Comparable analysis of outcomes for allogeneic peripheral blood stem cell transplantation from matched related and matched unrelated donors in acute myeloid leukemia

This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors in 142 consecutive patients with acute myeloid leukemia (AML). The cumulative incidence of acute graft-versus-host disease (GVHD) was 37.6% in the related PBSCT group and 53.7% in the unrelated PBSCT group. The cumulative incidence of extensive chronic GVHD was also higher in the unrelated PBSCT group (19.5%) than in the related PBSCT group (8.9%). The overall survival rate at 4 years was 62.4 ± 5.4 and 53.8 ± 1.2% (p = 0.535) in the related and unrelated PBSCT group, respectively. In a multivariate analysis, unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio = 3.019, p = 0.027). Unfavorable cytogenetics and the disease status at the time of transplantation were found to be related to overall survival. In the case of high-risk AML, the survival rate and relapse incidence were significantly better in the matched unrelated PBSCT group (p = 0.047 and 0.039, respectively). In conclusion, the allogeneic PBSCT outcomes for AML were comparable in the matched related and matched unrelated groups. Nonetheless, for high-risk AML patients, matched unrelated PBSCT was found to be preferable to matched related PBSCT.     

Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors

Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n?=?18) and mismatched related (haploidentical, n?=?29) donors. CD34?+?selection with magnetic microbeads resulted in 8?×?10(3)/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p?相似文献   

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.     

Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis

A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32-63). No primary graft failure occurred. The median time until leucocyte (>1.0 x 10(9)/l) and platelet (>20 x 10(9)/l) engraftment was 16 (range, 11-26) and 23 d (range, 9-139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft-versus-host disease (GvHD) grades II-IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0-32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow-up of 22 months (range, 4-59), the 3-year estimated overall and disease-free survival was 84% (95% CI: 67-100%).     

Successful haematopoietic stem cell transplantation from a matched unrelated donor following three graft failures from HLA-mismatched related donors

Graft rejection and graft failure are serious complications after allogeneic stem cell transplantation (SCT). We report a patient with CML in first chronic phase who finally engrafted with a transplant from an HLA-identical unrelated donor after graft failures from two related HLA-mismatched sibling donors. After failure of one BM and two PBSC grafts from two 1 HLA-antigen mismatched related donors, the patient was finally successfully transplanted from a subsequently identified HLA-identical unrelated donor (donor 3). At 5 years post transplant, the patient is in complete cytogenetic and molecular remission.     

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34⁺ and CD3⁺ cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34⁺ cell dose more than 4.5×10⁶/kg (HR: 0.56; P=0.002) and CD3⁺ cell dose more than 3×10⁸/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an “adapted Disease Risk Index” by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).     

T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis

Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. “Haploidentical expert” centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes (“haploidentical regular”, “haploidentical expert” and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10⁻⁵) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.     

血缘与非血缘供者异基因造血干细胞移植治疗白血病的比较研究

目的探讨血缘供者（RD）与非血缘供者（URD）造血干细胞移植（HSCT）治疗白血病的差异。方法115例白血病患者接受HLA血清学全相合异基因造血干细胞移植。流式细胞仪测定移植后1年内不同时间点患者的T细胞与B细胞重建情况。结果接受骨髓移植的RD-HSCT和URD—HSCT组WBC〉1．0×10^9／L分别为移植后（13．1±2．4）d、（16．3±3．0）d;PLT〉20×10^9／L分别为移植后（14．9±6．6）d、（20．2±7．3）d,两组WBC和PLT重建时间差异均有统计学意义（P值分别为0．003、0．042）;接受外周造血干细胞移植患者RD-HSCT和URD．HSCT组WBC〉1．0×10^9／L分别为（12．5±2．9）d、（13．1±4．1）d（P=0．488）,PLT〉20×10^9／L分另Ⅱ为（12．2±4．2）d、（15．7±7．1）d（P=0．020）。移植后1、3、6、9、12个月CD;CD;,1个月CD45RA^＋CD4^＋,3个月CD;CD;重建两组差异均有统计学意义。两组Ⅱ～Ⅳ度急、慢性移植物抗宿主病（GVHD）的发生率分别为45．5％、52．3％;45．3％、63．2％;GVHD的病死率分别为6．1％、15．9％,差异均无统计学意义。两组移植后复发率分别为18．2％、11．4％（P=0．424）。两组移植后早期感染率分别为42．4％、47．7％（P=0．696）。3年总生存率分别为（67．8±6．9）％、（61．6±7．7）％（P=0．133）,无病生存率分别为（62．3±6．9）％、（56．8±7．9）％（P=0．177）。结论URD-HSCT治疗白血病具有和RD-HSCT近似的疗效。     

Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission

We compared the treatment-related mortality, relapse rate, disease-free survival (DFS), and overall survival (OS) by cytogenetic risk group of 261 patients with acute myeloid leukemia in first complete remission (CR1) and 299 patients in CR2 in undergoing matched unrelated donor hematopoietic stem cell transplantation (HSCT). For patients in first CR, the DFS and OS at 5 years were similar for the favorable, intermediate, and unfavorable risk groups at 29% (95% confidence interval [CI], 8%-56%) and 30% (22%-38%); 27% (19%-39%) and 29% (8%-56%); and 30% (95% CI, 22%-38%) and 30% (95% CI, 20%-41%), respectively. For patients in second CR, the DFS and OS at 5 years were 42% (95% CI, 33%-52%) and 35% (95% CI, 28%-43%); 38% (95% CI, 23%-54%) and 45% (95% CI, 35%-55%); and 37% (95% CI, 30%-45%) and 36% (95% CI, 21%-53%), respectively. Cytogenetics had little influence on the overall outcome for patients in first CR. In second CR, outcome was modestly, but not significantly, better for patients with favorable cytogenetics. The graft-versus-leukemia effect appeared effective, even in patients with unfavorable cytogenetics. However, treatment-related mortality was high. Matched unrelated donor HSCT should be considered for all patients with unfavorable cytogenetics who lack a suitable HLA-matched sibling donor.     

母供子单倍体与无关供体异基因造血干细胞移植治疗恶性血液病临床对照研究

目的比较母供子单倍体异基因造血干细胞移植(allogeneichematopoieticstemcelltransplantation,Allo-HSCT)和无关供体Allo-HSCT治疗恶性血液病安全性及疗效。方法同期对照研究于2002年6月至2005年1月对苏州大学附属第一医院的18例母供子单倍体Allo-HSCT(A组)和10例无关供体Allo-HSCT(B组)的临床结果。供者动员方案:重组人粒细胞集落刺激因子(G-CSF)300μg,每日2次,5d后采集造血干细胞。预处理方案:髓系白血病采用改良白消安与环磷酰胺(Bu/Cy)方案,急性淋巴细胞白血病及非霍奇金淋巴瘤患者以一次全身照射(TBI)代替Bu。移植物抗宿主病(GVHD)预防,A组:环孢素A(CsA) 短程甲氨蝶呤(MTX) 霉酚酸酯(MMF) 胸腺细胞球蛋白(ATG);B组:CsA 短程MTX MMF。结果两组均顺利完成预处理并获造血重建。A、B两组达到ANC≥0·5×109/L、Plt≥20×109/L的时间差异无显著性(P>0·05);Ⅰ~Ⅱ度及Ⅲ~Ⅳ度aGVHD累积发生率分别为61·1%对40·0%及27·8%对30·0%(P>0·05),差异均无显著性;cGVHD及广泛型cCVHD累积发生率分别为58·8%对20·0%,17·6%对20·0%(P>0·05),差异亦无显著性。A、B两组累积存活率(49·8%对58·3%,P>0·05)差异均无显著性。结论初步研究表明,单倍体及无关供体Allo-HSCT治疗恶性血液病的安全性及有效性相当,母供体单倍体Allo-HSCT值得探索。     

Comparable outcomes of partially matched related and matched related allogeneic hematopoietic cell transplantation following reduced-intensity conditioning in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia

Reports from multiple centers have shown that reduced-intensity allogeneic hematopoietic cell transplantation (RIC-HCT) is able to benefit some adult patients suffering from Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). However, the relationship between donor cell source and outcome of RIC-HCT in (Ph?)ALL patients has not been elucidated. In this study, we present the outcome of 57 (Ph?)ALL patients treated with reduced-intensity conditioning (RIC) followed by HCT from HLA-matched related (MRD, n = 34) or HLA partially matched related (PMRD, n = 23) donors from a multicenter cohort. Neutrophil recovery at day 100 occurred in 91.3 % of the PMRD group and 97.1 % of the MRD group (P = 0.84). One hundred days after treatment, the cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) was 30.4 % (95 % confidence interval [CI], 13.0–53.0 %) in patients who received PMRD grafts, and 27.3 % (95 % CI, 15.0–48.0 %) for those who received MRD grafts (P = 0.76). The cumulative risk of developing chronic GVHD was 59.4 % (95 % CI, 31.0–72.0 %) in the MRD group and 23.4 % (95 % CI, 4.0–43.0 %) in the PMRD group (P = 0.03). The cumulative incidence of relapse in patients who received PMRD grafts was 18.8 % (95 % CI, 3.0–34.0 %), while for those who received MRD grafts it was 37.2 % (95 % CI, 15.0–48.0 %) (P = 0.32). Overall treatment-related mortality was 41.6 % (95 % CI, 20.0–62.0 %) in the PMRD group and 19.9 % (95 % CI, 7.0–35.0 %) in the MRD group (P = 0.08). Relapse was the most common cause of mortality in the MRD group, while infection contributed to the majority of deaths in the PMRD group. The 3-year probability of disease-free survival did not differ significantly between the two groups (55.5 % for the PMRD group vs. 48.4 % for the MRD group; P = 0.81). These data strongly suggest that RIC-HCT performed with PMRD may represent an alternative treatment option for adult patients with (Ph?)ALL.     

HLA-10/10 matched unrelated donor versus sibling donor hematopoietic stem cell transplantation for adult acute myeloid leukemia

<正>Objective To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center.Methods Consecutive AML adults who received MUD-     

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence

We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P < 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.     

Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma

The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.     

The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma

We performed a retrospective analysis of outcome in 45 patients with multiple myeloma receiving unrelated donor stem cell transplants (UD-SCT) in the UK between 1993 and 2002; 17 received myeloablative conditioning regimens and 28 received reduced intensity conditioning (RIC) protocols. Forty patients received pretransplant CAMPATH serotherapy. Forty-two of 45 patients had detectable disease at transplant, but 33 of 45 were chemoresponsive. Sixty per cent of patients had received a previous autograft. Myeloid engraftment was seen in 95% of recipients and was significantly faster in recipients receiving peripheral blood stem cells (P = 0.07) and RIC (P = 0.001). The incidence of severe (grade 3/4) acute graft versus host disease (aGvHD) was 5% (2/40). The 100-d non-relapse mortality was 18% (5/38) following RIC and 53% (9/17) following myeloablative regimens. Twenty-nine per cent of patients achieved a complete remission, 61% a partial remission, giving a 90% overall response rate. At median follow-up (513 d), overall survival was 40%: 54% in the RIC group (median follow-up: 489 d) and 18% in the myeloablative group (median follow-up: 560 d). In recipients of UD-SCT, RIC protocols that incorporated CAMPATH were associated with faster myeloid engraftment, less severe aGvHD and lower 100-d non-relapse mortality than myeloablative regimens, without a corresponding rise in relapse rate during the period of observation.     

Effect of allogeneic hematopoietic stem cell transplantation from matched siblings or unrelated donors during the first complete remission in patients with cytogenetically normal acute myeloid leukemia

We retrospectively examined the impact of hematopoietic stem cell transplantation (HSCT) during the first complete remission (CR1) in 81 patients with cytogenetically normal acute myeloid leukemia (CN-AML). Eligible patients were divided into three subgroups: HSCT recipients with allogeneic sibling or matched unrelated donors (MUD) (allogeneic HSCT, n = 47), recipients of autologous HSCT (n = 12), and patients receiving chemotherapy alone (n = 22). We examined factors associated with overall survival (OS) in these patients, focusing particularly on the effect of allogeneic HSCT. Comparing to those receiving chemotherapy alone, patients in the allogeneic HSCT group had significantly better OS, which was independent of the presence of comorbidities. Furthermore, patients who received allogeneic sibling HSCT had the best OS and disease-free survival (DFS). Patients who received MUD HSCT also had significant advantage in DFS but not in OS, when compared with patients in the chemotherapy group. The study results suggest that patients with CN-AML in CR1 who are eligible for HSCT may have a survival benefit from HSCT, especially the allogeneic HSCT. We suggest that future studies employ molecular classification of AML to better define the benefits of HSCT during CR1 in patients with CN-AML.     

Status quo of allogeneic stem cell transplantation for patients with sickle cell disease using matched unrelated donors

This mini review is based on an oral presentation reflecting the current status quo of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) using matched unrelated donors (MUDs) presented at the EBMT Sickle Disease Meeting held in Regensburg, Germany, in May 2019. Although the clinical trial landscape for MUD HSCT in patients with SCD is limited to date, some attempts to improve patient outcome in terms of overall survival and event-free survival have been made recently, including optimization of conditioning regimens and prevention of engraftment failure as well as graft-versus-host disease. The results achieved by these approaches are summarized in this review and are still unsatisfactory. Whether new haploidentical transplantation protocols will achieve superior results and are able to replace MUD HSCT for patients with SCD remains to be elucidated.