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  • 1
    Publication Date: 2007-11-16
    Description: Background: Genetic polymorphisms within the regulatory sequence of cytokine genes influence their expression and, ultimately, the immune reactivity. Such polymorphisms are therefore associated with the outcome of stem cell transplantation (SCT) supporting the hypothesis of a genetic predisposition towards certain complications post-SCT. Objective: To assess the association between donor (D) and recipient (R) genotypes for the IL-10 gene -1082 SNP (single nucleotide polymorphism) and -1064 STR (short tandem repeat) polymorphisms with the dynamics of chimerism and the development of complications after SCT. Patients and methods: The study included 39 conventional SCT from HLA-matched related donors. IL-10 genotypes were determined in an -1082 SNP allele-specific PCR (A vs G) including the -1064 (CA)n STR in the product which is revealed by capillary electrophoresis. Results were analyzed using Fisher’s exact test due to the reduced sample size. Results: The frequency of alloreactive genotypes (AA or A) for the SNP was 35,9% AA and 87,2% A in the D and 25,6% AA and 89,7% A in the R. No association was observed between the presence in the D or R of the alloreactive allele for the SNP genotype and the dynamics of chimerism or complications post-SCT. Alleles 4 (17 CA repeats) to 12 (25 CA repeats) for the STR genotype were found in the present series. The frequency (homozygous, +/+, or heterozygous, +) of the low IL-10 producer allele 7 (high alloreactivity allele) was 5,1% +/+ and 25,6% + in the D and 7,7% +/+ and 33,3% + in the R. The presence of allele 7 in the recipient was significantly associated with the development of graft failure/rejection (p=0,012; Table ). In these patients, the incidence of mixed chimerism (MC) in the CD3+ fraction (T lymphocytes) during the first month post-SCT was significantly higher (p=0,043; Table 1). Conclusions: The presence of the low producer allele 7 for the IL-10 -1064 STR polymorphism in the recipient would associate with a higher immune alloreactivity against donor cells. This would favour the establishment of mixed chimerism increasing the risk of graft failure/rejection. Therefore, our results suggest that recipient IL-10 -1064 STR polymorphism genotypes may influence SCT outcome in a chimerism mediated fashion. The analysis of a larger number of patients as well as further cytokines will eventually allow to confirm these observations and to establish this type of studies as a means for an improved management of transplanted patients. Table 1. Influence of the presence in the recipients of allele 7 for the IL-10 -1064 STR polymorphism on chimerism and complications post-STC. IL-10 -1064 allele 7 MC day+30 in T cells (CD3+) aGVHD II-IV cGVHD Graft failure/rejection Relapse Exitus Present 6/6 (100%) 6/12 (45,5%) 6/10 (60%) 5/13 (38,5%) 3/12 (25%) 6/13 (46,2%) Not present 6/13 (50%) 13/26 (50%) 16/18 (88,9%%) 1/26 (4%) 7/25 (28%) 12/26 (46,2%) p (Fisher’s Test) 0,043 NS NS 0,012 NS NS
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  • 2
    Publication Date: 2008-11-16
    Description: Introduction: Methylation of CpG dinucleotides is a fundamental mechanism of epigenetic regulation in eukaryotic genomes that controls the expression of certain genes. FOX-P3 is a member of the forkhead/winged-helix family of transcriptional regulators which expression is constitutive in regulatory T lymphocytes CD4/CD25 (Treg). Recent evidence suggests that human effector T cells express FOX-P3, albeit transiently and with significantly lower levels. Therefore, FOX-P3 mehtylation within the promoter region and gene expression could play a role in allogeneic stem cell transplantation (alloSCT). Objective: To analyze the association between the mehtylation status and the levels of expression of FOX-P3 with the dynamics of chimerism and the development of complications after alloSCT. Patients and methods: The degree of methylation was quantified in a 600 pb CpG island within the regulatory sequence of FOX-P3 by quantitative methylation-specific real time-PCR from 32 peripheral blood (PB) samples obtained within the first month post-alloSCT. Moreover, the expression level of FOX-P3 mRNA was analyzed by real-time quantitative PCR in 18 patients from which RNA samples were available. Results were analyzed using Fisher’s exact test due to the reduced sample size. Results: A statistically significant association (Table 1) was observed between a higher degree of methylation in the FOX-P3 promoter and a lower incidence of acute graft versus host disease (GVHD) grades II-IV (35.3% vs a 88.9% in low methylation patients; p=0.014). Moreover, patients with higher degree of methylation showed significantly higher incidence of disease relapse (41.2% vs a 0% in low methylation patients; p=0.05). The observation of a high degree of methylation would reflect a lower amount of FOX-P3 expressing cells, both Treg and effector cells. Since Treg comprises a minority population, such observation would result from relative low levels of effector T cells, which would explain the lower graft-versus-host and graft-versus-leukemia effect observed in high mehtylation group. Surprisingly, when FOX-P3 mRNA levels were analyzed, an association with statistical significance between a higher methylation status and a higher expression of FOX-P3 (90% vs 55.8%; p=0.047) was observed. It has been shown that FOX-P3 is mainly produced by Treg while effector T cells produce very low amounts of FOX-P3 mRNA. In this sense, a higher amount of Treg cells produces high FOX-P3 mRNA levels and reduces the number of effector T cells, resulting in a higher methylation status in PB samples, in which most cells would have methylated FOX-P3. Low FOX-P3 expression would, in turn, indicate a lower amount of Treg to suppress the immune activation, resulting in higher amount of effector T cells and therefore would be associated with a lower methylation. Additionally, a significant association between higher FOX-P3 expression and lower incidence of death (7.7% vs 80%; p=0.007) was observed. Moreover, the main cause of death (3/4) in the group with lower expression of FOX-P3 was acute GVHD. The lower amount of effector T cells in PB samples with high FOX-P3 expression would protect from the development of GVHD. Conclusions: Both FOX-P3 mRNA expression and promoter methylation are of prognostic value for the development of complications post-SCT. These determinations would favor an early establishment of the immunotherapeutic options for an improved management of transplanted patients. Table 1. Association between FOX-P3 promoter methylation and mRNA expression with chimerism and complications post-SCT. MC, mixed chimerism; PB, peripheral blood; Fail/Reject., graft failure/rejection. p, Fisher`s Test. Methylation MC (PB) Fail/Reject. aGVHD (II-IV) cGVHD Relapse Exitus High 6/19 (31.6%) 4/19 (21.01%) 6/17 (35.3%) 10/13 (76.9%) 7/17 (41.2%) 5/19 (26.3%) Low 2/9 (22.2%) 0/9 (0%) 8/9 (88.9%) 3/8 (37.5%) 0/9 (0%) 4/9 (44.4%) p NS NS 0.014 NS 0.05 NS Expression MC (PB) Fail/Reject. aGVHD (II-IV) cGVHD Relapse Exitus High 4/13 (30.8%) 2/13 (15.4%) 6/12 (50%) 10/11 (90.9%) 3/12 (25%) 1/13 (7.7%) Low 0/5 (0%) 0/5 (0%) 4/5 (80%) 3/4 (75%) 1/5 (20%) 4/5 (80%) p NS NS NS NS NS 0,007
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  • 3
    Publication Date: 2007-11-16
    Description: Several authors have reported ASCT as a feasible, safe and effective treatment in HIV associated lymphoma patients (pts) receiving Highly Active Antiretroviral Therapy (HAART), particularly when being autografted with chemosensitive disease. To gain a better understanding of the usefulness of ASCT in HIV+ Lymphoma pts a retrospective comparative study (HIV+ vs HIV- lymphoma pts with ASCT) has been performed using the EBMT-LWP Registry. Methodology: Registry-based, retrospective, individually matched case-control analysis. Within the participating centres one or two HIV- controls for each HIV+ pt were selected from the registry with the following inclusion criteria: Known HIV serological status at ASCT, lymphoma (HL or NHL), ASCT performed between 1999 and 2006 and pts over 18 years of age. Two cohorts (HIV+ vs HIV-) were matched for histology, IPI at diagnosis (NHL), stage at diagnosis, disease status at ASCT, age at ASCT, year and country of ASCT. Results: 40 HIV+ lymphoma pts undergoing an ASCT were matched with 46 HIV- pts. Pts and transplant features are shown in table 1. With a median follow up of 36 mo, the differences regarding OS and PFS were not significant: 62% for HIV+ vs 69% for controls, and 56.5 vs 58%, respectively. No differences were seen regarding HL and NHL pts. An overall TRM of 10% was observed in the HIV cohort, mainly related to infections, while no cases of TRM were seen within the control arm. Since survival rates between the HIV+ and the matched HIV- lymphoma populations remained comparable, the HIV condition should not preclude these pts from being treated according to the same criteria as the HIV negative lymphoma population. Nevertheless, infectious complications should be cautiously followed within the HIV+ lymphoma pts undergoing an ASCT. Patients and transplant features HIV+ HIV- n=40 % n=46 % Age [Median (range)] in years 41.4 (29.2–62.5) 44 (16–62.4) p= NS Male sex 35 87.5 25 54.3 p=0.001 Histology     DLBCL 24 60 25 54.3 p= NS     Burkitt lymphoma 2 5 2 4.3 p= NS     T-cell NHL 2 5 3 6.6 p= NS     HL 12 30 16 34.8 p= NS Disease status at ASCT     Complete remission (CR) 21 (12 in CR1) 52.5 (30 in CR1) 20 (11 in CR1) 43.5 (24 in CR1) p= NS     Chemosensitive disease 16 40 25 54.3 p= NS     Chemorefractory disease 3 7.5 1 2.2 p= NS CD34+ cells infused mill/kg [median (range)] 4.9 (1.6–21.2) 4.8 (0.9–21.2) p= NS     G-CSF prior to engraftment 36 90 21 46 p= 0.0001     Neutrophil engraftment 39 98% 46 100 p= NS Cause of Death     Relapse/progression 9 60% 10 84% p=0.08     Secondary malignancy 1 6.7% 1 8% p= NS     Transplant-related deaths 4 26.7% 0 0% p=0.06     Other 1 6.7% 1 8% p= NS
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  • 4
    Publication Date: 2010-11-19
    Description: Abstract 3532 In the absence of an HLA matched sibling donor, an unrelated adult donor matched (MUD) at 8 of 8 alleles for HLA A, B, C, DRB1 is considered as first alternative. However, only 50% of patients in Europe have an available suitable donor in a median time of 4 months. For those patients without a suitable MUD, we have adopted CB (cord blood) stem cell transplantation with the co-infusion of CD34+ cells from a third party non HLA-identical donor (Dual transplantation). The objective of this study was to analyze toxicity and overall survival (OS) rates of patients who underwent this procedure and compare them with a cohort of patients who received a myeloablative MUD transplantation in a single centre and during a similar period of time. Patients: Between 2005 and 2010, 16 consecutive patients with high risk disease underwent a total of 18 dual transplants and 17 patients, with similar pre-SCT characteristics recieved a myeloablative MUD transplantation with 12/12 HLA identity in a single centre (Table 1). Transplants performed before 2005, those with manipulated grafts and with HLA mismatches were excluded. Results: There were no significant differences in age, gender, pre-SCT disease status and previous therapy lines between both groups. Three cases among the dual group showed primary graft failure (2 of them showing third party donor cells engraftment) who were rescued by a second CB transplant in two cases and a MUD in one case (succesfull in 2). There were no graft failures in the MUD group. GVHD rates are shown in table 1. OS was 50% in the dual group and 53% in the MUD group with a median follow-up of 33 (1-67) y 13 months (1,1-48,5) respectively (Figure 1). The cumulative relapse incidence at 2 years was 54% in the dual group and 53% in the MUD group. There were no relpses after 2 years in both groups. All the transplant related deaths (TRM) took place within the first year after transplantation with no significant differences in cumulative incidence between both groups (p=0,69). Conclusions: In our experience, CB transplantion together with the co-infusion of CD34+ cells from a third party HLA-mismatched donor offers OS and DFS rates comparable to those from myeloablative HLA 12/12 MUD trasnplantation with an acceptable TRM. Therefore, dual transplantion is still our first choice for patients without an available MUD or for whom trasplant is urgent. Disclosures: No relevant conflicts of interest to declare.
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  • 5
    Publication Date: 2006-11-16
    Description: Following the widespread use of Highly Active Antiretroviral Therapy (HAART), ASCT has been reported as a feasible and effective treatment in the setting of HIV-Ly patients (pts). Nevertheless just series including up to 20 patients have been published so far. We present a preliminary analysis of the outcomes regarding the experience within the EBMT-LWP. Methodology: A retrospective analysis including HIV-Ly patients undergoing peripheral blood ASCT from 1999 to 2005 and reported to the EBMT was performed. Main endpoints: OS, EFS and TRM. Results: 44 pts from 14 institutions/7 countries were included: 39 males, median age 43 (29–62) years old. One pt underwent more than 1 ASCT (follow up censored at time of 2nd ASCT). In addition to HIV infection, 11 pts were co-infected by HBV, 8/43 by HCV and 16/36 pt met AIDS criteria (other than lymphoma) at the time of lymphoma diagnosis. Histology: 34 NHL (20 DLBCL; 7 Burkitt/Burkitt-like; 4 plasmablastic; 3 other), 59% of them with IPI〉2 at diagnosis; 10 HL (50% with Ann-Arbor stage〉IIB at diagnosis). Patients received a median of 2 (1–5) treatment lines pre-ASCT. Status at ASCT: 22 CR (13 in CR1); 18 in PR/chemo-sensitive relapse and 4 in primary induction failure/chemo-resistant relapse. Conditioning: 41 pts received BEAM/variants and 3 TBI-based regimens. Post-ASCT anti-tumour pre-emptive treatment was used in 10 pts (8 radiotherapy; 2 Rituximab). The median count of T-CD4+ cells/μl was 162 (8–702) at the time of ASCT; 26/38 had undetectable HIV viral loads. HAART was given in 39/42 pts during conditioning but was withdrawn in 9 of them. The median number of CD34+ cells infused was 5 (1,6–21,2) x106/kg. G-CSF was used until engraftment in 39/43 pt during a median of 8 (2–29) days. All pts but one who died on day +15 reached neutrophils〉500/μl at a median time of 11 (8–36) days. Platelet count 〉20.000/μl was reached in 39/44 pt at a median time of 14 (6–455) days. The pt engrafting platelets on day +455 was transfusion independent since day +49. Three new post-ASCT malignancies were reported: in situ epitelioma and myelodysplasia (+4 years) in 1 pt, and kidney adenocarcinoma (+3 years) in another one. Relapse occurred in 13 (29,5%) pts which status at SCT was CR in 4, PR/chemosensitive relapse in 5 and chemo-resistant disease in 4. The median time to relapse/progression was 5,2 (0,6–32,1) mo. Seventeen pts died (38,6%): disease relapse/progression (n=11), ASCT-related complication (n=4) -bacterial infection (n=3), secondary myelodysplasia (n=1)-, 1 pt died from an HIV-related complication and 1 pt died on day +15 of multi-organ failure within the context of a bacterial sepsis and pre-transplant renal dysfunction. With a median follow up time of 36,3 (3,2–72,3) mo, the OS and DFS probability at this point were 60,2% (67,5% when chemo-resistant pts were excluded from analysis) and 55% respectively. For those pts in CR1 at ASCT, OS at 36,3 mo was 85% vs 60% for those in CR〉1/PR/chemosensitive relapse. Conclusion: The results from the EBMT-LWP experience, the largest reported so far, show that ASCT remains a useful treatment in terms of TRM, long-term OS, and DFS for high risk HIV-Ly patients. These outcomes are comparable to those observed in HIV negative lymphoma patients.
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  • 6
    Publication Date: 2006-11-16
    Description: ASCT has been reported as a feasible, safe and effective treatment in HIV associated lymphoma patients (pts) receiving Highly Active Antiretroviral Therapy (HAART). Nevertheless comparative studies with HIV− lymphoma population have not yet been performed. We present a retrospective matched analysis comparing clinical outcomes in both HIV+ and HIV− auto-transplanted HL pts. Patients and Methods: 6 HIV+ HL pts who underwent ASCT since June 2000 were included. Twelve transplanted HIV− HL auto-transplanted pts were selected as controls. Both groups (HIV+ vs HIV−) were comparable for the most relevant clinical features (Mann-Whitney or chi-square tests p value 〉 0.05): median age (40 vs 36), Ann Arbor advanced stage (50% vs 25%), status at ASCT (CR〉1 or PR, 83% vs 75%), all 18 pts received 2 lines of chemotherapy before ASCT. BEAM was used as conditioning regimen in all 18 pts. In the HIV+ group HAART was maintained during mobilization and ASCT, except during the conditioning in 1 Pt, in which it was needed to be resumed due to an increase in viral load. The median number of infused CD34+ cells/kg was 3,65×106 in HIV+ pts and 4,75×106 CD34+ in HIV− pts (p: NS). G-CSF was used in all HIV+ pt until engraftment starting at a median of 5 days (d) after ASCT. Results: All 18 pts engrafted, at a median of 13,5 (9–29) d after ASCT in HIV+ pts and 14 (11–18) d in HIV- pts. The incidence of acute infectious and toxic events was not different in both groups. All pts developed neutropenic fever. Documented infections were (HIV+ vs HIV−): Gram+ bacteraemia (2 vs 3), Gram− bacteraemia (1 vs 0), CMV antigenemia (2 vs 1). Pneumonia was documented in one pt from each group. One HIV+ pt showed grade II liver toxicity and grade II renal toxicity occurred in 1 HIV− pt. All events were succesfully resolved. In 4 out of 6 HIV+ pts, HAART was withdrawn due to gastrointestinal toxicity. The median follow-up time was 36,5 mo in HIV+ pts and 37,5 mo in HIV− pts. Two pts relapsed in each group. Within the HIV+ group 1 pt died, due to disease progression. Within the HIV− group 3 pts died, 2 of disease progression and 1 due to post-ASCT secondary acute leukaemia. The OS at 36 mo was 83% for HIV+ pts and 80% for HIV− pts (p=NS). EFS at 36 mo was 55% in HIV+ pts and 70% in HIV− pt (p=NS). Conclusions: Our results show that clinical outcomes are comparable in HIV+ and HIV− HL pts undergoing ASCT. Engraftment, complication events and survival were not different. ASCT may be applied with guarantees in HIV associated HL on HAART pts in a similar way that in the HIV− setting.
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  • 7
    Publication Date: 2006-11-16
    Description: Background: Allogeneic umbilical cord blood (UCB) stem cell transplantation (SCT) shows some advantages (HLA matching requirements or availability) respect to SCT using other sources of matched unrelated donor (MUD) stem cells. However, it is correlated with slower engraftment, increasing risk of infections and early mortality. It has been recently shown that co-infusion of third party donor (TPD) CD34+ cells (dual SCT) is useful to speed up engraftment. Objective: To evaluate the usefulness of lineage-specific chimerism quantification in the management of this transplant setting. Patients and methods: 8 dual SCT (Tables 1, 2) in 7 patients (1 CML-BC, 2 AML-M2, 1 AML-M4, 1 ALL-Ph+, 1 biphen. ALL, 1 NHL). Chimerism was analyzed by STR-PCR (AmpFlSTR SGM Plus, Applied Biosystems; sensitivity 1%) and quantitative real-time PCR (qrt-PCR) of null alleles and insertion/deletion polymorphisms (Light Cycler, Roche; sensitivity 0,01%). Peripheral blood (PB) and leukocyte lineages (T cells, CD3+, and myeloid cells, CD15+), isolated by positive selection using automated immunomagnetic technology (AutoMACS, Miltenyi Biotec), were analyzed weekly. Bone marrow (BM) was analyzed at days +30, +100, +180 and +365). Results: 7/8 cases showed initially a high proportion of TPD cells in PB which were progressively replaced by UCB cells. UCB complete chimerism (UCB-CC, absence of recipient or TPD cells even in qrt-PCR assays) was acquired in a median of 22.5 days (range 18–39). In one patient, fully HLA-mismatched with the TPD, no TPD cells were observed after dual SCT. 4/8 cases showed recipient cells in PB after dual SCT during a median period of 12 days (range 4–18 days). In 3/8 cases, recipient cells were found after CC had been acquired, which allowed early diagnosis of 1 graft rejection and 2 relapses. T cells (CD3+) are mainly of UCB origin early after dual SCT and reach UCB-CC a median of 7 days (range 0–21) before PB. However, myeloid cells (CD15+) derive primarily from the TPD and reach CC together with PB. TPD cellularity favoured early engraftment (before UCB-CC took place) in 4 cases. In this context, only one important infectious complication (hepatosplenic tuberculosis) was observed, which resolved with the appropriate treatment. Conclusions: Lineage-specific chimerism quantification allowed a close monitoring of the dynamics of engraftment of cells of both donors which is of key importance in this SCT setting. Moreover, lineage-specific chimerism analysis was useful to diagnose one graft rejection and two relapses (the patient with NHL showed a ganglionar relapse in CC). Table 1. Transplantation characteristics. Table 2. Transplantation results. Median (range).
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  • 8
    Publication Date: 2004-11-16
    Description: Increasing mixed chimerism (MC) predicts morphological relapse after stem cell transplantation (SCT) in patients with acute leukemia. Early treatment of increasing MC reduces the onset of relapse and improves survival. However, conventional methods for chimerism analysis fail to detect MC prior to a considerable number of relapses. We have tested a new approach for chimerism follow-up, based on amplification by real-time quantitative PCR (rtq-PCR) of null alleles and insertion/deletion (indel) polymorphisms, and compared it with conventional variable number of tandem repeats (VNTR)-PCR. Four null alleles: GSTM1, GSTT1, RhD and SRY, and 10 indels: Xq28, rs4399, DCP1, R271, FVII, THYR, MID-1039, MID-1335, MID-1385, MID-2062, were quantified by rtq-PCR using allele-specific primers and probes (LyghtCycler technology). Sensitivity studies (by mixture of positive and negative DNA), and intra- or inter-assay variability experiments were performed. All markers showed high sensitivity (at least 0.01%) and reproducibility. Accuracy of the method was also confirmed by dilution of positive in negative cells with subsequent DNA extraction and rtq-PCR quantification. Donor/host informativity (presence of the sequence in the recipient and absence in the donor) was tested retrospectively in a series of 68 acute leukemia patients, and at least one informative marker was obtained in 85.3% of donor/host pairs. Chimerism follow-up was performed on peripheral blood (PB) and bone marrow (BM) samples obtained after SCT. In non-relapsed patients, PB host chimerism values progressively descended from transplantation until reaching donor complete chimerism (CC); conversely, BM chimerism decreased but did not reach CC more than 3 years after SCT. From 18 relapses evaluable with rtq-PCR, 16 (89%) showed increasing chimerism in PB samples prior to relapse; by contrast, only 73% of such relapses were preceded by increasing MC in BM. When compared to VNTR, rtq-PCR predicted a significantly higher number of relapses (89% vs 42%) and anticipated them earlier (median of 56 vs 38 days). In summary, rtq-PCR determination of null alleles and indels constitutes a new validated simple procedure to monitor hematopoietic chimerism after SCT. It improves the predictive results obtained with conventional VNTR-PCR, and is specially useful when PB samples are analyzed.
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  • 9
    Publication Date: 2018-11-29
    Description: Introduction . Allogeneic stem-cell transplantation (SCT) is a curative approach in acute myeloid leukemia (AML) by providing dose-intensive chemo-radiotherapy and enhancing a graft-versus-leukemia (GVL) effect. The GVL effect is provided by alloimmune T- cells and is usually closely associated with graft-versus-host disease (GVHD). Patients with GVHD have a lower incidence of relapse, but at high grades a higher incidence of non-relapse mortality (NRM). However, GVL can also occur independently of GVHD. The use of haplo-identical SCT is rapidly increasing over the last decade due to the introduction of non-T depleted methods, in particular with post-transplant cyclophosphamide (PTCy), with expected outcomes that are similar to other donor sources. The GVL effect after T- depleted haplo-identical SCT is mostly related to natural-killer cell alloreactivity and is not necessarily associated with GVHD. However, there is no definite data whether GVL after SCT in the non-T depleted setting is similarly associated with GVHD as in the matched donor setting. Methods . We assessed the impact of acute and chronic GVHD on SCT outcomes in patients with AML following non-T depleted haplo-identical SCT with PTCy, by using a series of landmark analyses. Results . The study included 605 patients with AML in CR1 (73%) or CR2 (27%) after non-T depleted haplo-identical SCT with PTCy, given during the years 2009-2016. The median age was 53 years (range, 18-76). 71% had myeloablative conditioning and 29% had reduced-intensity conditioning . The overall rate of acute GVHD grade II-IV and III-IV was 28.4% and 8.0%, respectively. The rates of chronic GVHD all grades and extensive were 32.7% and 12.3%, respectively. The rate of relapse and NRM were 21.8% and 18.2% and the rates of leukemia-free survival (LFS) and overall survival, 2 years after SCT were 59.9% and 64.1%, respectively. 509 patients were alive and leukemia-free 100 days after transplant. 366 had no prior acute GVHD at this landmark, 107 had acute GVHD grade II and 36 had grade III-IV. The overall rate of subsequent relapse was 20.3%, 18.3% and 11.9%, respectively (P=0.60). The overall rates of subsequent NRM were 10.3%, 19.0% and 35.7%, respectively (P
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  • 10
    Publication Date: 2009-06-04
    Description: Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV− lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV− lymphoma patients.
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