scholarly journals Evaluating the Impact of Antithymocyte Globulin on Lung Function at 1 Year after Allogeneic Stem Cell Transplantation

2011 ◽  
Vol 17 (5) ◽  
pp. 703-709 ◽  
Author(s):  
Filippo Milano ◽  
Margaret A. Au ◽  
Michael J. Boeckh ◽  
H. Joachim Deeg ◽  
Jason W. Chien
Keyword(s):  
Stem Cell ◽  
Lung Function ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
The Impact

scholarly journals The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation

2002 ◽  
Vol 30 (6) ◽  
pp. 347-354 ◽  
Author(s):  
R Pihusch ◽  
E Holler ◽  
D Mühlbayer ◽  
P Göhring ◽  
O Stötzer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Short Term ◽  
The Impact

scholarly journals Early bilirubinemia after allogeneic stem cell transplantation—an endothelial complication

2021 ◽  
Author(s):  
Hao Dai ◽  
Olaf Penack ◽  
Aleksandar Radujkovic ◽  
David Schult ◽  
Joshua Majer-Lauterbach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Serum Levels ◽  
Endothelial Activation ◽  
Stress Index ◽  
Clinical Correlations ◽  
Angiopoietin 2 ◽  
The Impact

AbstractHyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0–28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, interleukin (IL)18, CXCL8 and suppressor of tumorigenicity-2 (ST2) serum levels, and the endothelial activation and stress index (EASIX). Clinical correlations were validated in a sample of 388 patients transplanted in an independent institution. The EB cut off was determined at 3.6 mg/dL (61.6 µM). EB predicted OS (HR 1.60, 95% CI 1.21–2.12, p < 0.001), and NRM (CSHR 2.14; 1.28–3.56, p = 0.004), also independent of typical endothelial complications such as veno-occlusive disease, refractory acute graft-versus-host disease, or transplant-associated microangiopathy. However, EB correlated with high Angiopoietin-2, EASIX-pre and EASIX-day 0, as well as increased levels of posttransplant CXCL8, IL18, and ST2. In summary, EB indicates a poor prognosis. The association of EB with endothelial biomarkers suggests an endothelial pathomechanism also for this posttransplant complication.

Allogeneic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia After Prior Treatment with Nilotinib or Dasatinib

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2348-2348
Author(s):  
Michael Schleuning ◽  
Marijke Scholten ◽  
Anja van Biezen ◽  
Arnon Nagler ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
The Impact

Abstract Abstract 2348 Stem cell transplantation (SCT) will continue to be a treatment option for patients with chronic myeloid leukemia, despite the introduction of tyrosine kinase inhibitors (TKI). However, many patients will have received prior therapy with TKI, including Nilotinib or Dasatinib at the time of allogeneic SCT. While the use of Imatinib prior to SCT seems to have no adverse impact on the outcome of allogeneic SCT little is known on the impact of prior use of second generation TKI. Therefore we conducted a retrospective registry study and identified 56 patients with CML who received an allotransplant after having been treated with Nilotinib and/or Dasatinib. Best responses to second generation TKI were major molecular response in 11%, complete cytogenetic response in 7%, partial cytogenetic response in 18%, complete hematologic remission in 25% and no response in 34%, respectively. At SCT, 37% of the patients were in accelerated or in blast phase, 36% in CP2 or higher and 27% in first chronic phase. Graft failure occurred in two patients. The median follow-up for surviving patients is 19 months. At 24 months the estimated non-relapse mortality was 33% and the relapse incidence 15%. Probability of survival is more than 85% at 2 years in patients transplanted in CP1. In univariate analysis there was a non significant trend in favor for pretreatment with Nilotinib as compared to the other groups. However, in multivariate analysis only stage of the disease was a predictor for survival. With respect to overall survival no significant differences could be identified for the following variables: patient age, donor type, stem cell source, intensity of the conditioning, time diagnosis to transplant, in or ex vivo T-cell depletion, response to treatment with second generation TKI. Patients transplanted in blast crisis had a significant higher risk of non relapse mortality. In summary, despite the shortcomings of a retrospective study, the data reported clearly show the feasibility and efficacy of allo SCT in patients pretreated with second generation TKI and it should be emphasized that the timing of allogeneic stem cell transplantation remains crucial to avoid unacceptable high treatment related mortality. Disclosures: Ekblom: Bristol-Myers Squibb: Honoraria.

Reduced-Toxicity (RTC) Versus Myeloablative Conditioning (MAC) Prior to Allogeneic Stem Cell Transplantation in Pediatric Participants: Significant Improvement in Physical Functioning Following RTC Versus MAC

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2069-2069
Author(s):  
Jennifer A Oberg ◽  
Erin Morris ◽  
Lauren Harrison ◽  
Julia Glade Bender ◽  
James H Garvin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Social Functioning ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Physical Functioning ◽  
Effect Size ◽  
Size Difference ◽  
Post Hoc ◽  
The Impact

Abstract Abstract 2069 Over the past decade there has been a shift in treating pediatric patients with RTC followed by allogeneic stem cell transplantation (alloSCT) for malignant and non-malignant diseases (Satwani/Cairo et al, BBMT 2005). Advantages of RTC over MAC include reduced acute short- and long-term late complications, reduced risk of infections, and improved survival. However, relatively little is known about the impact of RTC on the longitudinal quality of life (QOL) of these patients following alloSCT. The objective of this study was to compare the physical, emotional, and social functioning of children who received RTC versus MAC regimens prior to and after alloSCT. Hierarchical linear modeling (HLM) was used to explore trends in the PedsQL 4.0 physical, emotional, and social functioning and select individual items of 80 children ≥ 5 years of age undergoing alloSCT between Nov. 2002 and Dec. 2008. QOL was assessed once pre-alloSCT and on days 100, 180, 365, and 730, post-alloSCT. In addition, post hoc exploratory analyses were performed to further evaluate the effect of RTC and MAC regimens on QOL outcomes. If significant between- or within-group differences were observed for any of the three sub-scales, HLM procedures were performed for each sub-scale item to identify the item(s) affected by treatment. Since post hoc analyses were exploratory no adjustments were made in the alpha level. This secondary data analysis was not powered to detect statistically significant differences. Effect size (ES) calculations were included to describe the magnitude of change in scores from baseline and were calculated using the within patient standard deviation (SD), whereas the magnitude of the difference in scores between RTC and MAC regimens were calculated using the between group SD and interpreted according to Cohen's thresholds. Mean age: 12.67 years; malignant/non-malignant 59%/41%; RTC/MAC 54%/46%. There was no significant difference (p = 0.87) between the baseline mean emotional functioning scores of patients treated with RTC (M = 75.90) or MAC (M = 75.30). In addition, there was no appreciable difference (p = 0.08) in the slope function between these two groups. Similarly, the baseline mean social functioning scores did not differ (p = 0.51) between groups with the RTC patients (M = 81.62) having equivalent function to MAC patients (M = 83.73). Furthermore, the rate of change over time between the two groups was not significantly different (p = 0.96). However, a significant change from baseline in overall physical functioning was estimated for RTC (M = 66.84) compared to MAC (M = 68.05) with RTC improving at a rate of 0.48 points per month (ppm)/ 5.82 points per year (ppy) and MAC improving by 0.04ppm/ 0.52ppy (t = 2.34; p = 0.02) (Figure 1). At 2-years post-alloSCT a moderate difference was estimated (ES = 0.71 SD) with RTC scoring 9.35 points higher than MAC. Post hoc analyses of physical functioning items revealed baseline impairments in lifting something heavy for both RTC (M = 55.55) and MAC (M = 56.06). However, the RTC group rapidly improved by 7.12ppm (t = 2.07; p = 0.03) with no lifting problems estimated by 6-months post-alloSCT. MAC improved by 1.27ppm, with some lifting difficulties predicted throughout the follow-up period. A large effect size difference in lifting scores was estimated at 2-years post-alloSCT with MAC scoring 6.74 SD lower than RTC. Greater improvements in fatigue scores were predicted for RTC (M = 60.11; 3.39ppm) compared with MAC (M = 65.19; 2.46ppm) (p > 0.05) with no fatigue estimated by 1-year post-alloSCT for both groups. RTC pain scores improved from baseline by 2.82ppm (M = 66.02) and 5.35ppm for MAC (M = 66.95). No difficulties with pain were estimated by 1-year for RTC and by 6-months for MAC. Emotional and social functioning were not influenced by the intensity of conditioning regimen received. Deficits in physical functioning appeared transient with most perturbations expressed in the acute post-alloSCT period. RTC versus MAC prior to AlloSCT in pediatric recipients was associated with significantly fewer deficits and faster recovery in overall physical functioning, strength, and fatigue. This study highlights the importance of including QOL as part of the treatment investigations to further define outcomes that are related to the intensity of conditioning regimens used in pediatric alloSCT.Figure 1:Estimated change in physical functioning between RTC vs. MAC in pediatric alloSCT recipientsFigure 1:. Estimated change in physical functioning between RTC vs. MAC in pediatric alloSCT recipients Disclosures: No relevant conflicts of interest to declare.

Impact of the New Anti-Myeloma Drugs on Outcome of Allogeneic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with High-Risk Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4456-4456
Author(s):  
Jean El-Cheikh ◽  
Roberto Crocchiolo ◽  
Jean Marie Boher ◽  
Sabine Furst ◽  
Anne Marie Stoppa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Graft Versus Host ◽  
Significant Difference ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 4456 The increasing use of the novel agents, lenalinomide and bortezomib, in the treatment of multiple myeloma (MM) has contributed to higher complete remission (CR) rates and longer overall (OS) and event free survival (EFS). We assessed the impact of these drugs on the outcome of high-risk MM patients treated with allogeneic stem-cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) over the last 10 years in our program. This retrospective study compared 45 patients (group1) transplanted in our centre between January 1999 and January 2006 and who had not received either novel agent prior to transplant (as induction or relapse therapy) with 34 patients (group 2) transplanted between January 2006 and June 2010 who received either one or both drugs before allo-SCT. The median time between diagnosis and Allo-SCT was 37 months (6–161) and 41 months (9–145) in the two groups respectively (p=NS). The median time between auto-SCT and allo-SCT was 9 months (2–89) and 27 months (2–49) respectively (p<0.0001). 36 patients (80%) in the first group vs. 8 patients (24%) in the second group received a tandem auto allo-SCT (p<0.0001). The disease status at transplantation was in CR in 2 patients (4%) vs. 10 patients (29%) and PR or stable disease in 35 patients (78%) vs. 21 patients (62%) in the first and the second group respectively (p<0.0033). in the table 1 we resumed some important data. Table 1Table 1:Patients Characteristic:Characteristics n=791999-2006 n=45 (57%)2006-2010 n=34 (43%)Fisher, p valueMedian age years (range)51 (27-65)55 (39-67)Number of prior therapies 1 2318 (40) 17 (38) 10 (22)8 (24) 18 (52) 8 (24)0.1509Cytogenetics at diagnosis Normal Del(13) Del (17) t (4;14) NA5 (11) 4 (9) 36 (80)3 (9) 12 (35) 19 (56)0.00504Disease status CR ou VGPR PR ou SD PD or refractory2 (4) 35 (78) 8 (18)10 (29) 21 (62) 3 (9)0.003359Donor type Matched Sibling Unrelated Donor45 (100) 021 (62) 13 (38)0.0004517Conditioning treatment With TBI With ATG19 (42) 26 (58)9 (26) 25 (74)0.1632Legend: Allo-SCT, allogeneic stem cell transplantation; Auto-SCT, autologous stem cell transplantation; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease. GVHD indicates graft-versus-host disease; CSP, cyclosporine; MMF, mycofenolate mofetyl; TBI, total-body irradiation; ATG, anti-thymoglobulin; TRM, Transplant related mortality. Groups differ in several aspects: In recent years allogeneic transplant was considered rather as salvage therapy in patients relapsing after auto-SCT than in a tandem auto-allo strategy, patients with cytogenetic aberrations (p<0.005), and stem cell source from unrelated donor (13 patients (38%) vs. none) (p<0.0004), and two days of anti-thymoglobuline (ATG 2,5mg/kg/day). (P<0.001), in the second group. Table 1 The median follow-up after transplant was 45 (2–127) and 16 (3–39) months in the first and second group respectively (p<0.001). The cumulative incidence of acute graft versus-host disease (GVHD) tended to be higher before 2006 (47% vs. 24%; p=0.0584). The cumulative incidence of chronic GVHD was statistically different (56% vs. 30%; p=0.0241). The estimated probability of TRM at day 100 was 12% in the first group vs. 0 % in the second group (p=0.077) and did not differ between groups at 2 years. (18% vs. 23% (p =0.537)). The overall survival (OS) at two years was 60% vs 70% in the first and second group respectively (p=0.1784). The progression-free survival (PFS) tended to be different at 2 years (45% vs. 65% (p=0.056)). The median of PFS is 22 months for patients transplanted prior 2006 and is not reached in the second group (p=0.1811). In our study there was no significant difference in OS or TRM between the 2 groups in multivariate analysis; only the number of previous auto-SCT with more than two high dose chemotherapies has a negative impact on the OS. There was a significant difference in the incidence of relapse between the 2 groups in the multivariate analysis. Although we cannot carry out the impact of other changes related to our practice in the same period, these data suggests an impact in transplant outcomes of novel drugs introduced in the therapy of MM (lower TRM, GVHD and higher disease control). This piece of information, if confirmed, should be taken into considerations for present and future approaches. Disclosures: No relevant conflicts of interest to declare.

Impact of Early Blast Clearance Following Induction Chemotherapy On the Outcome of Patients with Acute Myelod Leukemia Undergoing Allogeneic Stem Cell Transplantation in First Complete Remission

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1998-1998
Author(s):  
Philipp G. Hemmati ◽  
Theis H. Terwey ◽  
Philipp le Coutre ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Allogeneic Stem Cell Transplantation ◽  
High Dose ◽  
Significant Difference ◽  
The Impact ◽  
First Complete Remission

Abstract Abstract 1998 Purpose: In patients with newly diagnosed acute myeloid leukemia (AML) rapid achievement of remission by induction chemotherapy is an important predictor for long-term disease control. In turn, patients who fail to attain early blast clearance after the first chemotherapy course have an inferior outcome. Here, we investigated the impact of early blast clearance on the overall outcome of patients with AML undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) as consolidation therapy. Patients and Methods: 169 (90 female, 79 male) patients with AML who underwent alloSCT in CR1 at our center between 1994 and 2011 were included. Data were prospectively recorded in our transplant data base and retrospectively analyzed as of December 31st, 2011. In detail, 107 patients (64%) had de novo AML, 31 patients (18%) had AML evolving from myelodysplastic syndrome (MDS), and 31 patients (18%) had therapy-related AML. According to the criteria of the SWOG/ECOG, cytogenetic risk was either favorable (6 patients, 4%), intermediate (104 patients, 62%), or poor (47 patients, 27%). Prior to alloSCT all patients were treated in a German multicenter AML trial and received at least two courses of induction chemotherapy, i.e. either standard “7+3” (daunorubicin 60 mg/m2, day 3–5 and Ara-C 100 mg/m2, day 1–7) or a “high-dose Ara-C” containing regimen (Ara-C 1–3 g/m2). In 98 patients (58%) induction chemotherapy resulted in blast clearance after the first course, whereas 71 patients (42%) failed to achieve early remission, but entered remission after 1 or 2 subsequent courses. Median age at transplantation was 47 years (range: 17–69 years). In 146 patients (86%) alloSCT was performed using peripheral blood stem cells (PBSCs), whereas 23 patients (14%) received a bone marrow (BM) graft. Conditioning consisted of standard myeloablative conditioning (MAC: 6 × 2 Gy TBI and 2 × 60 mg/m2 cyclophosphamide) in 81 patients (48%), whereas 86 patients (52%) received reduced intensity conditioning (RIC: busulfan 2 × 4 mg/kg, fludarabine 6 × 30 mg/m2 and ATG 4 × 10 mg/kg). A matched related donor was available in 82 patients (49%), whereas 68 patients (40%) or 19 patients (11%) were transplanted from a matched-unrelated or mismatched unrelated donor. Results: After a median follow-up of 45 months (range: 3–196 months) for the surviving patients, 91 patients (54%) are alive and in continuous remission. Causes of death were relapse in 38 patients (22%) or NRM in 33 patients (19%). At 1, 3 or 5 years projected overall survival (OS) was 72±6%, 58±6%, or 54±8% for all patients. Probability of relapse or non-relapse mortality (NRM) at 1, 3, and 5 years was 20±10% (20±11%), 31±12% (20±11%), and 34±12% (20±11%). Although there was no statistically significant difference in OS at 3 and 5 years between patients who achieved early blast clearance as compared to patients who failed to do so (p=0.09), disease-free survival (DFS) and probability of relapse differed significantly between the two groups at 3 years (77±8% vs 55±14%) or 5 years (75%±9% vs 52%±14%) following alloSCT (p=0.02). There was no significant difference in NRM between the two subgroups. Likewise, there was no statistically significant difference between patients conditioned with either MAC or RIC. In multivariate analysis cytogenetic risk group and remission status were identified as independent prognostic factors for DFS and probability of relapse. Conclusions: These results suggest that in patients with AML undergoing alloSCT in CR1 early blast clearance, i.e. following the first course of induction chemotherapy, predicts a very favorable outcome. Disclosures: No relevant conflicts of interest to declare.

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