Impact of Donor-Recipient Ethnicity On Risk of Acute Graft-Versus-Host Disease, Leukemia Relapse and Survival in Hematopoietic Stem Cell Transplantation From HLA-Compatible Unrelated Donors. A Report From the International Histocompatibility Workshop Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 871-871
Author(s):  
Yasuo Morishima ◽  
Takakazu Kawase ◽  
Satoko Morishima ◽  
Mari Malkki ◽  
Stephen R Spellman ◽  
...  
Keyword(s):  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Leukemia Relapse ◽  
Grade 3 ◽  
Asian Pacific ◽  
Hla Haplotypes ◽  
Acute Graft

Abstract Abstract 871 Introduction: The association of ethnicity with the incidence of acute graft-versus-host disease (aGVHD) after HLA identical sibling bone marrow transplantation is well documented. However, there has been no international analysis for the association of ethnicity in hematopoietic stem cell transplantation (HSCT) from unrelated donors. The large scale international unrelated HSCT International Histocompatibility Workshop Group (IHWG) dataset provides a unique opportunity to compare the clinical outcomes according to donor-recipient ethnicity. Patients and methods: Of the 16,198 pairs in the IHWG database, 5543 patient/donor pairs met the following 3 criteria and were included in this analysis: (1) HLA-A, B, C, DRB1 and DQB1 allele matched donor; (2) diagnosis of leukemia or myelo-dysplastic syndrome, and (3) non-T cell depleted GVHD prophylaxis. Multivariable Cox regression analyses were conducted to evaluate the impact of the ethnicity on clinical outcomes considering factors as confounders including HLA-DPB1 matching, disease, leukemia risk, donor age, patient age, gender, GVHD prophylaxis and conditioning regimen. A subset of pairs who shared HLA alleles with those of common European or Japanese HLA-A, -C, -B, -DRB1 and -DQB1 haplotype were further analyzed for transplant outcomes. Results: The number of pairs and hazard risk (HR) of aGVHD, leukemia relapse and overall survival (mortality) after transplantation by ethnic group are shown in the table. Asian/Pacific pairs (n=2062) showed lower incidence of acute GVHD (39.2% of grade 2-4 and 15.0% of grade 3-4) than that of Caucasian pairs (55.2% of grade 2-4 and 21.9% of grade 3-4) significantly (p<0.001). Multivariate analysis revealed that HR of aGVHD, leukemia relapse and mortality in Caucasian pairs was significantly higher compared with Asian/Pacific pairs. Although the number of Hispanic pairs and Black pairs is small, the HR of mortality in these pairs is significantly higher than Asian/Pacific pairs. The incidence of aGVHD in pairs sharing HLA alleles with either 2 common Japanese HLA haplotypes was significantly lower than that in pairs sharing HLA alleles with any 4 common European HLA haplotypes. Conclusion and discussion: As clinical factors and HLA matching were adjusted statistically, these different outcomes between ethnic groups might be attributable to the genetic background of ethnic group. As most Asian/Pacific pairs (2039 out of 2062) were Japanese registered from the Japan Marrow Donor Program, the data is representative of the Japanese population rather than Asian/Pacific ethnicities as a whole. The results from this analysis provide a platform for future international analyses of unrelated HSCT outcomes and for the international exchange of unrelated donors. Disclosures: No relevant conflicts of interest to declare.

Influence of Human Leukocyte Antigen Haplotypes on Acute Graft Versus Host Disease Incidence after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2887-2887
Author(s):  
Sameer Gupta ◽  
Charu Aggarwal ◽  
Philip L. McCarthy ◽  
Swaminathan Padmanabhan ◽  
Minoo Battiwalla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Hla Haplotypes

Abstract There is increasing evidence that the Human Leukocyte Antigen (HLA) alleles may influence the incidence of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). Differential presentation of recipient antigens to donor-derived T-cells by the respective HLA molecules may be a responsible factor. We have reported a decreased rate of aGVHD in HLA DR15 positive patients (pt) undergoing alloHSCT for myeloid malignancies (Blood, 2006; 107:1970). We investigated the influence of different HLA alleles and the three most common HLA haplotypes in US Caucasians on grade 2–4 acute GVHD (graded using published criteria) in HLA matched alloHSCT. We conducted a retrospective review of 195 related and 70 unrelated consecutive first myeloablative alloHSCT pt treated from 01/1992 to 4/2005 at our center. HLA typing was determined by either molecular (n=176) or serologic (n=89) methods. Pt characteristics included: AML (n=84), CML (n=62), NHL (n=47), ALL (n=41), MDS (n=20), HD (n=7) and CLL (n=4); median age 39 years (range 6–66), < 40 years (n=130); Male (n=168), Female (n=97); Caucasian (>95%); Donor-Recipient Sex Mismatch (n=112); Total Body Irradiation (TBI) conditioning regimens (n=205); Etoposide/Cyclophosphamide(Cy)/TBI (n=122), Busulfan(Bu)/Cy (n=28), Bu/TBI (n=27), Thiotepa/TBI (n=23), Cy/TBI (n=22), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=27) and peripheral blood stem cell source (n= 35). HLA Haplotypes analyzed for their effect on aGVHD were A1B8DR3 (n=25), A3B7DR15 (n=20) and A2B44DR4 (n=13). There was no significant difference in the pt characteristics (donor relation, conditioning regimen, donor-recipient sex match, diagnosis, age, gender, performance status, disease status at transplant, stem cell source and GVHD prophylaxis) by each of the three haplotypes. We analyzed prior published HLA alleles that were associated with an increased or decreased risk of aGVHD and pt characteristics for their effect on grade 2–4 aGVHD incidence. By univariate analysis, donor relation (unrelated vs. related, 52% vs. 38%, p=0.0002), HLA A2 (44% vs. 33%, p=0.05) and HLA B8 were associated with increased aGVHD (61% vs. 37%, p=0.005) whereas HLA B18 was associated with decreased aGVHD (19% vs. 43%, p=0.017) in contrast to prior reports using serological typing only. By multivariate analysis, HLA A2 (RR=1.5, 95%CI: 1.0 to 2.2, p=0.04), HLA B8 (RR=1.9, 95%CI: 1.1 to 3.0, p=0.01) and unrelated donor (RR= 1.9, 95%CI: 1.3 to 2.9, p=0.001) were associated with increased aGVHD. HLA haplotype multivariate analysis demonstrated increased risk of aGVHD with haplotypes A1B8DR3 and A2B44DR4 (A1B8DR3: 64% vs. 32%, RR 2.6, 95% CI: 1.1 to 5.9, p=0.012 and A2B44DR4: 61% vs. 39%, RR 3.5, 95% CI: 1.7 to 7.5, p=0.04) whereas haplotype A3B7DR15 had less aGVHD compared to others (18% vs. 42%, RR 0.31, 95%CI: 0.098 to 0.98, p=0.049). This is the first published report of the effect of HLA haplotypes on aGVHD incidence. Results of our haplotype analysis substantiate our findings of single allele effects of HLA A2, HLA B8 and HLA DR15 suggesting a differential effect on aGVHD incidence. The ability to predict aGVHD after alloHSCT using HLA haplotypes may improve outcomes by allowing for individualized GVHD prophylaxis regimens.

scholarly journals ORAL CYCLOSPORINE AS AN ALTERNATIVE FOR INITIAL STANDARD PROPHYLAXIS IN ALLOGENEIC STEM CELL TRANSPLANTATION WHEN INTRAVENOUS FORMULATION IS UNAVAILABLE

2018 ◽  
Vol 11 (12) ◽  
pp. 108
Author(s):  
Eucario Leon-rodriguez ◽  
Monica M Rivera-franco
Keyword(s):  
Stem Cell ◽  
Care Center ◽  
Tertiary Care ◽  
Gender Disparity ◽  
Hematopoietic Stem ◽  
Entire Cohort ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Oral Group ◽  
Acute Graft

Objective: The objective of the study was to compare the incidence of acute graft versus host disease (aGVHD) between oral and intravenous (IV) initial standard cyclosporine A (CsA) prophylaxis in a tertiary care center in Mexico.Methods: A total of 117 consecutive patients who underwent allogeneic hematopoietic stem cell transplantations (HSCT) were retrospectively analyzed. GVHD prophylaxis consisted of CsA and methotrexate (MTX). CsA was administered IV, until 2005, when it was withdrawn from the market, and CsA was administered orally.Results: Most of the patients were male (55%), with a median age of 33 years (range, 15–63). 92 patients (79%) received CsA orally, and 25 (22%) intravenously. There were no significant differences in CsA concentrations during weeks 1, 2, 3, and 4 between the oral and IV group. From the entire cohort, 1 patient (4%) from the IV group and 16 (17%) from the oral group developed aGVHD, respectively. Sex, gender disparity, and HSCT source were statistically associated with aGVHD in the multivariate analysis.Conclusions: Using oral instead of IV CsA for aGVHD prophylaxis is feasible and could be financially efficient; nonetheless, our results showed a higher incidence of aGVHD in the oral group; however, our study has limitations and further prospective studies including a larger cohort are encouraged.

Elevated Serum Interleukin-7 Levels Precede the Development of Acute Graft-Versus-Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1064-1064
Author(s):  
Robert M. Dean ◽  
Terry Fry ◽  
Crystal Mackall ◽  
Seth M. Steinberg ◽  
Frances T. Hakim ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Multiple Time ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Interleukin 7 ◽  
Gvhd Prophylaxis ◽  
Acute Graft

Abstract BACKGROUND: Despite advances in transplantation immunology, there is no clinically practical tool to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Murine models indicate that aGVHD is promoted by interleukin-7 (IL-7), a homeostatic cytokine for naïve CD4+ and CD8+ T-cells. We hypothesized that serum IL-7 levels might be associated with the development of aGVHD in patients (pts) undergoing allogeneic HSCT, and evaluated this using serum samples obtained for this purpose in a prospective clinical trial. METHODS: Thirty-one pts underwent allogeneic HSCT from HLA-identical siblings. Pts received 1 to 3 pre-transplant chemotherapy cycles to induce profound, uniform host lymphopenia (CD4<100), followed by fludarabine-based reduced-intensity conditioning. GVHD prophylaxis was cyclosporine & methotrexate. Serum IL-7 was measured by ELISA at baseline and multiple time points from the day of transplant through 1 year after allogeneic HSCT. IL-7 levels were evaluated for associations with blood lymphocyte counts, aGVHD, and survival. Other variables examined for association with aGVHD were pt and donor age; CD3+ and CD34+ cell doses; donor gender; donor-recipient gender mismatch; donor or recipient CMV status, prior rituximab therapy; donor lymphoid or myeloid chimerism >95% at day +14; serum IL-15 levels; and levels of soluble tumor necrosis factor-α receptors 1 and 2 (sTNFR1 and sTNFR2). RESULTS: Grades I, II, and III aGVHD occurred in 3%, 23%, and 19%, respectively; none had grade IV. Median (range) IL-7 levels rose from baseline 12.1 (0–46.9) pg/ml to 37 (13.3–79.2) pg/ml on day 0 before allografting, then fell to 12.0 (1.3–74.7) pg/ml by day +14; these changes were inversely correlated with absolute lymphocyte counts, CD3, CD4, and CD8 counts at baseline and day +7. The development of aGVHD was associated with IL-7 levels at day +7 (p=0.01) and day +14 (p=0.000033) post-transplant (Figure), along with the allograft CD34+ cell dose (p=0.012). Higher IL-7 levels at day +14 corresponded to more severe grades of aGVHD (p<0.0001). Figure Figure In logistic regression models, these factors jointly classified pts according to development or avoidance of aGVHD with a maximum sensitivity of 86% and a specificity of 100%. IL-7 levels were more strongly associated with aGVHD than were sTNFR levels or other parameters. CONCLUSIONS: Determination of serum IL-7 levels in the early post-transplant period accurately predicted the risk of developing aGVHD after allogeneic HSCT and holds promise as a simple, reproducible test to select pts for pre-emptive therapy. These data support preclinical observations that demonstrate a critical role for IL-7 in inducing aGVHD and provide a rational basis for novel approaches to GVHD prophylaxis through modulation of the IL-7 homeostatic pathway.

Impact of highly conserved HLA haplotype on acute graft-versus-host disease

Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4664-4670 ◽  
Author(s):  
Satoko Morishima ◽  
Seishi Ogawa ◽  
Aiko Matsubara ◽  
Takakazu Kawase ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Extended Haplotypes ◽  
Hla Haplotypes ◽  
Acute Graft

Abstract Although the effects of human leukocyte antigen (HLA) locus matching on clinical outcome in unrelated hematopoietic stem cell transplantations have been characterized, the biologic implications of HLA haplotypes have not been defined. We demonstrated the genetic fixity of Japanese conserved extended haplotypes by multi–single nucleotide polymorphism analysis in 1810 Japanese donor-recipient pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially completely conserved at least in the 3.3-Mb HLA region from HLA-A to -DPB1, and extended far beyond HLA-A. The risk of acute graft-versus-host disease (GVHD) of these HLA haplotypes was assessed with multivariate Cox regression in 712 patients transplanted from HLA fully (HLA-A, B, C, DRB1, DQB1, and DPB1) matched unrelated donors. HP-P2 itself reduced the risk of grade 2 to 4 acute GVHD (hazard ratio [HR] = 0.63; P = .032 compared with HP-P2-negative), whereas HP-P3 tended to increase the risk (HR = 1.38; P = .07). Among 381 patients with HP-P1, HP-P1/P3 (HR = 3.35; P = .024) significantly increased the risk of acute GVHD compared with homozygous HP-P1. This study is the first to demonstrate that a genetic difference derived from HLA haplotype itself is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation.

scholarly journals Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 795-802 ◽  
Author(s):  
JE Wagner ◽  
J Rosenthal ◽  
R Sweetman ◽  
XO Shu ◽  
SM Davies ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Graft Versus Host Disease ◽  
Umbilical Cord Blood ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Acute Graft

Abstract To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus- host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.

scholarly journals Utility of Endoscopic Examination in the Diagnosis of Acute Graft-versus-Host Disease in the Lower Gastrointestinal Tract

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kosuke Nomura ◽  
Toshiro Iizuka ◽  
Daisuke Kaji ◽  
Hisashi Yamamoto ◽  
Yasutaka Kuribayashi ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Terminal Ileum ◽  
Villous Atrophy ◽  
Ileocecal Valve ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Endoscopic Findings ◽  
Grade 3 ◽  
Acute Graft

Background and Aims. We retrospectively investigated the incidence of acute graft-versus-host disease (GVHD) in the lower gastrointestinal (GI) tract and the diagnostic accuracy of endoscopy.Methods. Of 1231 patients who underwent allogeneic hematopoietic stem cell transplantation between January 2005 and December 2014, 186 of whom underwent colonoscopy and biopsy and had no cytomegalovirus infection. The endoscopic findings and histologic diagnosis from these 186 patients were retrospectively analyzed.Results. Based on the histopathological findings, 171 patients were diagnosed with GVHD, accounting for 13.9% of all transplant recipients. Useful endoscopic findings for the diagnosis of GVHD were atrophy of the ileocecal valve and villous atrophy in the terminal ileum and tortoise shell-like mucosae, edema, and low vascular permeability in the colon. Even when no mucosal abnormality was observed, the incidence of GVHD was 78.9% in the terminal ileum and 75.0% in the colon. Furthermore, patients with mucosal exfoliation, although infrequent, were all diagnosed with grade 3/4 GVHD.Conclusions. It is important to perform endoscopy proactively for the early diagnosis of GVHD, and biopsy should be performed even when no abnormality is observed. In addition, because patients with mucosal exfoliation are extremely likely to have grade 3/4 GVHD, early treatment should be initiated.

scholarly journals The efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experience

2020 ◽  
Vol 19 (2) ◽  
pp. 71-82
Author(s):  
N. V. Sidorova ◽  
A. S. Slinin ◽  
E. B. Machneva ◽  
V. V. Konstantinova ◽  
A. E. Burya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.

scholarly journals Investigating Antibiotic Exposure and Risk of Severe Acute Graft Versus Host Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4539-4539
Author(s):  
Razan Mohty ◽  
Remy Dulery ◽  
Giorgia Battipaglia ◽  
Eolia Brissot ◽  
Clemence Mediavilla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Exposure Group ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Grade 3 ◽  
Severe Grade ◽  
Neutrophil Engraftment

Several studies have shown that alteration of the microbiota, particularly in the gastrointestinal tract, can be associated with graft-versus-host disease (GvHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) usually get exposed to antibiotics (ATB), mainly in the peri-transplant period. Moreover, ATB, specifically those that target anaerobic bacteria, can alter the microbiota in a variety of body organs. This, in turn, renders several organs vulnerable to injury making them more prone to developing diseases such as GvHD. In this study, we evaluate whether the use of ATB, characterized by duration, timing and type, in the peri-transplant period, is associated with an increased incidence of acute GvHD (aGvHD) and aGvHD-related mortality. In this retrospective study, we included 318 consecutive patients who underwent allo-SCT including haploidentical and cord blood transplantation between December 2012 and June 2018 at a single center. ATB exposure was collected and classified into 3 groups according to the date of initiation of ATB: from the start of conditioning to day - 1 of allo-SCT (early ATB exposure), from day 0 to neutrophil engraftment (late ATB exposure) and a third group of patients who did not receive ATB (no ATB exposure). ATB were only initiated if a patient develop fever or show signs of infection. Patients did not receive any prophylactic ATB. Exposure was further categorized as primary or adjunct. Primary exposure included the use of 4 classes of ATB: carbapenems, anti-pseudomonal penicillin, 4thand 5thgeneration cephalosporins and fluoroquinolones. Adjunct ATB comprised other ATB and was further divided into 2 groups according to anaerobic coverage. The median age at transplant was 55 years. The stem cell source was peripheral blood in 85%, bone marrow in 10% and cord blood in 5% of the patients. Ninety-nine percent of the patients received cyclosporine A as GvHD prophylaxis and 80% and 7% of the patients received (along with cyclosporine A), mycophenolate mofetil and methotrexate, respectively. In addition, 35% and 89% of the patients received post-transplant cyclophosphamide and anti-thymocyte globulin, respectively, as GvHD prophylaxis. The median time to neutrophil engraftment was 16 days post-transplant. The median follow-up was 85 months. 93.7% of the patients received ATB in the peri-transplant period with 64.5% of them in the early ATB exposure group, and 29.2% of them in the late ATB exposure group. The 2-year overall survival and progression free survival were 74.3% and 63.6% in patients with early ATB exposure, compared to 79.5% and 70.8% in patients with late ATB exposure (p=0.11 and p=0.07 respectively). The 2-year cumulative incidence of non-relapse mortality was 16.5% in patients with early ATB exposure, compared to 15.1% in patients with late ATB exposure (p=0.63). The 180-days cumulative incidence of grade 2-4 and 3-4 aGvHD were 23.8% and 12.2% in patients with early ATB exposure, compared to 27.2% and 5.4% in patients with late ATB exposure (p=0.64 and p=0.06 respectively). In multivariate analysis, including the most important parameters associated with GvHD (stem cell source and donors, conditioning regimen, sex mismatch and patients age), early ATB initiation was the only parameter associated with a significantly higher risk of severe grade 3-4 aGvHD [HR 0.51 (0.28-0.90); p=0.02]. In conclusion, in the absence of any ATB prophylaxis, early initiation of ATB, before graft infusion,is associated with a significantly higher risk of severe grade 3-4 aGvHD. Weighing risk of morbidity and mortality associated with infections versus later on risk of developing aGvHD is essential. Hence, new strategies should be developed to risk stratify patients with fever and thus to avoid early non necessary ATB exposure especially in those who develop fever during anti-thymocyte globulin infusion. Studies evaluating such strategies will be necessary in the next years. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding. Malard:Astellas: Honoraria; JAZZ pharmaceutical: Honoraria; Sanofi: Honoraria; Keocyte: Honoraria; Janssen: Honoraria; Therakos/Mallinckrodt: Honoraria.

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