DFS and OS were 32·6 ± 10·2% and 44·4 ± 11·1%, respectively. For all recipients of intensive chemotherapy, 5‐year OS was 31·6 ± 8·7%. Cumulative incidence of treatment‐related death was 14·4%. All three recipients of second HSCT died. Amongst prognostic factors predicting improved survival, only disease status at HSCT (early first CR vs. others) proved significant in multivariate study (Hazard Ratio 2·42, 95% Confidence Interval 1·02–5·74, P = 0·045). Treatment with curative intent was able to salvage a minor but important subset of children with AML who relapsed post‐allogeneic transplant. 相似文献
3.
Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO‐AML 2004 study 下载免费PDF全文
Anne Tierens Elizabeth Bjørklund Sanna Siitonen Hanne Vibeke Marquart Gitte Wulff ‐Juergensen Tarja‐Terttu Pelliniemi Erik Forestier Henrik Hasle Kirsi Jahnukainen Birgitte Lausen Olafur G. Jonsson Josefine Palle Bem Zeller Jonas Abrahamsson 《British journal of haematology》2016,174(4):600-609
Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato‐Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event‐free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut‐off level. RD‐negative and ‐positive patients after first induction showed a 5‐year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD‐negative and ‐positive patients at start of consolidation therapy had a 5‐year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9–13·3] and OS (HR:7·0; 95%CI:2·0–24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials. 相似文献
4.
《British journal of haematology》2017,177(1):116-126
In children with acute myeloid leukaemia (AML ), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD ), by multicolour flow‐cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica‐AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1–1% in 16 and >1% in 51 patients. The 8‐year disease‐free survival (DFS ) of 125 children in morphological complete remission and with MRD <0·1%, 0·1–1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS . Our results show that MRD detected by flow‐cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post‐remission treatment. 相似文献
5.
Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan 下载免费PDF全文
Reiji Fukano Tetsuya Mori Ryoji Kobayashi Tetsuo Mitsui Naoto Fujita Fuminori Iwasaki Junji Suzumiya Motoaki Chin Hiroaki Goto Yoshiyuki Takahashi Junichi Hara Yong‐Dong Park Masami Inoue Yuhki Koga Jiro Inagaki Hisashi Sakamaki Souichi Adachi Keisei Kawa Koji Kato Ritsuro Suzuki 《British journal of haematology》2015,168(4):557-563
To evaluate haematopoietic stem cell transplantation (HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission (CR) was less common in allogeneic HSCT recipients (n = 24) than in autologous HSCT recipients (n = 23) (P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5‐year event‐free survival (EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment‐related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non‐CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non‐CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced‐intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non‐CR. These three patients achieved CR, surviving 32–65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy. 相似文献
6.
TP53 mutation in patients with high‐risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation 下载免费PDF全文
Jan M. Middeke Sylvia Herold Elke Rücker‐Braun Wolfgang E. Berdel Matthias Stelljes Martin Kaufmann Kerstin Schfer‐Eckart Claudia D. Baldus Reingard Stuhlmann Anthony D. Ho Hermann Einsele Wolf Rsler Hubert Serve Mathias Hnel Kristina Sohlbach Christian Klesse Brigitte Mohr Falk Heidenreich Friedrich Stlzel Christoph Rllig Uwe Platzbecker Gerhard Ehninger Martin Bornhuser Christian Thiede Johannes Schetelig 《British journal of haematology》2016,172(6):914-922
Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse‐risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three‐year probabilities of overall survival (OS) and event‐free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53‐mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML. 相似文献
7.
Chao Gao Shu‐Guang Liu Rui‐Dong Zhang Wei‐Jing Li Xiao‐Xi Zhao Lei Cui Min‐Yuan Wu Hu‐Yong Zheng Zhi‐Gang Li 《British journal of haematology》2014,166(2):221-228
Activating mutations of NOTCH1 are a common occurrence in T‐cell acute lymphoblastic leukaemia (T‐ALL), but its impact on T‐ALL treatment is still controversial. In this study, the incidence, clinical features, and prognosis of 92 Chinese children with T‐ALL treated using the Beijing Children's Hospital‐2003 and Chinese Childhood Leukaemia Group‐2008 protocols were analysed. NOTCH1 mutations were found in 42% of T‐ALL patients and were not associated with clinical features, prednisone response, and minimal residual disease (MRD) at day 33 and 78. However, proline, glutamate, serine, threonine (PEST)/transactivation domain (TAD) mutations were associated with younger age (15/16 mutant vs. 48/76 wild‐type, P = 0·018) and more central nervous system involvement (4/16 mutant vs. 3/76 wild‐type, P = 0·016); while heterodimerization domain (HD) mutations were associated with KMT2A‐MLLT1 (MLL‐ENL; 4/30 mutant vs. 1/62 wild‐type, P = 0·037). Furthermore, prognosis was better in patients with NOTCH1 mutations than in those with wild‐type NOTCH1 (5‐year event‐free survival [EFS] 92·0 ± 4·5% vs. 64·0 ± 7·1%; P = 0·003). Long‐term outcome was better in patients carrying HD mutations than in patients with wild‐type HD (5‐year EFS 89·7 ± 5·6% vs. 69·3 ± 6·2%; P = 0·034). NOTCH1 mutations and MRD at day 78 were independent prognostic factors. These findings indicate that NOTCH1 mutation predicts a favourable outcome in Chinese paediatric patients with T‐ALL on the BCH‐2003 and CCLG‐2008 protocols, and may be considered a prognostic stratification factor. 相似文献
8.
《British journal of haematology》2018,180(5):680-693
Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre‐HSCT and during the first and third trimesters after HSCT (post‐HSCT1 and post‐HSCT3). The overall event‐free survival (EFS) was 50%. The cumulative incidence of relapse and non‐relapse mortality was 41% and 9%. Any degree of detectable pre‐HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10−3 and ≥1 × 10−3, respectively, versus 73% in MRD‐negative patients (P < 0·001). This effect was maintained in different disease remissions, but low‐level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post‐HSCT1 and post‐HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre‐emptive immuno‐therapy. 相似文献
9.
Akitoshi Kinoshita Hayato Miyachi Hiromichi Matsushita Miharu Yabe Tomohiko Taki Tomoyuki Watanabe Akiko M. Saito Daisuke Tomizawa Takashi Taga Hiroyuki Takahashi Hidemasa Matsuo Kumi Kodama Kentaro Ohki Yasuhide Hayashi Akio Tawa Keizo Horibe Souichi Adachi 《British journal of haematology》2014,167(1):80-86
The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found ‘AML with myelodysplasia‐related changes’ (AML‐MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia‐related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with ‘AML, not otherwise specified’ (AML‐NOS), patients with ‘AML‐MRC’ presented at a younger age, with a lower white blood cell count, higher incidence of 20–30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD), NPM1 and CEBPA mutations. Complete remission rate and 3‐year probability of event‐free survival were significantly worse in ‘AML‐MRC’ patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3‐year overall survival and relapse‐free survival were comparable with ‘AML‐NOS’ patients. By multivariate analysis, FLT3‐ITD was solely associated with worse overall survival. These results support the distinctive features of the category ‘AML‐MRC’ even in children. 相似文献
10.
Gibson BE Webb DK Howman AJ De Graaf SS Harrison CJ Wheatley K;United Kingdom Childhood Leukaemia Working Group the Dutch Childhood Oncology Group 《British journal of haematology》2011,155(3):366-376
The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (<16 years) with AML were randomized between mitoxantrone/cytarabine/etoposide or daunorubicin/cytarabine/etoposide as induction chemotherapy and 270 entered a second randomization between a total of four or five courses of treatment. Ten‐year event‐free (EFS) and overall survival (OS) was 54% and 63% respectively; the relapse rate was 35%. There was no difference in complete remission rate between the induction regimens, but there was a benefit for mitoxantrone with regard to relapse rate [32% vs. 39%; Hazard ratio (HR) 0·73; 95% confidence interval (CI) 0·54, 1·00] and disease‐free survival (DFS; 63% vs. 55%; HR 0·72; 95% CI 0·54, 0·96). However, this did not translate into a better EFS or OS (HR 0·84; 95% CI 0·63, 1·12). Results of the second randomization did not show a survival benefit for a fifth course of treatment (HR 1·01; 95% CI 0·63, 1·62), suggesting a ceiling of benefit for conventional chemotherapy and demonstrating the need for new agents. EFS was superior compared to the preceding trial AML10, partly due to fewer deaths in remission, highlighting the importance of supportive care. 相似文献
11.
Jae‐Ho Yoon Hee‐Je Kim Seung‐Hwan Shin Seung‐Ah Yahng Sung‐Eun Lee Byung‐Sik Cho Ki‐Seong Eom Yoo‐Jin Kim Seok Lee Chang‐Ki Min Seok‐Goo Cho Dong‐Wook Kim Jong‐Wook Lee Woo‐Sung Min Chong‐Won Park Ji‐Hyang Lim 《European journal of haematology》2013,91(2):112-121
No consecutive analysis of BAALC and WT1 expressions associated with core‐binding factor AML (CBF‐AML) from diagnosis to hematopoietic stem cell transplantation (HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real‐time quantitative polymerase chain reaction (RQ‐PCR) at diagnosis, after induction chemotherapy, at pre‐HSCT, and at post‐HSCT period in 45 consecutive patients [t(8,21) (n = 28), inv(16) (n = 17)], who received HSCT as a post‐remission treatment. BAALC and WT1 RQ‐PCR decrement ratio (DR) was also calculated at post‐induction chemotherapy, at pre‐HSCT, and at post‐HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS (P = 0.031), EFS (P = 0.011), and higher CIR (P = 0.002) rates. At post‐HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS (P = 0.005, 0.016), EFS (P = 0.002, 0.006), and higher CIR (P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post‐HSCT were also associated with inferior OS (P = 0.018, 0.015) and higher CIR rates (P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2‐log at post‐HSCT showed significantly lower CIR rate (P = 0.028). This study showed that higher post‐HSCT BAALC and WT1 expressions in patients with CBF‐AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. 相似文献
12.
Similar outcome of upfront‐unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party,Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT 下载免费PDF全文
Carlo Dufour Paul Veys Elisa Carraro Neha Bhatnagar Marta Pillon Rob Wynn Brenda Gibson Ajay J. Vora Colin G. Steward Anna M. Ewins Rachael E. Hough Josu de la Fuente Mark Velangi Persis J. Amrolia Roderick Skinner Andrea Bacigalupo Antonio M. Risitano Gerard Socie Regis Peffault de Latour Jakob Passweg Alicia Rovo André Tichelli Hubert Schrezenmeier Britta Hochsmann Peter Bader Anja van Biezen Mahmoud D. Aljurf Austin Kulasekararaj Judith C. Marsh Sujith Samarasinghe 《British journal of haematology》2015,171(4):585-594
We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first‐line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second‐line therapy with unrelated donor HSCT post‐failed IST (n = 24). The 2‐year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post‐IST failure controls (P = 0·02).The 2‐year event‐free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post‐IST failure controls (n = 24) (P = 0·02). Outcomes for upfront‐unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post‐IST failure. Front‐line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first‐line therapy in selected paediatric patients who lack a MSD. 相似文献
13.
Robert S. Ohgami Lisa Ma Li Ren Olga K. Weinberg Mahesh Seetharam Jason R. Gotlib Daniel A. Arber 《British journal of haematology》2012,159(2):182-190
To determine the role of DNA methylation in the progression of acute myeloid leukaemia (AML), we analysed the methylation status of ALOX12, GSTM1, HS3ST2 and FZD9 in 127 AML patients. Aberrant methylation of ALOX12 was associated with the subcategory AML with myelodysplasia‐related changes (P = 0·0439) and specifically with megakaryocytic dysplasia (P = 0·0003). An association between HS3ST2 and AML patients with favourable cytogenetic risk was identified (P = 0·0469). In univariate and multivariate analysis, methylation of GSTM1 was associated with worse overall survival (OS) and disease‐free survival (DFS), with hazard ratios of 2·57 and 1·86, respectively. Furthermore, the significance of methylation of GSTM1 in predicting poor prognosis was maintained within the subcategories of AML not otherwise specified (NOS), AML with intermediate cytogenetic risk and normal karyotype AML. Finally, patients with both GSTM1 and ALOX12 methylated, demonstrated worse outcomes when all AML patients were assessed (OS; P = 0·000411) as well as within AML NOS (DFS; P = 0·0023), AML with intermediate cytogenetic risk (OS; P = 0·0104) and normal karyotype AML (OS; P = 0·00636). This study implicates methylation of specific genes in the classification and prognostication of AML and suggests that the morphological feature of multilineage dysplasia may be a surrogate marker of gene methylation in at least a subset of AML cases. 相似文献
14.
Sarah Pozzi Simona Geroldi Elisabetta Tedone Silvia Luchetti Raffaella Grasso Nicoletta Colombo Carmen Di Grazia Teresa Lamparelli Francesca Gualandi Adalberto Ibatici Stefania Bregante Maria Teresa Van Lint Anna Maria Raiola Alida Dominietto Riccardo Varaldo Alessio Signori Andrea Bacigalupo 《British journal of haematology》2013,160(4):503-509
We assessed WT1 expression (expressed as messenger copies/104 ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15–69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34–2833). Relapse was higher in 67 patients with WT1 expression, at any time post‐HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post‐HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5‐year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post‐HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post‐HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy. 相似文献
15.
《British journal of haematology》2017,176(3):431-439
This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML ) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced‐intensity conditioning (RIC ) and allogeneic haematopoietic stem cell transplantation (HSCT ). The transplants in 77 patients were from matched sibling donors (MSD s) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti‐T‐cell antibodies. The incidence of acute graft‐versus‐host disease (GVHD ) of grades II ‒IV was 32·1% and that of chronic GVHD was 30·2%. The 3‐year probability of non‐relapse mortality (NRM ) was 25·9%, that of relapse was 48·5%, that of GVHD ‐free and relapse‐free survival (GRFS ) was 17·8% and that of leukaemia‐free survival (LFS ) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II ‒IV [hazard ratio (HR ) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti‐T‐cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti‐T‐cell antibodies seems promising in patients with refractory AML . 相似文献
16.
Salvage chemotherapy followed by granulocyte colony‐stimulating factor‐primed donor leukocyte infusion with graft‐vs.‐host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes 下载免费PDF全文
Xiao‐Dong Mo Xiao‐Hui Zhang Lan‐Ping Xu Yu Wang Chen‐Hua Yan Huan Chen Yu‐Hong Chen Wei Han Feng‐Rong Wang Jing‐Zhi Wang Kai‐Yan Liu Xiao‐Jun Huang 《European journal of haematology》2016,96(3):297-308
This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony‐stimulating factor‐primed donor leukocyte infusion (Chemo‐DLI) according to minimal residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndromes who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft‐vs.‐host disease (GVHD) after Chemo‐DLI. The 3‐yr cumulative incidences of relapse, non‐relapse mortality, and disease‐free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early‐onset MRD. Forty‐four patients turned MRD negative 1 month after Chemo‐DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo‐DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early‐onset MRD, persistent MRD after Chemo‐DLI, and non‐cGVHD after Chemo‐DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo‐DLI. 相似文献
17.
Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics 下载免费PDF全文
Lynne Lennard Cher S. Cartwright Rachel Wade Ajay Vora 《British journal of haematology》2015,169(2):228-240
The impact of thiopurine methyltransferase (TPMT) genotype on thiopurine dose intensity, myelosuppression and treatment outcome was investigated in the United Kingdom childhood acute lymphoblastic leukaemia (ALL) trial ALL97. TPMT heterozygotes had significantly more frequent cytopenias and therefore required dose adjustments below target levels significantly more often than TPMT wild‐type patients although the average dose range was similar for both genotypes. Event‐free survival (EFS) for patients heterozygous for the more common TPMT*1/*3A variant allele (n = 99, 5‐year EFS 88%) was better than for both wild‐type TPMT*1/*1 (n = 1206, EFS 80%, P = 0·05) and TPMT*1/*3C patients (n = 17, EFS 53%, P = 0·002); outcomes supported by a multivariate Cox regression analysis. Poor compliance without subsequent clinician intervention was associated with a worse EFS (P = 0·02) and such non‐compliance may have contributed to the poorer outcome for TPMT*1/*3C patients. Patients prescribed escalated doses had a worse EFS (P = 0·04), but there was no difference in EFS by dose intensity or duration of cytopenias. In contrast to reports from some USA and Nordic trials, TPMT heterozygosity was not associated with a higher rate of second cancers. In conclusion, TPMT*1/*3A heterozygotes had a better EFS than TPMT wild‐type patients. Thiopurine induced cytopenias were not detrimental to treatment outcome. 相似文献
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High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3‐ITD,KMT2A‐PTD,and NUP98‐NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 trial 下载免费PDF全文
Norio Shiba Kentaro Ohki Tohru Kobayashi Yusuke Hara Genki Yamato Reo Tanoshima Hitoshi Ichikawa Daisuke Tomizawa Myoung‐ja Park Akira Shimada Manabu Sotomatsu Hirokazu Arakawa Keizo Horibe Souichi Adachi Takashi Taga Akio Tawa Yasuhide Hayashi 《British journal of haematology》2016,172(4):581-591
Recent reports described the NUP98‐NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98‐NSD1 fusion. PRDM16 gene expression levels were measured via real‐time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥ 0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT2A (also termed MLL)‐ partial tandem duplication, 100% vs. 0%, P < 0·001; NUP98‐NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event‐free survival (EFS) among PRDM16‐overexpressing patients were significantly worse than in patients with low PRDM16 expression (3‐year OS: 51% vs. 81%, P < 0·001, 3‐year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3‐internal tandem duplication‐positive AML patients (3‐year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate‐risk cytogenetic profiles and was independently associated with an adverse outcome. 相似文献
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Herbert Pichler Bettina Reismüller Manuel Steiner Michael N. Dworzak Ulrike Ptschger Christian Urban Bernhard Meister Klaus Schmitt Renate Panzer‐Grümayer Oskar A. Haas Andishe Attarbaschi Georg Mann 《British journal of haematology》2013,161(4):556-565
Adolescents aged 15–18 years with acute lymphoblastic leukaemia (ALL) have been historically reported to have a poorer prognosis than younger children. We retrospectively analysed the characteristics and outcome of 67 adolescents included in a population‐based series of 1125 non‐infant cases that were enrolled into four Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) multicentre trials at paediatric institutions within a 25‐year period. Five‐year event‐free survival (EFS) and overall survival (OS) were 66 ± 6% and 76 ± 5% respectively, and thus lower than in younger children (83 ± 1%, 91 ± 1%; P < 0·001). This was not due to an increased cumulative incidence of relapse (CIR) (5‐year CIR: 19 ± 5% vs. 13 ± 1%; P = 0·284), but due to an increased incidence of treatment‐related death [5‐year cumulative incidence of death (CID): 15 ± 4% vs. 3 ± 0%; P < 0·001] as a first event. Furthermore, while 44/67 (66%) non‐high‐risk adolescents had favourable 5‐year EFS and OS rates (76 ± 7%, 89 ± 5%), 18/67 (27%) high‐risk adolescents had an inferior outcome (5‐year EFS: 56 ± 12%, OS 61 ± 11%, P < 0·05). Among the latter patients the CID was significantly higher than in younger high‐risk children (22 ± 10% vs. 6 ± 2%; P = 0·020). Given that adolescent age is an independent risk factor for death as a first event, this specific age group may need particular vigilance when receiving intense BFM‐type chemotherapy, as relapse‐free survival is similar to younger children. 相似文献