Converting Mixed Chimerism to Full Donor Chimerism in Recipients of Campath-Containing Reduced Intensity Transplants Reduces the Relapse Risk and Results in Significantly Improved Survival Compared to Those with Persistent Full Donor Chimerism.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2026-2026
Author(s):  
Bronwen E. Shaw ◽  
Jenny L. Byrne ◽  
Emma Das-Gupta ◽  
Ian Carter ◽  
Nigel H. Russell
Keyword(s):  
Residual Disease ◽  
Complete Response ◽  
Disease Relapse ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Group D ◽  
Reduced Intensity

Abstract Donor leucocyte infusions (DLI) are frequently required following reduced intensity conditioned (RIC) allografts to convert mixed donor chimerism (MC) to full donor chimerism (FDC). The rationale is to prevent tolerance developing and therefore to maximise the graft versus tumour (GvT) responses. However, the impact that the chimeric state has on disease relapse and transplant outcome remains controversial. To address this we analysed the impact of the complete (global) chimerism pattern in 125 recipients of RIC transplants. The transplants were performed for a broad range of malignant haematological diseases. Conditioning regimens consisted of fludarabine, melphalan, campath (65), fludarabine, busulphan, campath (13), BEAM, campath +/− fludarabine (38) and other (9). The donors were HLA matched siblings (62, 50%), HLA mismatched siblings (6, 5%), matched unrelated (29, 23%) and mismatched unrelated (28, 22%). The median patient age was 52 and donor age was 42. The median follow up was 823 days (range 99–2674). Four patterns of chimerism were seen: A. always 100% donor chimerism (68, 54%), B. persisting MC post transplant including cases refractory to DLI (27, 22%) C. MC post transplant with subsequently development of FDC either spontaneously or post DLI (22, 18%), D. lost DC and had autologous reconstitution (8, 6%). A number of patients in both groups B and C had FDC early post transplant. In group A 18 (26%) patients received DLI for relapse or residual disease. A complete response was achieved in 6 (35%). In group B 10 (37%) patients had DLI: 4 for MC, 1 for residual disease, 2 for relapse and 3 for both MC and relapse; only partial responses were seen (20%). In group C DLI was given in 14 (64%) patients: 4 for MC, 5 for residual disease, 3 for relapse and 2 for both MC and relapse. A complete response was achieved in 12 (86%). The risk of relapse at 2 years was significantly associated with the pattern of chimerism (p=0.012) and was greatest for group D (75%). Patients in group C (DLI responders) had a relapse rate of 24% compared to 61% in group B (DLI non-responders). In group A it was 37%. This resulted in a significant survival advantage for patients in group C as compared to all other groups (p=0.009). Predicted overall survival at 2 years was 95% in group C, but 54% in group A, 57% in group B, and 58% in group D. We conclude that patients with MC who later achieve FDC have a lower incidence of disease relapse than those with persistent MC, supporting the use of DLI in this group. However the observation that the patients receiving DLI to achieve FDC have a superior outcome to those patients with persistent FDC (group A) suggests that this group may have benefited from a GvT effect against minimal residual disease. The use of pre-emptive DLI in this group (despite FDC) may reduce the risk of relapse and improve transplant outcome.

Low Pre-DLI Lymphocytes Counts Are Predictive of Good Disease Responses in Patients with Mixed Chimerism Following Campath-Containing Reduced Intensity Transplants.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 261-261
Author(s):  
Bronwen E. Shaw ◽  
Jenny L. Byrne ◽  
Emma Das-Gupta ◽  
Ian Carter ◽  
Nigel H. Russell
Keyword(s):  
Lymphocyte Count ◽  
Residual Disease ◽  
Suppressor Cells ◽  
Mixed Chimerism ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Significant Difference ◽  
Group B ◽  
The Impact ◽  
Reduced Intensity

Abstract Following reduced intensity conditioned (RIC) transplants, donor leukocyte infusions (DLI) are frequently used either to convert mixed chimerism (MC) to full donor chimerism (FDC) or for residual or relapsed disease. Unfortunately, DLI are not universally successful and few factors are known (e. g disease type and level of pre-DLI chimerism) which predict for good responses. We analysed the impact of the chimerism pattern in 125 recipients of (CAMPATH containing) RIC transplants for malignant diseases. Of these, 68 (55%) had FDC (group A), 49 (39%) developed MC and 8 (6%) lost DC and had autologous reconstitution (group D). The patients who developed MC could be further subdivided into those with persisting MC post transplant (27, 55%; group B: non-responders) and MC post transplant with subsequently development of FDC (22, 45%; group C: responders). These two groups were analysed further. The median patient age was 55 (range: 19–71). The donors were siblings (22) or unrelated (27). The diseases were as follows: AML/MDS 14, CML 4, Myeloma, 4, lymphoma/CLL 26, MF 1. Stem cell source was PBSC (38) and bone marrow (11). Conditioning consisted of fludarabine, melphalan and campath (fmc) in 24 patients; fludarabine, busulphan and campath (fbc) in 5; BEAM, campath +/− fludarabine in 18 and FLAG in 2. There were no significant differences in any of these features between groups B and C. 25/49 patients received DLI. This was for disease relapse in10 patients, residual disease in 6 and MC alone in 8 (Unknown in 1). A complete disease response (CDR) was seen in 9/14 (64%) evaluable cases. There was a highly significant difference in CDR between the two groups (group B: 0/4, group C: 9/10, p=0.005). The reason for the difference in response rate was investigated. Median time to DLI was 196 days (range: 57–2123), not significantly different between the groups (p=0.561). The indication for and total number of DLI, the underlying disease and the degree of pre-DLI donor chimerism were not significantly different. In addition there was no significant difference in the incidence of post DLI GvHD (p=0.137), although this was 10/13, 77% in those who responded and 2/5, 40% in those who did not. Conversely, there was a significant difference in the pre-DLI lymphocyte counts (p=0.036). The median count was 2.24 × 109/l. In group B 3/11 (27%) were below this while 10/14 (71%) in group C were below this. The pre-DLI lymphocyte count was not significantly correlated with the time post transplant at which DLI was given, the type of donor, the indication for DLI or the disease, conditioning or post transplant immunosuppression regimen. The predicted overall survival at 2 years was significantly better in group C than in group B (95% versus 57%, p=0.002). This was largely due to the higher relapse risk in group B (77%) compared to group C (32%) (p=0.043). In conclusion, in patients with MC, the development of FDC was significantly associated with a superior OS. In those receiving DLI, the factor most significantly predictive for a ‘responsive’ (C) versus ‘non-responsive’ (B) pattern was the presence of a low pre-DLI lymphocyte count, suggesting that a lack of ‘space’ for expansion or increased suppressor cells in the lymphoid compartment mediate DLI resistance. We postulate that DLI ‘non-responders’ (those with higher lymphocyte counts) may be converted to ‘responders’ by the addition of pre-DLI lymphoreduction, thus reducing relapse and improving outcome.

scholarly journals The Impact of Pain Control on Invasive Clinical Procedure on Children with Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5827-5827
Author(s):  
Jiayi WANG ◽  
Yingyi He ◽  
Zhimin Liang ◽  
Tiezhen Ye ◽  
Hui Zhang
Keyword(s):  
Local Anesthesia ◽  
Pain Control ◽  
Adverse Reactions ◽  
Low Dose ◽  
Invasive Procedure ◽  
Anesthesia Group ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Group D

Abstract Background: Palliative care is becoming more and more important for systemic cancer treatment in developed countries, while this remains infamous topic in developing countries, such as in China. Contemporary treatment strategies have greatly contributed to the improved outcome in childhood cancer patients, survivorship comes at the cost of developing some treatment-related health condition, such as pain-related depression, chronic pain etc. Thus, developing a well-tolerated pain control methods is of great importance within the cancer treatment. Objective: To evaluate the impact and outcome of different pain control applications on invasive procedure in children with leukemia, and record the adverse reactions. Methods: The enrollment of childhood leukemia patients in our hospital from November 2011 to November 2016 were divided into four groups, that is successively midazolam + local anesthesia (group A), midazolam + ketamine +local anesthesia (group B), midazolam + fentanyl + local anesthesia (group C), and fentanyl + propofol + local anesthesia (group D). The efficacy and adverse reactions were systemically recorded. The inter-group diffferences were calculated using x2 test. Results: No significancewas observed in age, gender, and disease distribution in these four groups by ANOVA ONEWAY analysis. The sedation outcome is more pronunced in group D than others. Also, the quality of procedural pain control in group D was the best (P<0.01). In terms of the analgesic effect, group B and D were better than that group A and C. There was significant difference in Hallucination was more easily detected in group B and C. Systemic recovery was delayed in group B other than group A, C, and D. Basing on the survey, we did found that the family members were more willing to accept pain control treatment for their sick kids under the safety assurance. The compliance was significantly improved in group D. Conclusion: Upon adequate auxiliary breathing preparation and rigorous monitor, propofol combined with low-dose fentanyl was the best sedative/analgesic option for pain control within leukemia patients receiving invasive procedure.The outcome of propofol combined with low-dose fentanyl wasvery safe, satisfactory and compliable. Up to now, this study is the first pain control study for invasive procedure in China mainland, it deserves being paid attention. Disclosures No relevant conflicts of interest to declare.

Full Donor Chimerism in Both Plasma and Mononuclear Cell after Haematopoietic Stem Cell Transplant (HSCT) at D28 Is Predictive of Acute Graft-Versus-Host Disease but Not Disease Relapse or Graft Failure.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5114-5114
Author(s):  
Shing Yan Ma ◽  
Wing Yan Au ◽  
Albert K.W. Lei ◽  
Eric Tse ◽  
Chor Sang Chim ◽  
...  
Keyword(s):  
Mononuclear Cell ◽  
Graft Rejection ◽  
Acute Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Group ◽  
Disease Relapse ◽  
Donor Chimerism ◽  
Group A ◽  
Plasma Donor ◽  
Group B

Abstract Mononuclear cell mixed donor/recipient chimerism has been shown extensively to have high predictive value in disease relapse and graft rejection. Recently, donor DNA in plasma of transplant recipient has been suggested as a potential tool for post HSCT monitoring for disease relapse and graft rejection but its role has not been defined. Moreover, the impact of GVHD on plasma donor DNA remains unknown. In the current study, both the plasma and mononuclear cell donor chimerism of 40 patients post HSCT (mean age = 40; 35 myeloablative, 5 non-myeloablative) were analyzed at D28. Each patient was followed-up for one year or when disease relapse/graft rejection occurred. GVHD of grade II or above was also recorded to establish its correlation with the chimerism status. At D28, all patients were engrafted and alive. 5 (13%) patients had full donor chimerism in both plasma and mononuclear cell (Group A), 7 (18%) patients had full donor chimerism in the mononuclear cell only but not the plasma (Group B) and 28 (70%) patients failed to have full chimerism in both plasma and mononuclear cell (Group C). The sex, age, HLA-matching, donor relationship and ABO blood group matching had no impact on the chimerism status. None of the Group A patient had disease relapse/graft rejection at 1 year when compared to 13/35 (37%) of Group B and C patients (p=0.154, not significant).However, all the patients in Group A had acute GVHD which was significantly more than those in Group B and C (5/5 vs 12/35, p=0.009) and the acute GVHD would not alter the chimerism status. These results provide a foundation for further research on the potential role of plasma donor chimerism in predicting disease relapse/graft rejection and GVHD so that early intervention can be instituted.

scholarly journals Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-5 inhibitors

2018 ◽  
Vol 90 (1) ◽  
pp. 44 ◽  
Author(s):  
Rossella Mazzilli ◽  
Gloria Angeletti ◽  
Soraya Olana ◽  
Michele Delfino ◽  
Virginia Zamponi ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Psychotropic Drugs ◽  
Remission Rate ◽  
Antidepressant Drugs ◽  
Serum Testosterone ◽  
Hormonal Profile ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Group D

Objectives: The aim of this study was to assess the prevalence of patients with Erectile Dysfunction (ED) receiving psychotropic drugs, the impact of these drugs on hormonal profile, and the efficacy of PDE5-i in these patients. Materials and methods: We recruited 1872 patients referring for ED to our Andrology Unit. Assessment included serum testosterone, gonadotropins, TSH, prolactin, and PSA, and the IIEF-5 questionnaire for ED diagnosis. Inclusion criteria were age 21-75 years and IIEF-5 total score ≤ 21; exclusion criteria included hypogonadism, diabetes mellitus, previous prostatectomy, other medication intake, and ED diagnosis prior to psychotropic drug treatment. Efficacy was rated with the IIEF-5 (remission: total score ≥ 22). Results: The prevalence of ED patients treated with psychotropic drugs since ≥ 3 months was 9.5% (178/1872), subdivided according to the drugs used into: Group A, 16 patients treated with atypical antipsychotics (9.0%); Group B, 55 patients with benzodiazepines (30.9%); Group C, 33 patients with antidepressant drugs (18.5%); and Group D, 74 patients with multiple psychotropic drugs (41.6%). Patients in Group A were significantly younger than other groups (p < 0.05). The hormonal profile presented only higher prolactin level in patients treated with antipsychotics, alone or in combination (p < 0.05). Overall, 146 patients received PDE5-i. Remission rate, after three months of treatment, was significantly higher in Group B compared to C and D groups (p < 0.05). Conclusions: A substantial portion of patients receiving psychotropic drugs show ED. Sexual performance in these patients benefits from PDE5-i. Age, effects of psychiatric disorders, psychotropic drugs, and PDE5-i treatment modality accounted for variability of response in this sample.

scholarly journals An Observational Study to Evaluate the Efficacy and Quality of Life Provided by Netupitant and Palonosetron Regimen against Ondansetron in Management and Prevention of CINV

2021 ◽  
Vol 68 (2) ◽  
Author(s):  
Meghana Dutta ◽  
Rooha K
Keyword(s):  
Quality Of Life ◽  
Treatment Plan ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Health Concern ◽  
Patient Reported ◽  
Group A ◽  
Group B ◽  
The Impact

Cancer is a public health concern amongst millions of humans and claims hundreds of lives every year. The maximum worry-inducing side effect of cancer treatment is nausea and vomiting. Therefore, stopping and managing chemotherapy-induced nausea and vomiting is an important part of a cancer patient’s treatment plan. In this study, we evaluated the efficacy and quality of life provided by two commonly used antiemetic regimens in the management and prevention of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. We assessed patient-reported nausea, vomiting, use of rescue medication, and Functional Living IndexEmesis (FLIE) questionnaire results, and used them as parameters to make comparisons. We also examined the percentage of patients showing complete response (CR; no emesis and non-use of rescue antiemetics), and the impact of CINV on patient’s daily life during the acute and delayed phases. The results show that the complete response is achieved by 26 patients in group-B and 18 patients in group-A, from the total 60 patients, while the FLIE scores indicated better quality of life is maintained in group-B (76.6%). In the study, the predominance of Netupitant and Palonosetron regimen to Ondansetron was demonstrated.

scholarly journals Impacts of Mycoplasma gallisepticum Vaccine on Newcastle Disease Vaccination and Protection in Parent Stock Flocks

1970 ◽  
Vol 24 (1) ◽  
pp. 62-64
Author(s):  
M Rayhan Faruque ◽  
Jens P Christensen
Keyword(s):  
Newcastle Disease ◽  
Haemagglutination Inhibition ◽  
Clinical Signs ◽  
Mycoplasma Gallisepticum ◽  
Post Mortem ◽  
Group A ◽  
Parent Stock ◽  
Group B ◽  
The Impact ◽  
Group D

The present study reports on the impact of Mycoplasma gallisepticum (MG) vaccination on vaccine respond and subsequent protection against Newcastle disease (ND) in parent stock flocks of Department of Livestock Services (DLS) using MG killed vaccine and conventional ND vaccines. Birds were grouped into four groups, each consisted of 50 birds from the same flock. Group A birds were vaccinated with ND, group B with ND and MG, group C with MG, and group D birds were kept as unvaccinated control. The parameters studied included detection of ND antibody, MG seroprevalance, mortality (%), and cause of death. The sera of groups B and C were sero-positive after administration of MG vaccine. The haemagglutination-inhibition (HI) titres of group A were higher than group B from week 4 after administration of MG vaccine to the birds of group B. The mortality was very low; one bird of group C died at week 5 due to traumatic injury and another bird of group D died at week 2 due to infectious bronchitis virus (IBV). After challenge, birds of groups A and B showed no clinical signs and normal post mortem findings were found. Birds of groups C and D showed clinical signs from day 3 and different pathological lesions were found in post mortem. The MG vaccination did not improve other parameters. Therefore, inoculation of MG INAC vaccine is not justified and is too expensive at farm levels.Keywords: Mycoplasma gallisepticum (MG) vaccine, Newcastle disease (ND) vaccination, Protection, MortalityDOI: http://dx.doi.org/10.3329/bjm.v24i1.1240   Bangladesh J Microbiol, Volume 24, Number 1, June 2007, pp 62-64 

Results of a Prospective Clinical Trial of Pre-DLI Lymphoreduction Using Oral Fludarabine In Patients with Mixed Chimerism Post Allogeneic Transplant.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1299-1299
Author(s):  
Bronwen E. Shaw ◽  
Jenny Byrne ◽  
Emma Das-Gupta ◽  
Mark Ethell ◽  
Daniel Figueroa ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Lymphocyte Count ◽  
Response Rates ◽  
Mixed Chimerism ◽  
Disease Relapse ◽  
Time Points ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Reduced Intensity

Abstract Abstract 1299 Donor leukocyte infusions (DLI) are frequently used following reduced intensity conditioned (RIC) transplants to convert mixed donor chimerism (MC) to full donor chimerism (FDC). In part, due to the significant correlation, which several studies have shown between persisting MC and an increased risk of disease relapse. There are few factors which have been consistently shown to predict for responsiveness. We recently reported response rates (conversion to FDC) of approximately 50% in patients with MC. Patients with a high peripheral blood lymphocyte count pre-DLI were significantly less likely to respond than patients with a low lymphocyte count (33% compared to 89%) (Shaw BE et al, BBMT 2007;13(5):550-9). Based on these and other data we hypothesised that the use of a lymphoreducing agent pre-DLI in those with a high lymphocyte count would enhance DLI responsiveness and hence improve clinical outcomes. We instituted a prospective pilot trial (CCR2942) to investigate this hypothesis. Inclusion criteria were: 1. mixed chimerism in whole blood (< 95% donor), 2. previous reduced intensity transplant for a haematological malignancy or failure to respond to a previous dose of DLI and 3. a lymphocyte count of >1.0 × 109/l. Patients consenting to the trial received three doses of oral fludarabine as an outpatient at 25mg/m2 on day -7, -6 and -5. DLI was given on day 0. The starting dose of DLI for patients with MC alone was 5 × 105 CD3/kg (unrelated donor) or 1 × 106 CD3/kg (sibling donor). Higher doses were used in those with evidence of both disease and MC. Samples were collected at various time points for Ki67 and T cell subset analysis. To date, 15 patients have been entered onto the trial and 13 have reached the study end point (day 90 chimerism) (1 early death due to leukaemia relapse, 1 currently too early for assessment). Each received a single dose of DLI. The disease categories were: AML (8), ALL (1), MDS (2), T-PLL (1), HD (1), DLBCL (1) and MCL (1). Only 2 patients had co-existing evidence of disease (morphological relapse of AML, 2% positive by immunophenotyping in T-PLL). The mean age was 51 years (range: 22–66), 9 males and 6 females. 11 HLA-matched sibling donors and 4 10/10 allele matched unrelated donors. The majority of patients (11) had conditioning with fludarabine, melphalan and alemtuzumab, with cyclosporine post transplant. The median time to DLI post-transplant was 7.2 months (range: 3–11). The median percentage of donor chimerism pre-DLI was 85% (range: 18–93). The median lymphocyte count pre-DLI was 1.3 (range: 1.0–2.7). Of the 13 eligible patients, 9 (69%) have responded to a single dose of DLI (CR=8 (>95%), PR=1 (chimerism 94% donor at study end)). Three patients developed GvHD – grade 1 (liver), grade III (liver/GI), grade IV (liver/skin). GVHD resolved completely in all cases and all patients achieved FDC. 3 patients reactivated a virus (CMV, 2 × EBV), although not all required treatment. The chimerism level pre-transplant was associated with response, with those below the median having a trend towards a worse response rate (p=0.052, Fishers exact test). As only 2 patients had measurable disease at study entry, this parameter was not statistically assessed, however the patient with a frank relapse of AML progressed rapidly despite DLI, suggesting that this strategy may not be sufficiently aggressive in that setting. We analysed the patterns in T cell subsets (CD8, CD4 and Tregs). There was a significant decrease in the absolute numbers of CD8 and CD4 cells between day -7 and day 0, while the absolute number of Tregs was not significantly changed. Interestingly, we found significantly higher absolute counts at all time points in both CD8 and Treg subsets in the DLI responders, compared to non-responders (unpaired t-test, mean: 13.66 vs 0.03, p<0.0001 and mean: 0.018 vs 0.008, p<0.004 respectively). There were no significant differences in CD4 counts. In conclusion, in patients with MC, the use of pre-DLI lymphoreduction results in good response rates, superior to a historical cohort. The incidence of GVHD and adverse events is low. Preliminary finding suggest that both CD8 and Treg subsets may play a role in responsiveness. For patients with very low levels of donor chimerism or frank disease relapse an increased intensity of pre-DLI chemotherapy is likely to be necessary. Larger patient numbers and randomised studies are required to investigate the efficacy of this approach further. Disclosures: No relevant conflicts of interest to declare.

The Presence of Minimal Residual Disease Pre- and Post-Transplant Is Predictive of Outcome in Recipients of Allogeneic Transplantation for Acute Myeloid Leukaemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2601-2601
Author(s):  
Fiona L Dignan ◽  
Chloe Anthias ◽  
Mark E Ethell ◽  
Ricardo Morilla ◽  
Alison Morilla ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Multivariate Analysis ◽  
Acute Myeloid Leukaemia ◽  
Residual Disease ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Post Transplant ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Abstract 2601 Poster Board II-577 Minimal residual Disease (MRD) monitoring is known to be of importance in guiding management in patients with acute myeloid leukaemia (AML) treated with chemotherapy. Many subtypes of AML do not, however, have a molecular marker available for MRD monitoring and in this setting the use of multiparametric flow cytometry (MFC) has been evaluated. Few studies have investigated the impact of MRD in the setting of allogeneic transplantation for AML. We speculate that, as with chemotherapy, the outcome in MRD positive patients will be inferior to MRD negative patients due to an increase in disease relapse. In order to investigate this hypothesis we studied 74 patients who underwent allogeneic transplantation for AML in a single centre from 2004–2008. The median age was 47.1 years (range: 20.8–70.1). The overall survival at 2 years was 48% with a median follow-up of 1.96 years. Conditioning was myeloablative in 37 patients and reduced intensity in 37 patients. 46 patients had T cell depletion as part of the conditioning. 48 patients had an unrelated donor and in 26 a sibling donor was used. MRD analysis by MFC (sensitivity 0.04%)in the bone marrow was performed pre-transplant and on day 28 and 100 post-transplant. Using conventional criteria, 47 patients were in CR1, 15 in CR2, 4 in CR > 2 and 8 patients were not in CR at the time of the transplant. Survival at 2 years was 58%, 50%, 25% and 12,5% respectively (p=0.001). We examined the impact of MRD by MFC in patients who were in CR at transplant. Survival at 2 years in patients who were MRD negative (MRD-) pre-transplant was 70% compared to 29% in those who were MRD positive (MRD+) (p=0.003). In multivariate analysis, the most significant factor affecting outcome was being MRD+ pre-transplant (RR of death of 3.04, p=0.011; 95% CI 1.2–7.1). Interestingly, there was no significant difference in survival seen between patients who were MRD+ and those who were not in CR (by conventional tests) pre-transplant (p=0.305). The MRD analysis at day 28 was not predictive of outcome. However, in patients alive and without relapse at day 100, MRD analysis was predictive of outcome (2 year: MRD-70% vs 27% MRD+; p=0.045). In patients who were MRD- at both time-points, survival at 2 years was 81% compared to 42% in those who were MRD+ at one or both time-point (p=0.040). The incidence of disease relapse was 32% at 2 years and non-relapse mortality (NRM) was 8% at day 100 and 22% at 1 year. Interestingly, while the pre-transplant stage was predictive of relapse (2 years: those in CR 28% (no difference for CR1 or >CR1) compared to those not in CR 63%, p=0.004), the presence of MRD positivity was not; neither pre-transplant (p=0.47) nor at day 100 (p=0.29). Conversely, the NRM was significantly higher in those who were MRD+ pre-transplant, but not at day 100. The NRM at day 100 was 4% in MRD- patients and 15% in MRD+ patients (p=0.01). In multivariate analysis this conferred a RR of NRM of 2.12 (p=0.014; 95% CI 1.1–3.8) to MRD+ patients. We conclude that the presence of MRD detected by flow cytometry pre- and day 100 post-transplant is predictive of a worse patient outcome. Interestingly this appears to be predominantly due to an increase in NRM rather than an increase in disease relapse. We speculate that differences in the duration and/or intensity of GVHD prophylaxis may be implicated in this finding and we are currently investigating this hypothesis. A better understanding of these factors will allow us to tailor treatment based on MRD status in an intelligent fashion. Disclosures: No relevant conflicts of interest to declare.

TCRbeta Gene Rearrangements for Detection and Monitoring of Minimal Residual Disease after Allogenic Stem-Cell Transplantation in Patients with Advanced Mycosis Fungoides and Sézary Syndrome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2340-2340
Author(s):  
Laura Corti ◽  
Giorgia Saporiti ◽  
Elisa Fermo ◽  
Emilio Berti ◽  
Luigia Venegoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Residual Disease ◽  
Patient Specific ◽  
Gene Rearrangements ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Skin Biopsies ◽  
Pcr Assays ◽  
Minimal Residual ◽  
Reduced Intensity

Abstract Advanced tumor-stage mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas (CTCL) characterized by very poor prognosis. Allogeneic haematopoietic stem cell transplantation (allo-SCT) represents an experimental treatment which has been shown to be very effective in achieving long lasting complete remission, possibly leading to cure in selected patients. However, high transplant-related mortality (TRM) limit its feasibility in the vast majority of patients with CTCL. Reduced-intensity conditioning regimens have been demonstrated to decrease TRM, allowing gradual establishment of full donor chimerism and possible graft-versus-lymphoma effect. In this setting, evaluation of minimal residual disease (MRD) is particularly useful to guide post-transplant strategies such as donor lymphocyte infusion (DLI). Detection of TCRgamma-chain gene rearrangements, owing to the relatively limited complexity of its genetic elements, is routinely used to detect MRD in T-cell malignancies. Nonetheless, due to the extensive combinatorial repertoire and the large hypervariable regions, TCRbeta represents the best target for MRD monitoring, allowing more sensitive detection of patient-specific rearrangements. With this study, we aimed to identify patient-specific TCRbeta rearrangements to monitor MRD in patients enrolled in a clinical phase II trial of reduced intensity allo-SCT for advanced stage refractory MF/SS. Skin biopsy and peripheral blood samples at diagnosis and at different time points after transplant were obtained from 6 out of 9 evaluable patients, all having achieved clinical complete remission (still enduring in 5). The BIOMED-2 multiplex TCRbeta PCR heteroduplex assay (InVivoScribe Technologies, USA) was used for identification of monoclonal TCRbeta rearrangements, clonal PCR products were directly sequenced in both directions using the complete set of V or J primers, and V, D, J segments identified using the ImMunoGeneTics database (http://imgt.cines.fr). Then, clonespecific PCR assays were performed on samples collected from every single patient and specificity tested by parallel amplification of normal polyclonal DNA samples. In all patients a monoclonal TCRbeta rearrangement has been sequenced allowing to obtain clone-specific primers for PCR assays. In 2 patients we identified the presence of a MRD at the early controls after transplant (+2 and +3 months, respectively) when both were polyclonal by standard TCRgamma rearrangement; clone-specific PCR assays for TCRbeta became negative afterwards, in concomitance with the achievement of full donor chimerism. In 3 patients polyclonality of TCRbeta was observed in all post-transplant controls. One developed chronic cutaneous GvHD and skin biopsies verified the absence of clone-specific T-lymphocytes. In another patient, all post-transplant assays performed by the standard TCRgamma-rearrangement were persistently positive, suggesting the presence of a non disease-specific monoclonality. The last of the 6 patients relapsed 52 months after transplant. Retrospective clone-specific analysis of TCRbeta rearrangements in DNA from skin biopsies unveiled the presence of molecular relapse already 24 months before, whereas standard TCRgamma assays became positive only after clinical relapse. Altogether, we observed good stability of monoclonal TCRbeta rearrangements over time. Our results suggest that the analysis of TCRbeta is more sensitive and more specific than the analysis of standard TCRgamma for detection of MRD in CTCLs, allowing earlier identification of relapses and adopatiention of pre-empatientive treatment such as DLI. With this method, we also demonstrated disappearance of MRD in concomitance with the achievement of full donor chimerism after allo-SCT. Finally, disease clone-specific TCRbeta rearrangement detection might be helpful in distinguishing cutaneous manifestations of acute GvHD from early relapse of MF. TCRbeta analyses of samples from the remaining 3 evaluable patients are ongoing and will be included in the final presentation.

P–498 Patient’s pregnancy rates after IVF fresh embryo transfer positively correlates to the number of visual connections to live blastocyst development images of own embryos

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Garcia-Faura ◽  
B Marques ◽  
V Montalvo ◽  
F Garcia ◽  
M Lopez-Teijon
Keyword(s):  
Time Lapse ◽  
Pregnancy Rates ◽  
Blastocyst Transfer ◽  
Blastocyst Development ◽  
Single Blastocyst Transfer ◽  
Group A ◽  
On Line ◽  
Group B ◽  
The Impact ◽  
Group D

Abstract Study question Looking at time-lapse images of own embryos during the five days of culture, as a patient’s active behaviour, may help to increase pregnancy rates? Summary answer The number of visual connections to live blastocyst development images of own embryos positively correlates to patient’s pregnancy rates after fresh single blastocyst transfer. What is known already In human reproduction, despite the evidence that infertility itself and reproductive treatments can produce anxiety and stress, the impact of emotions on pregnancy outcomes is unknown and probably underestimated. The interaction between psyche, nervous, immune and endocrine systems (PNIE) is well known and has been applied to understand and treat different pathological conditions. Patient’s active behaviour during IVF treatments appears to be a positive strategy to decrease women’s anxiety and stress, thus to increase fertility quality of life and pregnancy outcomes. Study design, size, duration Retrospective comparative study of 934 patients undergoing fresh IVF cycles during three years. To avoid any bias related to oocyte and embryo factors, we only included egg donation cycles in the study, and ≥3BB (Gardner score) single embryo transfers. All embryo cultures were performed in time-lapse incubator and patients could connect on-line to their embryo’s images before single blastocyst transfer. We evaluated the impact of visual connections to live embryo images on pregnancy rates. Participants/materials, setting, methods On day one of embryo culture, consenting patients received an individualized and secure link allowing them to connect on-line to images of their own embryos any time during the five days of culture. Patients were divided in five groups depending on the number of on-line visualisations (A = 0; B = 1–10; C = 11–20; D = 21–30; E &gt; 30). Pregnancy and clinical pregnancy rates were compared between the five groups. Chi-square test for a large contingency table was performed to compare all groups Main results and the role of chance The distribution of patients in the five groups, based on number of visualizations, resulted as follows: 287 in group A; 328 in group B; 156 in group C; 80 in group D; 83 in group E. The five groups were homogeneous and there were no statistically significant differences in recipient’s ages (A 42.8±3.9 years; B 41.9±3.9 years; C 41.8±4.5 years; D 42.8±4.1 years; E 41.9±4.4 years) and in donor’s ages (A 25.5±4.3 years; B 26.9±4.4 years; C 27.1±4.2 years; D 26.4±4.5 years; E 26.5±4.1 years) among the five groups. We observed a progressive positive trend between the number of on-line visualisations and pregnancy rates, reaching statistical significance for group E (&gt;30 visualizations) compared to the others groups. In group E, pregnancy rates and clinical pregnancy rates per fresh single blastocyst transfer were respectively 72.3% and 65.1%, significantly higher when compared to the others groups (p &lt; 0.01, p &lt; 0.001): group A 61% and 50.9%, group B 63.1% and 56.1%, group C 64.1% and 55.1%, group D 65% and 53.8%. Limitations, reasons for caution Time-lapse incubator is needed as well as a strong informatics setting to ensure secure and personalised on-line connection to each patient at any time during the five days of culture. Endocrine and endometrial biomarkers should be proposed and evaluated in further clinical trials to better understand these results. Wider implications of the findings: Repeated on-line visualization of own embryos images before fresh blastocyst transfer enhances pregnancy rates in IVF cycles. We propose that repeated visual stimuli of images produces a positive emotional connection between patients and their own developing embryos, thus reducing anxiety and enhancing recipient’s endometrial receptivity. Trial registration number Not applicable

Sign in / Sign up

Export Citation Format

Share Document