scholarly journals Sternum Dehiscence: A Preventable Complication of Median Sternotomy

2020 ◽  
Vol 23 (5) ◽  
pp. E599-E605
Author(s):  
Emin Can Ata ◽  
Metin Onur Beyaz
Keyword(s):  
Risk Assessment ◽  
Hospital Costs ◽  
Median Sternotomy ◽  
Sternal Dehiscence ◽  
Patient Dissatisfaction ◽  
Risk Patients ◽  
Group 2 ◽  
Preventable Complication ◽  
Related Mortality ◽  
Group 1

Background: The incidence of sternal dehiscence following cardiothoracic surgery via sternotomy is rare. It causes serious patient dissatisfaction and leads to higher hospital costs. For years, each clinic has made efforts to reduce this complication. Here, we aimed to summarize our techniques to prevent dehiscence. Material: This retrospective study included two groups operated via median sternotomy from March 2009 to May 2019. The first group included 1,105 consecutive patients who only received sternum wire for sternum closure from March 2009 to October 2013. The second group included 1,559 consecutive patients operated from January 2014 to May 2019; preventive closure techniques were performed for predefined high-risk patients in this group. These closure techniques included polyglyconate (Maxon) or simple longitudinal reinforced sutures, sternal cable or sternoband, sternal plate, and Robiscek technique. Results: All patients in Group 1, and 63.8% (995/1559) patients in Group 2 received sternal wire only (P < .001). In Group 2, we applied preventive closure techniques to 564 (36.2%) patients. There was no sternal dehiscence in Group 2, whereas 29 (2.6%) patients postoperatively suffered sternal dehiscence in Group 1; this was statistically significant (P = .001, OR:85.5, 95%CI:5.22-1400.4). The overall incidence of mediastinitis was 0.94%. The incidence significantly was lower in Group 2 (P = .004, OR:3.6, 95%CI:1.52-8.82). Sternum-related mortality in Group 2 also was lower (0.54% versus 0.06%, P = .048, OR:8.5, 95% CI: 1.02-70.75). Conclusion: Sternal dehiscence can be avoided by careful perioperative risk assessment and enhanced closure techniques. The same special consideration may significantly reduce mediastinitis and sternal-related mortality.

Coalescence of the German-Austrian and IMRAW Cytogenetic MDS Databases: Modification of Patient Risk Groups.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2468-2468 ◽  
Author(s):  
Christian Steidl ◽  
Julie Schanz ◽  
Michelle M. Le Beau ◽  
John M. Bennett ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Risk Stratification ◽  
Risk Group ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Group 3 ◽  
Group 2 ◽  
Stratification System ◽  
Risk Stratification System ◽  
Group 1

Abstract Introduction The International Prognostic Scoring System (IPSS) for evaluating prognosis in myelodysplastic syndromes (MDS) has been the standard for risk assessment in this disease for the past ten years. Based on a patient cohort comprising 816 primary MDS patients from the IMRAW, a refined bone marrow cytogenetic classification system was introduced. Recently, the GACMSG published cytogenetic data including 1155 primary MDS patients treated with supportive care only. Coalescence of these two large databases offered the opportunity to analyze the cytogenetic data jointly and to propose a modified cytogenetic risk stratification system. Patients and Methods 1971 patients with karyotype and survival data originating from the IMRAW and the GACMSG cohorts were included in this study. The collectives comprised patients with primary MDS treated with supportive care, only allowing short courses of low dose oral chemotherapy or hemopoietic growth factors. By reviewing the ISCN karyotypes, the patients were grouped into cytogenetic categories defined by median survival (MS) (Haase et al, Blood in press). The categories comprised karyotypes with the respective abnormality alone or in combination with one additional anomaly. Karyotypes with 3, or more than 3 abnormalities were considered separate categories. Results We found 15 cytogenetic categories each comprising 10 or more patients. These categories could be combined into 4 prognostic groups according to the MS: Group 1 (MS&gt;3 years): normal karyotype, del(5q), del(12p), del(20q), +21, −Y, −X; Group 2 (1.5–3 years): +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), +8, del(11q); Group 3 (1–1.5 years): 3 anomalies, −7, del(7q); Group 4 (MS&lt;1 year): &gt;3 anomalies. Further stratification of these categories led to a system with 4 distinct risk strata (number of patients): good (1374), int-1 (160), int-2 (99), and poor (166). Only 172 patients (9% of all patients) could not be classified according to this system. Survival analysis of these 4 groups showed distinct MS (Log-rank test: p&lt;0.0001): good, 50 months; int-1, 24 months; int-2, 15 months; poor, 6 months. When combining the non-classified patients into one group MS was 31 months. When comparing this new classification system with the original system defined by the IPSS, 66 formerly intermediate risk patients shifted into the good risk group and 114 poor risk patients into the intermediate risk group. Discussion Combined examination of the two databases introduces 7 new cytogenetic categories with distinct survival times as compared to the IPSS; Group 1: del(12p), +21, −X; Group 2: +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), del(11q); Group 3: 3 anomalies. Based on previously published data, the proposed system combines non-complex karyotypes in one category and distinguishes karyotypes with 3 or more than 3 abnormalities. With respect to future refined integrative scoring in MDS we present an approach that distinguishes groups of intermediate risk and a heterogeneous group of as yet unclassified rare cases harboring uncertain prognoses. In the latter cases, risk assessment should be based on other prognostic parameters rather than assigning an intermediate risk to this group. This new cytogenetic risk stratification system needs to be validated and tested using multivariate approaches.

scholarly journals Risk Assessment and Anesthesia Classification in Breast Cancer Surgery

2018 ◽  
pp. 168-172
Author(s):  
Kasra Karvandian ◽  
Jayran Zebardast ◽  
Nazila Zolfaghari Borra
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Breast Reconstruction ◽  
Cancer Surgery ◽  
Breast Cancer Surgery ◽  
Diep Flap ◽  
Breast Cancer Patients ◽  
Risk Patients ◽  
Group 2 ◽  
Group 1

Background: There are various factors affecting the effectiveness of the treatment of breast cancer patients. Although the disease pathology, along with surgery and other therapeutic modalities, plays the principal role in patient outcomes, anesthesia still plays an important role in the success of treatment. This study was designed to show the effects of anesthetic plans on risk classification and assessment in breast cancer surgeries. Methods: Two hundred sixty patients receiving different types of breast cancer surgery for therapeutic and reconstructive purposes were enrolled in this study. They were divided into three groups according to the anesthesia risk assessment. Group 1 consisted of low-risk patients (ASA I) who received small surgeries such as lumpectomy. Patients with intermediate risk of anesthesia (ASA II) or those who underwent breast cancer and axillary surgery with overnight admission (ASA I or II) were considered as group 2. Group 3 comprised the patients with higher risk for anesthesia (ASA class III) regardless of the surgery type or those in any ASA class who were about to undergo advanced and prolonged surgeries such as breast reconstruction with free or pedicle flaps. Results: Two hundred sixty-eight surgical interventions were done in 260 patients. There were 106, 107, and 47 patients in groups 1, 2, and 3, respectively. In group 1, five patients out of 106 were admitted in the hospital for 24 hours after surgery and the remaining 101 patients were discharged from the hospital in a few hours after the operation when they were fully conscious and could tolerate the diet completely. All 107 patients in group 2 were admitted in the hospital for a few days after the operation, though the vast majority of them (98 patients) discharged from the hospital the day after surgery. In the last group, 6 out of 47 patients showed the signs of surgical complications such as partial flap ischemia in the postoperative period, mostly after TRAM or DIEP flap breast reconstruction surgery. Conclusion: The findings of this study support the idea that breast surgeries can be done in an ambulatory situation with no considerable risk. In contrast, all medical and anesthetic considerations should be taken into account in more complex surgeries, especially when they are applied in high-risk patients.

scholarly journals Appropriate secondary prevention and clinical outcomes after acute myocardial infarction according to atherothrombotic risk stratification: The FAST-MI 2010 registry

2018 ◽  
Vol 26 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Victoria Tea ◽  
Marc Bonaca ◽  
Chekrallah Chamandi ◽  
Marie-Christine Iliou ◽  
Thibaut Lhermusier ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Secondary Prevention ◽  
High Risk Patients ◽  
Risk Patients ◽  
St Elevation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Full secondary prevention medication regimen is often under-prescribed after acute myocardial infarction. Design The purpose of this study was to analyse the relationship between prescription of appropriate secondary prevention treatment at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. Methods We used data from the 2010 French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) registry, including 4169 consecutive acute myocardial infarction patients admitted to cardiac intensive care units in France. Level of risk was stratified in three groups using the TRS-2P score: group 1 (low-risk; TRS-2P=0/1); group 2 (intermediate-risk; TRS-2P=2); and group 3 (high-risk; TRS-2P≥3). Appropriate secondary prevention treatment was defined according to the latest guidelines (dual antiplatelet therapy and moderate/high dose statins for all; new-P2Y12 inhibitors, angiotensin-converting-enzyme inhibitor/angiotensin-receptor-blockers and beta-blockers as indicated). Results Prevalence of groups 1, 2 and 3 was 46%, 25% and 29% respectively. Appropriate secondary prevention treatment at discharge was used in 39.5%, 37% and 28% of each group, respectively. After multivariate adjustment, evidence-based treatments at discharge were associated with lower rates of major adverse cardiovascular events (death, re-myocardial infarction or stroke) at five years especially in high-risk patients: hazard ratio = 0.82 (95% confidence interval: 0.59–1.12, p = 0.21) in group 1, 0.74 (0.54–1.01; p = 0.06) in group 2, and 0.64 (0.52–0.79, p < 0.001) in group 3. Conclusions Use of appropriate secondary prevention treatment at discharge was inversely correlated with patient risk. The increased hazard related to lack of prescription of recommended medications was much larger in high-risk patients. Specific efforts should be directed at better prescription of recommended treatment, particularly in high-risk patients.

scholarly journals Does pre-emptive onlay mesh reinforcement of midline laparotomies reduce incidence of incisional hernia in high–risk patients?

2019 ◽  
Vol 6 (7) ◽  
pp. 2300
Author(s):  
Hosam F. Abdelhameed ◽  
Samir A. Abdelmageed
Keyword(s):  
High Risk ◽  
Incisional Hernia ◽  
Chronic Wound ◽  
Midline Laparotomy ◽  
High Risk Patients ◽  
Wound Pain ◽  
Risk Patients ◽  
Onlay Mesh ◽  
Group 2 ◽  
Group 1

Background: One of the major morbidity after abdominal surgery is incisional hernia. In high risk patients its incidence reaches 11-20% despite various optimal closure techniques for midline laparotomy. Our aim is to evaluate the efficacy of onlay mesh placement in reducing the incidence of incisional hernia in those high risk patients.Methods: A total of 65 high risk patients suspected to develop post-operative incisional hernia underwent midline abdominal laparotomies. Patients were divided into two groups; group1 (30 patients) for whom the incision was closed by conventional method and group2 (35 patients) for whom the incision was closed with reinforcement by onlay polypropylene mesh. The primary end point was the occurrence of incisional hernia while the secondary end point was post-operative complications including subcutaneous seroma, chronic wound pain, and surgical site infection (SSI). Patients were followed up for two years.Results: The base line characteristics of the two groups were similar. The incidence of incisional hernia is significantly reduced 1/35 (2.8%) in group 2 while it was 6/30 (20%) in group 1. As regard seroma and chronic wound pain they increased in (group2) 6/35 (17.14%) and 5/35(14.28%) respectively compared to (group 1) which was 4/30 (13.33%) and 2/30 (6.66%). SSI occurred in 1/35 (2.85%) in group 2 and in 1/30 (3.33%) in group 1.Conclusions: Prophylactic onlay mesh reinforcement of the midline laparotomy for high risk patients can be used safely and markedly reduces the incidence of incisional hernia with little morbidity.

Adding herbal extracts to silicone gel on post-sternotomy scar: a prospective randomised double-blind study

2020 ◽  
Vol 29 (Sup4) ◽  
pp. S36-S42
Author(s):  
Palakorn Surakunprapha ◽  
Kengkart Winaikosol ◽  
Bowornsilp Chowchuen ◽  
Kriangsak Jenwitheesuk ◽  
Kamonwan Jenwitheesuk
Keyword(s):  
Aloe Vera ◽  
Median Sternotomy ◽  
Centella Asiatica ◽  
Herbal Extract ◽  
Double Blind Study ◽  
Herbal Extracts ◽  
Double Blind ◽  
Silicone Gel ◽  
Group 2 ◽  
Group 1

Objective: Silicone gel has been shown effective in improving healing post-sternotomy scars. It remains to be determined whether adding herbal extracts to the gel would augment the healing effect. Method: After median sternotomy, patients were randomised into two groups. Group 1: topical silicone gel plus herbal extract gel (Allium cepa, Centella Asiatica, Aloe vera and Paper Mulberry) and Group 2: silicone gel. Patients were treated for six months. The postoperative scars were assessed at three and six months by plastic surgeons using the Vancouver Scar Scale (VSS) and the patient assessment scar scale. Results: Each group comprised 23 patients (n=46 in total). The VSS was significantly lower in Group 1 than in Group 2 (p=0.018 and p=0.051, respectively). In Group 1, the four differences from baseline were vascularity scores at three and six months (–0.391, p=0.025; –0.435, p=0.013, respectively), and pigmentation scores at three and six months (–0.391, p=0.019; –0.609, p=0.000, respectively). In Group 2, differences from baseline were the pigmentation and vascularity score at six months (–0.6609, p=0.000; –0.348, p=0.046, respectively). Conclusion: Our results suggest, post-sternotomy scars trend to have better vascularity and pigmentation when treated with silicone gel plus herbal extracts.

P0245PERCUTANEOUS RENAL BIOPSY IN FRAIL AND HIGH RISK PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dario Roccatello ◽  
Roberta Fenoglio ◽  
Joelle Kamgaing ◽  
Emanuele De Simone ◽  
Giulio Del Vecchio ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Risk ◽  
Kidney Biopsy ◽  
Histological Diagnosis ◽  
Renal Amyloidosis ◽  
Av Fistula ◽  
Cast Nephropathy ◽  
Risk Patients ◽  
Group 2 ◽  
Group 1

Abstract Background and Aims: Many patients with End Stage Kidney Disease do not undergo percutaneous kidney biopsy (KB) and do lack a definite diagnosis. Whether KB is beneficial in the extreme patients’ categories, i.e., age &gt;75 years and very late referrals with kidney disease requiring renal replacement therapy at the first evaluation, remains controversial. Aim: To analyse the benefit/risk balance in terms of therapeutic options and general outcome of KB procedure in these borderline categories. Method Files for all biopsies performed in our Centre between 2013 and 2019 (# 903 inpatients’ native kidney) were retrospectively analysed with special focus on histological diagnosis, biopsy complications, and post-biopsy patient’s outcome. Two groups of high risk patients were identified 1. &gt;75 years old patients, and 2. patients requiring dialysis at the first clinical evaluation. A rigorous protocol of screening of the bleeding risks was adopted. Results Of the 903 biopsies, 217 cases (24%) had group 1, and 92 (10%) group 2 criteria. Group 1: mean age 80 years (range 75-92), main histological diagnoses: ANCA associated vasculitis (AAV) (12,4%); membranous nephropathy (MN) (11,5%), diabetic nephropathy (10,1%), IgA glomerulonephritis (IgAGN) (9,2%), cast nephropathy (9,2%), renal amyloidosis (9.2%), focal segmental glomerulosclerosis (FSGS - 7,8 %). Group 2: mean age 60 years (range 20-92), most frequent histological diagnosis: AAV (26,1%); cast nephropathy (19,6 %), nephroangiosclerosis (9,8%), IgAGN (7,6 %), diabetic nephropathy (6,5%), renal amyloidosis (5,4%); FSGS (4,3%). Five major complications (2,3%), including AV fistula with spontaneous resolution in 4 patients and 1 case of severe bleeding requiring arterial embolization, and 14 minor complications (6,5%), including post biopsy haematomas &lt;2cm in 12 patients and haematuria in 2 patients were observed in group 1. Only 1 (1%) major complication (AV fistula) and 4 minor complications (4,3%), including post biopsy &lt;2cm haematomas in group 2 were identified in group 2. Histological diagnosis conditioned or changed treatment strategy in 71% of elderly patients (group 1), and 63% of patients in dialysis (group 2). Dialysis discontinuation was achieved in 30 out of 92 patients (36,6%) with a sparing of over 1 million euro/year. Conclusion Given its high diagnostic value (especially in patients who are willing to be transplanted), the prognostic significance (and the assessment of the extent of the renal sclerotic changes), and the potential impact on the treatment policy, indications to percutaneous kidney biopsy in elderly and dialysis patients should be probably revised.

Less Treatment Related Mortality with Variable Intensity Conditioning Than Non-Myeloablative Conditioning in Unrelated and Related Adult Allogeneic Transplant Recipients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5051-5051
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie Elkins ◽  
Cheryl L. Hardy ◽  
Joe Clark Files
Keyword(s):  
Acute Gvhd ◽  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Myeloablative Conditioning ◽  
Variable Intensity ◽  
Group 2 ◽  
One Year ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Group 1

Abstract For the past four years our adult allogeneic transplant program has employed two alternative approaches to standard recipient conditioning, the use of non-myeloablative “mini” conditioning and variable intensity conditioning. We now report a retrospective comparison of relapse, day +100 and one year survival, engraftment and grades I-II and III-IV acute GVHD in unrelated as well as related recipients in these two preparative regimen groups. Patients with a variety of malignancies were not randomized to receive either non-myeloablative (Group 1) or variable intensity (Group 2) conditioning. Twenty patients with a median age of 49 (range 27–64, Group 1) and 17 patients also with a median age of 49 (range 24–58, Group 2) received either marrow or peripheral blood stem cells, usually with a 6/6 match grade; one recipient in Group 2 received a cord blood transplant (4/6 match). Group 1 regimen consisted of fludarabine 30 mg/m2 x 3d and TBI 200 cGY. Group 2 regimen consisted of Campath 20 mg/d either 5 or 3 days, fludarabine x 5d and melphalan 140 mg/m2 x 1d. GVHD prophylaxis was the same in both groups (standard dose cyclosporine or tacrolimus and MMF.) All patients received an adequate CD34+ cell dose and none of the products was manipulated. Relapse rate was 37% in Group 1 and 53% in Group 2. Day+100 survival and one year survival were 55% and 20%, respectively, in Group 1 vs 69% and 33% in Group 2. Only one patient in Group 2 had acute GVHD, grades I-II; none had grades III-IV. However, in Group 1, 6 patients had grades I-II and 8 had grades III-IV (40%). Graft failure occurred in five patients in Group 1, while no patients in Group 2 experienced it. We conclude, first, that in our program the application of variable intensity conditioning has been quite successful in unrelated transplant recipients, as well as in related. Second, significant treatment related mortality in the form of graft failure and acute GVHD occurred less frequently in recipients who received this conditioning than in those receiving non-myeloablative conditioning. This regimen requires some further modification to enhance its tumoricidal properties; however, its treatment-related toxicity is minimal and allows us to offer this therapy to patients with co-morbid conditions and older age.

Outcome of Adult AML at First Relapse Following a Risk-Oriented Strategy: An Update of the Northern Italy Leukemia Group (NILG) Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4385-4385 ◽  
Author(s):  
Irene Cavattoni ◽  
Enrico Morello ◽  
Elena Oldani ◽  
Tamara Intermesoli ◽  
Ernesta Audisio ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Risk Category ◽  
High Dose ◽  
High Risk Patients ◽  
Risk Patients ◽  
First Relapse ◽  
Group 2 ◽  
Standard Risk ◽  
Group 1

Abstract INTRODUCTION The impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) was retrospectively analyzed in 172 patients (patients) with relapsed non-APL AML, who had been initially treated with standard induction and risk-adapatiented consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All 172 patients were at first recurrence following consolidation of CR1 with high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinical-cytogenetic criteria) or allo-SCT in case of high-risk prognostic profile. Median age at relapse was 55 y (range 21–70). CR1 duration was &lt;6 months in 50 patients (29%), ranging from 0.6 to 52,7 mo (median 9,1). High risk patients were 128/172 (74%) and 43/172 patients (25%) had an unfavourable cytogenetics (CG). One hundred-eleven patients (64%) received HiDAC and 24 (14%) an allo-SCT according to study design. RESULTS 140 patients (81%) received salvage treatment. The remaining 32 patients (19%) received palliation and all of them died. The median OS was 17.1 mo, with a 2yOS of 34%. Favorable prognostic factors identified by univariate analisys were: favourable or intermediate CG (p=0,007), standard risk category according to first line protocol (p=0.004), availibility of a HLA matched donor (p= 0.048), achievement of an early CR1(p=0,000), HiDAC as first line therapy(p=0,000), alloHSCT perfomed at relapse (p=0,000) and a DFS from CR1&gt;12 mo (p=0,000). In multivariate analysis favourable or intermediate CG and DFS &gt;12 mo were confirmed as independent prognostic factors (p=0,036 and p=0,001 respectively). Among the 140 patients, 50 received an allo-SCT following relapse (36%, group 1), and the remaining 90 (64%, group 2) received high dose chemotherapy alone (85), autologous SCT (2), or DLI (3, in case of previous alloSCT). Both groups were comparable regarding age &gt;55 y, prior allo-SCT and risk class at diagnosis. After salvage therapy, 44 patients(88%) in the group 1 achieved CR2, compared to 26 patients (29%) in the group 2. The median duration of CR2 was 9 mo (range 2–64) and 3 mo (range 1–34) in group 1 and 2 respectively. NRM was 17/140: 12 patients (24%) in the allo-SCT group and 5 (6%) in group 2. The 2yOS was 57% and 23% respectively (p=0,000). Moreover, among 50 alloSCT patients, survival was affected by risk category at diagnosis: 2yOS of 19 (38%) standard risk patients was 83% compared to 42% in 31 high risk patients (62%) (p=0.01). This risk stratification has no impact on OS in the group 2. CONCLUSIONS DFS &gt; 12 mo and standard risk category at diagnosis, according to NILG protocol, are the most important independent positive prognostic factors impacting OS of AML relapsed patients. The availibility of a HLA matched donor and a subsequent intensification with alloSCT may offer substantial salvage rates and its outcome is affected by the risk stratification at diagnosis. Nevertheless, high risk patients could benefit from alloSCT, reaching an 2yOS of 42%.

Addition of More Immunosuppressive Drugs As Graft-Versus-Host Disease (GVHD) Prophylaxis Does Not Improve Gvhd Outcomes in Reduced Intensity Allogeneic Hematopoietic Cell Transplantation from Unrelated Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5786-5786
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Fiorenza Barraco ◽  
Xavier Thomas ◽  
Marie Balsat ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Immunosuppressive Drugs ◽  
Advisory Committees ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Group 3 ◽  
Group 2 ◽  
Related Mortality ◽  
Group 1

Abstract Background: Reduced-intensity conditioning (RIC) regimens have led to a dramatic reduction of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The concept of RIC is to deliver adequate immunosuppression with manageable graft-versus-host disease (GVHD) and the eventual development of a potent graft-versus-leukemia effect. Nevertheless, GVHD prophylaxis remains a challenging task after allo-HSCT. While the combination of cyclosporine A (CsA) and a short course of methotrexate (Mtx) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allo-HSCT from HLA-identical siblings, there is no consensus on the optimal preventive GVHD prophylaxis after RIC allo-HSCT. On the other hand, recent and ongoing studies are evaluating a promising GVHD prophylaxis strategy using post-transplantation cyclophosphamide (PTCy). The aim of this study is to evaluate the impact of different GVHD prophylaxis used after RIC allo-HSCT in patients receiving peripheral blood stem cells (PBSC) from unrelated donors for hematological malignancies. Patients and methods: We evaluated 127 consecutive patients with hematological malignancies who received RIC allo-HSCT and were followed in our center between January 2008 and January 2016; 74 (58%) were males, median age was 58 years (range: 18-70), 52 (41%) had acute myeloid leukemia, 36 (28%) myelodysplastic syndrome, 12 (10%) myeloproliferative syndrome, 9 (7%) Non-Hodgkin lymphoma, 9 (7%) chronic lymphocytic leukemia, 6 (5%) multiple myeloma and 3 (2%) chronic myeloid leukemia. At transplantation, 65 (51%) patients were in complete response (CR) or chronic phase (CP). RIC regimen consisted on fludarabine, intermediate doses of IV busulfan and anti-thymocyte golbulins (ATG) (Thymoblobulin) in 56 (44%) patients and a sequential FLAMSA regimen in 71 (56%) patients and who also received similar doses of ATG (Thymoglobulin). PBSC donors were 10/10 HLA matched in 81 (64%) patients and 9/10 HLA mismatched in 46 (36%) patients. Patients were divided according to GVHD prophylaxis into 3 groups: group 1 consisted on CsA alone with 23 (18%) patients, group 2 include patients who received either CsA + mycophenolate mofetil (MMF), n= 64 (50%) or CsA + Mtx, n= 20 (16%) or CsA + cyclophosphamide n= 5 (4%), and group 3 included patients receiving CsA + MMF + tacrolimus n= 15 (12%) patients. Results: After transplantation, all patients in group 1 engrafted after a median of 17 (3-25) days, 81/89 (91%) engrafted in group 2 after a median of 17 (5-58) days and 14/15 (94%) engrafted in group 3 after a median of 16 (9-24) days. We did not observe any significant impact of the type of GVHD prophylaxis on the 100-day incidence of grade II to IV acute GVHD, which occurred in 6/15 (40%), 34/81 (42%) and 7/14 (50%) for the groups 1, 2 and 3 respectively (p=0.18). Grade III-IV acute GVHD occurred in 3 (20%), 24 (29%) and 5 (33%) in the three groups respectively (p=0.11). Similarly, cumulative incidence of 1 year chronic GVHD was not different between groups 1, 2 and 3 reaching 46%, 43% and 46% respectively (p=0.6) among them 3/15 (20%), 18 (22%) and 3/14 (21%) patients had an extensive form. After a median follow-up of 22 months for surviving patients, although there was no significant difference between the three groups in terms of non-relapse mortality, we observed more infection-related mortality with 45% and 83% in groups 2 and 3 respectively compared to 47% in group 1. The cumulative incidence of relapse at 2 years was 22%, 31 and 26% for the three groups respectively (p=0.23). Overall survival rates at two years were 43%, 31% and 44 % for groups 1, 2 and 3 respectively (p=0.42). The multivariate analysis taking into account the type of disease, donor HLA matching, disease status at transplantation, type of RIC and the type of prophylaxis, showed that the incidence of acute GVHD was influenced only by the use of FLAMSA regimen from mismatched donors, HR= 2.2 [1.3-3.1], p=0.05 which had also the same impact on the occurrence of chronic GVHD. Conclusion: Despite its limitations and the need for prospective randomized studies, the results of our study suggest that in the RIC allo-HSCT from unrelated donors, the different GVHD prophylaxis associations lead to similar GVHD outcomes. Patients with more immunosuppressive drugs had a higher incidence of infection-related mortality and in which PTCy could be a better option. Disclosures Nicolini: BMS: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in HLA matched sibling donor stem cell transplantation for patients with acute leukemia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19523-e19523
Author(s):  
Alaa Nabil Elshamy ◽  
Essam Ali Abdelmohsen ◽  
Mai Denewer ◽  
Mohamed Nasr Mabed
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Graft Versus Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Group 2 ◽  
Related Mortality ◽  
Group 1

e19523 Background: Graft-versus-host disease (GVHD) is a life-threatening complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Calcineurin inhibitor (CNI) and methotrexate (MTX) have been used as the standard GVHD prophylaxis in HLA-matched HSCT. Promising clinical trial data using high dose post-transplant Cyclophosphamide (PT-Cy) with or without additional immunosuppressive agents (IS) have shown that it’s an effective, well tolerated alternative. However, experiences are limited with controversial results. Methods: We analyzed 62 patients with Acute Leukemia (39 males, 23 females) with age ranges from 18 to 60 years underwent allogeneic HSCT from matched sibling donors (MSD) using reduced intensity chemotherapy at Maadi Armed Forces Medical Hospital after informed consent. They were randomized into 2 groups according to GVHD prophylaxis regimen. The 1st group (40 patients) received MTX in the following doses; day+2 (15mg), day +4 (10 mg), day +6 (10 mg) with Cyclosporine (5mg/kg) from day -3 till day +90 and Mycophenolate (MMF) (2 -3gm/day) from day +1 till day +30. The 2nd group(22 patients) received PT-Cy (45 mg/kg/day) on days +3 and +4 with Cyclosporine (5mg/kg) from day +5 till day +30 & MMF:(2-3gm /day) from day +5 till +30. Results: At median 1 year Post Allo, PT-Cy was associated with statistically significant lowering of chronic GVHD (cGVHD) incidence compared to MTX group (22.7%, 56.4%) respectively (P = 0.011). Incidence of acute GVHD (aGVHD) at day +100 was (40%, 22.7%) in group 1, 2 respectively (P = 0.169). 92% of patients in group 1 and 86.4 % of patients in group 2 were engrafted with full donor chimerism on day +30 (P = 0.659). The cumulative incidence of relapse at 4 years after transplantation was 17.9 % for group 1 and 36.4 % for group 2 (P > 0.05). Relapse related mortality were 16.2% among MTX group while 27.3% in PT-Cy group (P = 0.10). Transplant related mortality (TRM) in MTX group were; Severe aGVHD (8%), cGVHD (10%), Hepatic Toxicity (8%), Nephrotoxicity (2.7%) & ARDS (5.4%). In PT-Cy group TRM were; septicemia (18%), severe aGVHD (4.5%) & ARDS (4.5%). Cumulative 4 years Disease Free Survival (DFS) & Overall survival (OS) in PT-Cy group were (51.8 %, 46.4%) respectively while (69.3%, 39%) in MTX group which is statistically non-significant (P > 0.05). Conclusions: For GVHD prophylaxis in MSD, PT-Cy is a safe alternative that reduces the risk of cGVHD in comparison with MTx based regimen without affecting Relapse rate, DFS or OS.

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