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1.
《British journal of haematology》2018,182(2):231-244
Weekly ixazomib with lenalidomide‐dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety and efficacy of twice‐weekly ixazomib plus Rd in NDMM; 64 patients were enrolled across both phases. Patients received twice‐weekly oral ixazomib 3·0 or 3·7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in cycles 9–16) for up to sixteen 21‐day cycles, followed by maintenance with twice‐weekly ixazomib alone. No dose‐limiting toxicities were reported in cycle 1; the RP2D was 3·0 mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% ≥very good partial response; 24% complete response). Median progression‐free survival was 24·9 months. Responses (median duration 36·9 months for patients receiving the RP2D) deepened during treatment. Grade 3 drug‐related adverse events (AEs) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug‐related AEs. Thirteen patients discontinued due to AEs. Twice‐weekly ixazomib‐Rd offers substantial activity with promising long‐term outcomes in NDMM patients but may be associated with greater toxicity compared with weekly ixazomib‐Rd in this setting. 相似文献
2.
S. Vincent Rajkumar Morton Coleman Roger Pearse Selina Chen‐Kiang Vivek Roy David S. Jayabalan John A. Lust Ruben Niesvizky 《American journal of hematology》2010,85(9):664-669
The objective of this case‐matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low‐dose dexamethasone (BiRd) vs. lenalidomide/low‐dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital‐Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention‐to‐treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very‐good‐partial‐response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time‐to‐progression (median 48.3 vs. 27.5 months, P = 0.071), and progression‐free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3‐year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3–4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case‐matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
3.
《British journal of haematology》2017,178(4):561-570
High‐dose rituximab (HD‐R) combined with carmustine, cytarabine, etoposide and melphalan (BEAM) and autologous stem cell transplant (ASCT) was effective and tolerable in a single‐arm prospective study of relapsed aggressive B‐cell non‐Hodgkin lymphoma (R‐NHL). We performed a randomized phase 2 study comparing HD‐R versus standard‐dose rituximab (SD‐R) in R‐NHL. Ninety‐three patients were randomized to HD‐R (1000 mg/m2) (n = 42) or SD‐R (375 mg/m2) (n = 51) administered on post‐transplant days +1 and +8, using a Bayesian adaptive algorithm. The 2 treatment arms were balanced in regards to patient demographic and clinical characteristics. At a median follow‐up of 7·92 years, the 5‐year disease‐free survival (DFS) and overall survival (OS) were 40% and 48%, respectively. We found no statistically significant differences between HD‐R and SD‐R in 5‐year DFS (36% vs. 43%; P = 0·205) and OS (43% vs. 52%; P = 0·392). In multivariate analyses, only disease status before ASCT [residual disease versus complete remission (CR)] (hazard ratio [HR] 1·79, 95% confidence interval [CI]: 1·08–2·95) and number of prior treatments received (>2 vs. ≤2 lines of treatment) (HR 1·89, 95% CI: 1·13–3·18) were associated with worse DFS and OS. Patients who had SCT while in CR or who received ≤2 lines of treatment prior to SCT had better 5‐year OS (57% vs. 35%; P = 0·02 and 54% vs. 30%, P = 0·001, respectively) in both arms. No differences in engraftments or adverse events were noted in the 2 arms. When combined with BEAM and ASCT in relapsed aggressive B‐cell NHL, HD‐R provided no DFS or OS advantage over SD‐R. In patients who have been exposed to rituximab in the frontline or salvage setting, the addition of rituximab in the peri‐transplant setting remains controversial. 相似文献
4.
Katharine Patrick Rachel Wade Nick Goulden Chris Mitchell Anthony V. Moorman Clare Rowntree Sarah Jenkinson Rachael Hough Ajay Vora 《British journal of haematology》2014,166(3):421-424
We investigated the outcome for children and young people with Early T‐precursor acute lymphoblastic leukaemia (ETP‐ALL), a recently described poor prognosis sub‐group of T‐ALL, treated on a contemporary protocol, UKALL 2003. After a median follow‐up of 4 years and 10 months, the ETP sub‐group, representing 16% of T‐ALL patients, had non‐significantly inferior 5‐year event‐free survival (76·7% vs. 84·6%, P = 0·2) and overall survival (82·4% vs. 90·9%, P = 0·1), and a higher relapse rate (18·6% vs. 9·6%, P = 0·1) compared to typical T‐ALL. ETP‐ALL has an intermediate risk outcome, which does not warrant experimental treatment or first remission allogeneic transplant for the group universally. 相似文献
5.
Merav Leiba Meirav Kedmi Adrian Duek Tzachi Freidman Mia Weiss Ronit Leiba Arnon Nagler Abraham Avigdor 《British journal of haematology》2014,166(5):702-710
Three‐drug induction regimens have become the standard of care in newly diagnosed transplant‐eligible multiple myeloma patients. Two frequently used protocols are bortezomib, cyclophosphamide and dexamethasone (VCD) and bortezomib, thalidomide and dexamethasone (VTD). Comparisons between the two are lacking. The present study aimed to identify the differences in response rate and toxicity between the two regimens. Databases were searched using the terms ‘VTD’ or ‘VCD’ and ‘induction regimens for newly diagnosed multiple myeloma’. Prospective trials evaluating initial response in transplant eligible patients were included. The main outcome measures were response rates and adverse events. Eight clinical trials were eligible for analysis. Overall 672 patients were treated with either VCD (n = 157) or VTD (n = 515) as induction therapy. Patients treated with VTD presented with a significantly higher complete/near complete response (34% vs. 6%, P = 0·002) as well as a higher very good partial response rate or better, following induction therapy (62% vs. 27%, P < 0·0001). Although grade 3–4 neurotoxicity was more frequent during VTD therapy (11% vs. 6%, P = 0·057), a higher incidence of overall grade 3–4 adverse events was found in the VCD‐treated patients (74% vs. 51%, P < 0·001). VTD induction therapy may be superior in achieving deeper response rate following induction therapy, and is better tolerated. 相似文献
6.
Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase III trial
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Ruth Pettengell Catherine Sebban Pier Luigi Zinzani Hans Gunter Derigs Sergey Kravchenko Jack W. Singer Panteli Theocharous Lixia Wang Mariya Pavlyuk Kahina M. Makhloufi Bertrand Coiffier 《British journal of haematology》2016,174(5):692-699
This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28‐d cycles of 85 mg/m2 pixantrone dimaleate (equivalent to 50 mg/m2 in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2–6) with pixantrone and 3 (2–6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression‐free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26–1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B‐cell NHL in the 3rd or 4th line setting, independently of previous rituximab. 相似文献
7.
Follow‐up of post‐transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react
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Cécile Pochon Emmanuel Oger Gérard Michel Jean‐Hugues Dalle Alexandra Salmon Brigitte Nelken Yves Bertrand Hélène Cavé Jean‐Michel Cayuela Nathalie Grardel Elizabeth Macintyre Geneviève Margueritte Françoise Méchinaud Pierre Rohrlich Catherine Paillard François Demeocq Pascale Schneider Dominique Plantaz Marilyne Poirée Jean‐François Eliaou Gilbert Semana Séverine Drunat Philippe Jonveaux Pierre Bordigoni Virginie Gandemer 《British journal of haematology》2015,169(2):249-261
Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days ?30, 30, 90 and 150 post‐transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre‐ or post‐transplant MRD status ≥10?3. Only nine patients received DLI. Pre‐ and post‐transplant MRD status, and the duration of ciclosporin were independently associated with 5‐year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre‐transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post‐transplantation was a valuable prognostic tool to guide therapeutic intervention. 相似文献
8.
Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3‐ITD acute myeloid leukaemia in first complete remission
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Andrew M. Brunner Shuli Li Amir T. Fathi Martha Wadleigh Vincent T. Ho Kerry Collier Christine Connolly Karen K. Ballen Corey S. Cutler Bimalangshu R. Dey Areej El‐Jawahri Sarah Nikiforow Steven L. McAfee John Koreth Daniel J. Deangelo Edwin P. Alyea Joseph H. Antin Thomas R. Spitzer Richard M. Stone Robert J. Soiffer Yi‐Bin Chen 《British journal of haematology》2016,175(3):496-504
We performed a retrospective study analysing the effect of sorafenib, an oral fms‐Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post‐transplant maintenance in adult patients with FLT3‐internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3‐ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post‐HCT initiation of sorafenib (yes/no) was evaluated as a time‐varying covariate in the overall survival/progression‐free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow‐up was 27·2 months post‐HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post‐HCT; 43 controls were alive without relapse at this cut‐off. Sorafenib patients had improved 2‐year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2‐year PFS (82% vs. 53%, P = 0·0081) and lower 2‐year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2‐year non‐relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1‐year chronic graft‐versus‐host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post‐HCT sorafenib in FLT3‐ITD AML, and support further evaluation of post‐HCT FLT3 inhibition. 相似文献
9.
《British journal of haematology》2017,177(4):567-577
There is limited information regarding the immunological predictors of post‐allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T‐cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post‐alloSCT and the ability of post‐transplant immunomodulation to treat relapse. Mixed T‐cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post‐alloSCT; upon 3‐ and 6‐month landmark analysis, this was associated with inferior progression‐free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II–IV acute graft‐versus‐host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty‐three patients were treated with immunomodulation for relapse post‐alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T‐cell chimerism post‐alloSCT for CLL. 相似文献
10.
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
11.
Aurélien Delluc Aurélie Rousseau Mickael Le Galudec Olivier Canceil Barry Woodhams Sylvie Etienne Michel Walter Dominique Mottier Patrick Van Dreden Karine Lacut 《British journal of haematology》2014,164(2):272-279
Past reports have suggested that antiphospholipid (aPL) antibodies may emerge as a response to antipsychotics treatment, as a high prevalence of aPL antibodies in antipsychotics users has been observed. However, no control group of non‐medicated psychiatric patients was included in these reports. In a cross sectional study we determined the prevalence of aPL antibodies in 333 psychiatric inpatients. We compared the proportions of positive aPL antibodytests between users and non‐users of antipsychotics with adjustments for potential confounders. The proportion of antipsychotics users carrying at least one aPL antibody ranged from 10·8% to 27·0% compared with 6·8% to 27·2% in non‐users (P = 0·24, P = 0·24) depending on the method of detection of lupus anticoagulant (LA). The prevalence of LA detected by dilute Russell viper venom time or partial thromboplastin time‐LA was not different between antipsychotics users and non‐users (8·1% vs. 5·4%, P = 0·53 and 18·4% vs. 18·2%, P = 0·22), as well as the prevalence of IgM and IgG anti‐β2‐glycoprotein‐I antibodies, IgM and IgG anti‐cardiolipin antibodies(3·8% vs. 2·0%, P = 0·75, 0·0% vs. 0·0%, P = not applicable, 1·1 vs. 1·4%, P = 0·91, 2·7% vs. 3·4%, P = 0·71). In conclusion, aPL antibodies were frequently found in patients with psychiatric diseases and no significant increase in the prevalence of aPL antibodies was observed in antipsychotics users. 相似文献
12.
High‐dose CD20‐targeted radioimmunotherapy‐based autologous transplantation improves outcomes for persistent mantle cell lymphoma
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Ryan D. Cassaday Philip A. Stevenson Theodore A. Gooley Thomas R. Chauncey John M. Pagel Joseph Rajendran Brian G. Till Mary Philip Johnnie J. Orozco William I. Bensinger Leona A. Holmberg Andrei R. Shustov Damian J. Green Stephen D. Smith Edward N. Libby David G. Maloney Oliver W. Press Ajay K. Gopal 《British journal of haematology》2015,171(5):788-797
Autologous stem cell transplant (ASCT) can improve outcomes for mantle cell lymphoma (MCL) patients, yet relapses are frequent. We hypothesized that high‐dose anti‐CD20 radioimmunotherapy (RIT)‐based conditioning could improve results in this setting. We thus assessed 162 consecutive patients with MCL at our centre undergoing ASCT following high‐dose RIT‐based (n = 61) or standard (n = 101) conditioning. RIT patients were less likely to be in first remission (48% vs. 72%; P = 0·002), be in complete remission (CR) (26% vs. 61%; P < 0·001) and have chemosensitive disease (84% vs. 96%; P = 0·006). RIT‐based conditioning was associated with a reduced risk of treatment failure [hazard ratio (HR) 0·40; P = 0·001] and mortality (HR 0·49; P = 0·01) after adjusting for these imbalances. This difference increased as disease status worsened (from CR to partial remission to stable/progressive disease), with respective HRs of 1·14, 0·53 and 0·04 for mortality, and 0·66, 0·36 and 0·14 for treatment failure. RIT‐based conditioning appears to improve outcome following ASCT for MCL patients unable to achieve CR after controlling for imbalances in important risk factors. These data support the further study of RIT and radiation‐based strategies in a risk‐adapted approach to ASCT for persistent MCL. 相似文献
13.
Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation
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Rohtesh S. Mehta Rima M. Saliba Julianne Chen Gabriela Rondon Aimee E. Hammerstrom Amin Alousi Muzaffar Qazilbash Qaiser Bashir Sairah Ahmed Uday Popat Chitra Hosing Issa Khouri Elizabeth J. Shpall Richard E. Champlin Stefan O. Ciurea 《British journal of haematology》2016,173(3):444-455
Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT. 相似文献
14.
Fiorina Giona Maria L. Moleti Daniela De Benedittis Michelina Santopietro Mauro Nanni Anna M. Testi Sonia Orlando Anna P. Iori Alfonso Piciocchi Enrico Gottardi Walter Barberi Daniela Diverio Giuseppe Saglio Robin Foà 《British journal of haematology》2016,173(5):749-753
We analysed the long‐term outcome of 35 children and adolescents (<20 years at diagnosis) with chronic myeloid leukaemia (CML) in chronic phase: 20 patients had received interferon‐alpha and/or tyrosine kinase inhibitors (TKIs), and 15 underwent a haematopoietic stem cell transplant. The 10‐year survival probabilities were similar in transplanted and non‐transplanted patients (73·3% vs. 72·1%, respectively), whereas the survival probability was significantly lower in patients diagnosed before 1999 compared to those diagnosed afterwards (62·1% vs. 100%, P = 0·0384). The availability of TKIs and the standardized molecular monitoring have significantly improved treatment, management and outcome in children and adolescents with CML. 相似文献
15.
《British journal of haematology》2017,178(6):927-935
The optimal therapeutic approach for young diffuse large B‐cell lymphoma (DLBCL) patients with high‐intermediate and high‐risk age‐adjusted international prognostic index (aaIPI) remains unknown. Hereby we report a 10‐year single‐centre study of 63 consecutively treated patients. To optimize outcome, two approaches were carried out: Cohort 1 patients received four cycles R‐CHOP‐21 (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone over 21 days) followed by first‐line high‐dose chemotherapy with autologous stem‐cell support (HDCT‐ASCT), resulting in 2‐year progression‐free (PFS) and overall survival (OS) of 60·6% and 67·9%. 39·4% of those patients were not transplanted upfront, mainly due to early progressive disease (24·2%). Cohort 2 patients received an early intensified protocol of six cycles of CHOP‐14 (cyclophosphamide, daunorubicin, vincristine, prednisolone over 14 days) with dose‐dense rituximab and high‐dose methotrexate resulting in promising overall response‐ (93·3%) and complete remission (90%) rates and sustained survival (2‐year PFS and OS: 93·3%). In an intention‐to‐treat analysis, 2‐year PFS (60·6% vs. 93·3%, hazard ratio [HR] 7·2, P = 0·009) and OS (69·7% vs. 93·3%, HR 4·95, P = 0·038) differed significantly, in favour of the early intensified protocol (Cohort 2). In a multivariate Cox‐regression model, PFS (HR 8·12, 95% confidence interval [CI] 1·83–35·9, P = 0·006) and OS (HR 5·86, 95% CI 1·28–26·8, P = 0·02) remained superior for Cohort 2 when adjusted for aaIPI3 as the most important prognostic factor. Survival of young poor‐prognosis DLBCL patients appears superior after early therapy intensification. 相似文献
16.
《British journal of haematology》2017,178(1):61-71
This phase II study explored the effects of bortezomib consolidation versus observation on myeloma‐related bone disease in patients who had a partial response or better after frontline high‐dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35‐day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent‐to‐treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End‐of‐treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression‐free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival. 相似文献
17.
Treatment patterns and clinical outcomes in high‐risk newly diagnosed multiple myeloma patients carrying the 17p deletion: An observational multi‐center retrospective study
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Yael C. Cohen Avi Saranga Moshe E. Gatt Noa Lavi Chezi Ganzel Hila Magen Irit Avivi Tamar Tadmor Celia Suriu Osnat Jarchowsky Dolberg Amitai Papushado Svetlana Trestman Ron Ram 《American journal of hematology》2018,93(6):810-815
Del17p is a genomic imbalance occurring in ~7%‐10% of myeloma at diagnosis newly diagnosed myeloma patients (NDMM) and comprises a poor prognostic factor. The goal of this study is to analyze real world data and outcomes among NDMM patients carrying 17p deletion. We report an observational, retrospective, multicenter study. Sixty consecutive patients diagnosed with multiple myeloma in the 8 participating centers diagnosed between 1/2008 and 1/2016 proven to carry 17p deletion by means of fluorescence in situ hybridization (FISH) were identified. Most received a bortezomib‐based induction, over half underwent autologous hematopoietic cell transplantation (HCT); 30% of the patients gained early access to new novel agents via clinical trials, access programs or private insurance. Overall response rate (ORR) after induction was 85%; 94% for transplant eligible (TE); and 75% for transplant ineligible (NTE), and declined in subsequent treatment lines, 64% achieved ≥ VGPR. Median overall survival (OS) was 43 months; median progression free survival (PFS) was 11 months, 19 months for TE and 7 for NTE. In multivariate analysis: higher M‐Spike, presence of extramedullary disease, and >50% of cells baring del17p were associated with adverse PFS; Autologous HCT and higher hemoglobin were associated with longer PFS; OS was 59 months for patients with early access to newer agents. Older age and higher M‐Spike levels were associated with adverse OS, Autologous HCT was associated with favorable OS, 59.7 vs 28.7 months for NTE patients. Despite the improvement achieved with autologous HCT and new novel agents, the prognosis of patients with 17p deletion is still inferior, emphasizing the need for novel approaches. 相似文献
18.
Yi‐Jin Gao Xiao‐Wen Qian Feng‐Juan Lu Xiao‐Wen Zhai Hong‐Sheng Wang Jun Li 《British journal of haematology》2013,160(3):363-367
We report the outcome of 92 non‐high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin‐Frankfürt‐Münster (BFM) Intercontinental ALL ‐based protocol. Compared with a matched historical control group, we found a lower incidence of treatment‐related early death (1·2% vs. 10·9%, P = 0·015), a higher 6‐year event‐free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in‐hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in‐hospital days (164 vs. 296, P < 0·001). This ALL‐BFM based protocol was quite tolerable in our institution and will be extended to high‐risk patients. 相似文献
19.
Post‐transplant consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone in multiple myeloma: A systematic review
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