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1.
《Biology of blood and marrow transplantation》2014,20(3):425-429
Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality. 相似文献
2.
《Biology of blood and marrow transplantation》2014,20(1):111-117
Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted. 相似文献
3.
《Biology of blood and marrow transplantation》2014,20(1):58-65
Because of its potent immunomodulatory effect, an infusion of donor mononuclear early apoptotic cells (ApoCell) was tested in addition to cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA-matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor. In a phase I/IIa clinical trial, we treated 13 patients (median age, 37 years; range, 20 to 59 years) with hematologic malignancies: 7 patients with acute lymphoblastic leukemia, 5 patients with acute myeloid leukemia, and 1 patient with chronic myeloid leukemia, who received conventional myeloablative conditioning, with 35, 70, 140, or 210 × 106 cell/kg of donor ApoCell, on day -1 of transplantation. Engraftment was successful in all patients with median time to neutrophil recovery of 13 days (range, 11 to 19), and platelet recovery of 15 days (range, 11 to 59). Serious adverse effects were reported on 10 occasions in the trial, all of which were considered unrelated (n = 7) or unlikely to be related (n = 3) to ApoCell infusion. The nonrelapse mortality at day 100 and 180 after transplantation was 7.7% and the overall survival at 100 and 180 days after transplantation was 92% and 85%, respectively. All ApoCell preparations showed an in vitro significant tolerogenic effect upon interaction with dendritic cells. The overall incidence of acute grades II to IV GVHD was 23%, whereas among those receiving the 2 higher doses (n = 6), the rate was 0%. These results suggest that a single infusion of donor ApoCell in HLA-matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute GVHD occurring after myeloablative conditioning. No dose limiting toxicity was observed. (Clinicaltrials.gov no. NCT00524784). 相似文献
4.
《Biology of blood and marrow transplantation》2013,19(7):1094-1101
Donor leukocyte infusion (DLI) can induce potent graft-versus-leukemia (GVL) activity in patients with relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, except in patients with chronic-phase chronic myelogenous leukemia, responses to DLI have been disappointing. GVL induction is likely to be most effective in the setting of minimal residual disease. Prevention of relapse through the provision of prophylactic DLI to high-risk patients may improve the outcome of allogeneic HSCT. We previously reported that ex vivo costimulated T cell infusion of activated DLI (aDLI) as treatment for relapse is safe and has potent GVL effects. We hypothesized that prophylactic aDLI can be given safely and prevent relapse in high-risk patients after allogeneic HSCT. Eighteen patients with acute myeolgenous leukemia (n = 14), acute lymphoblastic leukemia (n = 3), or myelodysplastic syndrome (n = 1) underwent allogeneic HSCT after a reduced-intensity conditioning (RIC) regimen with alemtuzumab, fludarabine, and busulfan. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate with a planned early and rapid taper of tacrolimus. Patients without GVHD, off immune suppression, and in remission received aDLI at a dose of 1 × 107 CD3+ cells/kg (aDLI 1) at day +120, followed by a second infusion of 1 × 108 CD3 cells/kg (aDLI 2) at day +180. At a median follow-up of 58 months, 5 of the 18 patients (28%) were alive, and 4 patients were in remission. Eleven patients (65%) relapsed, at a median time of 191 days. Twelve of the 18 patients received at least one aDLI, and 6 of these 12 patients also received aDLI 2. Six patients did not receive any aDLI owing to early relapse (n = 2), protocol ineligibility (n = 1), or GVHD (n = 3). Only 2 of the 12 patients who received aDLI 1 developed GVHD. Two out of the 12 patients remain in remission at the time of this report. Disease recurrence was the cause of death in 10 of the 13 patients (77%) who died. Our data indicate that prophylactic ex vivo costimulated CD3/CD28 DLI is safe, feasible, and not associated with significant GVHD. Relapse remains the major cause of treatment failure after RIC HSCT even with rapid withdrawal of immune suppression and the use of prophylactic aDLI, and better strategies to prevent relapse are needed. 相似文献
5.
《Biology of blood and marrow transplantation》2020,26(10):1868-1875
Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapse-free survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P= .002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P = .006), and superior 2-year GRFS (35.5% versus 20.0%, P = .003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials. 相似文献
6.
《Biology of blood and marrow transplantation》2013,19(8):1167-1174
Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient– and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health–defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI. 相似文献
7.
《Biology of blood and marrow transplantation》2014,20(9):1426-1434
Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28 days. Study patients (n = 34) had a median age of 51 years (range, 10 to 67 years) and had undergone unrelated (n = 22) or related (n = 12) donor HSCT. Study patients were treated with etanercept (.4 mg/kg, maximum 25 mg/dose) twice weekly for 4 to 8 weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28 days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1 year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2 years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28 days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P = .08) and 18% (3% versus 18%, P = .05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P = .06) and regenerating islet-derived 3-alpha (P = .01) 28 days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375. 相似文献
8.
《Biology of blood and marrow transplantation》2014,20(12):2042-2048
The fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is associated with a high relapse rate for patients with acute myeloid leukemia (AML) even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor, which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.gov NCT01398501). Patients received a variety of conditioning regimens and graft sources. A dose escalation 3 + 3 cohort design was used to define the maximum tolerated dose (MTD), with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT and continued for 12 28-day cycles. Twenty-two patients were enrolled (status at HSCT: first complete remission [CR1], n = 16; second complete remission [CR2], n = 3; refractory, n = 3). The MTD was established at 400 mg twice daily with 1 dose-limiting toxicity (DLT) observed (pericardial effusion). Two patients died of transplantation-related causes, both unrelated to sorafenib. Two patients stopped sorafenib after relapse and 5 stopped because of attributable toxicities after the DLT period. Median follow-up for surviving patients is 16.7 months after HSCT (range, 8.1 to 35.0). There was 1 case of grade II acute graft-versus-host disease (GVHD) after starting sorafenib and the 12-month cumulative incidence of chronic GVHD was 38% (90% confidence interval [CI], 21% to 56%). For all patients, 1-year progression-free survival (PFS) was 85% (90% CI, 66% to 94%) and 1-year overall survival (OS) was 95% (90% CI, 79% to 99%) after HSCT. For patients in CR1/CR2 before HSCT (n = 19), 1-year PFS was 95% (90% CI, 76% to 99%) and 1-year OS was 100%, with only 1 patient who relapsed. Sorafenib is safe after HSCT for FLT3-ITD AML and merits further investigation for the prevention of relapse. 相似文献
9.
《Biology of blood and marrow transplantation》2012,18(1):106-112
Allogeneic hematopoietic cell transplantation (HSCT) is considered a curative treatment for acute myelogenous leukemia (AML). Extramedullary relapse after HSCT for AML is a rare event and is less well defined than systemic, hematologic relapse. We retrospectively studied all patients with AML (n = 436) who underwent HSCT at the University of Minnesota between 1996 and 2008 who developed either a bone marrow (BM) or extramedullary (EM) relapse, and examined the incidence and risk factors for BM and EM relapse. Of 128 patients who relapsed post-HSCT, 25 had relapse in EM sites, either isolated (n = 13) or with concurrent BM relapse (n = 12). Relapse sites included bone (n = 1), central nervous system (n = 6), gastrointestinal (n = 4), lymphatic (n = 4), skin (n = 5), genitourinary (n = 1), pulmonary (n = 1), and soft tissue (n = 3). The time to relapse was longer in the EM sites (median, 328 days vs 168 days). Patients with EM relapse were more likely to have had preceding acute graft-versus-host disease (GVHD) (77% vs 49%; P = .03) or chronic GVHD (46% vs 15%; P = .02) compared with those with BM relapse. The 6-month survival postrelapse was significantly better in patients with isolated EM relapse (69%) compared with those with combined EM and BM relapse (8%) or those with BM relapse alone (27%) (P < .01). Compared with local therapy alone, systemic therapy yielded better 6-month survival in patients with EM relapse. This study suggests differing pathogenesis of BM relapse versus EM relapse of AML after allogeneic HSCT. GVHD and its accompanying graft-versus-leukemia effect may better protect BM sites, but patients with EM relapse have better responses to combined therapy and improved survival compared with those with BM relapse. 相似文献
10.
《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
11.
《Biology of blood and marrow transplantation》2020,26(11):2082-2088
We assessed differences in presentation and response to therapy in 394 consecutive patients who developed acute or chronic graft-versus-host disease (GVHD) after receiving their first allogeneic transplantation (HSCT) from a 10/10 HLA allele-matched unrelated donor (MUD; n = 179) using calcineurin inhibitors or a T cell-replete haploidentical donor (haplo; n = 215) and post-transplantation cyclophosphamide at our center between 2005 and 2017. The median duration of follow-up for survivors was 52.5 months. The cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were similar, at 39% and 14%, respectively, for haplo-HSCT compared with 50% and 16% for MUD HSCT (P not significant). Haplo-HSCT recipients had a lower cumulative incidence of moderate to severe chronic GVHD, at 22% (severe, 19%), compared with 31% (severe, 29%) for MUD HSCT recipients (P = .026). The time to onset of moderate to severe chronic GVHD was faster for haplo-HSCT recipients (213 days versus 280 days; P = .011). Among patients with grade II-IV acute GVHD, there was no significant between-group difference in organ involvement, with skin the most affected (75% for haplo-HSCT versus 70% for MUD HSCT), followed by the gastrointestinal tract (71% versus 69%) and liver (14% versus 17% MUD). For chronic GVHD, haplo-HSCT recipients had less involvement of the eyes (46% versus 75% for MUD; P < .001) and of the joints/fascia (12% versus 36%; P = .001). Also for cGVHD patients, haplo-HSCT recipients and MUD HSCT recipients had similar all-cause mortality (22% versus 18%; P = .89), but the former were more likely to be off immunosuppression at 2 years post-HCT (63% versus 43%; P = .03) compared with MUD. 相似文献
12.
《Biology of blood and marrow transplantation》2020,26(3):600-605
Acute graft-versus-host disease (GVHD) contributes to poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Data are limited regarding the economic burden of acute GVHD, particularly steroid-refractory or high-risk (SR/HR) disease. This retrospective analysis of the Premier Healthcare Database reports inpatient healthcare resource utilization (HCRU), costs, and mortality during initial hospitalization for allogeneic HCT and through 100 days post-HCT among patients who developed acute GVHD, including a subgroup with SR/HR disease, compared with patients without GVHD. The analysis included adults discharged for first HCT between January 1, 2011, and June 30, 2016 (acute GVHD, n = 906; SR/HR acute GVHD, n = 158; no GVHD, n = 1529). During the initial hospitalization for HCT, patients with acute GVHD and SR/HR acute GVHD (n = 455 and 125, respectively) had significantly longer median lengths of stay (31 and 46 days versus 24 days) and higher median total costs ($153,849 and $205,880 versus $97,417) versus patients with no GVHD (n = 1529; P < .0001 for all). During the 100-day post-HCT period, patients with acute GVHD and SR/HR acute GVHD had higher readmission rates (78.3% and 77.2% versus 28.3%; P < .0001) and inpatient mortality rates (20.2% and 35.4% versus 8.9%; P < .0001) versus patients with no GVHD. In summary, acute GVHD, especially SR/HR disease, is associated with longer inpatient stays, higher readmission rates, and higher inpatient mortality compared with no GVHD. 相似文献
13.
《Biology of blood and marrow transplantation》2013,19(4):602-606
The role of allogeneic blood or marrow transplantation (alloBMT) for peripheral T cell lymphoma (PTCL) remains to be defined. There is growing interest in reduced-intensity conditioning (RIC) regimens and/or utilization of human leukocyte antigen haploidentical (haplo) grafts given concerns about treatment-associated toxicities and donor availability. We reviewed the outcomes of 44 consecutive, related donor alloBMTs for PTCL performed at Johns Hopkins Hospital from 1994 to 2011, including 18 RIC/haplo alloBMTs. Patients receiving RIC (n = 24) were older, with median age of 59 years (range, 24 to 70), than patients receiving myeloablative conditioning (MAC, n = 20), with median age of 46 years (range, 18 to 64), P = .01. The median age at RIC/haplo alloBMT was 60 years. The estimated 2-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 26% to 55%) and overall survival (OS) was 43% (95% CI, 28% to 59%). In older patients (≥60, n = 14), the estimated 2-year PFS and OS were 38% (95% CI, 18% to 79%) and 45% (95% CI, 24% to 86%), respectively. On unadjusted analysis, there was a tendency toward superior outcomes for alloBMT in first remission versus beyond first remission, with an estimated 2-year PFS of 53% (95% CI, 33% to 77%) versus 29% (95% CI, 9% to 45%), P = .08. On competing risk analysis, the 1-year cumulative incidence of relapse was 38% for MAC/HLA-identical alloBMTs and 34% for RIC/haplo alloBMTs. Estimated 1-year nonrelapse mortality was 10% for MAC and 8% for RIC (11% for RIC/haplo alloBMT). On unadjusted landmark analysis, patients with acute grade II-IV or chronic graft-versus-host disease (GVHD) had a 17% probability of relapse (95% CI, 0% to 39%), compared with 66% (95% CI, 48% to 84%) in patients without GVHD, P = .04. Utilization of RIC and alternative donors expands treatment options in PTCL to those who are older and unable to tolerate high-dose conditioning, with outcomes comparable with approaches using myeloablative regimens and HLA-matched donors. AlloBMT may be appropriate in first remission in select high-risk cases. 相似文献
14.
《Biology of blood and marrow transplantation》2014,20(9):1440-1443
Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor–mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34+ cells was 3.4 × 106/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34+ selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated. 相似文献
15.
《Biology of blood and marrow transplantation》2020,26(7):1298-1302
Antithymocyte globulin (ATG) is used to reduce the incidence and severity of graft-versus-host disease (GVHD) with hematopoietic cell transplantation, yet optimum dosing has yet to be determined. We have previously demonstrated that 2.5 mg/kg ATG in conditioning can reduce the incidence of GVHD in unrelated donor transplants. Recent literature has suggested that ATG dosing based on absolute lymphocyte count (ALC) could lead to more optimum exposure of the drug. We sought to determine if ALC at the time of transplant could impact clinical outcomes. We conducted a retrospective single-center study analyzing all consecutive patients at The Ottawa Hospital who received a matched unrelated donor stem cell transplant with ATG between 2009 and 2014. Patients received rabbit ATG (thymoglobulin) at 0.5 mg/kg on day –2 and 2.0 mg/kg on day –1. Univariate and multivariate analyses were used to determine if any patient- or transplant-related factors, including weight, ALC, and total ATG dose given, impacted GVHD, relapse, or mortality. In total, 111 patients met inclusion, with a median age of 50 years (range, 19 to 70). The most common diagnoses were acute myelogenous leukemia (43%), Myelodysplasia/myeloproliferative neoplasms (13%), and lymphoma (12%). The median weight at time of conditioning was 80.3 kg (range, 45 to 216). The median ALC on the first day of ATG administration was 0.1 × 109/L (range, 0 to 190). The median total dose of ATG received was 201 mg (range, 112 to 540 mg). The incidence of acute and chronic GVHD was 35.1% and 21.6%, respectively. In the multivariate model, the actual dose of ATG given to patients was not associated with GVHD (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.99 to 1.25; P = .07), relapse (HR, 1.13; 95% CI, 0.98 to 1.30; P = .1), or mortality (HR, 1.09; 95% CI, 0.92 to 1.28; P = .32). Similarly, the pretransplant ALC was not associated with GVHD (HR, 1; P = .82), relapse (HR, 1; P = .90), or mortality (HR, 1; P = .39). If patients had received ALC-based dosing according to previously published work (Admiraal et al., Lancet Haematol 2017), the mean total dose of ATG received would have been 1205 mg, more than 5 times the mean dose that was actually given based on weight. With GVHD outcomes being similar to that published by Admiraal et al. and ALC not independently associated with outcomes in our study, further studies are still needed to compare standard weight-based dosing to ALC-based dosing of ATG in matched unrelated donor stem cell transplant. 相似文献
16.
《Biology of blood and marrow transplantation》2014,20(10):1573-1579
We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor. 相似文献
17.
《Biology of blood and marrow transplantation》2013,19(1):75-81
The value of prophylactic donor lymphocyte infusion (pDLI) is unclear and differs among diseases and transplantation protocols. Experience with this approach in patients with acute leukemia undergoing hematopoietic cell transplantation (HCT) with an alemtuzumab-incorporating conditioning protocol is lacking. We conducted a single-center prospective study to investigate the applicability and efficacy of prophylactic donor lymphocyte infusion (pDLI) in patients with leukemia undergoing HCT with a low-dose alemtuzumab-containing conditioning regimen. Inclusion criteria were high-risk acute myelogenous leukemia, acute lymphoblastic leukemia, or increasing mixed chimerism. All patients included were tapered off of immunotherapy. Exclusion criteria were a history of ≥grade II or active graft-versus-host disease (GVHD). Of the 56 consecutive patients who underwent HCT with an alemtuzumab-containing regimen, 15 patients (8 with acute myelogenous leukemia and 7 with acute lymphoblastic leukemia) met the study inclusion criteria and received prophylactic DLI (total of 45 infusions) from 7 sibling donors and 8 unrelated donors. The first infusion was given at a median of 162 days posttransplantation. The median number of DLIs was 3, and the median cumulative CD3+ cell dose was 2 × 106cells/kg. Six of the 8 patients (75%) who received pDLI while in mixed chimerism converted to stable, complete donor chimerism. Some 47% of DLI recipients developed GVHD (4 acute GVHD and 3 with chronic GVHD) after a median cumulative dose of 2 × 106 CD3+ cells/kg. After a median follow-up of 575 days, 11 (73%) pDLI recipients were alive. All 4 deaths were due to GVHD-related causes. None of the patients who received pDLIs relapsed. Patients with leukemia who received low-dose pDLI after conditioning with alemtuzumab are at low risk for relapse; however, this approach is associated with a relatively high incidence of severe GVHD. 相似文献
18.
《Biology of blood and marrow transplantation》2020,26(8):1459-1468
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival. 相似文献
19.
《Biology of blood and marrow transplantation》2013,19(3):486-491
Although the use of cord blood transplantation (CBT) is increasing, the optimal methods for conditioning and graft-versus-host disease (GVHD) prophylaxis remain to be established. Among previous reports, the Institute of Medical Science, University of Tokyo (IMSUT) has reported remarkably favorable results of CBT for hematologic malignancies as a single-institute experience. The aim of the present multicenter prospective study was to assess the safety and efficacy of CBT performed precisely according to IMSUT transplantation procedures. Thirty-three adult patients with hematologic malignancies, such as acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome, either lacking an HLA-identical sibling/HLA-matched unrelated donor or requiring urgent transplantation were enrolled. Conditioning consisted of total body irradiation (12 Gy), cytarabine, and cyclophosphamide. Cyclosporine A and methotrexate were used for GVHD prophylaxis. Diagnoses were acute leukemia in 26 patients, chronic myelogenous leukemia in 4, and myelodysplastic syndrome in 3; 12 patients were in first complete remission, and the others were in advanced stages at the time of CBT. Thirty-one patients achieved engraftment, and the cumulative incidence of grade II-IV acute GVHD was 45% (95% confidence interval, 28%-62%). With a median follow-up of 46.2 months in 16 surviving patients, the 1-year cumulative incidence of nonrelapse mortality was 15% (95% confidence interval, 5%-30%). Causes of nonrelapse mortality were infection (n = 4) and graft failure (n = 1). The overall and disease-free survival rates were 51% (95% CI, 34%-68%) and 42% (95% CI, 26%-59%), respectively. These results suggest that the IMSUT CBT procedures can safely provide a high disease-free survival rate in patients with high-risk hematologic malignancies. 相似文献
20.
Betul Oran Sergio Giralt Rima Saliba Chitra Hosing Uday Popat Issa Khouri Daniel Couriel Muzaffar Qazilbash Paolo Anderlini Partow Kebriaei Shubhra Ghosh Antonio Carrasco-Yalan Ernesto de Meis Athanasios Anagnostopoulos Michele Donato Richard E Champlin Marcos de Lima 《Biology of blood and marrow transplantation》2007,13(4):454-462
Reduced-intensity conditioning has extended the use of allogeneic hematopoietic stem cell transplantation (HSCT) to patients otherwise not eligible for this treatment due to older age or frailty. One hundred twelve acute myelogenous leukemia/myelodysplastic syndromes patients received fludarabine and melphalan (FM) conditioning with allogeneic HSCT. Most patients (73%) were not in remission. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini-methotrexate. Median age was 55 years (range, 22-74). Donors were related (53%) and unrelated (47%). Median follow-up of surviving patients (n = 43) was 29.4 months (range, 13.1-87.7). The complete remission (CR) rate was 82%. Estimates of 2-year survival were 66%, 40%, and 23% for patients in CR, with active disease without and with circulating blasts at HSCT, respectively. In multivariate analysis, survival was negatively influenced by active disease at HSCT and development of grade II-IV acute GVHD. Presence of circulating blasts at HSCT negatively influenced freedom from disease progression. Incidence of nonrelapse mortality (NRM) was significantly higher for patients with active disease, but was not influenced by patient age. Patients in CR had a day-100 and 2-year NRM of 0% and 20%, respectively. Use of unrelated donors increased the risk of NRM only among patients with active disease. FM and HSCT elicited long-term disease control in a significant fraction of this high-risk cohort. 相似文献