Factors of local immunity in patients with rectal cancer after prolonged radiotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15164-e15164
Author(s):  
Oleg Ivanovich Kit ◽  
Aleksandr V. Snezhko ◽  
Elena Yu. Zlatnik ◽  
Inna A. Novikova ◽  
Nabil Al-haj ◽  
...  

e15164 Background: Immunological study of the blood and tumor tissues was performed in patients with rectal cancer receiving neoadjuvant chemoradiotherapy. Methods: 30 patients with rectal cancer (13 women and 17 men aged 37-68 years with stage II-III adenocarcinomas G1-G3) were divided into groups according to results of DNA cytometry and their response to neoadjuvant treatment. When tumor proliferative activity was stable for 4 weeks of treatment, patients received surgery on time (group 1), while patients with verified inhibition of tumor proliferation (the index decrease by 1.5 times and more) continued treatment for 6-8 weeks and then were operated on (group 2). The immune status of patients (T, B, NK, DN, Tregs) was assessed during treatment. Homogenates of tumor tissue samples obtained during surgery were studied for the levels of lymphocytes (flow cytometry) and cytokines TNF-α, IL-1ß, IL-1RA, IL-6, IL-8, IFN-α, IFN-γ (ELISA); tumor proliferation index was assessed by DNA cytometry. Results were analyzed by Statistica 10.0 program. Results: The dynamics of parameters of the cellular immunity was different in patients of two groups. In group 1, percentage of T lymphocytes in blood decreased (from 66.7±3.3 to 50.4±1.6%), as well as their main subsets (CD4+ and CD8+ cells: from 33.6±2.7 to 27.0±1.7% and from 26.7±2.4 to 20.7±1.7% respectively). Patients of group 2 developed an increase in levels of NK cells from 10.1±1.2 to 15.3±2.2%, and levels of CD3+, CD4+ and CD8+ cells were significantly higher than in group 1: 35.0±1.8% for CD4+ and 28.3±2.9% for CD8+ (p < 0.05). The groups also differed in indices of local immunity: DN cells levels in group 2 were lower than in group 1 (5.8±1.0 vs. 18.4±5.4%) and CD4+ were higher (36.6±3.3 vs. 26.2±3.1%; p < 0.05). Patients of group 2 showed lower levels of IL-1ß, IL-6, IL-10, while IFNγ was elevated by 5.4 times, indicating a more favorable local cytokine status of the patients, compared to group 1. Conclusions: In rectal cancer patients with effect confirmed by DNA cytometry, prolongation of chemoradiotherapy to 6-8 weeks provides the formation of a more favorable immunological microenvironment of the tumor, and in such cases it is considered appropriate.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mariana F. Coraglio ◽  
Martin A. Eleta ◽  
Mirta R. Kujaruk ◽  
Javier H. Oviedo ◽  
Enrique L. Roca ◽  
...  

Abstract Background Nonoperative management after neoadjuvant treatment in low rectal cancer enables organ preservation and avoids surgical morbidity. Our aim is to compare oncological outcomes in patients with clinical complete response in watch and wait strategy with those who received neoadjuvant therapy followed by surgery with a pathological complete response. Methods Patients with non-metastatic rectal cancer after neoadjuvant treatment with clinical complete response in watch and wait approach (group 1, n = 26) and complete pathological responders (ypT0N0) after chemoradiotherapy and surgery (group 2, n = 22), between January 2011 and October 2018, were included retrospectively, and all of them evaluated and followed in a multidisciplinary team. A comparative analysis of local and distant recurrence rates and disease-free and overall survival between both groups was carried out. Statistical analysis was performed using log-rank test, Cox proportional hazards regression model, and Kaplan-Meier curves. Results No differences were found between patient’s demographic characteristics in both groups. Group 1: distance from the anal verge mean 5 cm (r = 1–12), 10 (38%) stage III, and 7 (27%) circumferential resection margin involved. The median follow-up of 47 months (r = 6, a 108). Group 2: distance from the anal verge mean 7 cm (r = 2–12), 16 (72%) stage III, and 13 (59%) circumferential resection margin involved. The median follow-up 49.5 months (r = 3, a 112). Local recurrence: 2 patients in group 1 (8.3%) and 1 in group 2 (4.8%) (p = 0.6235). Distant recurrence: 1 patient in group 1 (3.8%) and 3 in group 2 (19.2%) (p = 0.2237). Disease-free survival: 87.9% in group 1, 80% in group 2 (p = 0.7546). Overall survival: 86% in group 1 and 85% in group 2 (p = 0.5367). Conclusion Oncological results in operated patients with pathological complete response were similar to those in patients under a watch and wait strategy mediating a systematic and personalized evaluation. Surgery can safely be deferred in clinical complete responders.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianxing Qiu ◽  
Jing Liu ◽  
Zhongxu Bi ◽  
Xiaowei Sun ◽  
Xin Wang ◽  
...  

Abstract Purpose To compare integrated slice-specific dynamic shimming (iShim) diffusion weighted imaging (DWI) and single-shot echo-planar imaging (SS-EPI) DWI in image quality and pathological characterization of rectal cancer. Materials and methods A total of 193 consecutive rectal tumor patients were enrolled for retrospective analysis. Among them, 101 patients underwent iShim-DWI (b = 0, 800, and 1600 s/mm2) and 92 patients underwent SS-EPI-DWI (b = 0, and 1000 s/mm2). Qualitative analyses of both DWI techniques was performed by two independent readers; including adequate fat suppression, the presence of artifacts and image quality. Quantitative analysis was performed by calculating standard deviation (SD) of the gluteus maximus, signal intensity (SI) of lesion and residual normal rectal wall, apparent diffusion coefficient (ADC) values (generated by b values of 0, 800 and 1600 s/mm2 for iShim-DWI, and by b values of 0 and 1000 s/mm2 for SS-EPI-DWI) and image quality parameters, such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of primary rectal tumor. For the primary rectal cancer, two pathological groups were divided according to pathological results: Group 1 (well-differentiated) and Group 2 (poorly differentiated). Statistical analyses were performed with p < 0.05 as significant difference. Results Compared with SS-EPI-DWI, significantly higher scores of image quality were obtained in iShim-DWI cases (P < 0.001). The SDbackground was significantly reduced on b = 1600 s/mm2 images and ADC maps of iShim-DWI. Both SNR and CNR of b = 800 s/mm2 and b = 1600 s/mm2 images in iShim-DWI were higher than those of b = 1000 s/mm2 images in SS-EPI-DWI. In primary rectal cancer of iShim-DWI cohort, SIlesion was significantly higher than SIrectum in both b = 800 and 1600 s/mm2 images. ADC values were significantly lower in Group 2 (0.732 ± 0.08) × 10− 3 mm2/s) than those in Group 1 ((0.912 ± 0.21) × 10− 3 mm2/s). ROC analyses showed significance of ADC values and SIlesion between the two groups. Conclusion iShim-DWI with b values of 0, 800 and 1600 s/mm2 is a promising technique of high image quality in rectal tumor imaging, and has potential ability to differentiate rectal cancer from normal wall and predicting pathological characterization.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3246-3246
Author(s):  
Ghislaine Gallez-Hawkins ◽  
Lia Thao ◽  
Simon F. Lacey2 ◽  
Joybelle Martinez ◽  
Anne E. Franck ◽  
...  

Abstract Immunity declines with age as demonstrated by cell-mediated and humoral responses to alloantigens. The susceptibility of these elderly subjects to endogenous virus infection, such as human cytomegalovirus (HCMV) reactivation, is a particular concern during the process of hematopoietic stem cell transplantation (HCT) and immune reconstitution. In this report, the host contribution to stem cell engraftment and differentiation was evaluated by comparing the HCMV immune response in older subjects (&gt; 50 y.o.) to a younger (&lt; 50 y.o.) transplant population. This was a retrospective analysis of a subset of data collected prospectively and with IRB approval for characterization of the CMV immune response of allogeneic transplant patients. Within the dataset, two groups of patients were compared. Group 1 consisted of 10 patients &gt;50 y.o. who had received reduced intensity or non-myeloablative conditioning regimen, and Group 2 consisted of 13 patients &lt;50 y.o., most of whom had received a myeloablative regimen. Because 9 of 10 in Group 1 had had CMV reactivation, Group 2 was selected from the subset of younger patients with known post-transplant CMV infection. CMV infection was defined as either a positive CMV blood culture using shell vial assay or a positive CMV PCR on plasma. Subjects were assessed on days 40, 90, 120, 150, 180, and 360 post-HCT by CMV-specific tetramer-binding assay using CD8 cells, assays for intracellular INF-g response of CD4 and CD8 cells, and a T-cell receptor excision circle (TREC) assay. There were no significant differences observed in the CD4+/IFN-g+ cell responses to CMV antigen nor were the rates of activated CD4+/CD69+/IFN-g+ cells different between the groups. Group 1 was also characterized by a robust CD8+/IFN-g+ response to HLA-specific CMV peptides, and all subjects had ≥ 2cells/μl by day 150 post-HCT. The frequency of CMV tetramer positive cells (≥ 2cells/μl) was 50% in Group 1 by day 90 post-HCT and was not statistically different from Group 2. The T cell renewal in the thymus as measured by the TREC spanned over 0 -- 92 copies/μg of total cellular DNA in Group 1 and from 0 – 129 copies/μg in Group 2 during the first year post-HCT (n.s.). In conclusion, CMV immune reconstitution in older transplant subjects, who undergo a reduced intensity or non-myeloablative regimen, is robust and, in this small sampling, did not differ from that observed in a younger adult group.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 73-73
Author(s):  
D. Wang ◽  
J. K. Smit ◽  
H. Hollema ◽  
J. T. Plukker

73 Background: Neoadjuvant chemoradiation (CRT) is important in the treatment ofesophageal cancer. Rationales are tumor-downstaging and elimination of micrometastases improving resectability and curability rate. In this study we evaluated the effect of neo-adjuvant CRT on nodal micrometastases (NMM) in pN0 esophageal cancer patients. Methods: From a prospective database, we selected a matched group of patients on cT-stage, histological type and treatment without (group 1) or with neo-adjuvant CRT (group 2). Patients were staged by EUS, PET-scan, CT-scan and EUS guided cytology. CRT was given in a randomized clinical trial and consisted of paclitaxel 50 mg/m2 and carboplatin AUC = 2 for 5 weeks and concurrent radiotherapy (41.4 Gy/23 frs). All patients (n = 19) underwent a curative intended transthoracic esophagectomy with extended 2-field nodal dissection. After reviewing routine pathological examination all tumors were confirmed as stage pN0. Four sections of every examined lymph node (n = 261) were made at different levels according to a sentinel node protocol and further analyzed immunohistochemically with anti-CK8/18 (CAM 5.2) to detect NMM. Results: Patients characteristics were equally distributed. All patients had a microscopically radical (R0) resection. In group 2 (n = 9) the response rate was 55% which was complete (CR) in 33%. The median number of resected nodes was comparable: 15 ± 6.5 and 15 ± 5.6 in both groups. Thirtheen of the 261 (5%) pN0 nodes in these 19 pts contained NMM. In group 1 (n = 10); 12 of the 136 (9%) examined pN0 lymph nodes were positive and in group 2 only one of the 125 (0.8%) examined pN0 nodes was positive (p = 0.003). NMM were found in 7 pts (70%) in group 1 and in only one patient (11%) in group 2 (p = 0.02). Interestingly, this last patient had responded well to CRT. Conclusions: Neo-adjuvant CRT seems to have a significant impact on the numbers of NMMs in esophageal cancer. Based on the presence of NMM even in patients with good responses, we still advocate a curatively intended nodal dissection. No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Rodrigo Otavio de Castro Araujo ◽  
Fernando Meton Vieira ◽  
Ana Paula Ornellas ◽  
Claudia Carrada Torres ◽  
Ivanir Martins ◽  
...  

Abstract Introduction :Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), and sphincter preservation is a desirable endpoint, but quality of life (QOL) is often impaired after treatment. Objective To evaluate QOL in five different moments of treatment in a randomized trial comparing two different neoadjuvant regimens. Methods Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (Group 1) or 5-Fu and leucovorin (Group 2) concomitant to long course radiotherapy. EORTCs QLQ C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and one year after end of treatment or stoma closure (T4). Wexner scale was used for continence evaluation at T4. A C30 summary score (Geisinger et cols) was calculated to compare QOL results.Results 32 patients were assigned to Group 1and 31 to Group 2. QOL was improved comparing T0 to T1 (mean 80.5 vs 88.0, p<0.001), and decreased comparing T1 to T2 (mean 88.0 vs 80.4, p<0.001). No difference in QOL summary was detected comparing T2 to T3 (79.8 vs 82.4, p=0.194) or T3 to T4 (83.0 vs 83.0, p=0.993). No difference in QOL was detected comparing the two treatment groups as clinical response was comparable. Mean Wexner scale score was 9.2, and a score ≥10 correlated with symptoms of diarrhea and defecation problems at T4. Conclusion : QOL improved after neoCRT but worsened following rectal resection, with no significant recovery during follow-up. Capecitabine and 5-Fu/Lv were equivalent in neoadjuvant regimen. Incontinence was high after sphincter preservation. C30 summary score was useful to detect differences in overall Quality of Life in addition to C30 multiple item questionnaire.


2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
D. V. Kuzmichev ◽  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
Zh. M. Madyarov ◽  
S. I. Tkachev ◽  
...  

Objective:to analyze treatment outcomes in patients with locally advanced rectal cancer that received various combinations of neoadjuvant chemotherapy and chemoradiotherapy.Materials and methods. In this retrospective study, we analyzed a cohort of prospectively recruited patients with stage mrT3(CRM+)/ T4N0–2M0 locally advanced rectal cancer. Participants were divided into three groups. Patients in Group 1 received preoperative longcourse radiotherapy given concurrently with capecitabine, followed by 2–6 cycles of consolidation chemotherapy with capecitabine and oxaliplatin (CapOx). In Group 2, patients initially received 1–2 cycles of induction chemotherapy with CapOx, followed by radiotherapy + capecitabine, and then consolidation chemotherapy with CapOx (“sandwich” method). Participants in Group 3 were treated with 1–3 cycles of induction CapOx chemotherapy with subsequent long-course chemoradiotherapy. After the combination treatment, all patients underwent surgery. The primary endpoint of this study was therapeutic pathomorphosis. Secondary endpoints included complete clinical response, toxicity, local recurrence, distant metastasis, and relapse-free survival.Results.This study included 155 patients (98 in Group 1, 44 in Group 2, and 13 in Group 3). Grade III toxicity was documented in 6.12 %, 4.55 %, and 23.08 % of cases in Groups 1, 2, and 3 respectively. None of the patients had grade IV toxicity. Grade III therapeutic pathomorphosis was achieved in 33.7 %, 22.7 %, and 23.1 % of patients in Groups 1, 2, and 3 respectively. Grade IV therapeutic pathomorphosis was observed in 14.3 %, 15.9 %, and 7.69 % of patients in Groups 1, 2, and 3 respectively. Complete clinical response was registered in 16.3 %, 11.4 %, and 0 % of cases in Groups 1, 2, and 3 respectively. Median follow-up was 47.2 months with no signs of progression. Relapses were observed in 1.02 % and 2.27 % of patients from Group 1 and Group 2 respectively, whereas Group 3 demonstrated no relapses. A total of 11.22 %, 13.64 %, and 23.1 % of participants from Groups 1, 2, and 3 respectively developed distant metastasis.Conclusion.Polychemotherapy used within the consolidation and «sandwich» treatment regimens is a promising option for the treatment of locally advanced rectal cancer. The efficacy of induction chemotherapy should be further studied with a larger sample.


2021 ◽  
Vol 74 (7) ◽  
pp. 1642-1648
Author(s):  
Dina V. Shorikova ◽  
Eugene I. Shorikov

The aim: To study the clinical manifestations, capillary blood saturation, frequency of respiratory failure in patients with complicated forms of acute respiratory viral infections (ARVI). Materials and methods: The study included 70 patients with ARVI (mean age was 46.5±9.2 years). Patients observed were randomized into 2 groups. In group 1 (n=30), the only basic therapy was prescribed. In group 2 in addition to the basic therapy the inhalations with high concentrated oxygen with Camomile Oil were used. Results: It is proved that the use of highly concentrated oxygen with camomile oil in the inhalation treatment regimen significantly reduces the duration of local respiratory symptoms (p<0.001) and symptoms of general intoxication (p<0.001), prolonged hospital stay decreases by an average of 5 days (p<0.001). The relief of symptoms of RF in group 2 was noted for 10 days of hospitalization with an increase in capillary blood saturation (SatO2,%) to 95.2±2.91. Absolute therapeutic efficacy (absolute efficacy) of the correction of RF during complex treatment with the addition of highly concentrated oxygen was 88.0% versus 57.0% in group 1. Relative efficacy (RE) – 0.65 [0.46-0.90], odds ratio (OR) – 0.19 [0.06-0.61], p<0.05. The positive effect of highly concentrated oxygen for local immunity state – the level of secretory immunoglobulin A (p<0.001) and lysozyme (p<0.001) was established. Conclusions: High-concentrated oxygen inhalations adding camomile oil is effective in complex treatment at patients with complicated forms of acute respiratory viral infections.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 660-660 ◽  
Author(s):  
Shailesh V. Shrikhande ◽  
Bhawna Sirohi ◽  
Alok Gupta ◽  
Vipul Sheth ◽  
Mukta Ramadvar ◽  
...  

660 Background: Neoadjuvant Chemoradiotherapy (NACTRT) improves local recurrence rate in LA rectal cancer with no survival benefit. Pathological complete response (pCR) and better tumour regression grade (TRG) is associated with improved outcome. Debate is ongoing as to what is the best time to operate—if greater downstaging can be achieved by a longer interval to surgery and have an impact on sphincter saving surgery rates. In this study, we have correlated the pCR rate and TRG post completion of NACTRT with timing of surgery (TD). Methods: This is a retrospective study of prospective database of patients with LA adenocarcinoma of rectum treated from Jan 2012 to May 2013. 89 pts who completed NACTRT (50Gy/25 fractions with capecitabine 825 mg/m2BD) followed by surgical resection were included. For response evaluation patients were divided into two groups, group 1 (TD < 60 days, n=34) and 2 (TD > 60 days, n=55). Results: Of 89 pts (median age 48 y (22-76), 64 M/25F; 16/89 (18%) had signet ring histology) 93% pts underwent R0 resection; 7% R1 resection. Response to NACTRT was CR in 8 pts, PR in 65 (73%) pts and 15 SD, 1 not assessed. Median time from completion of NACTRT to surgery was 64 d (32-141). Median number LN resected were 11 (1-50). Overall, 25 (28%) pts achieved pCR; 6/89 (7%) pts had positive circumferential resection margin. 25 (74%) patients in group 1 compared to 28 (51%) pts in group 2 underwent sphincter preserving surgery (P=0.045). Eight (24%) pts in group 1 and 17 (31%) in group 2 achieved pCR (P=0.479). The median TRG in group 1 was 2.5 and in group 2 was 2 (P=NS). In pts who achieved pCR, median TD was 67 d compared to 63 d in pts who did not achieve pCR. Of the 16 pts with signet histology 4(25%) had pCR compared to 21(29%) in those with non-signet histology (P=NS). Conclusions: We conclude that the timing of surgery is not an important variable post completion of NACTRT and our data suggests that it's possible that earlier surgery may be better for organ conservation. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomised trial.


2018 ◽  
Vol 1 ◽  
pp. 17-26
Author(s):  
Yuliya Mazur ◽  
Vira Pyrohova

Physiological cervical ectopy (CE) is commonly found in young women, during pregnancy or intake of oral contraceptives. The complicated (pathological) CE, particularly in conditions of vaginal microbiota disturbances and human papillomavirus (HPV) infection, requires intervention, including optimal treatment and effective relapse prevention approaches. Aim. The aim of the research was to investigate the complicated CE clinical course and recurrence features on the basis of a retrospective analysis of archival medical records in order to optimize the tactics of the complicated CE management and the relapse prevention measures. Materials and methods. In the observational cross-sectional retrospective study using the continuous sampling method were included 740 case reports of women, who underwent inpatient treatment of gynecological pathology in Lviv Municipal Clinical First Aid Hospital in 2006–2017. The inclusion criterion was the presence of firstly diagnosed or recurrent CE. Exclusion criteria: absence of CE colposcopic or morphological confirmation, presence of physiological CE (on conditions of cytological, bacterioscopical, bacteriological and colposcopical abnormalities absence). Subsequently, three groups were formed: control group (n=150) – healthy women, who applied for a regular gynecological examination; group 1 (n=483) – women with firstly diagnosed CE; group 2 (n=257) – women with recurrent CE. Differences in mean values were considered significant with a probability level of at least 95 % (p<0.05). Results. Patients with recurrent CE had more pregnancies (p<0.05) than the ones with firstly diagnosed CE and women of control group. The proportion of women with high parity in group 1 and group 2 was three times higher (p<0.05), than in group 3. The proportion of artificial abortions in patients of groups 1 and 2 was more than two times higher (p<0.05), than in women in the control group, group 2 patients had more miscarriages and missed miscarriages(p<0.05) in comparison to the control group. Menarche in patients with recurrent CE set in later in comparison to women of control group (p<0.05). In group 2, the proportion of women with polymenorrhea was three times higher (p<0.05), than in group 1 and control group respectively. The compromised gynecological history was more often (p<0.05) detected in group 1 and group 2, than in the control group. In patients with recurrent CE a third of gynecologic diseases in the history (32.30±2.92 %) and 23.60±1.93 % - in patients with the firstly diagnosed CE were pelvic inflammatory diseases, significantly (p<0.05) higher in comparison to the control group (3.33±1.47 %). Almost half of patients in group 1 (48.25±2.27 %) and group 2 (47.84±3.13 %) had the history of frequent infectious diseases, this indicator was significantly (p<0.05) higher in comparison to the control group (24.67±3.52 %). In patients with recurrent CE chronic diseases of different etiology were diagnosed more often (p<0.05) - their share made up 8.24±1.72 %, while in patients with firstly diagnosed CE - 4.33±0.92 %, in women of the control group - 1.33±0.94 %.The firstly diagnosed CE was more frequent (in comparison to recurrent CE) (p<0.001) characterized by asymptomatic course, whereas about half of patients with recurrent CE (46.69±3.11 %) presented with different complaints. Cytological indicators of cervicitis were found more often in patients with firstly diagnosed and recurrent CE, than in women of control group, as well as vaginal candidosis (p<0.05). Patients with recurrent CE more often (p<0.05) underwent diathermoconization (24.12±2.67 %) and cryodestruction of the cervix (8.17±1.71 %) in comparison to patients of group 1. The most often performed treatment method in patients of both groups was diathermoconization. Treatment methods aimed to restore the hormonal balance, to normalize the state of vaginal microbiota were rarely found in both group 1 and 2, drugs that affect the reparation and regeneration of the epithelium have not been used in any case. Conclusions. Recurrent symptomatic complicated CE should be interpreted as a complex problem that requires a multi-polar approach aimed at hormonal homeostasis, local immunity, and vaginal biocenosis normalizing. These measures should precede invasive treatment and further create optimal conditions for regeneration of the cervix.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1075-1075
Author(s):  
Evelyne Willems ◽  
Emilie Castermans ◽  
Frédéric Baron ◽  
Etienne Baudoux ◽  
Nadine Wanten ◽  
...  

Abstract Background: In a previous pilot study, we demonstrated that CD8-depletion of the graft apparently reduced the severity of AGvHD without impairing the GvL effect after peripheral blood stem cell (PBSC) transplantation with a nonmyeloablative conditioning (NMSCT). Aim of the study: To evaluate the effect of CD8-depletion on graft rejection, AGvHD and CGvHD, and relapse. Patients: 53 patients were randomised between CD8-depletion (group 1) (n=25) and no manipulation (group 2) (n=28). Two patients in the CD8 group were excluded for poor CD34+ cell count collected. Diagnoses were: AML (n=3), CML-AP (n=2), MDS (n=14), MPD (n=3), CLL (n=5), NHL (n=14), MM (n=8) and RCC (n=2). Median age was 57 (range 36–69) yrs. After conditioning with 2 Gy TBI with (n=39) or without (n=12) fludarabine, patients received PBSC from family (n=21) or unrelated (n=30) HLA-matched donors. CD8-depletion was carried out using the Eligix system and GvHD prophylaxis consisted in CyA and MMF. Results: CD8 depletion removed 96% of CD8+ cells so that the number of CD8+ cells infused was 6.8 vs 136.8 x108 cells/Kg in group 2 (p&lt;0.0001). AGvHD of any grade was observed in 13 (56%) patients in group 1 and 17 (61%) in group 2 (NS); it was grade 3–4 in 1 (4%) and 5 (18%) patients in groups 1 and 2, respectively (NS). Limited and extensive CGvHD developed in 3 and 1 patients in group 1 and in 7 and 2 patients in group 2, respectively (NS). Nine patients in group 1 and 12 in group 2 received unmanipulated DLI for poor chimerism or disease progression. Eight (3 initial and 5 late) graft failures were observed in group 1 and one (late) in group 2. Full donor chimerism was achieved in 57% (group 1) and 50% (group 2) at day 100, and in 73% (group 1) and 59% (group 2) (NS) at 1 yr. The 2-yr OS and PFS rates are 55% and 43 % in group 1 vs 59% and 46% in group 2, respectively (NS). Four (17%) patients died of their disease in group 1 vs 3 (11%) in group 2 (NS). Two patients died of severe AGvHD in group 2 vs none in group 1. Conclusion: In vitro CD8-depletion results in higher rates of graft failure after NMSCT. The incidence of acute and chronic GvHD is not reduced but there is a trend towards reduced severity of AGvHD. Relapse and survival rates are not changed by this strategy.


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