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1.
《Biology of blood and marrow transplantation》2019,25(9):1720-1729
Attaining complete remission of acute lymphoblastic leukemia (ALL) before hematopoietic stem cell transplantation (HSCT) correlates with better post-transplant outcomes. Inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, has shown significantly higher rates of remission, minimal residual disease negativity, and HSCT versus standard chemotherapy in treating relapsed/refractory (R/R) ALL. We investigated the role of previous transplant and proceeding directly to HSCT after remission as factors in determining post-transplant survival in the setting of InO treatment for R/R ALL. The analyzed population comprised InO-treated patients who proceeded to allogeneic HSCT in 2 clinical trials (phase 1/2: NCT01363297 and phase 3: NCT01564784). Overall survival (OS) was defined as time from HSCT to death (any cause). Of 236 InO-treated patients, 101 (43%) proceeded to allogeneic HSCT and were included in this analysis. Most received InO as first salvage (62%); 85% had no previous HSCT. Median (95% confidence interval [CI]) post-transplant OS was 9.2 months (5.1, not evaluable) with 2-year survival probability (95% CI) of 41% (32% to 51%). In first-HSCT patients (n = 86), median (95% CI) post-transplant OS was 11.8 months (5.9, not evaluable) with 2-year survival probability (95% CI) of 46% (35% to 56%); some patients relapsed and needed additional treatment before HSCT (n = 28). Those who went directly to first HSCT upon remission with no additional salvage/induction treatment (n = 73) fared best: median post-transplant OS was not reached with a 2-year survival probability (95% CI) of 51% (39% to 62%). In patients with R/R ALL, InO followed by allogeneic HSCT provided an optimal long-term survival benefit among those with no previous HSCT who went directly to transplant after remission. 相似文献
2.
《Biology of blood and marrow transplantation》2008,14(12):1394-1400
We studied the relative impact of donor source on outcomes following myeloablative hematopoietic stem cell transplantation (HSCT) for adult patients with acute lymphocytic leukemia (ALL). In this single center study, 138 patients aged 18-61 (median 31) years underwent myeloablative conditioning followed by allogeneic HSCT. Stem cell source was an HLA matched related donor (MRD) in 90, HLA matched unrelated donor (URD:M) in 15, HLA mismatched unrelated donor (URD:MM) in 14, and HLA 0-2 (A, B, DRB1) mismatched umbilical cord blood (UCB) in 19 patients. At the time of HSCT, 70 patients were in first clinical remission (CR1), 57 in CR2, and 11 in ≥CR3. Twenty-one patients had T-lineage disease; 43 patients (31%) had high-risk cytogenetics of either t(9;22) (n = 33), t(4;11) or t(1,19) abnormalities, with the remainder (69%) having normal cytogenetics. White blood cell count (WBC) ≥30 × 109/L at diagnosis was documented in 33%. Demographics and disease characteristics were similar in all 4 groups except all UCB recipients were treated since 1996 and received growth factors. Overall survival (OS) at 3 years for the UCB group was 66% (95% confidence interval [CI] 44%-89%) compared to 27% (95% CI 17%-36%) in the MRD group, and only 13% (95% CI 0%-31%) and 14% (95% CI 0%-33%) in the URD:M and URD:MM groups, respectively. Similarly leukemia free survival (LFS) at 3 years was better in the UCB group at 61% (95% CI 38%-84%) than 27% (95% CI 18%-36%) in the MRD and only 13% (95% CI 0%-31%) in the URD:M group and 14% (95%CI 0%-33%) in URD:MM group. Relapse rates at 3 years were 5% (95% CI 0%-15%) in the UCB group compared to 26% (95% CI 16%-35%) in the MRD, 20% (95% CI 1%-39%) in the URD:M groups, and 0% in the URD:MM groups. Transplant-related mortality (TRM) at 3 years was the lowest in the UCB group at 34% and higher in the other donor groups: MRD 47%, URD:M 67%, and URD:MM 86%. In multiple regression analysis, 5 independent risk factors were significantly associated with poorer OS and LFS: use of URD:MM (relative risk [RR] 2.5, 95% CI, 1.2-5.1, P = .01), ≥CR3 at HSCT (RR 3.5, 95% CI, 1.2-9.6, P = .02), WBC ≥30 × 109/l (RR 1.9, 95% CI, 1.2-3.0, P = .01) at diagnosis, recipient and donor (R/D) cytomegalovirus (CMV) seropositive (RR 3.8, 95% CI, 2.0-7.4, P < .01), and ≥2 induction regimens to achieve initial CR (RR 3.5, 95% CI, 1.2-9.6, P = .02). Graft-versus-host disease (GVHD) was associated with improved LFS (RR 0.4, 95% CI, 0.2-0.6, P < .01). When compared with URD:M, OS with UCB was better (RR 0.3, 95% CI, 0.1-0.7, P = .01), supporting the use of UCB as an alternative stem cell source for adults with ALL. 相似文献
3.
N C Gorin 《Stem cells (Dayton, Ohio)》2002,20(1):3-10
Autologous stem cell transplantation (ASCT) as well as allogeneic stem cell transplantation and conventional chemotherapy (CT) are less effective at treating acute lymphocytic leukemia (ALL) than acute myelocytic leukemia (AML). Chemoresistance and late relapses are hallmarks of ALL. In this context, the question of whether ASCT is superior to CT remains unanswered. In vitro marrow purging using monoclonal antibodies is not routinely used. This review summarizes the results of ASCT for adult and childhood ALL. Statistics from the European Group for Blood and Marrow Transplantation reveal a transplant-related mortality at 5 years of 11% +/- 1%, a relapse incidence of 60% +/- 2%, and a leukemia-free survival (LFS) and overall survival (OS) of 36% +/- 2% and 42% +/- 2%, respectively in 1,366 adults autografted in first remission (CR1). In 269 children, the LFS and OS were 50% +/- 3% and 54% +/- 3%, respectively. There was no evidence in favor of purging the autograft in vitro. In contrast, multicentric and single-institution studies have found better results in adults autografted in CR1, with LFS at 5 years from 46% to 64%, possible efficacy of marrow in vitro purging with mafosfamide (LFS 52%), and improvement in outcome with additional measures post-ASCT, such as maintenance chemotherapy (LFS 57%). Further, as already observed for AML, analyses by risk groups suggest that ASCT may essentially benefit good- but not poor-risk patients. For patients with the Ph1/bcr-abl translocation, the role of STI571 anti-tyrosine kinase for in vivo purging before stem cell harvesting is being investigated. 相似文献
4.
《Biology of blood and marrow transplantation》2019,25(12):2388-2397
We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatmentA total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%). 相似文献
5.
Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation. 总被引:7,自引:0,他引:7
Derek L Stirewalt Katherine A Guthrie Lan Beppu Eileen M Bryant Kris Doney Ted Gooley Frederick R Appelbaum Jerald P Radich 《Biology of blood and marrow transplantation》2003,9(3):206-212
6.
Xiangyu Zhao Xiaosu Zhao Huan Chen Yazhen Qin Lanping Xu Xiaohui Zhang Kaiyan Liu Xiaojun Huang Ying-Jun Chang 《Biology of blood and marrow transplantation》2018,24(9):1936-1943
The aim of this study was to examine the value of minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) at the early stage after hematopoietic stem cell transplantation for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+-ALL). Patients who maintained complete molecular remission (BCR-ABL <.01%) status at 1 and 3 months were associated with a lower relapse rate (P?=?.02 and <.001) and better LFS (P?=?.014 and .013) than were those without a complete molecular remission. Negative MFC at 1, 2, and 3 months was associated with a lower relapse rate (P?=?.01, .004, and .04, respectively) and better LFS (P?=?.044, <.0001, and .013, respectively). Multivariate analysis showed that MRD positivity identified by MFC or RQ-PCR at 3 months was an independent risk factor for relapse (hazard ratio [HR], 6.042 (95% confidence interval [CI], 2.283 to 15.988), P?<?.001), LFS (HR, 3.614 (95% CI, 1.610 to 8.111), P = .002), and overall survival (HR, 2.547, 95% CI, 1.008 to 6.443), P = .048). In summary, MRD detection by MFC and RQ-PCR detection of BCR-ABL at the early stage were important predictors of outcome in patients with Ph+-ALL, and these tests played complementary roles in predicting prognosis. 相似文献
7.
《Biology of blood and marrow transplantation》2008,14(10):1100-1107
Little information is available regarding central nervous system (CNS) relapse of adult leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, we reviewed the data of 1226 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML) who received first allogeneic HSCT between 1994 and 2004, using the database of the Kanto Study Group for Cell Therapy (KSGCT), and analyzed the incidence, risk factors, and outcome of patients with CNS relapse. Twenty-nine patients developed CNS relapse at a median of 296 (9-1677) days after HSCT with a cumulative incidence of 2.3%. Independent significant factors associated with CNS relapse included ALL as the underlying diagnosis (relative risk [RR] = 9.55, 95% confidence interval [CI] = 1.26-72.2, P = .029), nonremission at HSCT (RR = 2.30, 95% CI = 1.03-5.15, P = .042), the history of CNS invasion before HSCT (RR = 5.62, 95% CI = 2.62-12.0, P = 9.2 × 10−6), and the prophylactic intrathecal chemotherapy after HSCT (RR = 2.57, 95% CI = 1.21-5.46, P = .014). The 3-year overall survival (OS) after CNS relapse was 18%. In 7 of 29 patients with CNS relapse, leukemia was observed only in CNS. Three of 7 patients were alive without systemic relapse, resulting in 3-year survival after CNS relapse of 46%. Although the outcome of patients with CNS relapse was generally poor, long-term disease-free survival could be achieved in some patients. 相似文献
8.
Lene Sofie Granfeldt Østgård Jennifer L. Lund Jan Maxwell Nørgaard Mette Nørgaard Bruno C. Medeiros Bendt Nielsen Ove Juul Nielsen Ulrik Malthe Overgaard Maria Kallenbach Claus Werenberg Marcher Anders Hammerich Riis Henrik Sengeløv 《Biology of blood and marrow transplantation》2018,24(2):314-323
To examine the outcomes of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared with chemotherapy alone in a population-based setting, we identified a cohort of patients with acute myeloid leukemia (AML) aged 15 to 70 years diagnosed between 2000 and 2014 in Denmark. Using the Danish National Acute Leukemia Registry, we compared relapse risk, relapse-free survival (RFS), and overall survival (OS) between patients with unfavorable cytogenetic features receiving postremission therapy with conventional chemotherapy only versus those undergoing HSCT in CR1. To minimize immortal time bias, we performed Cox proportional hazards regression, included date of allogeneic HSCT as a time-dependent covariate, and stratified the results by age (<60 or ≥60 years) and cytogenetic risk group. Overall, 1031 patients achieved a CR1. Of these, 196 patients (19%) underwent HSCT. HSCT was associated with a lower relapse rate (24% versus 49%) despite a similar median time to relapse (287 days versus 265 days). In all subgroups, the risk of relapse was lower and both RFS and OS were superior in recipients of HSCT (OS, adjusted mortality ratios: all patients, .54 [95% confidence interval (CI), .42-.71]; patients?age <60 years, .58 [95% CI, .42-.81]; patients?age ≥60 years, .42 [95% CI, .26-.69]; patients with intermediate-risk cytogenetics, .63 [95% CI, .43-.87]; patients with adverse-risk cytogenetics, .40 [95% CI, .24-.67]). In conclusion, in this population-based nationwide cohort study, HSCT was associated with improved survival in both younger and older patients and in patients with both intermediate and adverse cytogenetic risk. 相似文献
9.
《Biology of blood and marrow transplantation》2019,25(6):1172-1178
Access to hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) primarily depends on disease-related factors but may be influenced by social and economic determinants. We included all children aged < 15 years with newly diagnosed ALL in Canada between 2001 and 2018 using the Cancer in Young People in Canada national registry. We examined factors potentially associated with the likelihood of receiving HSCT using univariate and multivariable logistic regression models. A total of 3992 patients with newly diagnosed ALL were included. Three hundred twenty-five (8.1%) received an HSCT and formed the transplant cohort. In multivariable analysis factors independently associated with an increased odds of receiving HSCT were male sex (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05 to 1.93), initial WBC ≥ 50,000 × 109/L (OR, 1.58; 95% CI, 1.09 to 2.28), mixed phenotype acute leukemia relative to B-precursor ALL (OR, 34.32; 95% CI, 16.64 to 70.79), T cell relative to B-precursor ALL (OR, 1.77; 95% CI, 1.07 to 2.91), unfavorable relative to standard cytogenetics (OR, 3.96; 95% CI, 2.56 to 6.12), and relapse before HSCT (OR, 32.77; 95%, 23.89 to 44.96). No association was found between race, neighborhood income quintile or region at diagnosis, and receipt of HSCT. Diagnosis at an HSCT treating center (OR, 1.51; 95% CI, 1.09 to 2.09) and residential distance from the ALL treating center (OR, 1.84 for ≥300 km compared with <100 km; 95% CI, 1.17 to 2.91) were associated with higher odds of receiving HSCT. In a publically funded healthcare system, children with ALL had equitable access to HSCT, which was largely governed by biologic disease-related factors. Patients diagnosed at an HSCT performing center and patients who live farthest away from their treatment center had higher odds of receiving HSCT, although the effect was small, possibly suggesting preferential referral to HSCT for some patients. 相似文献
10.
Jean-Hugues Dalle Adriana Balduzzi Peter Bader Arjan Lankester Isaac Yaniv Jacek Wachowiak Anna Pieczonka Marc Bierings Akif Yesilipek Petr Sedlaçek Marianne Ifversen Sabina Sufliarska Jacek Toporski Evgenia Glogova Ulrike Poetschger Christina Peters 《Biology of blood and marrow transplantation》2018,24(9):1848-1855
Allogeneic hematopoietic stem cell transplantation (HSCT) is beneficial for pediatric patients with relapsed or (very) high-risk acute lymphoblastic leukemia (ALL) in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007 I-BFM study and were stratified according to relapse risk (standard versus high versus very high risk of relapse) and donor type (matched sibling versus matched donor versus mismatched donor). A total of 148 patients (60% boys; median age, 8.7 years; B cell precursor ALL, 75%) were transplanted from mismatched donors, which was defined as either less than 9/10 HLA-compatible donors or less than 5/6 unrelated cord blood after myeloablative conditioning regimen (total body irradiation based, 67%) for high relapse risk (HRR; n?=?42) or very HRR (VHRR) disease (n?=?106). The stem cell source was either bone marrow (n?=?31), unmanipulated peripheral stem cells (n?=?28), T cell ex vivo depleted peripheral stem cells (n?=?59), or cord blood (n?=?25). The median follow-up was 5.1 years. The 4-year rates of overall survival (OS) and event-free survival were 56%?±?4% and 52%?±?4%, respectively, for the entire cohort. Patients transplanted from mismatched donors for HRR disease obtained remarkable 4-year OS and event-free survival values of 82%?±?6% and 80%?±?6%, respectively, whereas VHRR patients obtained values of 45%?±?5% and 42%?±?5% (P?<?.001), respectively. The cumulative incidence of relapse was 29%?±?4% and that of nonrelapse mortality 19%?±?3%. The cumulative incidence of limited and extensive chronic graft-versus-host disease was 13%?±?3% and 15%?±?4%, respectively, among the 120 patients living beyond day 100. Multivariate analysis showed that OS was lower for transplanted VHRR patients (P?=?.002; hazard ratio [HR], 3.62; 95% confidence interval [CI], 1.60 to 8.20) and for patients beyond second complete remission (CR2) versus first complete remission (P?<?.001; HR, 3.68; 95% CI, 1.79 to 7.56); relapse occurred more frequently in patients with VHRR disease (P?=?.026; HR, 3.30; 95% CI, 1.16 to 9.60) and for those beyond CR2 (P?=?.005; HR, 4.16; 95% CI, 1.52 to 10.59). Nonrelapse mortality was not significantly higher for cytomegalovirus-positive recipients receiving cytomegalovirus-negative grafts (P?=?.12; HR, 1.96; 95% CI, .84 to 4.58). HSCT with a mismatched donor is feasible in pediatric ALL patients but leads to inferior results compared with HSCT with better matched donors, at least for patients transplanted for VHRR disease. The results are strongly affected by disease status. The main cause of treatment failure is still relapse, highlighting the urgent need for interventional strategies after HSCT for patients with residual leukemia before and/or after transplantation 相似文献
11.
Isaac Yaniv Aviva C. Krauss Eric Beohou Arnaud Dalissier Selim Corbacioglu Marco Zecca Boris V. Afanasyev Massimo Berger Miguel Angel Diaz Krzysztof Kalwak Petr Sedlacek Stefania Varotto Christina Peters Peter Bader 《Biology of blood and marrow transplantation》2018,24(8):1629-1642
Outcome data were collected from the European Society for Blood and Marrow Transplantation registry on 373 children from 120 centers with relapsed leukemia (214 with acute lymphoblastic leukemia [ALL] and 159 with acute myelogenous leukemia [AML]) who underwent second allogeneic hematopoietic stem cell transplantation (HSCT) between 2004 and 2013. Overall survival (OS) was 38% at 2 years and 29% at 5 years, and leukemia-free survival (LFS) was 30% at 2 years and 25% at 5 years. Median follow-up after second HSCT was 36.4 months in the ALL group and 50.2 months in the AML group. In the ALL group, OS was 43% at 2 years and 33% at 5 years, and LFS was 34% at 2 years and 31% at 5 years. In the AML group, OS was 32% at 2 years and 24% at 5 years, and LFS was 24% at 2 years and 17% at 5 years. The 2-year nonrelapse mortality (NRM) rate was 22% in the ALL group and 18% in the AML group. Favorable prognostic factors (P?<?.05) for OS and LFS included >12 months between transplantations and chronic graft-versus-host disease after the first HSCT (in both groups), complete response before the second HSCT (ALL group only), and age >12 years (AML group only). Findings were more consistent over time in the ALL group, with no significant differences between 2-year and 5-year rates of relapse, NRM, and LFS. Children with relapsed acute leukemias have a substantial likelihood of long-term survival following second HSCT. Given the many novel targeted and immunomodulation therapies currently under development, it is important to identify specific patient subpopulations that may benefit from a second HSCT compared with those better suited to new approaches. 相似文献
12.
《Biology of blood and marrow transplantation》2013,19(2):208-213
Consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a survival benefit to patients with acute lymphoblastic leukemia (ALL). We have previously reported comparable survival and relapse rates after T cell–depleted (TCD) allo-HSCT compared with unmodified transplantations for acute myelogenous leukemia, myelodysplastic syndrome, and non-Hodgkin lymphoma with significantly decreased graft-versus-host disease (GVHD). We performed a 56-patient retrospective study to evaluate TCD allo-HSCT for the treatment of ALL after myeloablative total body irradiation–based therapy. The 2-year and 5-year overall survival rates for patients with ALL after TCD allo-HSCT were 0.39 (95% confidence interval [CI], 0.26-0.52) and 0.32 (95% CI, 0.19-0.44), respectively, and the 2-year and 5-year disease-free survival rates were 0.38 (95% CI, 0.25-0.50) and 0.32 (95% CI, 0.20-0.44). There was a trend toward improved survival of patients who underwent TCD allo-HSCT in first complete remission compared with those who did so in other remission states. The cumulative incidence of grade II-IV acute GVHD at 1 year was 0.20 (95% CI, 0.10-0.31), and no patients developed grade IV acute GVHD. The cumulative incidence of chronic GVHD in 41 evaluable patients at 2 and 5 years was 0.15 (95% CI, 0.04-0.26), and that of extensive chronic GVHD at 2 and 5 years was 0.05 (95% CI, 0-11.6). We demonstrate OS and DFS rates that compare favorably to unmodified allo-HSCT with lower rates of GVHD. 相似文献
13.
Bachanova V Burke MJ Yohe S Cao Q Sandhu K Singleton TP Brunstein CG Wagner JE Verneris MR Weisdorf DJ 《Biology of blood and marrow transplantation》2012,18(6):963-968
Data on pretransplantation minimal residual disease (MRD) and outcomes of umbilical cord blood transplantation (UCBT) are limited. Out of the 143 patients with acute lymphoblastic leukemia (ALL) who underwent UCBT at the University of Minnesota between 2004 and 2010, we evaluated 86 patients with available MRD assessment data by 4- and 8-color flow cytometry analysis immediately before transplantation. Ten patients (11.6%) were MRD-positive, and 76 were MRD-negative (88.4%). Most of the patients (82%) received myeloablative conditioning. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. In multivariate analysis, age, disease status (complete remission [CR] 1 versus CR2/CR3), disease group (precursor B cell ALL versus Philadelphia chromosome-positive ALL versus T cell ALL), and time to transplantation had no impact on relapse. Patients with MRD before UCBT had a greater incidence of relapse at 2 years (relapse rate, 30%; 95% confidence interval [CI], 4%-56%) and lower 3-year disease-free survival (30%; 95% CI, 7%-58%) compared with those without MRD (relapse rate, 16%; 95% CI, 8%-25%; P = .05; disease-free survival, 55%; 95% CI, 43%-66%; P = .02). Our data suggest that in patients with ALL, achieving an MRD-negative state before UCBT improves outcomes. 相似文献
14.
《Biology of blood and marrow transplantation》2009,15(2):257-265
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulotyce-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P = .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P = .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest. 相似文献
15.
Lujia Dong Tong Wu Mei-Jie Zhang Zhi-Yong Gao Dao-Pei Lu 《Biology of blood and marrow transplantation》2007,13(12):1515-1524
Haploidentical transplantation is a feasible alternative for patients with life-threatening hematologic diseases who lack a matched donor. Factors affecting the clinical outcomes of haploidentical transplantation remain under investigation. We analyzed 157 consecutive patients with leukemia who underwent transplantation with nonmanipulated granulocyte colony-stimulating factor (G-CSF)-mobilized marrow and peripheral blood cells (G-BMPBs) from haploidentical donors after receiving myeloablative chemotherapy (Ara-C + BuCy + antithymocyte globulin). Follow up observations after transplantation were made from 48 days to 1191 days (median, 448 days). Multivariate analysis indicated that the cohort given higher doses of CD3(+) cells (> or = 177 x 10(6) /kg) in allograft transplantation had a significantly lower treatment-related mortality (TRM) (relative risk [RR] = 0.35; 95% CI = 0.16-0.77; P = .0090), better leukemia-free survival (LFS) (RR = 0.46; 95% CI = 0.26-0.84; P = .0106), and better overall survival (OS) (RR = 0.42; 95% CI = 0.23-0.78; P = .0058). Inversely, advanced-stage disease was a strong predictor of greater posttransplantation relapse (RR = 3.48; 95% CI = 1.26- 9.60; P = .0159), worse LFS (RR = 2.56; 95% CI = 1.33-4.95; P = .0050), and worse OS (RR = 2.77; 95% CI = 1.39-5.53; P = .0038). A high number of CD3(+) cells (> 177 x 10(6)/kg) given to patients resulted in statistically less TRM and more intensive graft versus leukemia effect without producing more severe grades of GVHD, all resulting in a significantly better overall clinical outcome from haploidentical transplantation. 相似文献
16.
《Biology of blood and marrow transplantation》2019,25(8):1611-1620
The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in the tyrosine kinase inhibitor (TKI) era is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of Ph+ ALL in the TKI era. We analyzed clinical data of Ph+ ALL patients aged 1 to 18 years who received imatinib added to intensive chemotherapy at the start of induction therapy. Among the 68 patients who completed at least 2 consolidation cycles, 44 underwent transplantation (transplant arm) and 24 received continuous TKI with chemotherapy (nontransplant arm). At the 3-year follow-up the cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 23.5%, 73.4%, and 80.3%, respectively. Multivariate analysis showed that hematologic response (whether complete remission [CR] was achieved) at the induction end, BCR-ABL levels (whether major molecular response [MMR] was achieved) at 3 months, and transplantation were independent affecting factors for CIR, EFS, and OS. In the risk stratification analysis based on the first 2 prognostic factors mentioned above, no significant difference existed between the transplant and nontransplant arms for the probabilities of 3-year OS, EFS, and CIR in the standard-risk group (no poor prognostic factors). Meanwhile, OS, EFS, and CIR rates were significantly better in the transplant arm in the high-risk group (≥1 poor prognostic factor). Among the 44 patients in the transplant arm, 37 underwent haplo-HSCT. Achieving CR at the induction end, MMR at 3 months, and haplo-transplant were also independent favorable factors of CIR, EFS, and OS in the nontransplant and haplo-HSCT arms. Haplo-HSCT showed a significant survival advantage in the high-risk group only. Hematologic response at the induction end and BCR-ABL levels at 3 months are likely to be useful for identifying pediatric Ph+ ALL patients at a high risk of relapse in the TKI era. Children with Ph+ ALL in first CR may benefit from allo-HSCT, particularly those at high risk. Haplo-HSCT could achieve good long-term survival for pediatric Ph+ ALL. Thus, haplo-HSCT can be an alternative approach for high-risk Ph+ ALL patients. 相似文献
17.
《Biology of blood and marrow transplantation》2013,19(7):1059-1064
For patients with acute lymphoblastic leukemia (ALL) who relapse after allogeneic hematopoietic stem cell transplantation (HSCT), treatment options are limited, and the clinical course and prognostic factors affecting outcome have not been well characterized. We retrospectively analyzed outcomes of 123 adult patients with ALL who relapsed after a first HSCT performed at our center between 1993 and 2011. First-line salvage included second HSCT (n = 19), donor lymphocyte infusion with or without prior chemotherapy (n = 11), radiation therapy (n = 6), cytoreductive chemotherapy (n = 30), mild chemotherapy (n = 27), or palliative care (n = 23), with median postrelapse overall survival (OS) of 10 months, 6.5 months, 3 months, 4 months, 4 months, and 1 month, respectively. Despite a complete remission rate of 38% after first-line salvage in the treated patients, the OS rate remained limited with 1- and 2- year OS rates of 17% (95% confidence interval, 13 to 29) and 10% (95% confidence interval, 6 to 20), respectively. On univariate analysis, adverse factors for OS included active disease at the time of first HSCT and short time to progression from first HSCT (<6 months). There was no difference in the 6-month survival postrelapse in patients with isolated extramedullary relapse (44%) compared with combined extramedullary and bone marrow relapse (29%) or those with isolated bone marrow relapse (34%) (P = .8). Our data provide more insight into the disease behavior and treatment outcomes of ALL at relapse after HSCT against which future trials may be compared. 相似文献
18.
《Biology of blood and marrow transplantation》2008,14(12):1356-1364
Extranodal natural killer (NK)/T cell lymphoma, nasal type, is a recently recognized distinct entity and the most common type of non–B cell extranodal lymphoma in Asia. This retrospective analysis studied the potential survival benefits of hematopoeitic stem cell transplantation (HSCT) compared with a historical control group. A total of 47 patients from 3 previously published series of HSCT were matched according to NK/T cell lymphoma International Prognostic Index (NKIPI) risk groups and disease status at transplantation with 107 patients from a historical control group for analysis. After a median follow-up of 116.5 months, the median survival time was not determined for the HSCT group, but it was 43.5 months for the control group (95% confidence interval [CI] = 6.7 to 80.3 months; P = .127, log-rank test). In patients who were in complete remission (CR) at the time of HSCT or at surveillance after remission, disease-specific survival rates were significantly higher in the HSCT group compared with the control group (disease-specific 5-year survival rate, 87.3% for HSCT vs 67.8% for non-HSCT; P = .027). In contrast, in subgroup analysis on non-CR patients at the time of HSCT or non-HSCT treatment, disease-specific survival rates were not significantly prolonged in the HSCT group compared with the control group (1-year survival rate, 66.7% for HSCT vs 28.6% for non-HSCT; P = .141). The impact of HSCT on the survival of all patients was significantly retained at the multivariate level with a 2.1-fold (95% CI =1.2- to 3.7-fold) reduced risk of death (P = .006). HSCT seems to confer a survival benefit in patients who attained CR on postremission consolidation therapy. These findings suggest that, in particular, patients in CR with high NKIPI risk scores at diagnosis should receive full consideration for HSCT. 相似文献
19.
Annalisa Ruggeri Fernanda Volt Franco Locatelli Gerard Michel Cristina Diaz de Heredia Manuel Abecasis Marco Zecca Ajay Vora Karima Yakouben Tracey A. OBrien Stefano Giardino Jacqueline Cornish Vanderson Rocha Christina Peters Peter Bader Eliane Gluckman Jean Hugues Dalle 《Biology of blood and marrow transplantation》2017,23(1):96-102
Infant acute leukemia still has a poor prognosis, and allogeneic hematopoietic stem cell transplantation is indicated in selected patients. Umbilical cord blood (UCB) is an attractive cell source for this population because of the low risk of chronic graft-versus-host disease (GVHD), the strong graft-versus-leukemia effect, and prompt donor availability. This retrospective, registry-based study reported UCB transplantation (UCBT) outcomes in 252 children with acute lymphoblastic leukemia (ALL; n?=?157) or acute myelogenous leukemia (AML; n?=?95) diagnosed before 1 year of age who received a single-unit UCBT after myeloablative conditioning between 1996 and 2012 in European Society for Blood and Marrow Transplantation centers. Median age at UCBT was 1.1 years, and median follow-up was 42 months. Most patients (57%) received a graft with 1 HLA disparity and were transplanted in first complete remission (CR; 55%). Cumulative incidence function (CIF) of day 100 acute GVHD (grades II to IV) was 40%?±?3% and of 4-year chronic GVHD was 13%?±?2%. CIF of 1-year transplant-related mortality was 23%?±?3% and of 4-year relapse was 27%?±?3%. Leukemia-free-survival (LFS) at 4 years was 50%?±?3%; it was 40% and 66% for those transplanted for ALL and AML, respectively (P?=?.001). LFS was better for patients transplanted in first CR, regardless of diagnosis. In multivariate model, diagnosis of ALL (P?=?.001), advanced disease status at UCBT (<.001), age at diagnosis younger than 3 months (P?=?.012), and date of transplant before 2004 were independently associated with worse LFS. UCBT is a suitable option for patients diagnosed with infant acute leukemia who achieve CR. In this cohort, patients with AML had better survival than those with ALL. 相似文献
20.
Salyka Sengsayadeth Myriam Labopin Ariane Boumendil Jürgen Finke Arnold Ganser Matthias Stelljes Gerhard Ehninger Dietrich Beelen Dietger Niederwieser Didier Blaise Peter Dreger Ghulam Mufti Patrice Chevallier Audrey Mailhol Katie S. Gatwood Norbert Gorin Jordi Esteve Fabio Ciceri Arnon Nagler 《Biology of blood and marrow transplantation》2018,24(7):1406-1414
Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P?=?.01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P?=?.02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed. 相似文献