Incidence,Risk Factors,and Long-Term Outcomes of Sclerotic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Sclerotic chronic graft-versus-host disease (sclGVHD) is associated with significant morbidity and a poor quality of life. We reviewed 502 patients diagnosed with chronic GVHD and analyzed the incidence and risk factors of sclGVHD and long-term outcomes and immunosuppressive therapy (IST) cessation in patients with sclGVHD. With a median onset at 18 months the cumulative incidence of sclGVHD was estimated at 22.6% at 5 years (95% confidence interval, 18.6% to 26.8%). Univariate and multivariate analysis identified 2 risk factors for sclGVHD: non-T cell depletion (hazard ratio [HR] 9.09, P < .001) and peripheral blood stem cell (HR 3.87, P < .001). Overall survival (OS) at 5 years was significantly better in the sclGVHD group (88.1%) compared with the non-sclGVHD group (62.7%; P < .001), as were nonrelapse mortality (7.3% versus 21.5% at 5 years) and relapse rates (9.1% versus 19.3% at 5 years). There was no difference in the rate of IST cessation at 5 years (44.8% versus 49.9%, P = .312), but there was a trend of longer IST duration in the sclGVHD group compared with the non-sclGVHD group (median 71.6 months versus 62.9 months). In conclusion, T cell depletion and graft source affect the risk of sclGVHD. SclGVHD did not adversely affect long-term outcomes or IST duration.     

Gastrointestinal Acute Graft-versus-Host Disease in Children: Histology for Diagnosis,Mesenchymal Stromal Cells for Treatment,and Biomarkers for Prediction of Response

Steroid-nonresponsive acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation carries a poor prognosis. Various groups have reported beneficial effects of mesenchymal stromal cell (MSC) infusion as salvage treatment. Response to treatment is typically evaluated using the diagnostic clinical criteria for aGVHD. In this study, we evaluated the usefulness of additional gastrointestinal biopsy specimens paired with serum biomarkers. In a cohort of 22 pediatric patients, persistent or recurrent diarrhea was seen in 18 children treated with MSC infusion for steroid-refractory aGVHD. To exclude other causes of gastrointestinal pathology, patients were biopsied for histological analysis. Eight of 12 patients exhibited residual tissue damage and villous atrophy, but no active aGVHD. Serum biomarkers have been identified as an alternative tool for monitoring the response to aGVHD treatment. The value of biomarkers for inflammation, tissue, and endothelial cell damage was evaluated in our cohort. Although predictive of response to treatment and survival, these markers lack the necessary specificity and sensitivity to predict response to MSC therapy. Objective endpoints for clinical trials on the treatment of steroid-refractory aGVHD remain to be defined. Thus, we recommend including biopsies and biomarkers to discriminate between ongoing aGVHD and postinflammatory malabsorption.     

Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation

Idiopathic cytopenias are frequently observed in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported the effect of graft-versus-host disease (GVHD) on bone marrow (BM) in murine models, indicating that the osteoblast injury mediated by donor T cells was associated with bone marrow suppression and delayed immune reconstitution. In this study, we prospectively evaluated the relevance of these findings in 51 patients. Patients with chronic GVHD manifested the loss of osteoblasts, contributing to cytopenic symptoms (P = .0427 compared with patients without cytopenic symptoms). The loss of osteoblasts was significantly associated with the extensive type of chronic GVHD (P = .012), and flow cytometric analyses revealed lower numbers of CD19⁺ B cells and a significantly increased CD4 to CD8 ratio (P = .0002) in these patients. Our data, for the first time to our knowledge, summarize the detailed analyses of the effect of GVHD on BM in the clinical allo-HSCT patients.     

Incidence and Outcomes of Bacterial Bloodstream Infections during Acute Graft-versus-Host Disease Involving the Gastrointestinal Tract after Hematopoietic Cell Transplantation

Despite the association of acute graft-versus-host disease (aGVHD) and bacterial bloodstream infections (BSIs) in hematopoietic cell transplant (HCT) recipients, relatively little is known about BSIs, specifically during gastrointestinal (GI) tract aGVHD (aGHVD-GI). The purpose of this study was to evaluate the incidence, risk factors, and mortality of BSIs complicating aGVHD-GI. This was a retrospective review of adult HCT recipients with grades I to IV aGVHD-GI between January 2009 and October 2017 at Oregon Health and Sciences University. BSIs occurring within 30 days of onset of aGVHD-GI were included. BSIs were categorized as "clinical" or "surveillance" based on chart review. A subgroup analysis of patients with grade IV aGVHD-GI examined potential BSI risk factors and cumulative survival at 30 and 45 days after onset of aGVHD-GI. Included were 229 patients. There were 45 unique BSIs in 39 patients (17%): 31 clinical (68.9%) and 14 surveillance (32.1%). The median time from aGVHD-GI onset to BSI was 18.5 days. BSIs were significantly more common during grade IV aGVHD-GI compared with grades I, II, or III. Fifty-two organisms were isolated during BSIs: 23 (44.2%) gram-positive and 29 (55.8%) gram-negative. Sixteen BSIs (36%) occurred during antibiotic exposure, and those were more likely to be caused by multidrug-resistant organisms. Prior BSI occurring between the time of HCT and onset of aGVHD-GI and receipt of etanercept for steroid-refractory aGVHD-GI were independently associated with BSI. Eight patients, all with grade IV aGVHD, representing 30.8% of patients with BSI in this subgroup, experienced infection-associated mortality. Cumulative survival at days 30 and 45 after onset of grade IV aGVHD-GI was similar among patients with and without BSI. BSI is a common complication of grade IV aGVHD-GI, resulting in significant infection-associated mortality. Interventions targeting those at highest risk may be warranted.     

Role of Acute Graft-Versus-Host Disease in the Risk of Bacteremia and Invasive Fungal Disease after Allogeneic Hemopoietic Stem Cell Transplantation in Children. Results from a Single-Center Observational Study

Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P < .0001, respectively). Finally, infectious episodes occurred late after HSCT, especially in presence of severe aGVHD, and bacteremias were 3 to 6 times more frequent than IFD. These data may be important to design management strategies of infections in pediatric allogeneic HSCT.     

Extramedullary Relapse of Acute Leukemia after Haploidentical Hematopoietic Stem Cell Transplantation: Incidence,Risk Factors,Treatment, and Clinical Outcomes

We examined the incidence, risk factors, treatment, and clinical outcomes of extramedullary relapse (EMR) in 961 acute leukemia patients undergoing HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between 2002 and 2013. Multiple control subjects were selected at random from the same cohort and matched to EMR cases for diagnosis, disease status at HSCT, age at the time of the HSCT, and year of HSCT. Forty patients exhibited EMR, with a median time to EMR of 207 days. The cumulative incidence of EMR was 4.0% at 3 years, and the incidence was higher in acute lymphoblastic leukemia patients compared with acute myeloid leukemia patients (5.6% versus 2.4%). In the multivariate analysis, non–complete remission (CR) status at HSCT (hazard ratio [HR] = 4.6; P = .018) and non–chronic graft-versus-host disease after HSCT (HR = 3.2; P < .001) were the independent risk factors for EMR after haplo-HSCT. Twenty-seven patients received combination treatments, and the proportion of patients who achieved CR was higher than those who received single treatment. Multifocal involvement at EMR (HR = 2.7; P = .024) and non-CR after EMR treatments (HR = 4.6; P < .001) were the independent risk factors for poor survival rates among EMR patients. We found that graft-versus-leukemia effect may help to prevent EMR after haplo-HSCT.     

Comparison of Chimerism and Minimal Residual Disease Monitoring for Relapse Prediction after Allogeneic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.     

Donor Lymphocyte Infusion for the Treatment of Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Because the efficacy of donor lymphocyte infusion (DLI) for acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains uncertain, especially in the Asian population, a nationwide registry study was retrospectively performed by the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation to identify the factors affecting the patient survival after DLI. Among 143 adult AML patients who received DLI for the treatment of first hematological relapse after HSCT, the overall survival rates at 1 year, 2 years, and 5 years were 32% ± 4%, 17% ± 3%, and 7% ± 3%, respectively. Complete remission (CR) at the time of DLI, which was obtained in 8% of the patients, was the strongest predictive factor for survival after DLI. Therefore, long-term survival after DLI was achieved almost exclusively in patients who successfully achieved a CR before DLI, indicating the limited efficacy of DLI in a minority of patients.     

Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I/IIa Clinical Trial

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).     

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.     

Human Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results. Case reports, reviews, articles focusing on inherited chromosomally integrated HHV-6, poster presentations, and articles not published in English were excluded. The remaining 467 articles were reviewed for the following requirements: a statistical analysis of HHV-6B reactivation and aGVHD was described, HHV-6B reactivation was defined by PCR, and blood (plasma, serum, or peripheral blood mononuclear cells) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n?=?33). Publications were assigned to 1 of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n?=?14), (2) aGVHD was analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n?=?1), and (3) analysis without temporal specification (n?=?18). A statistically significant association (P?<?.05) between HHV-6B reactivation and aGVHD was observed in 10 of 14 studies (71%) in group 1, 0 of 1 study (0%) in Group 2, and 8 of 18 studies (44.4%) in Group 3. Of the 14 studies that analyzed HHV-6B as a risk factor for subsequent aGVHD, 11 performed a multivariate analysis and reported a hazard ratio, which reached statistical significance in 9 of these studies. Meta-analysis of these 11 studies demonstrated a statistically significant association between HHV-6B and subsequent grades II to IV aGVHD (hazard ratio, 2.65; 95% confidence interval, 1.89 to 3.72; P?<?.001). HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.     

Comparison of Outcomes after Two Standards-of-Care Reduced-Intensity Conditioning Regimens and Two Different Graft Sources for Allogeneic Stem Cell Transplantation in Adults with Hematologic Diseases: A Single-Center Analysis

Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v. busulfan 3.6 mg/kg/day for 2 days + rabbit antithymocyte globulin 2.5 mg/kg/day for 2 days) supported by peripheral blood stem cells (PBSCs) and the TCF regimen (fludarabine 200 mg/m² for 5 days + cyclophosphamide 50 mg/kg for 1 day + low-dose [2 Gy] total body irradiation) supported by dUCB units are currently the most widely used RIC regimens in many centers and could be considered standard of care in adults eligible for an RIC allo-SCT. Here we compared, retrospectively, the outcomes of adults patients who received the FB2A2-PBSC RIC regimen (n = 52; median age, 59 years; median follow-up, 19 months) and those who received the dUCB-TCF RIC regimen (n = 39; median age, 56 years; median follow-up, 20 months) for allo-SCT between January 2007 and November 2010. There were no significant between-group differences in patient and disease characteristics. Cumulative incidences of engraftment, acute grade II-IV and chronic graft-versus-host disease were similar in the 2 groups. The median time to platelet recovery, incidence of early death (before day +100), and 2-year nonrelapse mortality were significantly higher in the dUCB-TCF group (38 days versus 0 days [P <.0001]; 20.5% versus 4% [P = .05], and 26.5% versus 6% [P = .02], respectively). The groups did not differ in terms of 2-year overall survival (62% for FB2A2-PBSC versus 61% for dUCB-TCF), disease-free survival (59% versus 50.5%), or relapse incidence (35.5% versus 23%). In multivariate analysis, the presence of a lymphoid disorder was associated with a significantly higher 2-year overall survival (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87; P = .02), whereas patients receiving a FB2A2-PBSC allo-SCT had a significantly lower 2-year nonrelapse mortality (hazard ratio, 0.24; 95% confidence interval, 0.1-0.7; P = .01). There were no factors associated with higher 2-year disease-free survival or lower relapse incidence. This study suggests that the dUCB-TCF regimen provides a valid alternative in adults lacking a suitable donor and eligible for RIC allo-SCT. Prospective and randomized studies are warranted to establish the definitive role of dUCB RIC allo-SCT in adults. In addition, strategies for decreasing nonrelapse mortality after dUCB RIC allo-SCT are urgently needed.     

Wilms' Tumor 1 Gene Expression Using a Standardized European LeukemiaNet-Certified Assay Compared to Other Methods for Detection of Minimal Residual Disease in Myelodysplastic Syndrome and Acute Myelogenous Leukemia after Allogeneic Blood Stem Cell Transplantation

Overexpression of the Wilms' tumor 1 (WT1) gene is informative in many patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages, WT1 has not broadly been established as a marker for minimal residual disease (MRD) monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to limited patient numbers, differing sample sources, and nonstandardized in-house methods. To estimate the value of WT1 as an MRD marker, we serially quantified PB WT1 expression using a standardized European LeukemiaNet-certified assay in 59 patients with AML and MDS after allo-HSCT. We compared its performance with routine methods such as chimerism, XY-fluorescence in situ hybridization (FISH), disease-specific cytogenetic, and molecular analyses, which were accessible in 100%, 34%, 68%, and 37%, respectively. Twenty-four patients (41%) relapsed within a median of 126 days after allo-HSCT, and 20 of them showed at least 1 elevated WT1 value above the validated cutoff. The other 35 patients (59%) remained in complete remission, and only 1 patient had a transient increase in WT1 expression. This reflects a sensitivity of 83% and a specificity of 97% for WT1 and appears to be favorable compared with the sensitivities and specificities observed for chimerism (33% and 91%), XY-FISH (67% and 73%), cytogenetic (33% and 77%), and molecular (78% and 85%) analyses. Further supporting its predictive impact, elevated WT1 expression prompted an earlier BM biopsy and consecutively the diagnosis of relapse in 62% of patients. The results of this real-life experience imply that PB WT1 expression is measurable by a standardized assay and predicts imminent relapse after allo-HSCT with high sensitivity and specificity in most patients with AML and MDS.     

Increased Health Care Utilization and Costs during Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndromes in Adolescents and Young Adults Compared with Children: A Multicenter Study

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute leukemia and myelodysplastic syndromes (MDS) but is associated with significant cost. Compared with children (age <15 years), adolescents and young adults (AYA; age 15 to 39 years) undergoing HCT have an increased risk for transplantation-related complications. However, whether such complications translate into increased resource utilization and costs during HCT remains unknown. Therefore, we conducted a multicenter database study using the Pediatric Health Information System database, an administrative database containing resource utilization data from 49 US tertiary children's hospitals to compare inpatient costs and resource utilization in children and AYA undergoing HCT for acute leukemia and MDS. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients and transplantation-related complications occurring up to 1 year post-HCT. We identified 1693 HCT recipients at pediatric centers between January 2010 and September 2014. Eighty percent of the total costs (from admission for HCT up to 1 year post-HCT) occurred during the initial transplantation admission. During initial admission, although AYA and children had a similar median length of stay (LOS) of 43 days, AYA incurred significantly greater adjusted costs ($338,458 versus $275,723; P < .001) and costs per hospital day ($7122 versus $5838; P < .001). Median total costs and costs per day during subsequent time periods post-HCT were also significantly greater in the AYA group. In multivariable analysis, increasing age at HCT, LOS, use of cord blood or an unrelated donor, occurrence of any graft-versus-host disease, infection, and use of dialysis or mechanical ventilation were significant drivers of increased cost at initial admission. In conclusion, allogeneic HCT for acute leukemia and MDS is associated with higher costs in AYA recipients than in children. Therefore, directing efforts and resources aimed at reducing HCT-related costs may be advantageous in this high-risk group.     

Prior Gemtuzumab Ozogamicin Exposure in Adults with Acute Myeloid Leukemia Does Not Increase Hepatic Veno-Occlusive Disease Risk after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis

Gemtuzumab ozogamicin (GO) therapy before allogeneic hematopoietic cell transplantation (alloHCT) has been historically associated with an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in patients with acute myeloid leukemia (AML). The current analysis examined VOD/SOS risk and outcomes in a cohort of patients who in recent years were reported to the Center for International Blood and Marrow Transplant Research. Adults with AML who had GO exposure before myeloablative alloHCT were matched 1:4 by age and disease status at transplant to recipients without GO exposure (control subjects). One hundred thirty-seven patients with GO exposure and 548 matched control subjects who underwent alloHCT between 2008 and 2011 were included in this analysis. With a median ∼8-year follow-up of survivors, the 5-year overall survival probability was similar in the 2 cohorts: 38% and 38% in the GO-exposed versus control groups (P = .97). Incidence of VOD/SOS and severe VOD/SOS, respectively, at 100 days was 4% (95% confidence interval [CI], 1% to 7%) and 3% (95% CI, 1% to 6%) in GO-exposed patients and 3% (95% CI, 2% to 5%) and 1% (95% CI, 0% to 2%) in control subjects. Correspondingly, among patients who developed VOD/SOS, 1-year survival probability after VOD/SOS diagnosis was 33% (95% CI, 5% to 72%) and 27% (95% CI, 11% to 47%; P = .78). In multivariate analyses, GO exposure before alloHCT was not associated with an increased risk of VOD/SOS (odds ratio, 1.10; P = .85) or death (hazard ratio, 1.08; P = .57). Three deaths (3%) in the GO group and 3 deaths (<1%) in the control group were attributed to VOD/SOS. Our results suggest that GO treatment before myeloablative alloHCT in the recent era is not associated with an increased risk of post-transplant VOD/SOS or death.     

Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P = .005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P < .001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P = .78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P = .30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P = .0001) or CR2 (HR, 1.51; P = .02) compared with CR1, female recipients (HR, 0.71; P = .006), adverse cytogenetics (HR, 2.52; P = .01), and prior graft-versus-host disease (HR, 1.31; P = .04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P = .97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P = .15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types.