scholarly journals Selecting between HLA-Matched Siblings and HLA- Haploidentical Related Donors for Acute Leukemia in the Era of Post-Transplant Cyclophosphamide: The Center for International Blood and Marrow Transplant Registry and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplant

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 851-851
Author(s):  
Tara M. Robinson ◽  
Ephraim J. Fuchs ◽  
Mei-Jie Zhang ◽  
Myriam Labopin ◽  
Andrew St. Martin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Cox Regression ◽  
Chronic Gvhd ◽  
Matched Pair ◽  
Patient Age ◽  
Patient Âgé ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Overall Mortality

Abstract An HLA-matched sibling has been considered the optimal donor for allogeneic hematopoietic cell transplantation (HSCT). However, several potential transplant recipients may have a haploidentical sibling or an offspring who may also serve as donors. In this study, we sought to determine the optimal alternative related donor (haploidentical sibling or an offspring) as compared to an HLA-matched sibling. The primary objective was comparison of chronic graft-versus-host disease (GVHD). Secondary outcomes included acute GVHD, non-relapse mortality (NRM), relapse, treatment failure (relapse or death, inverse of relapse-free survival) and overall mortality. The study population included 4540 donor-recipient pairs (n=218 haploidentical sibling; n=218 offspring; n=4104 HLA-matched sibling) with acute myeloid (n=3617) and acute lymphoblastic (n=923) leukemia transplanted in 2008 to 2015. There were few offspring (n=87) who donated to patients aged 18-54 years and haploidentical siblings (n=61) who donated to patients aged 55-76 years and were excluded from the analysis. Post-transplant cyclophosphamide (PT-Cy) with calcineurin inhibitor (CNI) and mycophenolate was used for GVHD prophylaxis for all haploidentical HSCTs. HLA-matched siblings received CNI-containing GVHD prophylaxis; CNI with methotrexate was the predominant prophylaxis regimen. Patient age was correlated with donor age and donor-recipient relationship. Bone marrow was the predominant graft for haploidentical HSCTs (64%) and peripheral blood (89%) for HLA-matched sibling HSCTs. Younger patients (age 18-54 years) of were more likely to receive reduced intensity conditioning regimens for haploidentical HSCTs compared to HLA-matched sibling HSCTs (22%). Among older patients, conditioning regimen intensity did not differ by donor type. Exploratory analysis confirmed differences in survival by patient age. Therefore, based on differences in survival by patient age, two age groups were created: 18 - 54 years and 55 - 76 years and within each patient age group, donor-recipient relationship and its effect on transplant outcomes were tested using Cox regression models. In addition to the standard Cox regression model, we also performed a matched-pair analysis. Recipients of haploidentical HSCT (cases; n=436) were matched to HLA-matched siblings (controls; n=1707) on age, disease and disease risk index. 88% of patients aged 18-54 years were matched to 4 controls and 96% of patients aged 55-76 years were matched to 4 controls. The median difference in age between cases and controls were 0.08 (range 0-9.9) years for patients aged 18-54 years and 0.05 (0 - 9.5) years for patients aged 55-76 years. The results of multivariate Cox regression and matched-pair analysis are shown in Tables 1, 2. Among patients aged 18-54 years, chronic GVHD risks were lower after haploidentical sibling compared to HLA-matched sibling HSCT. There were no differences in acute GVHD, NRM, relapse, treatment failure or overall mortality. Among patients aged 55-76 years, acute and chronic GVHD risks were lower after offspring compared to HLA-matched sibling HSCT. But risks for NRM, treatment failure and overall mortality were higher after offspring compared to HLA-matched sibling HSCT. The 2-year probabilities of overall survival, adjusted for disease risk index and sex are shown in Figure 1. In summary, chronic GVHD rates were lower after haploidentical HSCT with PT-Cy containing GVHD prophylaxis regimens compared to HLA-matched sibling HSCT for all patients. Whether this can be attributed solely to the GVHD prophylaxis regimen or in part attributed to use of peripheral blood grafts for HLA-matched sibling HSCT must be studied further in a setting in which PT-Cy containing GVHD prophylaxis is used for HLA-matched sibling HSCT. Despite lower chronic GVHD with haploidentical sibling donor HSCT with PT-Cy, NRM and overall survival did not differ by donor type for patients aged 18-54 years. However, for patients aged 55 - 76 years, despite lower chronic GVHD with offspring donor HSCT with PT-Cy, NRM was higher and overall survival was lower compared to HLA-matched sibling HSCT. Definitive proof of these findings would require a prospective randomized trial. Disclosures Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty: Sanofi: Honoraria, Speakers Bureau.

Stem-Cell Transplantation in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia in First Complete Remission: A Prospective Multicenter Trial Comparing Haploidentical Donors with Identical Sibling Donors

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 62-62 ◽  
Author(s):  
Yu Wang ◽  
Wu Depei ◽  
Qifa Liu ◽  
Lan-Ping Xu ◽  
Xiao-Hui Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Patient Age ◽  
Free Survival ◽  
Patient Âgé ◽  
Disease Free ◽  
First Complete Remission

Abstract Purpose and design The effect of HLA-identical sibling donor (ISDs) haematopoietic stem cell transplantation (HSCT) on adults with high-risk acute lymphoblastic leukaemia (ALL) in the first complete remission (CR1) has been established. Our recent single-institute, retrospective study showed that haploidentical HSCT was superior to chemotherapy alone for patients with high-risk ALL in CR1. To test the hypothesis that haploidentical HSCT would be a valid option as post-remission therapy for ALL patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multi-centre study. Patients Between July 2010 and Dec 2013, 186 patients with Philadelphia-negative high-risk ALL were biologically randomized to undergo un-manipulated HIDs (103 patients) or ISDs HSCT (83 patients) according to donor availability. Results Among HIDs and ISDs recipients, the 3-year disease free survival (DFS) rate was 68% and 64% (P =.56), respectively; overall survival (OS) rate was 75% and 69% (P = .51, respectively; cumulative incidences of relapse were 18% and 24% (P = .30), and those of the non-relapse-mortality (NRM) were 13% and 11% (P = .84), respectively. The 28-d myeloid recovery rates were both 99% in each group; the incidences of severe acute graft-versus-host-disease (GVHD) and chronic GVHD were also comparable between the two groups. Among recipients of transplantations from HIDs, no significant differences in DFS, OS, or NRM were observed between 3/6 and 4-5/6 matched grafts; in contrast, maternal donor was related with lower OS compared with other donor sources (P = .04); limited chronic GVHD was associated with better DFS (P = .01). The stem cell source had no effect on DFS. Conclusion Un-manipulated haploidentical-HSCT achieves outcomes similar to those of ISD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation was proved to be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. (Chictr.org.cn number ChiCTR-OCH-10000940) Table. Results of multivariate analysis of outcomes Outcome Hazard ratio (95%Confidence interval) p value Disease free survival Haploidentical vs Identical sibling 0.88 (0.50-1.53) .65 Patient age <30 vs >30 years 0.74 (0.42-1.28) .28 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.48 (0.86-2.56) .16 Female-to-male vs other sex pair 0.95(0.52-1.75) .86 Limited chronic GVHD vs no or extended 0.59 (0.29-1.17) .13 Overall survival Haploidentical vs Identical sibling 0.91 (0.50-1.70) .77 Patient age <30 vs >30 years 0.60 (0.33-1.11) .11 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.64 (0.89-3.01) .11 Female-to-male vs other sex pair 1.22 (0.64-2.31) .54 Limited chronic GVHD vs no or extended 0.59 (0.27-1.28) .18 Relapse Haploidentical vs Identical sibling 0.67(0.33-1.36) .27 Patient age <30 vs >30 years 1.06 (0.50-2.28) .87 Patient sex male vs female 1.52 (0.64-3.62) .35 Time to transplant <6 vs >6 months 1.42 (0.69-2.90) .33 Female-to-male vs other sex pair 0.61(0.26-1.45) .27 Limited chronic GVHD vs no or extended 0.65 (0.26-1.62) .36 Non-Relapse-Mortality Haploidentical vs Identical sibling 1.38(0.58-3.35) .46 Patient age <30 vs >30 years 0.47 (0.19-1.17) .11 Patient sex male vs female 0.66 (0.19-2.33) .52 Time to transplant <6 vs >6 months 1.66 (0.70-3.92) .25 Female-to-male vs other sex pair 1.53(0.64-3.69) .34 Limited chronic GVHD vs no or extended 0.63 (0.21-1.86) .40 Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

2016 ◽  
Vol 34 (26) ◽  
pp. 3141-3149 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Reem Karmali ◽  
Vanderson Rocha ◽  
Kwang Woo Ahn ◽  
Alyssa DiGilio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calcineurin Inhibitor ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Free Survival ◽  
Blood And Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Reduced Intensity

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis

2014 ◽  
Vol 120 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Abraham Noorbakhsh ◽  
Jessica A. Tang ◽  
Logan P. Marcus ◽  
Brandon McCutcheon ◽  
David D. Gonda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Age Groups ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Total Resection ◽  
Patient Age ◽  
Surgical Practice ◽  
Survival Difference ◽  
Patient Âgé

Object There is limited information on the relationship between patient age and the clinical benefit of resection in patients with glioblastoma. The purpose of this study was to use a population-based database to determine whether patient age influences the frequency that gross-total resection (GTR) is performed, and also whether GTR is associated with survival difference in different age groups. Methods The authors identified 20,705 adult patients with glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) registry (1998–2009). Surgical practice patterns were defined by the categories of no surgery, subtotal resection (STR), and GTR. Kaplan-Meier and multivariate Cox regression analyses were used to assess the pattern of surgical practice and overall survival. Results The frequency that GTR was achieved in patients with glioblastoma decreased in a stepwise manner as a function of patient age (from 36% [age 18–44 years] to 24% [age ≥ 75]; p < 0.001). For all age groups, glioblastoma patients who were selected for and underwent GTR showed a 2- to 3-month improvement in overall survival (p < 0.001) relative to those who underwent STR. These trends remained true after a multivariate analysis that incorporated variables including ethnicity, sex, year of diagnosis, tumor size, tumor location, and radiotherapy status. Conclusions Gross-total resection is associated with improved overall survival, even in elderly patients with glioblastoma. As such, surgical decisions should be individually tailored to the patient rather than an adherence to age as the sole clinical determinant.

Comparison of Two Different Rabbit-ATG Preparations on the Outcome after Unrelated Stem Cell Transplants for Chronic Phase CML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2768-2768
Author(s):  
Michael Schleuning ◽  
Joerg Kaltenhaeuser ◽  
Mazur Heshmat ◽  
Irena Burlakova ◽  
Dirk Judith ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Option ◽  
Cox Regression ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Matched Pair ◽  
Time Interval ◽  
Allogeneic Bone

Abstract Allogeneic bone marrow transplantation (BMT) remains a curative treatment option for patients with CML. Unrelated donor (URD)-BMT is a realistic treatment option for a large group of patients (pts) in need. To ensure engraftment and to reduce the incidence of acute and chronic GVHD antithymocyte globulin (ATG) has been incorporated into the preparative regimen by many centers. However, little is known if the various preparations available yield comparable results. This analysis reports a single center experience on URD-BMT in chronic phase CML pts with special emphasis on the different ATG preparations used (immunization of rabbits with human thymus, ATG Merieux/Sangstat/Genzyme (ATG-M) or with the leukemic cell line Jurkat, ATG Fresenius (ATG-F)). Since 1995 61 pts (40 male; 21 female) with CML received an URD-BMT. Three pts (1 male, 2 female) from the ATG-F group were excluded because they also received ATG-M after early graft failures, which possibly were attributable to dose adjustments for obesity, to HHV6 infection, and prior use of Imatinib mesylate. Median patient age was 38 years (16–61). 46 pts were transplanted in first chronic phase and 12 in accelerated or second chronic phase and 76% received a fully matched (HLA-A, B, DRB1) transplant. 13 pts received a 1 antigen and 1 patient a 2 antigen mismatched transplant. All pts received in vivo T-cell depletion with ATG during conditioning. 46 pts received ATG-M and 12 pts ATG-F. As analyzed by July 2004 after a median follow-up of 3.3 years for surviving pts. the estimated probability for overall survival is 61%. For eventfree survival, despite the low number and short follow-up of pts who received ATG- F, there was a strong trend (p=0.0611; Log-Rank) in favor of ATG-F as compared to ATG-M, which reached significance in a matched pair analysis (p=0.03). In multivariate cox regression analysis for pretransplant risk assessment for overall survival a time interval of more than a year from diagnosis to transplant (RR 2.5, 1.0–6.3) and a CMV-IgG negative donor for a CMV-IgG positive patient (RR 2.9, 1.1–7.7) and for eventfree survival again the time interval from diagnosis to transplant (RR 2.3, 0.9–5.7) and the use of ATG-M (RR 4.7, 0.6–35.2) were independent negative predictors. The incidence of acute GVHD grade III - IV was higher in the ATG-M group (17% vs. 8%) as was the rate of extensive chronic GVHD (29% vs. 0%). This also translated into a higher risk of death without relapse (35% vs. 8%). However, these observations may be biased to some extent, since most patients who were receiving ATG-F received a conditioning regimen based on intravenous busulfan, whereas most patients who were receiving ATG-M received conditioning regimens mainly based on oral untargeted busulfan, although the type of conditioning was no independent risk factor in the Cox regression model used. Nevertheless, our data indicate that the results of URD-BMT in chronic phase CML patients can further be improved by reducing the rate of acute and chronic GVHD. A promising approach seems to be a conditioning regimen based on intravenous busulfan incorporating ATG-Fresenius.

Comparison of Cyclosporine and Methotrexate with Cyclosporine and Mycophenolate Mofetil for Gvhd Prophylaxis in Myeloablative Allogeneic Bone Marrow Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2240-2240 ◽  
Author(s):  
Robert Dean ◽  
Lisa Rybicki ◽  
Ronald Sobecks ◽  
Edward Copelan ◽  
Matt Kalaycio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Gvhd ◽  
Mucosal Injury ◽  
Post Transplantation ◽  
Myeloablative Conditioning ◽  
Sibling Donor ◽  
Allogeneic Bmt ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Neutrophil Engraftment

Abstract Cyclosporine (CSA) and methotrexate (MTX) is a standard, effective regimen for prophylaxis of GVHD following allogeneic BMT. However, MTX increases mucosal injury and delays hematopoietic recovery in myeloablative allografts. We demonstrated in a prospective, randomized trial that CSA and mycophenolate mofetil (MMF) decreased mucositis and permitted more rapid neutrophil engraftment versus CSA/MTX in 40 patients undergoing myeloablative allogeneic BMT from matched sibling donors, with similar rates of acute and chronic GVHD, relapse, and 6-month survival. We subsequently adopted CSA/MMF as our preferred regimen for GVHD prophylaxis in matched sibling donor allografts. The objective of this analysis is to describe peri-transplant and long-term outcomes in an expanded cohort, comparing CSA/MMF with CSA/MTX. Inclusion criteria: adult patients (18 years or older) who underwent allogeneic BMT with myeloablative conditioning from a matched sibling donor with either CSA/MTX (n=76) or CSA/MMF (n=89) for GVHD prophylaxis. Median age was 45 years (range, 18–65). Diagnoses: AML (50%), CML (15%), ALL (15%), MDS (9%), NHL (6%), other (8%). Only 21% of patients had more than 2 prior regimens, and 9% had prior radiotherapy. Preparative regimens included busulfan (Bu) and cyclophosphamide (Cy) (64%), Bu/Cy + etoposide (19%), TBI-based (13%), or other (4%). All but 1 patient who received Bu/Cy + etoposide also received CSA/MTX. No other baseline characteristic differed between the groups. Median CD34+ cell dose: 1.78 x 10E6/kg overall, no difference between groups; CD3+ cell doses were incomplete for most patients who received CSA/MTX, but median values were equal between CSA/MMF and CSA/MTX patients with available data. Compared with CSA/MMF patients, those who received CSA/MTX had worse mucositis (median score 0.17 versus 1.0, P&lt;0.001) and longer length of hospital stay for transplantation (27 versus 34 days, P&lt;0.001). The risk of mucositis remained elevated for patients who received CSA/MTX versus CSA/MMF after adjusting for the influence of etoposide in the preparative regimens (P&lt;0.001). Patients who received CSA/MMF had more rapid neutrophil engraftment (ANC &gt; 500, median 11 versus 19 days, P&lt;0.001) and platelet engraftment (platelets &gt; 20,000, median 19 versus 24 days, P&lt;0.001) post-transplantation. Median follow-up post allogeneic BMT was shorter for CSA/MMF patients (36 vs. 82 months, P&lt;0.001). The probabilities of acute GVHD (all grades, grades II-IV, grades III-IV) were similar for CSA/MMF (58%, 36%, 18%) and CSA/MTX (66%, 42%, 15%) (P=NS). CSA/MMF patients experienced a lower likelihood of chronic GVHD than CSA/MTX patients (overall 42% vs. 53%, P=0.04; extensive 20% versus 37%, P=0.01). Overall infection rates were similar (P=NS), although CMV reactivation or infection was somewhat more frequent in CSA/MMF patients (58% versus 43% at 1 year, P=0.08). Five-year rates of relapse (36% versus 39%), non-relapse mortality (39% versus 39%), and overall survival (39% versus 37%) also did not differ between CSA/MMF and CSA/MTX patients. In multivariable models, CSA/MTX prophylaxis was the only factor associated with a greater risk of chronic GVHD (overall, HR 1.79, 95%CI 1.06– 3.02, P=0.03; extensive, HR 2.27, 95%CI 1.16–4.44, P=0.02). CONCLUSION: GVHD prophylaxis with CSA/MMF in matched sibling donor allografts reduces mucositis, time to engraftment, length of stay, and the risk of chronic GVHD compared with CSA/MTX, without adversely influencing rates of relapse, non-relapse mortality, or overall survival. The protective effect of CSA/MMF against chronic GVHD may be related to the fact that MMF is administered for a longer period post-transplantation than MTX, or the reduction in peri-transplant mucosal injury with MMF could result in decreased activation of potentially alloreactive T-cells. CSA/MMF is a safe and effective regimen for prophylaxis against GVHD in matched sibling donor allogeneic BMT with myeloablative conditioning.

Effect of Race on Outcomes After Allogeneic Hematopoietic Cell Transplantation for Severe Aplastic Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1020-1020
Author(s):  
Michael J Eckrich ◽  
Kwang W Ahn ◽  
Zhiwei Wang ◽  
H. Joachim Deeg ◽  
Mary M. Horowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
African Americans ◽  
Aplastic Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Unrelated Donor ◽  
Matched Sibling ◽  
Overall Mortality

Abstract Abstract 1020 Severe aplastic anemia (SAA) is the most common non-malignant indication for hematopoietic cell transplantation (HCT). Although survival after HCT for SAA has improved in recent years, it is not known whether the observed higher survival rates are uniform across racial groups or whether there are differences similar to those seen with HCT for hematologic malignancies. Our primary objective was to compare overall survival after HCT for SAA in patients of African American and Caucasian races. The study population included patients who received HCT in the U.S. between 1990 and 2008. Eighty-four African Americans (cases) and 215 Caucasians (controls) were matched on factors known to be associated with survival after HCT for SAA, including age at HCT (±3 years), donor type (HLA-matched sibling, matched unrelated donor, mismatched unrelated donor), graft type (bone marrow or peripheral blood progenitor cells) and transplant year (±1 year). For 39 cases the match ratio for controls was 1:4, for 14 cases, 1:3, for 22 cases, 1:2 and the remaining 9 cases, 1:1. The median age of cases and controls was 17 years and the median interval from diagnosis to HCT was 3.4 months. Forty-five percent of transplants were from unrelated and 55% from HLA-matched sibling donors. A third of unrelated donor-recipient pairs were HLA-mismatched. Bone marrow was the predominant source of stem cells. The median follow-up of cases and controls was 5 years. In multivariate analysis, risk of overall mortality was higher for African Americans compared to Caucasians, relative risk [RR] 1.75, 95% CI 1.14–2.69, p=0.01. Risks of overall mortality were also higher during the early post-transplant period; odds ratio (OR) 2.42, 95% CI 1.09–5.37, p=0.03) and OR 2.61, 95% CI 1.33–5.47, p=0.005) at 3-months and 1-year post-transplantation, respectively. The 5-year probability of overall survival adjusted for interval from diagnosis to HCT, performance score and conditioning regimen, the other significant variables associated with higher mortality was 58% for African Americans and 73% for Caucasians. The likelihood of neutrophil recovery was similar in both groups (OR 1.03, 95% CI 0.46–2.33, p=0.94). Acute grades II–IV graft-versus-host disease (GVHD) risks did not differ between African Americans and Caucasians (RR 0.81, 95% CI 0.56–1.17, p=0.26). However, chronic GVHD risk was higher for African Americans, although the difference did not reach statistical significance (RR 1.55, 95% CI 0.98–2.44, p=0.06). Thirty-seven (45%) of 82 African Americans died compared to 56 (27%) of 207 Caucasians. The proportion of patients dying with GVHD was higher in African Americans (12 of 37; 32%) than among Caucasians (9 of 56; 16%). Death secondary to organ failure was higher in Caucasians (12 of 56; 26%) compared to African Americans (4 of 37; 11%). There were no differences between African Americans and Caucasian in regards to deaths from graft failure, infection or hemorrhage. These data suggest recent improvements in overall survival rates after HCT for SAA are largely limited to Caucasians. Higher mortality in African Americans may be explained by greater genetic diversity, which renders the identification of donors by high-resolution HLA-typing more challenging, genetic polymorphisms impacting drug metabolism and unmeasured co-morbidities. Novel strategies aimed at lowering acute and chronic GVHD rates are needed to lower GVHD-related deaths. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcomes of Therapy Related Acute Lymphoblastic Leukemia in Adults after Allogeneic Stem Cell Transplantation - Twenty-Year Experience from a Tertiary Care Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5717-5717
Author(s):  
RAM V Nampoothiri ◽  
Arjun Law ◽  
Wilson Lam ◽  
Zeyad Al-Shaibani ◽  
David Loach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cox Regression Analysis ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
Prior Malignancy ◽  
Related Mortality

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

scholarly journals Analysis of Streptococcus pyogenes reinfection in pediatric patients in Japan

2021 ◽  
Vol 6 (3) ◽  
pp. 076-082
Author(s):  
Masaaki Minami ◽  
Ryoko Sakakibara ◽  
Mika Watanabe ◽  
Hideo Morita
Keyword(s):  
Treatment Failure ◽  
Streptococcus Pyogenes ◽  
Pediatric Patients ◽  
Rapd Analysis ◽  
Random Amplified Polymorphic Dna ◽  
Drug Susceptibility ◽  
Antimicrobial Treatment ◽  
Test Results ◽  
Patient Age ◽  
Patient Âgé

Acute pharyngitis and tonsillitis caused by Streptococcus pyogenes are common pediatric infectious diseases. Although the presence of penicillin-resistant S. pyogenes has not been confirmed in Japan, the re-isolation rate of S. pyogenes after antimicrobial treatment has been increasing. Thus, we attempted to determine whether the presence of S. pyogenes in pediatric patients treated with antimicrobial treatment was because of treatment failure or reinfection. We examined 19 patients who visited Daido Hospital between 2013 and 2017. The patient age, drug susceptibility patterns of the isolated bacteria, and random amplified polymorphic DNA (RAPD) analysis results were evaluated. The patient age ranged from 3 months to 9 years, seven patients were 5 years old. Seven patients showed consistent drug susceptible test results, and 12 patients showed inconsistent drug susceptible test results. Among these 12 patients, nine patients showed a greater decrease in drug susceptibility than the other three patients. Genetic mismatch was confirmed by RAPD analysis in all seven patients with consistent drug susceptible results. The paired S. pyogenes isolates from the same patient showed the presence of different bacteria. Our results indicate that, in many cases, re-isolation of S. pyogenes is not due to treatment failure, but due to reinfection with other clinical isolates.

scholarly journals Atrial High-Rate Event Incidence and Predictors in Patients With Permanent Pacemaker Implantation

2021 ◽  
Vol 8 ◽  
Author(s):  
Jian Hua Chen ◽  
Guo Yao Chen ◽  
Hong Zheng ◽  
Quan He Chen ◽  
Fa Yuan Fu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Previous History ◽  
Pacemaker Implantation ◽  
Permanent Pacemaker ◽  
High Rate ◽  
Atrial Pacing ◽  
Patient Age ◽  
Cox Regression Analysis ◽  
Patient Âgé

Objective: The present study aims to investigate the incidence and predictors of atrial high-rate events (AHREs) in patients with permanent pacemaker implants.Methods: A total of 289 patients who were implanted with a dual-chamber pacemaker due to complete atrioventricular block or symptomatic sick sinus syndrome (SSS) and had no previous history of atrial fibrillation were included in the present study. AHREs are defined as events with an atrial frequency of ≥175 bpm and a duration of ≥5 min. The patients were divided into two groups according to whether or not AHREs were detected during the follow-up: group A (AHRE+, n = 91) and group N (AHRE–, n = 198).Results: During the 12-month follow-up period, AHREs were detected in 91 patients (31.5%). The multivariate Cox regression analysis revealed that patient age [odds ratio [OR] = 1.041; 95% confidence interval [CI], 1.018–1.064; and P &lt; 0.001], pacemaker implantation due to symptomatic SSS (OR = 2.225; 95% CI, 1.227–4.036; and P = 0.008), and the percentage of atrial pacing after pacemaker implantation (OR = 1.010; 95% CI, 1.002–1.017; and P = 0.016) were independent AHRE predictors.Conclusion: The AHRE detection rate in patients with pacemaker implants was 31.5%. Patient age, pacemaker implantation due to symptomatic SSS, and the percentage of atrial pacing after pacemaker implantation were independent AHRE predictors.

scholarly journals Peritransplant Ruxolitinib Administration is Safe and Effective in Patients with Myelofibrosis: a Pilot Open-Label Study

2021 ◽  
Author(s):  
Haris Ali ◽  
Ni-Chun Tsai ◽  
Timothy Synold ◽  
Sally Mokhtari ◽  
Weimin Tsai ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Pilot Trial ◽  
Conditioning Regimen ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade 3

We report results of our prospective pilot trial (NCT02917096) evaluating safety/feasibility of peri-transplant administration of ruxolitinib for myelofibrosis treatment. Primary objectives were to determine the safety and identify maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was given at two dose levels (DL) of 5 and 10mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus GVHD prophylaxis. We enrolled 6 and 12 patients in DL-1 and DL-2, respectively. Median age at transplant was 65 years (range:25-73) for all patients. Per DIPSS, 4 patients were at high and 14 were at intermediate risk. PBSCs was the graft source from a matched sibling (n=5) or unrelated (n=13) donor. At each DL one patient developed DLTs: Grade 3 cardiac and GI with Grade 4 pulmonary in DL-1 and Grade 3 kidney injury in DL-2. All patients achieved engraftment. Cumulative incidence (CI) of acute GVHD grade 2-4 and 3-4 were 17% (95% CI: 6-47) and 11% (95% CI: 3-41), respectively. CI of 1-year chronic GVHD was 42% (95% CI: 24-74). With the median follow-up of 22.6 months (range:6.2-25.8) in surviving patients the 1-year overall and progression free survival were 77% (95% CI: 50-91) and 71% (95% CI: 44-87), respectively. Causes of death (n=4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results showed that peri-HCT ruxolitinib was safe and well-tolerated with the MTD determined as 10 mg BID, associated with dose-dependent PK and cytokine profile. The early efficacy data are highly promising in this group of high-risk older patients with MF.

Sign in / Sign up

Export Citation Format

Share Document