Total Body Irradiation-based Myeloablative Conditioning Research Articles

Allogeneic stem cell transplant with TBI-based myeloablative conditioning in adolescents and young adults with Philadelphia chromosome-negative ALL treated with pediatric protocols

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16–39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post-transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.

Prognostic factors of children and adolescents with T-cell acute lymphoblastic leukemia after allogeneic transplantation.

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high-risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T-cell ALL (T-ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20years old who underwent their first HSCT for T-ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow-up period was 6.9years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5-year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p<0.001). Among patients receiving HSCT at CR1, grade II-IV acute graft versus host disease was associated with worse overall and LFS than grade 0-I (5yLFS 69.5% vs. 82.1%, p=0.026) mainly due to high non-relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total-body irradiation-based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p=0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T-ALL.

Impact of Total Body Irradiation-Based Myeloablative Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-Analysis

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation (TBI)-based and chemotherapy only-based myeloablative transplantation conditioning regimens have been applied, but the optimal regimen remains unclear. We performed a systematic review to assess the efficacy of TBI-based versus chemotherapy only-based myeloablative conditioning regimens. We searched PubMed, Embase, and Cochrane databases and meeting abstracts for all studies comparing TBI-based and chemotherapy only-based conditioning regimens in patients who underwent allo-HCT for ALL. Two authors independently reviewed all studies for inclusion and extracted data related to overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD). Eight studies were included in the final analysis. The overall methodological quality of the included studies was optimal. TBI-based regimens showed evidence of benefit compared with chemotherapy only-based conditioning regimens in terms of relapse (relative risk [RR], 0.82; 95% confidence interval [CI], 0.72 to 0.94; 6 studies, 5091 patients), OS (hazard ratio [HR], 0.76; 95% CI, 0.64 to 0.89; 7 studies, 4727 patients), and PFS (HR, 0.74; 95% CI, 0.63 to 0.85; 7 studies, 4727 patients). The TBI-based regimen did not increase the likelihood of grade II-IV acute GVHD (RR, 1.12; 95% CI, 0.92 to 1.36; 5 studies, 4996 patients) or chronic GVHD (RR, 1.10; 95% CI, 1.00 to 1.21; 5 studies, 4490 patients), or NRM (RR, 0.94; 95% CI, 0.69 to 1.28; 6 studies, 4522 patients). However, TBI-based regimens were associated with an increased risk of grade III-IV acute GVHD (RR, 1.29; 95% CI, 1.01 to 1.63; 3 studies, 3675 patients). A subgroup comparison of patients age ≥16 years showed similar results. This systematic review represents evidence supporting the use of TBI-based conditioning regimen in patients undergoing allo-HCT for ALL who are candidates for myeloablative conditioning, as it offers better OS, PFS, and less relapse with acceptable NRM.

Improved Outcomes of Haploidentical Hematopoietic Cell Transplantation with Total Body Irradiation-Based Myeloablative Conditioning in Acute Lymphoblastic Leukemia

The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI)-based versus chemotherapy (CT)-based MAC regimens in patients with acute lymphoblastic leukemia (ALL). The study included 427 patients who underwent first haplo-HCT with post-transplantation cyclophosphamide (PTCy), following TBI-based (n=188; 44%) or CT-based (n=239; 56%) MAC. The median patient age was 32 years. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most frequently used TBI- and CT-based regimens, respectively. In the TBI and CT cohorts, 2-year leukemia-free survival (LFS) was 45% versus 37% (P=.05), overall survival (OS) was 51% versus 47% (P=.18), relapse incidence (RI) was 34% versus 32% (P=.44), and nonrelapse mortality (NRM) was 21% versus 31% (P < .01). In the multivariate analysis, TBI was associated with lower NRM (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33 to 0.86; P=.01), better LFS (HR, 0.71; 95% CI, 0.52 to 0.98; P =.04), and increased risk for grade II-IV acute graft-versus-host disease (GVHD) (HR, 1.59; 95% CI, 1.08 to 2.34; P=.02) compared with CT-based MAC. The type of conditioning regimen did not impact RI, chronic GVHD, OS, or GVHD-free, relapse-free survival after adjusting for transplantation-related variables. TBI-based MAC was associated with lower NRM and better LFS compared with CT-based MAC in patients with ALL after haplo-HCT/PTCy.

Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for T Cell Acute Lymphoblastic Leukemia: A Report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting.

Role of Initiating Supportive Care Preceding Veno-occlusive Disease Diagnosis Following Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Severe veno-occlusive disease (VOD) following hematopoietic stem cell transplantation has a high mortality rate. The clinical course of VOD, role of preemptive and aggressive supportive care, and outcomes were investigated in a retrospective study from 2007 to 2014. Defibrotide was not available in all but one case with VOD at our center during the study. Forty-nine allogeneic transplants with intravenous busulfan-based or total body irradiation-based myeloablative conditioning were included. The median after hematopoietic stem cell transplantation day for suspicion of developing VOD (pre-VOD phase) was 6 due to weight gain, hepatomegaly, and/or mild increase in total bilirubin without fulfilling the modified Seattle criteria in 22 cases (45%). Despite fluid restriction, aggressive diuresis, and fresh frozen plasma infusions, 16 patients (33%) developed VOD by +10 days. Five cases (31%) had severe, 9 (56%) moderate, and 2 (13%) mild VOD. Eight cases (50%) required transfer to intensive care. One patient was given defibrotide, which was later discontinued due to concerns of adverse effects. Day +100 survival was 100% with complete resolution of VOD. Preemptive and aggressive supportive care could help achieve favorable outcomes in VOD and may have ameliorated the severity. This approach may be combined with other measures in the prevention/treatment of VOD.

Prophylaxis and Treatment Strategy for Endothelial Cell Damages after Hematopoietic Cell Transplantation in Children

Introduction Sinusoidal obstruction syndrome (hSOS) and thrombotic microangiopathy (TMA) are life-threatening complications caused by endothelial cell damage (ECD) associated with hematopoietic cell transplantation (HCT). Danaparoid sodium (DS) is a heparinoid comprising a mixture of low molecular weight glycosaminoglycans with anti-Xa and anti-IIa effects, which prevent fibrin formation. Recombinant thrombomodulin (rTM) comprises the active extracellular domain of thrombomodulin and inactivates coagulation by binding to thrombin. Both of them were expected to play crucial roles in the management of disseminated intravascular coagulation (DIC) and ECD after HCT. Objectives We aimed to evaluate the efficacy and feasibility of DS for prophylaxis and rTM for the treatment of hSOS and TMA after HCT in children. Methods Between January 2011 and December 2017, 91 children (median age 7.6 years, range 0.6–18.2; with hematologic malignancies [n = 54], solid tumors [n = 9], or benign diseases [n = 28]) underwent 118 consecutive HCTs (9 autologous and 109 allogeneic settings; busulfan-based myeloablative conditioning [n = 23], total body irradiation-based myeloablative conditioning [n = 35], or reduced intensity [n = 60]) at our institution. All of them were treated prophylactically with DS (intravenously injection, 30 international units [IU] per kg of body weight, twice a day from the initiation of the conditioning regimen to day 50 after HCT) to prevent ECD. Any patient who developed ECD despite prophylaxis were treated with rTM (intravenous drip infusion, 380 IU per kg, once a day). We reviewed their clinical records and evaluated the efficacy and feasibility of rTM for these children. Results Nine patients developed SOS (severe 5, moderate 1, and mild 3) at a median of 19 days after HCT (range, 6–173), and 6 patients developed TMA at median day 38 (range, 27–106). The cumulative incidences of SOS and TMA at 100 days were 6.8% and 4.4%, respectively. A total of 17 patients received 18 courses of rTM for complications after HCT. The median dose and duration of rTM treatments were 367 IU/kg/day (range, 189–404) and 7 days (range, 3–22), repectively. rTM treatments initiated at a median of 30 days after HCT (range, 6–173). The cause of rTM administration included SOS (n = 9), infection with DIC (n = 4), TMA (n = 3), or engraftment syndrome with DIC (n = 2). All these complications were resolved or improved by rTM treatment along with supportive care. Among the 17 patients receiving rTM treatment, no hemorrhagic events or deaths due to HCT-related toxicity were observed; however, 7 died of their underlying disease. Multivariate analysis revealed that neither SOS nor TMA had a negative impact for transplant outcome. Conclusion DS and rTM are effective and safe for the management of ECD after HCT in children. A larger multicenter prospective study is warranted to confirm these findings.

Determinants of Idiopathic Pneumonia Syndrome in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Transplantation with Total Body Irradiation-Based Myeloablative Conditioning

Determinants of Idiopathic Pneumonia Syndrome in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Transplantation with Total Body Irradiation-Based Myeloablative Conditioning

Allogeneic hematopoietic stem cell transplantation using myeloablative conditioning including total body irradiation for pediatric acute lymphoblastic leukemia: a single-center retrospective analysis

This study aimed to investigate the clinical outcomes of hematopoietic stem cell transplantation (HSCT) with total body irradiation-based myeloablative conditioning (TBI-MAC) in pediatric patients with acute lymphoblastic leukemia (ALL). We retrospectively examined patients with ALL who underwent HSCT with TBI-MAC from January 2000 to August 2016 at our institute. We enrolled 67 patients with a median follow-up period of 8 years. The 5-year event-free survival (EFS) and overall survival (OS) were 51.2% and 59.6%, respectively. At the first complete remission, HSCT exhibited significantly superior EFS and OS in our patients than that in patients with other diseases. We encountered 57.9% of patients with at least one late complication. Major late complications were short stature (26.3%) and hypogonadism (18.4%). While late complications were observed in several recipients of HSCT, late complication-related deaths occurred in three patients. The TBI-MAC regimen led to favorable clinical outcomes in pediatric patients with ALL who underwent HSCT. Thus, proper evaluation and management of late complications are mandatory.

Analysis of Real-world Data on Postremission Therapy for Acute Myeloid Leukemia With Intermediate Risk Cytogenetics in First Complete Remission

BackgroundWe retrospectively analyzed data from 310 patients with acute myeloid leukemia with intermediate-risk cytogenetics in first complete remission (CR1) to evaluate the usage and efficacy of various types of postremission therapy. Patients and MethodsCox regression with time-dependent covariates, landmark analysis, and competing risk models were used to estimate the outcomes and effects of treatment and patient- and disease-related risk factors. ResultsThe early relapse rate and early nonrelapse mortality (NRM) were 12.8% and 4.4%, respectively. In our study, 77.2% of patients completed postremission therapy: 44% received allogeneic hematopoietic cell transplantation (HCT), 20% completed treatment with high-dose cytarabine (HIDAC), and 13% completed treatment with intermediate-dose cytarabine. The 3-year overall survival rate was 67.5% for patients treated with HIDAC and 63.4% after HCT (P = .5876). The NRM and relapse rate at 3 years were 0% and 58.9% after HIDAC and 21.9% and 29.3% after HCT, respectively. HCT reduced the risk of relapse (hazard ratio, 0.6; 95% confidence interval, 0.36-0.98). Total body irradiation-based myeloablative conditioning increased NRM compared with busulfan-based conditioning (hazard ratio, 8.33; 95% confidence interval, 2.52-27.45). ConclusionMost patients with acute myeloid leukemia with intermediate-risk cytogenetics received allogeneic HCT, which decreased the risk of relapse but increased NRM, leading to a similar overall survival for patients who received HCT and HIDAC. Our data support the use of allogeneic transplantation for patients in CR1 from a human leukocyte antigen-matched related or unrelated donor after a busulfan-based myeloablative conditioning regimen as a primary strategy of postremission therapy for eligible younger patients.

Factors Influencing Pulmonary Toxicity in the Setting of Total Body Irradiation-Based Myeloablative Conditioning in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Factors Influencing Pulmonary Toxicity in the Setting of Total Body Irradiation-Based Myeloablative Conditioning in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Mustafa Abugideiri , Ronica H. Nanda , Charlotte Butker , Sungjin Kim , Elizabeth Butker , Mohammad K. Khan , Natia Esiashvili . 1 The George Washington University School of Medicine and Health Sciences, Washington, DC; 2 Radiation Oncology, Emory University, Winship Cancer Institute, Atlanta, GA; 3 Emory University, Atlanta, GA; 4 Biostatistics, Emory University, Winship Cancer Institute, Atlanta, GA

Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission

Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy in adult acute lymphoblastic leukemia (ALL), but there is genuine uncertainty regarding the optimal approach. To assess the effect of matched sibling donor vs. no donor status for adults with ALL in first complete remission (CR1). We performed a search of CENTRAL, MEDLINE and EMBASE electronic databases in September 2010 along with handsearching of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field. Review was performed by two authors, and Inclusion criteria included the following: controlled trials with donor vs. no donor comparison with assignment by genetic randomizationin adults with ALL in CR1. We extracted data on benefits (overall survival, progression-free survival) and harms (treatment-related mortality, relapse) of compared treatments. Adverse events were considered, but analysis of individual adverse events was not possible from the reported literature. We pooled summary results from each study using a random-effects model. We assessed heterogeneity. We performed subgroup analyses for disease risk categories. We performed sensitivity analyses according to methodological quality. A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi(2) 40.51, df = 6, P < 0.00001; I(2) = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review. The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens.

Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia In First Complete Remission: A Systematic Review and Meta-Analysis

AbstractAbstract 3511 Background:While multi-agent induction chemotherapy produces impressive complete remission rates, long term survival remains elusive for most patients with adult acute lymphoblastic leukemia (ALL). Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT), and allogeneic HCT represent potential treatment alternatives for post-remission therapy, but there is genuine uncertainty regarding the optimal approach. Objectives:To synthesize evidence from all existing randomized controlled trials with a donor vs. no donor comparison in adults with ALL in first complete remission. Our objectives were to determine whether or not there is a survival advantage with allogeneic HCT for ALL in CR1, and also to discern the benefit of this therapy according to disease risk subgroups. Search methods: A broad search of the Medline and Embase electronic databases was performed along with hand search of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field. Selection criteria: Include trials were those consisting of adults with ALL in CR1, and prospective randomized controlled trial (RCT) design with ‘genetic randomization’ (i.e. based on availability of matched sibling donor vs. not). Data collection and analysis: Data from relevant trials was abstracted and reviewed by two investigators independently. We extracted data on benefits (OS, PFS) and harms (treatment related mortality, relapse) of compared treatments. Time-to-event data (OS, PFS) were reported as hazard ratios (HR) and dichotomous data (relapse and NRM) were reported as risk ratios (RR). The summary results from each study were pooled under a random effects model. Heterogeneity was assessed both by visual inspection of the forest plots for each outcome, as well as by formal statistical testing for heterogeneity using the chi square and I2 test. Subgroup analyses were performed for disease risk categories. Sensitivity analyses were performed according to domains of methodological quality. Results:A total of 14 relevant trials were identified, consisting of a total of 3215 patients. There was a statistically significant overall survival advantage in favor of the donor vs. no donor group HR of 0.79 (95% CI 0.7 – 0.90; p = 0.0003). The following was observed according to disease risk: standard risk ALL (HR of 0.62 (95% CI 0.46 – 0.84), p = 0.002); high risk ALL (HR of 0.8 (95% CI 0.63 – 1.01), p = 0.06). There was also a statistically significant improvement in disease-free survival in the donor vs. no donor group HR of 0.78 (95% CI 0.66 – 0.92), p = 0.003. Those in the donor group realized a statistically significant reduction in primary disease relapse, RR 0.54 (95% CI 0.4 – 0.73), p < 0.0001, but at the cost of statistically significant increase in non-relapse mortality, RR 2.8 (95% CI 1.66 – 4.73; p = 0.001). There were no significant subgroup differences or heterogeneity demonstrated in sensitivity analyses according to methodological quality domains. Conclusion:The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in adults age greater than or equal to 15. This therapy offers superior overall survival, disease-free survival, significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. These data importantly are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning, and, therefore, can not be generalized to pediatric ALL, alternative donors including HLA mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens. [Display omitted] Forrest plot of overall survival according to donor vs. no-donor status. Disclosures:No relevant conflicts of interest to declare.

Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation

AbstractDonor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P = .27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P = .29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P = .27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD.