Reduced Incidence of Acute and Chronic Graft-versus-Host Disease (GvHD) without Increased Relapse in Patients with High-Risk Myeloid Disorders Given Thymoglobulin (THY) as Part of the Transplant Conditioning Regimen: A Dose-Finding Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 181-181 ◽  
Author(s):  
H. Joachim Deeg ◽  
F. R. Appelbaum ◽  
B. Storer ◽  
M. Cassarella ◽  
B. Scott ◽  
...  
Keyword(s):  
At Risk ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Area Under The Curve ◽  
State Level ◽  
Dose Finding ◽  
Refractory Anemia ◽  
Finding Study ◽  
Patients At Risk

Abstract GvHD is a major cause of morbidity and mortality after allogeneic hemopoietic cell transplantation (HCT). Recent data suggest that rabbit anti-thymocyte globulin (THY) given pre-transplant is effective in reducing the incidence of GvHD. We transplanted 54 patients, 9-65 (median 49) years of age, with advanced myelodysplastic syndrome (MDS, beyond Refractory Anemia[RA], n=29), myelofibrosis (n=12), or other myeloid disorders (n=13), after conditioning with a regimen of targeted busulfan (BU; steady state level 800-900ng/ml), cyclophosphamide (CY) and THY (Thymoglobulin, Sangstat) which was given on days -3,-2 and -1. The starting dose was 4.5 mg/kg (total), to be escalated (in cohorts of 15 patients) to 6.0 and 7.5 mg/kg, dependent upon GvHD incidence and EBV reactivation ≥1000 copies). Patients also received methotrexate (MTX) + cyclosporine (CSP). Seventeen ( patients were accrued in the first cohort (2 did not receive the prescribed dose of THY), and none activated EBV; among 20 patients in the second cohort (5 with incomplete THY dose) one re-activated EBV, and, thus, the third cohort was to receive the same dose, 6 mg/kg, (n=17; two with incomplete THY dose). Donors were HLA-identical siblings in 28, and HLA matched unrelated volunteers in 26 patients. All but two patients had sustained engraftment; 32 (59%) developed acute, and 24 of 46 patients at risk (52%) developed chronic GvHD. The incidence of acute/chronic GvHD was 41%/45% for related, and 60%/36% for unrelated patients given the prescribed doses of THY (80%/85% for the 9 patients in both groups with incomplete THY dose). Relapse incidence for patients given the prescribed dose of THY was 16% for related, and 2% for unrelated recipients; it was 44% among the 9 patients who did not receive the full dose of THY. There was a suggestion that greater ‘area under the curve’ for the CY metabolite CEPM was correlated with non-relapse mortality. Overall, 38 patients (70%) are surviving with a follow-up of 3-20 (median 13) months. Concurrently, 27 patients, 11-64 (median 51) years of age, with low-risk MDS (RA) were conditioned with the identical targeted BUCY regimen (and MTX+CSP) but without THY, and transplanted from HLA-identical related (n=14) or unrelated donors(n=13). All patients engrafted, and none relapsed; 24 (89%) developed acute, and 24 of 25 patients at-risk (96%) developed chronic GvHD. Overall 18 patients (67%) are surviving at 9-39 (median 23) months; there was no difference between related and unrelated transplants. These data suggest that THY, added to targeted BUCY, reduced the incidence of acute and chronic GvHD. With EBV monitoring it may be possible to further escalate the dose of THY and further reduce the incidence of GvHD. However, because of actual or presumed toxicity, 16% of patients did not receive the prescribed dose of THY. There was no evidence for an increase in infections or relapse compared to historical data. The projected survival of patients with advanced disease is encouraging, but longer follow-up is needed.

Long Remission Are Possible after Non Myeloablative Transplant in Patients with Follicular Non-Hodgkin’s Lymphoma (NHL): Results of Two Prospectives Multicenter Trials.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3024-3024
Author(s):  
María-Dolores Caballero ◽  
Rodrigo Martino ◽  
María-Victoria Mateos ◽  
Javier Briones ◽  
Javier de la Serna ◽  
...  
Keyword(s):  
Stable Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Peripheral Blood Stem Cells ◽  
Multicenter Trials ◽  
Incurable Disease ◽  
Short Course ◽  
Patients At Risk ◽  
Blood Stem Cells

Abstract Myeloablative transplant has been investigated in poor prognosis indolent lymphoma; although recurrence rate is low it is associated with high mortality; the use of non-myeloablative conditioning regimens could reduce TRM maintaining the GVH effect. Up to May 2006, 35 patients with follicular NHL received a Non Myeloablative related allogeneic according to two prospective multicenter trials; conditioning regimen consisted of Fludarabine 150 mg and Melphalan 70–140 mg. GVHD prophylaxis consisted of CSA plus short-course MTX. All patients received filgrastim-stimulated peripheral blood stem cells from a HLA related identical donor. Median age at transplant was 50 years (34–62) and 16 (46%) had received a previous autologous transplant. At transplant, 5 patients (14%) were in CR1 (after several lines of chemotherapy), 9 (25%) in >CR1, 12 (34%) in PR, 1 (3%) had stable disease (after 3 chemotherapy lines) and 8 (23%) progressive disease. All patients engrafted. Acute GVHD developed in patients 19 (54%) (17patients (48%) grade II-IV). Chronic GVHD developed in 18 out of 27 patients at risk (67%), being extensive in 11 (41%). Disease was evaluated at day +100 and at that moment 23 patients were in CR, (85%) 1 (4%) in PR, two (7%) had stable disease and 9 patients ( 26%) have died. With a median follow up of 60 months (range: 32–80 months), 20 patients (57%) are alive disease free, and 14 (43%) have died, 12 of them (37%) due to transplant toxicity and 2 patients (6%) due to progression. Overall Survival (OS) and Event Free Survival (EFS) are 57 and 54 % respectively. Analysing variables which influence on OS and EFS, patients 55 years have a OS significantly shorter than those <55 years old (22% vs 69%; p:0,007). Moreover, patients who develop chronic GVHD have an EFS significantly better than those which do not develop it (78 % vs 44%; HR: 3,9 (1,0–14,6); p: 0,03). In conclusion, our results demonstrates high efficacy of non-myeloablative transplant in follicular NHL with a very low relapse rate, indicating the important role of chronic GVHD in the control of the disease; however, mortality rate is still high, mainly in patients 55 years. Although follicular lymphoma is considered as an incurable disease, our results after a large follow-up suggest that allogeneic effect could change this concept.

scholarly journals Gait Speed as a Predictor for Diabetes Incidence in People with or at Risk of Knee Osteoarthritis: A Longitudinal Analysis from the Osteoarthritis Initiative

2021 ◽  
Vol 18 (9) ◽  
pp. 4414
Author(s):  
Aqeel M. Alenazi ◽  
Bader A. Alqahtani ◽  
Vishal Vennu ◽  
Mohammed M. Alshehri ◽  
Ahmad D. Alanazi ◽  
...  
Keyword(s):  
At Risk ◽  
Gait Speed ◽  
Area Under The Curve ◽  
Incident Diabetes ◽  
Future Research ◽  
Cutoff Score ◽  
Diabetes Incidence ◽  
Knee Oa ◽  
Osteoarthritis Initiative

Background: This study examined the association between baseline gait speed with incident diabetes mellitus (DM) among people with or at elevated risk for knee OA. Materials and Methods: Participants from the Osteoarthritis Initiative, aged 45 to 79 years, where included. Participants with or at risk of knee OA from baseline to the 96-month visit were included. Participants with self-reported DM at baseline were excluded. DM incidence was followed over the 4-time points. Gait speed was measured at baseline using a 20-m walk test. Generalized estimating equations with logistic regression were utilized for analyses. Receiver operator characteristic curves and area under the curve were used to determine the cutoff score for baseline speed. Results: Of the 4313 participants included in the analyses (58.7% females), 301 participants had a cumulative incidence of DM of 7.0% during follow-up. Decreased gait speed was a significant predictor of incident DM (RR 0.44, p = 0.018). The threshold for baseline gait speed that predicted incident DM was 1.32 m/s with an area under the curve of 0.59 (p < 0.001). Conclusions: Baseline gait speed could be an important screening tool for identifying people at risk of incident diabetes, and the determined cutoff value for gait speed should be examined in future research.

scholarly journals FRI0234 A HIGH NEMO SCORE IN VIDEOCAPILLAROSCOPY IS PREDICTIVE OF FUTURE DEVELOPMENT OF DIGITAL ULCERS IN PATIENTS WITH SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 700.1-701
Author(s):  
N. Del Papa ◽  
F. Pignataro ◽  
W. Maglione ◽  
A. Minniti ◽  
D. Sambataro ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Future Development ◽  
Area Under The Curve ◽  
Subsequent Development ◽  
State Level ◽  
Receiver Operating Curve ◽  
Digital Ulcers ◽  
Cumulative Number ◽  
Predictive Values

Background:Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation and follow-up of the microvascular changes that mark the course of Systemic Sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, namely the cumulative Number of microhaEMOrrhages and microthromboses, is a good indicator of the steady state level and over time changes of disease activity (DA) in SSc (1-3).Objectives:To verify whether a high NEMO score, and then a high level of active microvascular derangement in the fingers may be predictive of the subsequent development of ischemic digital ulcers (IDUs).Methods:The NEMO score was assessed at baseline (T0) in 98 patients affected by SSc, according to the ACR-EULAR criteria. Out of them, 90 were females, 48 had the limited form and 50 the diffuse cutaneous variant of SSc. ACA and anti-Scl-70 antibodies were positive in 42 and 50 patients, respectively. The NVC pattern was early, active and late in 16, 42 and 40 patients, respectively.Afterwards, patients were closely followed up for 3 years, and the appearance of new IDUs was recorded in any time of the follow up.The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated, by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the development of IDUs.Results:During the follow up, 38 out of 98 patients developed one or more DUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (CI 11.0-21.5), and 4.5 (CI 4.0-6.0), respectively, p<.0001]. The AUC was 0.79 (CI 0.69-0.86, p<0.0001). A NEMO score of 12 or more had a sensitivity of 83.3 (CI 71.5-91.7), and a specificity of 63.2 (CI 46.0-78.2), with positive (P) and negative (N) predictive values (PV) of 59.1 (CI 44.9-72.3), and 85.6 (CI 71.7-94.3), respectively. A NEMO score of 16 or more had a sensitivity of 95.0 (CI 86.1-99.0), and a NPV of 93.3 (CI 77.4-99.2).Conclusion:NEMO score is not only a valid tool to assess the level of DA in the course of SSc, but this NVC parameter could also be used as a good predictor of the future development of IDUs in patients with this disease.References:[1]Sambataro et al. Arthritis Res Ther 2014;16:462-69[2]Andracco et al. Arthritis Res Ther 2017;19:133-41[3]Pignataro et al. Arthritis Res Ther. 2019;21(1):258Disclosure of Interests:Nicoletta Del Papa: None declared, Francesca Pignataro: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Gabriele Valentini Grant/research support from: BMS, MSD, NOVARTIS, LILLY, PFIZER, ABBVIE, CELGENE, Claudio Vitali: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

Long-term results of acetabular reconstruction using irradiated allograft bone

2018 ◽  
Vol 100-B (11) ◽  
pp. 1449-1454 ◽  
Author(s):  
C. M. Green ◽  
S. C. Buckley ◽  
A. J. Hamer ◽  
R. M. Kerry ◽  
T. P. Harrison
Keyword(s):  
At Risk ◽  
Aseptic Loosening ◽  
Acetabular Component ◽  
Long Term Results ◽  
Acetabular Reconstruction ◽  
Allograft Bone ◽  
Patients At Risk ◽  
Irradiated Allograft

Aims The management of acetabular defects at the time of revision hip arthroplasty surgery is a challenge. This study presents the results of a long-term follow-up study of the use of irradiated allograft bone in acetabular reconstruction. Patients and Methods Between 1990 and 2000, 123 hips in 110 patients underwent acetabular reconstruction for aseptic loosening, using impaction bone grafting with frozen, irradiated, and morsellized femoral heads and a cemented acetabular component. A total of 55 men and 55 women with a mean age of 64.3 years (26 to 97) at the time of revision surgery are included in this study. Results At a mean follow-up of 16.9 years, there had been 23 revisions (18.7%), including ten for infection, eight for aseptic loosening, and three for dislocation. Of the 66 surviving hips (58 patients) that could be reassessed, 50 hips (42 patients; 75.6%) were still functioning satisfactorily. Union of the graft had occurred in all hips with a surviving implant. Survival analysis for all indications was 80.6% at 15 years (55 patients at risk, 95% confidence interval (CI) 71.1 to 87.2) and 73.7% at 20 years (eight patients at risk, 95% CI 61.6 to 82.5). Conclusion Acetabular reconstruction using frozen, irradiated, and morsellized allograft bone and a cemented acetabular component is an effective method of treatment. It gives satisfactory long-term results and is comparable to other types of reconstruction. Cite this article: Bone Joint J 2018;100-B:1449–54.

Abstract 038: A Novel Histology Based Classification System to Identify Patients at Risk for Postoperative Atrial Fibrillation

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Mahek Mirza ◽  
Anton Strunets ◽  
Ekhson Holmuhamedov ◽  
Jasbir Sra ◽  
Paul H Werner ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
At Risk ◽  
Classification System ◽  
Area Under The Curve ◽  
Postoperative Atrial Fibrillation ◽  
Right Atrial ◽  
Class Iii ◽  
Atrial Fibrosis ◽  
Patients At Risk ◽  
The Impact

Postoperative atrial fibrillation (PoAF) is a common complication in up to 40% of patients after cardiac surgery, increasing morbidity, hospital stay and costs. The myocardial substrate underlying PoAF is not fully characterized. The objective was to assess the impact of atrial fibrosis on incident AF and define the fibrosis threshold level predictive of PoAF. Methods: Right atrial appendages removed from patients undergoing elective CABG with no history of AF or class III/IV heart failure were used to characterize the ratio of collagen to myocardium (Masson’s trichrome; NIH ImageJ software; Fig A), which was correlated with incident AF. Percentage burden of fibrosis predictive of PoAF with high sensitivity and specificity was determined by ROC curve. Results: Of 28 patients (67±10 years, 64% males), 15 had PoAF. There were no age, gender or comorbidity differences between groups. Compared to the group that remained in sinus rhythm, patients with PoAF had a significantly higher ratio of extracellular collagen to myocardium (45±16% vs. 5±4%, p <0.001; Fig B). A threshold ratio of 12.7% collagen to myocardium (ROC area under the curve 0.997; z statistic 137; P<0.0001) with 96% sensitivity and 97% specificity identified those with PoAF (Fig C). A classification system based on histological extent of atrial fibrosis is proposed for identifying patients at risk for PoAF (Fig D). Conclusion: Ongoing studies will confirm the predictive value of this new classification system for identifying the atrial substrate predisposing PoAF and correlate with preoperative cardiac imaging and circulatory serum biomarkers to provide a novel noninvasive tool to stratify patients at risk for PoAF.

scholarly journals MEWS++: Enhancing the Prediction of Clinical Deterioration in Admitted Patients through a Machine Learning Model

2020 ◽  
Vol 9 (2) ◽  
pp. 343 ◽  
Author(s):  
Arash Kia ◽  
Prem Timsina ◽  
Himanshu N. Joshi ◽  
Eyal Klang ◽  
Rohit R. Gupta ◽  
...  
Keyword(s):  
Machine Learning ◽  
At Risk ◽  
Area Under The Curve ◽  
Learning Model ◽  
Clinical Deterioration ◽  
Early Warning Score ◽  
Support Vector ◽  
Adult Age ◽  
Machine Learning Model ◽  
Patients At Risk

Early detection of patients at risk for clinical deterioration is crucial for timely intervention. Traditional detection systems rely on a limited set of variables and are unable to predict the time of decline. We describe a machine learning model called MEWS++ that enables the identification of patients at risk of escalation of care or death six hours prior to the event. A retrospective single-center cohort study was conducted from July 2011 to July 2017 of adult (age > 18) inpatients excluding psychiatric, parturient, and hospice patients. Three machine learning models were trained and tested: random forest (RF), linear support vector machine, and logistic regression. We compared the models’ performance to the traditional Modified Early Warning Score (MEWS) using sensitivity, specificity, and Area Under the Curve for Receiver Operating Characteristic (AUC-ROC) and Precision-Recall curves (AUC-PR). The primary outcome was escalation of care from a floor bed to an intensive care or step-down unit, or death, within 6 h. A total of 96,645 patients with 157,984 hospital encounters and 244,343 bed movements were included. Overall rate of escalation or death was 3.4%. The RF model had the best performance with sensitivity 81.6%, specificity 75.5%, AUC-ROC of 0.85, and AUC-PR of 0.37. Compared to traditional MEWS, sensitivity increased 37%, specificity increased 11%, and AUC-ROC increased 14%. This study found that using machine learning and readily available clinical data, clinical deterioration or death can be predicted 6 h prior to the event. The model we developed can warn of patient deterioration hours before the event, thus helping make timely clinical decisions.

scholarly journals Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors

2019 ◽  
Vol 112 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Lucas K Vitzthum ◽  
Paul Riviere ◽  
Paige Sheridan ◽  
Vinit Nalawade ◽  
Rishi Deka ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Cancer Survivors ◽  
Critical Role ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Opioid Abuse ◽  
Opioid Use ◽  
Multivariable Logistic Regression Model ◽  
Patients At Risk

Abstract Background Although opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse. Methods Within a cohort of 106 732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique. Results The rate of persistent opioid use in cancer survivors was 8.3% (95% CI = 8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI = 2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI = 2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78). Conclusion This study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.

Molecular Remission Can Be Attained in Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphomas after Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLO-SCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2317-2317
Author(s):  
Lucia Farina ◽  
Matteo Carrabba ◽  
Anna Dodero ◽  
Elena Rizzo ◽  
Elisabetta Zorzan ◽  
...  
Keyword(s):  
Nested Pcr ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphocytic Leukemia ◽  
Clinical Relapse ◽  
Molecular Remission ◽  
Continuous Increase ◽  
Taqman Pcr ◽  
Follicular Lymphomas

Abstract RIC followed by allo-SCT is an effective salvage treatment for some relapsed hematologic malignancies due to the postulated graft versus tumour (GVT) effect. In order to evaluate the quality of the clinical response, we have investigated the molecular status of patients receiving allo-SCT for relapsed disease. Forty-four patients (19 chronic lymphocytic leukemias (CLL), 21 follicular lymphomas (FCL) and 4 small lymphocytic lymphomas (SLL)) were enrolled in a prospective phase II study. The median age was 54 years (range: 32–69 years). The median number of previous chemotherapy regimens was 2 (range: 1–5) and 23% of patients had already failed an auto-SCT. Before transplant 34% of patients were chemorefractory and 34% of the chemosensitive patients were in complete remission (CR). The conditioning regimen consisted of thiotepa 10mg/kg, fludarabine 60mg/ms and cyclophosphamide 60mg/kg; short course of methotrexate and cyclosporin were used as GVHD prophylaxis. Minimal residual disease (MRD) was monitored by nested PCR for IgH or Bcl-2 genes; in PCR-positive patients a TaqMan based quantitative monitoring was also employed. All patients engrafted. On day +30 after transplant 39% of patients achieved CR. Acute GVHD (aGVHD) was observed in 57% of patients and 52% of 42 evaluable patients developed chronic GVHD; no difference in the incidence of GVHD between FCL and CLL/SLL was observed. In 30 of 44 patients (68%) a PCR marker for MRD monitoring was found. Twenty-five patients (10 CLL, 2 SLL, 13 FCL) of 37 patients in CR after allo-SCT were monitored by nested PCR and 4 PCR-positive patients were monitored by TaqMan PCR. At a median molecular follow up of 15 months (range: 3–62) 15 of 25 patients (60%) were alive and in molecular remission; one CLL patient died of TRM in molecular remission (MR); five of these patients were chemorefractory. Nine patients (3 FCL, 5 CLL, 1 SLL) never achieved PCR negativity and 3 of them relapsed (2 CLL; 1 SLL) after a median time of 270 days. In one of these patients the TaqMan PCR system could detect a continuous increase of tumour genomes in the marrow prior to the clinical relapse. The SLL patient achieved MR after chemotherapy and DLI, developing limited cGVHD; the other two patients never developed GVHD, even after DLI. Eighty percent of PCR-negative patients developed GVHD and it preceded or was concomitant with the achievement of MR. The better molecular outcome of FCL seems to be due to a longer follow up (19 months vs 12 months) if compared to CLL/SLL, in which a slow clearance of MRD has been observed. In conclusion, MR can be achieved in relapsed and chemorefractory patients affected by indolent lymphoproliferative disorders; quantitative PCR monitoring can be used to modulate post-transplant immunotherapy; a longer follow up is warranted to evaluate if the GVT effect can sustain MR in the long-term.

Allogeneic Transplant in Patients with Poor Prognosis B-Chronic Lymphocytic Leukemia (B-CLL): Comparative Study between Myeloablative(M) and Non-Myeloablative(NM) Conditioning Regimen.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2306-2306 ◽  
Author(s):  
M.D. Caballero ◽  
J.A. García-Marco ◽  
R. Martino ◽  
J. Esteve ◽  
M.V. Mateos ◽  
...  
Keyword(s):  
At Risk ◽  
Poor Prognosis ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphocytic Leukemia ◽  
Allogeneic Transplant ◽  
Peripheral Blood Stem Cells ◽  
Group A ◽  
Group B ◽  
Patients With Poor Prognosis

Abstract Sustained complete remissions (CR) have been reached with allogeneic transplant in patients with poor prognosis B-CLL; however, mortality rates are high (20–50%); in order to reduced TRM, NM conditioning are widely used in haematological malignancies; however it is not clear if the use of NM regimens can maintain the efficacy reducing the toxicity. IN this report we performed a retrospective comparison between 30 patients (group A) who have received myeloablative conditioning consisted of TBI plus Cy in 23 pts (74%), TBI, Cy plus VP-16 in 6 pts (19%) and BuCy in 1 patient and 31 patients (Group B) who have received a NM transplant. Conditioning regimens in Group B included: Fludarabine plus Melphalan, 20 pts (64%), Fludarabine, Busulphan and ATG, 5 pts (16%), Fludarabine, TBI and ATG, 4 pts (13%) and Fludarabine plus TBI, 1 patient. All patients received peripheral blood stem cells from a HLA related identical donor. T-cell depletion was performed in 14 patients of the group A. Median age at transplant was significantly higher in the group B patients (53 versus 45, respectively) (p&lt;0,005); no differences were observed in terms of status at transplant and n° of previous chemotherapy lines as well in the risk of graft versus host disease (GVHD) and transplant related mortality (TRM) (See Table, below). With a median follow-up of 71 and 36 months for groups A and B respectively,Overall Survival and Event Free Survival are similar for both groups (53% versus 64% and 60% versus 68%, respectively). Although patients in the NM transplant group were older toxicity was similar in both groups; moreover a similar efficacy has been observed suggesting the clear role of graft versus tumour effect in B-CLL probably more important that the type ofconditining. Table 1 GROUP A Myeloablative Group B Non-myeloablative p Number of previuous chemotherapy lines 2 (1-6) 2 (1-8) NS Acute GVHD 15/30 (48%) 20/31 (64%) NS Grade II-IV 11/30 (35%) 12 /31(38%) NS Chronic GVHD 12/26pts at risk (46%) 18/27 pts at risk (66%) NS Extense 8 pts (30%) 9 pts (33%) NS TRM 7/30 (23%) 7/31 (22%) NS

Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) for Patients with Severe Aplastic Anemia (SAA) above the Age of 40 Years.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3019-3019
Author(s):  
Dario Sangiolo ◽  
Rainer Storb ◽  
Wendy Leisenring ◽  
George Georges
Keyword(s):  
Median Time ◽  
Immune Suppression ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Term Survival ◽  
Allogeneic Hct ◽  
Number Of Patients ◽  
Clinical Records

Abstract Allogeneic HCT for SAA is definitive curative therapy for this otherwise fatal hematologic disease. For younger SAA patients, long-term survival of approximately 90% can be expected after HCT from HLA-identical siblings with cyclophosphamide/ antithymocyte globulin (CY/ATG) conditioning and post-grafting methotrexate/cyclosporine (MTX/CSP) immunosuppression. Most transplant center guidelines and many published reports restrict allogeneic HCT to SAA patients under the age of 40 years, due to concern of increased morbidity and mortality from HCT in older patients. We reviewed the clinical records of all 20 patients with a diagnosis of SAA who were treated with HCT from an HLA-identical sibling at the Fred Hutchinson Cancer Research Center from July 1988 to January 2006 and were above the age of 40 years at the time of HCT. The conditioning regimen consisted of CY/ATG for all but 2 patients who did not receive ATG. MTX and CSP were used as post grafting immunosuppression. The median age of the 10 men and 10 women was 47 (40–63) years. The median time from diagnosis to HCT was 2.7 (0.8–48.5) months. Ten patients had previously received immunosuppressive treatment and all 20 patients had received multiple red blood cell and platelet transfusions before HCT. The median follow-up of surviving patients was 86 (range, 17–194) months after HCT. One patient had graft rejection on day 28 and is alive and well following reconditioning and repeat marrow grafting from original donor. The incidence of acute grades II and III graft-versus-host-disease (GVHD) was 41% and 6%, respectively, the incidence of chronic GVHD (cGVHD) was 37% (6 patients). Overall survival was 70% (fig. 1). Three patients died before engraftment: from preexisting disseminated aspergillosis (n=1), congestive heart failure likely related to CY toxicity (n=1) and preexisting disseminated candidiasis (n=1) on days 2, 3 and 6, respectively. Three patients died from infections on days 83, 179 and 223; in the latter 2 cases, the infections were related to cGVHD and its treatment. The median time to discontinuation of immune suppression was 6 (range, 6–46) months (fig. 1). At last follow-up, 2 patients remain on immune suppression for treatment of cGVHD at 24 and 41 months, respectively. Three patients experienced avascular joint necroses 3, 6 and 9 years after HCT; they had cGVHD (n=2) and/or received extensive steroid treatment before HCT (n=2). Two patients developed superficial basal cell carcinoma at 5.5 and 15 years after HCT. Our data suggest that allogeneic HCT from sibling donor can be successfully extended to SAA patients older than 40 years. Although the number of patients are limited, survival after HLA-identical sibling HCT appears superior to published results of immune suppression therapy for patients >40 years of age. Pre-HCT cardiac screening is indicated to minimize the risk of conditioning related toxicity. Improved treatment to effectively treat or prevent cGVHD and associated infections remain important issues. Figure Figure

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