Database : MEDLINE
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[PMID]: 29512932
[Au] Autor:Huang K; Zhou DH; Li Y; Xu HG; Que LP; Chen C; Xue HM; Guo HX; Weng WJ; Huang SL; Fang JP
[Ad] Address:Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
[Ti] Title:Modified conditioning regimen improves outcomes of unrelated donor peripheral blood stem cell transplantation for ß-thalassaemia major patients.
[So] Source:Pediatr Blood Cancer;, 2018 Mar 07.
[Is] ISSN:1545-5017
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with ß-thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD-PBSCT). METHODS: A modified conditioning regimen based on intravenous busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin was performed in 50 consecutive childhood patients with ß-TM and a median age of 4.6 years (range, 2-12 years). According to Pesaro's classification, three classes of risk are identified using the criteria of degree of hepatomegaly, portal fibrosis, and quality of the chelation treatment. Patients with three adverse criteria constituted class III, none of the adverse criteria constituted class I, and one or two of the adverse criteria formed class II. Ten patients were class I, 36 class II, and four class III. All patients were transplanted with UDs containing 37 of 10/10 human leukocyte antigen (HLA)-matched pairs, 11 of 9/10 matched pairs, and two of 8/10 matched pairs. The median follow-up was 36 months (range, 9-96 months). RESULTS: All patients successfully achieved engraftment, two of whom developed persistent thrombocytopaenia. The incidence of acute graft-versus-host disease (aGVHD) grade III-IV and chronic graft-versus-host disease (cGVHD) were 12% and 8%, respectively. However, 8.3% of HLA-matched and 15.4% of HLA-mismatched patients developed aGVHD. The incidence of severe bacterial infections and fungal pneumonia was 12% and 20%, respectively. The 3-year overall survival, disease-free survival, graft rejection, and transplant-related mortality were 94%, 92%, 2%, and 6%, respectively. CONCLUSION: This modified conditioning protocol effectively improved outcomes of UD-PBSCT for patients with ß-TM.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher
[do] DOI:10.1002/pbc.27026

  2 / 5425 MEDLINE  
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[PMID]: 29490698
[Au] Autor:Xu L; Liu Z; Wu Y; Yang X; Cao Y; Li X; Yan B; Li S; Da W; Wu X
[Ad] Address:Department of Hematology, The First Affiliated Hospital of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100048, China.
[Ti] Title:Clinical evaluation of haploidentical hematopoietic combined with human umbilical cord-derived mesenchymal stem cells in severe aplastic anemia.
[So] Source:Eur J Med Res;23(1):12, 2018 Mar 01.
[Is] ISSN:2047-783X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). METHODS: Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan. GVHD was prevented using cyclosporine A, ATG, anti-CD25 monoclonal antibody, and mycophenolate material. RESULTS: The incidence of acute GVHD was 50%. The incidence of severe acute GVHD was not related to gender, age, donor-recipient relations, and patient/donor pair, while patient/donor pair (r = 0.541, P = 0.022) was significantly correlated with incidence of chronic GVHD. Upon follow-up for a median of 13 months, 5 of the 24 patients (20.8%) were dead. The survival rates at 3 and 6 months in all patients were 87.5% (21/24) and 83.3% (20/24), respectively. CONCLUSION: Cotransplantation of haplo-HSCs combined with UC-MSCs was an effective and safe approach for the treatment of patients with SAA. The appropriate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.1186/s40001-018-0311-3

  3 / 5425 MEDLINE  
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[PMID]: 29197676
[Au] Autor:Kebriaei P; Anasetti C; Zhang MJ; Wang HL; Aldoss I; de Lima M; Khoury HJ; Sandmaier BM; Horowitz MM; Artz A; Bejanyan N; Ciurea S; Lazarus HM; Gale RP; Litzow M; Bredeson C; Seftel MD; Pulsipher MA; Boelens JJ; Alvarnas J; Champlin R; Forman S; Pullarkat V; Weisdorf D; Marks DI; Acute Leukemia Committee of the CIBMTR
[Ad] Address:Department of Stem Cell Transplantation, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: pkebriaei@mdanderson.org.
[Ti] Title:Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia.
[So] Source:Biol Blood Marrow Transplant;, 2017 Dec 25.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher

  4 / 5425 MEDLINE  
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[PMID]: 29501779
[Au] Autor:Nieto Y; Thall PF; Ma J; Valdez BC; Ahmed S; Anderlini P; Popat U; Jones RB; Shpall EJ; Hosing C; Qazilbash M; Kebriaei P; Alousi A; Timmons M; Gulbis A; Myers A; Oki Y; Fanale M; Dabaja B; Pinnix C; Milgrom S; Champlin R; Andersson BS
[Ad] Address:Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center. Electronic address: ynieto@mdanderson.org.
[Ti] Title:Phase II Trial of High-Dose Gemcitabine/Busulfan/Melphalan with Autologous Stem-Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin's Lymphoma.
[So] Source:Biol Blood Marrow Transplant;, 2018 Mar 01.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem-cell transplantation (ASCT) in Hodgkin's lymphoma (HL) patients with primary refractory or poor-risk relapsed disease (extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect a 2-year progression-free survival (PFS) rate improvement from a historical 50% (using BEAM) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received BEAM at our center. No patient received post-ASCT maintenance. The Gem/Bu/Mel trial enrolled 80 patients: median age 31, 41% primary refractory and 59% relapsed (36% extranodal relapses), and 30% PET-positive lesions at ASCT. The concurrent BEAM (N=45) and Gem/Bu/Mel cohorts were well balanced except for more Gem/Bu/Mel patients with bulky relapses and PET-positive tumors. There were no transplant-related deaths in either cohort. At median follow-up of 34.5 months (range, 26-72), Gem/Bu/Mel resulted in improved 2-year PFS (65% vs. 51%) (P=0.008) and overall survival (89% vs. 73%, P=0.0003). In conclusion, Gem/Bu/Mel is safe, yielding, in this nonrandomized comparison, improved outcomes compared with a concurrently treated and prognostically matched cohort of primary refractory or poor-risk relapsed HL patients receiving BEAM.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

  5 / 5425 MEDLINE  
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[PMID]: 29410181
[Au] Autor:Messina C; Zecca M; Fagioli F; Rovelli A; Giardino S; Merli P; Porta F; Aricò M; Sieni E; Basso G; Ripaldi M; Favre C; Pillon M; Marzollo A; Rabusin M; Cesaro S; Algeri M; Caniglia M; Di Bartolomeo P; Ziino O; Saglio F; Prete A; Locatelli F
[Ad] Address:Department of Women's and Children's Health, Pediatric Hemato-Oncology, University Hospital of Padova, Padova, Italy.
[Ti] Title:Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy.
[So] Source:Biol Blood Marrow Transplant;, 2018 Feb 02.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

  6 / 5425 MEDLINE  
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[PMID]: 29412158
[Au] Autor:Parta M; Shah NN; Baird K; Rafei H; Calvo KR; Hughes T; Cole K; Kenyon M; Schuver BB; Cuellar-Rodriguez J; Zerbe CS; Holland SM; Hickstein DD
[Ad] Address:Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland. Electronic address: mark.parta@nih.gov.
[Ti] Title:Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen.
[So] Source:Biol Blood Marrow Transplant;, 2018 Feb 03.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher

  7 / 5425 MEDLINE  
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[PMID]: 29341904
[Au] Autor:Xiao Y; Li X; Fu X
[Ad] Address:Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, CA 90027, United States.
[Ti] Title:A rapid and simple LC-MS/MS method for personalized busulfan dosing in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT).
[So] Source:Clin Chim Acta;479:190-195, 2018 Apr.
[Is] ISSN:1873-3492
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Busulfan is commonly used as a conditioning regimen before hematopoietic stem cell transplantation (HSCT). There is a big inter-individual variability in busulfan exposure and the narrow therapeutic index, especially in pediatric population. Therefore, to achieve therapeutic efficacy and safety concurrently, personalized busulfan dosing, guided by pharmacokinetic study with serial plasma samples, is needed a few hours afterwards. METHODS: A fast, sensitive, and accurate method for busulfan measurement was developed, validated, and implemented with liquid-chromatography-mass spectrometry (HPLC-MS/MS). The sample preparation procedure involves only protein precipitation and dilution, and the HPLC-MS/MS method takes 3 min/sample. The assay was linear from 10 ng/ml to 7500 ng/ml (R = 0.99). Recoveries were above 90%. The precision was determined at 3 levels (30, 300 and 4000 ng/ml): the intra-day variability (%CV) ranged from 1.4% to 2.5% (n = 20); the inter-day variability ranged from 2.2% to 5.5% (n = 20). The accuracy of the HPLC-MS/MS test was evaluated with an old HPLC-fluorescence method (n = 84), and a Correlation Coefficient (R) of 0.99 was observed. CONCLUSIONS: The analytical performance of the assay allows for timely dose adjustment and has been implemented in clinical service for better clinical outcome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:In-Process

  8 / 5425 MEDLINE  
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[PMID]: 29440301
[Au] Autor:Sharma M; Braun RE
[Ad] Address:The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
[Ti] Title:Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis.
[So] Source:Development;145(5), 2018 Mar 01.
[Is] ISSN:1477-9129
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:In the murine testis, self-renewal of spermatogonial stem cells (SSCs) requires glial cell line-derived neurotrophic factor (GDNF) secreted from neighboring somatic cells. However, it not clear how GDNF promotes self-renewal or what downstream signaling pathways are required for SSC maintenance. We found that GDNF is normally expressed cyclically during spermatogenesis. Stage-specific ectopic expression of GDNF caused the accumulation of a GFRA1 LIN28 A population, which has enhanced SSC activity compared with wild type, suggesting that GDNF normally limits self-renewal to specific stages. Despite the increase in SSC cell number, EdU labeling during steady-stage spermatogenesis, and during recovery after busulfan-mediated spermatogonial depletion, indicated that GDNF promotes self-renewal by blocking differentiation and not by promoting proliferation. Increased GDNF signaling led to increased phosphorylation of AKT3 in undifferentiated spermatogonia, but not of AKT1 or AKT2, and was independent of RPS6 phosphorylation, suggesting that AKT3 functions in SSC self-renewal or progenitor cell expansion.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180302
[Lr] Last revision date:180302
[St] Status:In-Data-Review

  9 / 5425 MEDLINE  
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[PMID]: 29335155
[Au] Autor:White-Koning M; Osborne C; Paci A; Boddy AV; Chatelut E; Veal GJ
[Ad] Address:CRCT (Cancer Research Centre of Toulouse), Université de Toulouse, Inserm UMR 1037, Université Paul Sabatier, 31059 Toulouse Cedex 9, France. Electronic address: melanie.white-koning@univ-tlse3.fr.
[Ti] Title:Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence.
[So] Source:Eur J Cancer;91:56-67, 2018 Mar.
[Is] ISSN:1879-0852
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: To make systemic anti-cancer therapy (SACT) preparation more practicable, dose-banding approaches are currently being introduced in many clinical centres. The present study aimed to determine the potential impact of using recently developed National Health Service in England (NHSE) dose-banding tables in a paediatric setting. METHODS: Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with five drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide and etoposide), individual exposures (area under the plasma drug concentration versus time curve; AUC) obtained using doses rounded according to the published NHSE tables were calculated and compared with those obtained by standard dose calculation methods. RESULTS: For all five drugs, the relative variation between the NHSE dose and the recommended dose (RecDose) (standard individually calculated dose) was between -6% and +5% as expected. In terms of AUC, there was no statistically significant difference in precision between exposures obtained by the RecDose and those obtained with dose banding (absolute value of relative difference 15-34%). CONCLUSION: Based on pharmacokinetic data for these five drugs, the results generated support the implementation of NHSE dose-banding tables. Indeed, inter-patient variability in drug clearance and exposure far outweighs the impact of relatively small drug dose changes associated with dose banding.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[St] Status:In-Data-Review

  10 / 5425 MEDLINE  
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[PMID]: 29474820
[Au] Autor:Boga C; Yeral M; Gereklioglu C; Asma S; Maytalman E; Aytan P; Kozanoglu I; Sariturk C; Ozdogu H
[Ad] Address:Hematology Department, Adana Adult BMT Center, Faculty of Medicine, Baskent University, Ankara, Turkey. Electronic address: drcanboga@hotmail.com.
[Ti] Title:Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.
[So] Source:Hematol Oncol Stem Cell Ther;, 2018 Feb 20.
[Is] ISSN:1658-3876
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE/BACKGROUND: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. METHODS: This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. RESULTS: Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). CONCLUSION: Dose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:Publisher


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