Myeloablative Umbilical Cord Blood Transplantation for Hematologic Malignancies Is Comparable to Unrelated Donor Transplantation: A Retrospective Single-Center Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1995-1995
Author(s):  
Filippo Milano ◽  
Theodore A. Gooley ◽  
Paul O'Donnell ◽  
Boglarka Gyurkocza ◽  
H. Joachim Deeg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Disease Risk ◽  
Unrelated Donor ◽  
Platelet Recovery ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Difference ◽  
Risk Of Relapse

Abstract Abstract 1995 Background: The number of cord blood transplants (CBT) is rapidly increasing with suggestion of outcomes comparable to those obtained after unrelated donor transplantation (URD). We conducted, a retrospective analysis comparing post-transplant outcomes between myeloablative CBT and myeloablative URD at our Institution. Methods: Between January 2006 and December 2011 a total of 488 patients received either a CBT (n=88) or URD (n=400). Of these 400, 358 (90%) received a 10/10 HLA-matched (MURD) and 42 (10%) a ≤9/10 HLA-mismatched (MMURD) graft. All patients received a double CB graft except for 12 patients (13%) who received a single CB unit. In addition, 25 (28%) patients received an ex vivo expanded graft as part of either a single or double CBT. Mycophenolate mofetil and cyclosporine were used for graft-versus-host disease (GVHD) prophylaxis in all CBT recipients, while FK506 + methotrexate was preferentially used among URD patients (n=339, 84%). Conditioning regimens for both groups are summarized in Table 1. Time-to-event outcomes were compared between groups using Cox regression, and logistic regression was used for acute GvHD. All models were adjusted for age, disease risk and CMV serostatus. Results: Patient characteristics are shown in Table 1. Differences between groups included higher median age in URD recipients and a higher proportion of non-caucasian and CMV seropositivity in CB recipients. Disease risk was similar between the 2 groups. Peripheral blood stem cells (PBSC) was used for the majority of URD grafts (61%). The median time to neutrophil [URD 19 days vs CBT 23 days; hazard ratio (HR) 1.91 (1.46–2.51, p<0.0001)] and platelet recovery [URD 19 days vs CBT 45 days; HR=2.76 (2.05–3.71, p<0.0001)] was significantly shorter for URD recipients. In multivariate analysis, the risk of mortality was similar in URD vs CBT (HR=1.11 (0.71–1.73, p=0.64)). When HLA-match status was considered in the URD group, the risk of death was higher in the MMURD group compared to CBT, although the difference was not statistically significant (HR=1.37 (0.83–2.26, p=0.22)). The risk of relapse was suggestively higher in the URD group overall relative to CBT (HR=1.90 (0.94–3.84, p=0.07)), and this difference was enhanced when HLA matching and source of stem cells in URD were considered. In particular, recipients of unrelated (matched or mismatched) PBSC had a higher risk of relapse relative to CBT (HR=2.33 (1.11–4.91, p=0.03)), as did the MMURD (BM or PBSC) group (HR=2.34 (1.07–5.11, p=0.03)). Furthermore, unrelated recipients of matched or mismatched PBSC each had a higher risk of relapse relative to CBT (matched PBSC: HR=2.44 (1.11–5.38, p=0.03); mismatched PBSC: HR=3.89 (1.63–9.30, p=0.002)). The combined results for mortality and relapse led to an increased risk of relapse-free survival (RFS) failure (earliest of relapse or death) for patients receiving PBSC from a mismatched URD (HR=1.88 (1.08–3.27, p=0.03)); the risk of failure was also increased for PBSC recipients from a matched URD, but the difference was not statistically significant (HR=1.42 (0.87–2.32, p=0.16)). The risk of non-relapse mortality (NRM) was similar between URD and CBT (HR=0.89 (0.52–1.53, p=0.67)), and while there was less chronic GvHD in the URD group, the difference was not statistically significant, and this slight reduction was largely due to the effect in BM recipients (URD BM vs CBT, HR=0.59 (0.35–0.98, p=0.04); URD PBSC vs CBT, HR=1.01 (0.62–1.66, p=0.95)). The risks of grades 2–4 and 3–4 acute GvHD were similar between URD and CBT groups (odds ratio (OR) 1.10 (0.57–2.11, p=0.78)), and (OR=0.70 (0.38–1.31, p=0.26)), respectively. Conclusions: Our data suggest that OS, RFS and NRM after CBT are not inferior to those observed after URD transplantation, and OS and RFS might be higher when the URD group is restricted to recipients of PBSC, particularly those who are mismatched with their unrelated donor. Relapse occurred less frequently for CBT recipients especially when compared to MMURD or URD with PBSC. The retrospective nature of this study and the heterogeneity of the population do not allow us to draw definitive conclusions, however, our results reinforce the need for a randomized study to definitively address these comparisons. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Prognostic Calculator Easix Predicts Acute Gvhd, Non-Relapse Mortality and Overall Survival in Adult Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2069-2069
Author(s):  
Miriam Sanchez-Escamilla ◽  
Patrick Hilden ◽  
Molly Maloy ◽  
Samira A Fatmi ◽  
Doris Ponce ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Acute Gvhd ◽  
Endothelial Damage ◽  
Adult Patients ◽  
Stress Index ◽  
Unrelated Donor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Reduced Intensity

Abstract Keywords Allogeneic transplantation; endothelial damage; biomarkers. Background Endothelial damage is associated with severe complications and increased risk of death after allogeneic hematopoietic cell transplantation (AlloHCT). The recently developed Endothelial Activation and Stress Index (EASIX) is a prognostic tool that uses clinical lab values and has been shown to predict non-relapse mortality (NRM) and overall survival (OS) at onset of acute graft versus host disease (aGVHD) in reduced intensity (RIC) alloHCT (Luft, Lancet Haematol 2017). We hypothesized that EASIX may be valuable for more broadly predicting aGVHD, NRM and OS after AlloHCT, beyond time of onset of aGVHD. Design We evaluated 152 adult patients who received an unmodified RIC AlloHCT from a related or unrelated donor with uniform GVHD prophylaxis of sirolimus/tacrolimus and low-dose MTX for treatment of lymphoid malignancies, between April 2008 and May 2017. The EASIX formula (LDH*Creatinine/platelet counts) was calculated at multiple timepoints (pre-HCT, day 30, day 100, onset TMA and aGVHD). For all EASIX assessments post-HCT, a landmark analysis was conducted at the given timepoint A log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. A one-unit increase in log2 EASIX is associated with a doubling (one-fold increase) of EASIX on the original scale. Kaplan-Meier, cumulative incidence, and cox modeling (cause specific for NRM and aGVHD) were used to evaluate EASIX as it relates to outcomes of interest. Relapse and death or relapse were considered competing risks for NRM and aGVHD respectively. Results The median age at transplant was 54 years (range 23-78), 70% were males, a majority had non-Hodgkin lymphoma (68%), and most had sensitive disease at time of HCT (CR=56%; PR=33%). All patients, except two, received peripheral blood stem cells. Sixty-three patients had an HLA-identical related donor, while the remaining 89 had an unrelated donor transplant (HLA-matched in 75 patients, and HLA-mismatched in 14 patients). HCT-CI was 0 in 49 patients, 1-2 in 41 and ≥ 3 in 62 patients. With a median follow-up in surviving patients of 5.4 years (range, 0.8-10), the 1 and 3 years OS rate was 84.2% (95% CI, 77.3-89.1) and 67.9% (95% CI, 59.6-74.8), respectively. The NRM rate at 1 and 3 years was 7.9% (95% CI, 4.3-12.9) and 16.4% (95% CI, 10.9-22.8), respectively. The 1-year cumulative incidences of grades 1-4, 2-4 and 3-4 aGVHD were 56.6% (95% CI, 48.3-64.1), 42.1% (95% CI, 34.2-49.8) and 7.9% (95% CI, 4.3-12.9), respectively. Post-HCT thrombotic microangiopathy was only observed in 13 patients, representing too few events for EASIX analysis. As expected, HCT-CI was significantly associated with both OS and NRM. Pre-HCT EASIX was significantly associated with increased NRM (HR=1.60 [95% CI, 1.15-2.23], p=0.005) and aGVHD grade 1-4 and 2-4 (HR=1.33 [95% CI, 1.08-1.64], p=0.006 and HR=1.39 [95% CI, 1.10-1.75], p=0.005; respectively), but not OS or grade 3-4 aGVHD (Table 1). EASIX at day 30 and day 100 was significantly associated with both OS and NRM (Figures 1-4). Furthermore, confirming the results of Luft, EASIX calculated at onset of any grade aGVHD was significantly associated with OS (HR=1.34 [1.10-1.63], p=0.004) and NRM (HR=1.47 1.11-1.94], p=0.007). Finally, there was no correlation between HCT-CI and EASIX score. Conclusions We conclude that the EASIX formula, calculated at various timepoints pre and post AlloHCT, is significantly associated with NRM and OS. Pre-HCT EASIX also predicts risk of aGVHD, confirming prior results, EASIX at onset of acute GVHD is a predictor of NRM and OS in adult recipients RIC AlloHCT. EASIX provides an independent and easily accessible tool to predict important AlloHCT outcomes that can be used in addition to HCT-CI to better risk stratify patients. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees; Novartis: Other: Personal fees.

Negative Effect of KIR Alloreactivity in Recipients of Umbilical Cord Blood Transplantation Depends on Transplantation Conditioning Intensity

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 152-152
Author(s):  
Claudio Brunstein ◽  
John E. Wagner ◽  
Daniel Weisdorf ◽  
Sarah Cooley ◽  
Harriet Noreen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Acute Gvhd ◽  
Nk Cell ◽  
Cord Blood Transplantation ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
Increased Risk ◽  
Reduced Intensity

Abstract Transplant strategies involving natural killer (NK) cell alloreactivity (KIR-ligand mismatch [KIR-L mismatch]) have demonstrated superior outcomes for patients receiving T cell depleted HLA haploidentical hematopoietic stem cell allografts. It is unknown whether KIR-L mismatch has a similar effect in recipients of partially HLA-matched umbilical cord blood (UCB) grafts which contain comparatively few T-cells. We examined the clinical impact of KIR-L mismatch in 257 UCB recipients treated with either a myeloablative (n=155) or reduced intensity (n=102) regimen. After myeloablative conditioning, KIR-L mismatch had no demonstrable effect on grades III–IV acute GVHD (17% [CI, 6–28%] vs. 17% [CI, 10–24], p=.97), transplant-related mortality (TRM) (27% [CI, 14–40%] vs. 18% [CI, 11–25%], p=.19), relapse at 2 yrs (18% [95%CI, 6–30%] vs. 28% [95%CI, 19–27%], p=.37) and survival at 3 yrs (50% [CI, 32–68%] vs. 57% [CI, 47–67%], p=.46). In contrast, following reduced intensity conditioning when the engrafting unit was KIR-L mismatched there was a significantly higher incidence of grades III–IV acute GVHD (42% [CI, 27–59) vs. 13% [CI, 5–21], p &lt; .01). Multivariate analysis confirmed NK cell alloreactivity as the only predictive factor associated with severe acute GVHD was (RR 1.8, CI [1.1–2.9]; p=.02). TRM was higher (27% [CI, 12–42%] vs. 12% [CI, 5–19%], p=.03) and three year survival was poorer (32% [CI, 15–59%] vs. 52% [CI, 47–67%], p=.03) when the engrafting unit was KIR-L mismatched, but relapse was unaffected (39% [95%CI, 21–57%] vs. 47% [95%CI, 34–60%], p=.72). KIR-L mismatch in recipients of a RIC UCB transplant was associated with a significant increased risk of death (RR 1.8, 95%CI, 1.0–3.1, p=.05). This data identify divergent effects of NK cell alloreactivity which are unmasked when comparing myeloablative versus RIC transplant platforms. We conclude that KIR-L mismatch should be avoided in recipients of a reduced intensity UCB transplant.

scholarly journals Post Transplantation Fludarabine and Cyclophosphamide Selected and Promoted Low Dose of Unrelated UCB Implanation in Combined Transplantation of Haploid and UCB Stem Cells in Childhood Leukemia: 40 Cases Report in Double Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Yuhua Xiao ◽  
Sixi Liu ◽  
Chunfu Li ◽  
Wing Hang Leung ◽  
Xiaoqin Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Low Dose ◽  
Acute Gvhd ◽  
Implantation Rate ◽  
Virus Reactivation ◽  
Post Transplantation ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Risk Of Relapse

Abstract Background: For patients without HLA matched donor, Haploid stem cell transplantation with PTCY method has relatively higher risk of relapse and graft-versus-host disease (GVHD). Umbilical cord blood (UCB) is readily available and has helped expand the donor pool to almost all patients requiring a transplant. Meanwhile UCB transplant improves EFS in leukaemia with lower risk of relapse and GVHD. However, the clinical application of UCB is limited due to lower implantation rate because of its low dose of stem cells than other sources of hematopoietic stem cells (HSC). Aims: This study is to explore the feasibility and efficacy of post-transplantation fludarabine and cyclophosphamide to select and promote the unrelated UCB to engraft in combined transplantation of haploid and UCB stem cells for the treatment of childhood and adolescent leukemia. Methods: Total 40 children and adolescent patients with leukemia in Nanfang Hospital and Shenzhen Children's Hospital enrolled this study from Sept.2019 to Jun.2021. These patients were diagnosed as AML (20 HR, 5 IR, 2 relapsed AML), ALL (5 HR, 2 IR, 2 relapsed ALL), AL (1), JMML (2), MDS (1) and BPDCN (1) with a median age of 80 months (range 7 months -17 years). The biggest body weight reached to 77kg. The haploid stem cell was 5/10-9/10 mismatched and UCB was selected as 6/10-10/10 HLA matched or mismatched. The condition regimen was busulfan+fludarabine+CY+Ara-C. Haploid PBSC was infused in day0. All received PTCy 50 mg/kg and post-transplantation fludarabine 40mg/m 2 on days 3 and 4 along with tacrolimus or cyclosporine and mycophenolate mofetil for prophylaxis of acute GVHD. UCB was infused in day6. A median of haploid stem cells of 20.00×10 8/kg (13.00-32.10) of mononuclear cells was infused while a median of UCB cells of 4.32×10 7/kg (1.48-22.78) of total nucleated cells was infused. A median of CD34+ cells of haploid stem cells 13.00×10 6/kg (1.51-32.00) was infused while a median of CD34+ cells of UCB cells 1.74×10 5/kg (0.26-4.80) was infused. The survival rate, umbilical cord blood implantation rate, hematopoietic recovery and the rate of transplant-related complications were analyzed. Results: At a median follow-up of 8 months (range 1-21 months), there were 2/40（5%）cases of transplant-related death. All surviving patients were leukemia free, with one-year overall survival rate 92.8±5.0%. Among these patients, 37/40(92.5%, 95%CI: 84.0%~100.0%) of patients achieved complete chimerism of unrelated UCB cells and 3/40(7.5%, 95%CI: -1.0%~16.0%) of patients achieved mixed chimerism of unrelated UCB cells and haploid cells. In these transpltantation, the CD34+ cell dose of UCB less than 1.0×10 5/kg accounted for 10/40 (25.0%), and less than 2.0×10 5/kg accounted for 23/40 (57.5%).Two patients had primary poor graft function. Neutrophil reconstitution was achieved in 39/40 patients with a median time of 29 days (range 17 - 44 days) without G-CSF after transplantation. Platelet recovery was achieved in 37/40 patients with a median time of 37 days (range 8-92 days). There was a significant linear relationship between platelet recovery time and the dose of total nucleated cells and CD34+ cells in UCB（r=-0.368, P=0.025; r=-0.355, P=0.031）.The incidence of gradeⅠand gradeⅡGVHD was 32.5%（95%CI:17.3%-47.7%）and 42.5%（95%CI:26.5%-58.5%）, respectively. There was no grade Ⅲ-Ⅳ aGVHD and only 1/40(2.5%) case of extensive chronic GVHD. The incidence of chronic limited GVHD was 22.5% (95%CI: 9.0%-36.0%). Twenty-four of 40(60.0%, 95%CI:44.1%-75.9%) patients experienced clinically significant CMV reactivations or infections. One of 40（2.5%, 95%CI: -2.6%-7.6%）patients experienced EB virus reactivation. Two of 40（5.0%, 95%CI: -2.1%-12.1%）patients experienced human herpesvirus 6 infection. Thirteen of 40（32.5%, 95%CI: 17.3%-47.7%）patients presented with hemorrhagic cystitis. Conclusion: In our primary clinical study, post-transplantation fludarabine and cyclophosphamide could effectively select and promote the unrelated UCB to implant rather than haploid cells in combined transplantation of haploid and UCB stem cells even if the CD34+ cells of UCB less than 1.0×10 5/kg. Although acute GVHD was common but just milder degree and with lower incidence of EB virus reactivation. This new strategy has the potential to promote the wilder clinical use of unrelated UCB in the treatment of leukemia. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cord Blood Transplants Supported By Unrelated Donor CD34 Progenitor Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4646-4646
Author(s):  
Alexandra Gomez-Arteaga ◽  
Danielle Guarneri ◽  
Usama Gergis ◽  
Jingmei Hsu ◽  
Sebastian A. Mayer ◽  
...  
Keyword(s):  
Cord Blood ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Unrelated Donors ◽  
Second Degree

Abstract Introduction: Umbilical cord blood (UCB) transplant supported by third party CD34-selected cells results in rapid count recovery, UCB mediated GVL effects and low rates of chronic GvHD. For patients lacking haplo-identical relatives, other sources of CD34 progenitors are needed. Methods: We identified partially matched unrelated donors for patients lacking suitable haplo-identical donors -including second-degree relatives - and who otherwise were candidates for haplo-cord transplant. Most were treated on prospective studies (clinicaltrials.gov 00943800 and 01810588). For 5 patients, UCB were obtained through NCT01351545. Results: Between 12/2014 to 7/2018 of 126 candidates for haplo-cord transplant, 26 (21%) had no suitable related donor. Most common reasons were: no first or second degree partially matched donors, ill or unavailable relative, high titers of HLA-antibodies against all relatives, or evidence of hematological familial hereditary syndrome. Diagnoses were: 16 AML/MDS, 5 ALL, 2 MPN, 1 NHL, 1 plasma cell leukemia and 1 SAA. Median age was 57 (24-75). 50% were women. 42% non-Hispanic white (NHW), 19% non-Hispanic blacks (NHB), 19% Hispanic, 8% other minorities. CIBMTR Disease Risk Index (DRI): 46% intermediate, 38% high and 8% very high. Median HCT-CI was 3.5 (25%-75% IQR 2-6). Conditioning: 16 Flu/Mel/TBI (94% 400cGray), 8 Flu/Mel,1 Flu/Cy, 1 Etoposide/TBI. All except 1 received ATG 4.5 mg/kg and all received post-transplant Tacrolimus and MMF. UCB matching was 4/8, 5/8, 6/8 or 7/8 HLA in 12%, 27%, 23%, and 38%, respectively. HLA matching for unrelated haplos was 5-6/12, 7-8/12, >9/ 12 HLA in 15%, 54% and 19%, respectively. For UCB, median cells collected were 2.1 (range1.1-4.0) ×107 TNC/kg. CD34 cell dose of unrelated donor graft was 3-5 ×106 CD34/kg. Median time to ANC engraftment was 11 days (range 9-35) and platelet engraftment was 18 days (range11-124). Chimerism on day 56 are shown in figure 1. There were three patients with graft failures: Pt #5 with complete graft rejection, autologous reconstitution, but ongoing clinical remission that persists to date (Day+ 1223); Pt #13 with graft failure and subsequent relapse, rescued with second UCB HSCT but died of progression of disease; and pt #18 who died from infectious complications after graft failure. Acute GvHD occurred in 35% of patients (4 Grade I-II, 4 Grade III, and 1 Grade IV). cGvHD was rare: One patient with mild severity and a second with severe lung involvement. After a median follow up of 209 days, 6 months cumulative incidence of relapse (CIR) was 16% and non-relapse mortality (NRM) was 20%. Median OS was 14 months (95%CI 7-27). Conclusion: 20% of adults without matched related or unrelated donors, also lack suitable first or second degree haplo-identical donors. UCB transplant with partially matched unrelated donor accessory cells provides an alternative for transplantation. Engraftment is rapid, rates of acute GVHD are acceptable and incidence of chronic GVHD is very low. Prolonged survival is encouraging in this patient cohort with adverse characteristics and who would not be candidate for haplo-identical HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5628-5634 ◽  
Author(s):  
Claudio G. Brunstein ◽  
John E. Wagner ◽  
Daniel J. Weisdorf ◽  
Sarah Cooley ◽  
Harriet Noreen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Acute Gvhd ◽  
Immunoglobulin Receptor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Negative Effect ◽  
Reduced Intensity ◽  
Grade Iii

We examined the clinical impact of killer-immunoglobulin receptor-ligand (KIR-L) mismatch in 257 recipients of single (n = 91) or double (n = 166) unit umbilical cord blood (UCB) grafts after myeloablative (n = 155) or reduced intensity (n = 102) conditioning regimens. Analyses of double unit grafts considered the KIR-L match status of the dominant engrafting unit. After myeloablative conditioning, KIR-L mismatch had no effect on grade III-IV acute graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse, and survival. In contrast, after reduced intensity conditioning, KIR-L mismatch between the engrafted unit and the recipient resulted in significantly higher rates of grade III-IV acute GVHD (42% [CI, 27-59] vs 13% [CI, 5-21], P < .01) and TRM (27% [CI, 12%-42%] vs 12% [CI, 5%-19%], P = .03) with inferior survival (32% [CI, 15%-59%] vs 52% [CI, 47%-67%], P = .03). Multivariate analysis identified KIR-L mismatch as the only predictive factor associated with the development of grade III-IV acute GVHD (RR, 1.8 [CI, 1.1-2.9]; P = .02) and demonstrated a significant association between KIR-L mismatch and increased risk of death (RR, 1.8; 95% CI, 1.0-3.1; P = .05). Our results do not support the selection of UCB units based on KIR-L status and suggest that KIR-L mismatching should be avoided in reduced intensity UCB transplantation.

Cyclosporine dose Intensity Is a Critical Determinant of Outcome after a T Cell Depleted Reduced Intensity Allograft.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1153-1153
Author(s):  
Charles F. Craddock ◽  
Sandeep Nagra ◽  
Cassandra Brookes ◽  
Nick Duncan ◽  
Alison H Thomson ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Dose Intensity ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Post Transplant ◽  
Increased Risk ◽  
Reduced Intensity ◽  
Risk Of Relapse

Abstract The ability of reduced intensity conditioned (RIC) allografts to deliver long term disease free survival is dependent on the genesis of an immunologically mediated graftversus tumor (GVT) effect. Post-transplant immunosuppression plays an important role in limiting graft-versus-host disease (GVHD) but also modulates a GVT effect. Although cyclosporine A (CsA) is the most commonly utilised immunosuppressive agent in patients allografted using a RIC regimen the impact of CsA dose intensity on disease relapse and overall survival (OS) has not been studied. We have therefore measured CsA exposure in the first 21 days post-transplant and correlated individualised CsA area under the curve (AUC) values with OS and disease relapse in patients undergoing a RIC allograft. 132 patients with a diagnosis of acute myeloid leukemia (AML) (n=41), myelodysplasia (MDS) (n=17), Non-Hodgkin’s lymphoma (NHL)(n=51) or Hodgkin’s disease (n=23) were transplanted using an alemtuzumab containing RIC regimen. All patients with a myeloid malignancy (AML or MDS) were transplanted using a regimen consisting of fludarabine, melphalan and alemtuzumab (FMA). Patients with an underlying lymphoid disease (NHL or HD) were transplanted using FMA (n=31) or a regimen consisting of BCNU, etoposide, cytosine arabinoside, melphalan and alemtuzumab (BEAMA) (n=43). 39 patients had chemoresistant disease at the time of transplant. All patients received intravenous CsA at a loading dose of 5 mg/kg on day -1 followed by 2.5 mg/kg b.i.d. Patients were switched to oral CsA prior to discharge. Trough CsA levels were measured thrice weekly for the first three weeks after stem cell infusion and the dose of CsA adjusted to achieve levels in the region of 200–300 mg/l during this period. Trough levels obtained during the first 21 days post-transplant were used to calculate the CsA AUC for each patient. The median age of patients studied was 48 years (range 17–68). 71 patients were transplanted from HLA identical siblings and 61 from volunteer unrelated donors. The incidence of acute GVHD (Grades 2–4) was 34%. The median CsA AUC was 3682 mg.hr/l (range 2162- 8084 mg.hr/l). In univariate analysis the presence of chemoresistant disease at the time of transplant and a high CsA AUC were both associated with a decreased OS. In multivariate analyses chemoresistant disease (HR=2.60, 95% CI 1.44–4.65, p=0.002), increased age (HR=1.04, 95% CI 1.01–1.07, p=0.002) and linearly increasing CsA AUC were associated with an increased hazard of death (HR=1.1, 95%CI 1.02–1.24, p=0.02). The two year OS for patients with a CsA AUC less than 3682 mg.hr/l was 77% compared to 30% for patients with CsA of 3682 mg.hr/l and over (p&lt;0.0001). Increased CsA AUC and the presence of chemorefractory disease at the time of transplant were associated with an increased risk of relapse in univariate analysis. In multivariate analyses only increased CsA AUC was significantly associated with a higher risk of relapse (OR=4.1, 95% CI 2.50–6.81, p&lt;0.0001). Decreased CsA AUC and the use of an unrelated donor were associated with an increased risk of acute GVHD in univariate analysis. Multivariate analyses demonstrated that the use of an unrelated donor (HR=2.9, 9%% CI 1.36–6.36, p=0.006) and linearly decreasing CsA AUC were significantly associated with an increased risk of acute GVHD (HR=1.2, 95% CI 1.05–1.43, p=0.01). These data demonstrate the central importance of the intensity of post-transplant immunosuppression in determining outcome after a T cell depleted RIC allograft and support a randomised trial comparing CsA dose regimens in this population of patients. It will be important to determine whether post-transplant CsA exposure plays a similar role in determining outcome after a T replete RIC allograft.

scholarly journals Searching for unrelated donor hematopoietic stem cells: Availability and speed of umbilical cord blood versus bone marrow

2002 ◽  
Vol 8 (5) ◽  
pp. 257-260 ◽  
Author(s):  
Juliet N Barker ◽  
Timothy P Krepski ◽  
Todd E DeFor ◽  
Stella M Davies ◽  
John E Wagner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Unrelated Donor ◽  
Hematopoietic Stem

scholarly journals HLA-DRB3/4/5 mismatches are associated with increased risk of acute GVHD in 10/10 matched unrelated donor hematopoietic cell transplantation

2018 ◽  
Vol 93 (8) ◽  
pp. 994-1001
Author(s):  
Stéphanie Ducreux ◽  
Valérie Dubois ◽  
Kahina Amokrane ◽  
Ibrahim Yakoub-Agha ◽  
Myriam Labalette ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Increased Risk

scholarly journals 370. Comparing Trends and Outcomes among HIV-Infected vs. HIV Uninfected Patients with Tuberculosis: A 5-Year Experience Within the Florida Department of Health in Hillsborough County

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S194-S194
Author(s):  
Shylah M Moore-Pardo ◽  
Anteneh Addisu ◽  
Tea Reljic ◽  
Sadaf Aslam ◽  
Beata Casanas
Keyword(s):  
United States ◽  
The United States ◽  
Homeless Persons ◽  
Sputum Smear ◽  
Foreign Born ◽  
Female Ratio ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Difference ◽  
Hiv Negative

Abstract Background Although the rate of tuberculosis (TB) has significantly declined in the United States, elimination has plateaued. Florida is one of the states with the greatest number of cases. The majority of cases occur in foreign-born individuals. Human immunodeficiency virus (HIV) is also a major contributor. HIV-TB coinfection leads to reciprocal interactions with significant clinical impact. We aim to compare the risk factors, clinical findings, and outcomes among HIV-infected vs. HIV uninfected patients. Methods A retrospective cohort study of TB cases over a 5 year period (2012–2017) was conducted. All patients with HIV co-infection with age- and gender-matched HIV negative controls were included. The diagnosis of TB was made via clinical, microbiological, radiological, and/or PCR based methods. SPSS was used for statistical data analysis. Results A total of 411 TB cases were identified and 66 patients (33 HIV-infected plus 33 HIV un-infected) were eligible for inclusion. The median age was 49 years (range 22–70). The male to female ratio was 21:12 and 50% of patients had TB symptoms; the rest had abnormal imaging or lab finding. Cases were confirmed via positive sputum smear, culture, or PCR (Figures 1–3). Only 11 patients were lost to follow-up, thus 83.3% completed therapy. A total of 5 persons died (Table 1). Conclusion The rate of HIV-TB coinfection in the United States was 5.3% in 2018; higher among injection drugs users, homeless persons, inmates, and alcoholics. In our study, the rate of HIV-TB coinfection was slightly higher (8%). The difference was not statistically significant in regards to foreign born, homelessness, and incarceration. Only 3 patients admitted to injection drug use and 9 used alcohol (all HIV negative). Traditionally, HIV-TB coinfected patients have extra-pulmonary TB with higher rates of negative sputum and are at increased risk of death. In our cohort, the difference was statistically significant (P = 0.009) only for cavitary TB (predominated in HIV un-infected) but no difference in outcomes was observed between the two groups. These findings suggest changing trends in HIV-TB coinfection which may be partly related to our setting and demographics but may be attributed to better access to care and antiretroviral therapy at large. Disclosures All authors: No reported disclosures.

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