scholarly journals Spontaneous Post-Transplant Air-Leak Syndrome in Adult Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5780-5780
Author(s):  
Sheng-Hsuan Chien ◽  
Yao-Chung Liu ◽  
Nai-Wen Fan ◽  
Chia-Jen Liu ◽  
Tzeon-Jye Chiou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stem Cell ◽  
Chronic Gvhd ◽  
Adult Patients ◽  
Air Leak ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Air Leak Syndrome ◽  
Grade Iii

Abstract Introduction: Post-transplant air-leak syndrome (ALS) is a rare but potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (SCT). All forms of thoracic air leak are defined as ALS, including spontaneouspneumomediastinumorpneumopericardium, subcutaneous emphysema, interstitial emphysema and pneumothorax.The risk factors and pathogenesis of this rare complication have not been well defined, and we reviewed adult patients undergoing hematopoietic SCT in our hospital between January 2003 and December 2014 with focus on this complication. Method We reviewed 423 adult patients undergoing allogeneichematopoieticSCT from 2003 to 2014in Blood and Marrow Transplant Center of Taipei Veterans General Hospital in Taiwan. Pre-transplant and transplant-related clinical data including age, sex, pre-transplant biological data, disease diagnosis, comorbidities, type of transplant, human leukocyte antigen matching, conditioning regimens, graft-versus-host disease (GVHD) and other clinical complications were collected for analysis.We used multivariate logistic regression models adjusting for possible independent confounding factors to determine the independent risk factor of ALS. A log-rank test was used to compare survival curves for statistical significance. Results Thirteen out of 423 patients (3.07%) developed post-transplant ALS in study period. The median age at SCT was 33 years (interquartile-range: 27-46) and male were predominant (69%) among ALS patients.The median time for ALS development was at 253 days (range: 40-2680) after SCT.Multivariate analysis revealed that grade III-IVacute GVHD(odds ratio [OR] 4.36, 95% confidence interval [CI] 1.30-14.66; p = 0.017), extensive chronic GVHD (OR 4.22, 95% CI 1.26-14.12; p = 0.019) and prior history of pulmonary invasive fungal infection (OR 11.84, 95% CI 1.98-70.69; p = 0.007) were significant risk factors for ALS (Table 1) and a trend as risk factor in patients with age ≤42 years (OR 3.41, 95% CI 0.85-13.67; p = 0.083). In patients with chronic GVHD, those with ALS had significantly worse survival time than those without ALS (log-rank p = 0.04, Figure). Conclusion Currently, there are less published data analyzing and exploring post-transplant ALS in adult allogeneichematopoieticSCT. Our study showed a large patient cohort andwe confirmed the risk factors for developing post-transplant ALS, including grade III-IV acute GVHD, extensivechronic GVHD and patients with pulmonary invasive fungus infection history. Patients with young age also had a trend of risk in developing ALS. Patients with post-transplant ALS had a poor survival, especially in patients with chronic GVHD.Prospective studies are needed to determine the etiology andoptimal management of ALS after adult allogeneic hematopoietic SCT. Figure Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Analysis of Air-Leak Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4870-4870
Author(s):  
Wei Zhao ◽  
Man Chen ◽  
Yanli Zhao ◽  
Hui Wang ◽  
Peihua Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Survival Rate ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Air Leak ◽  
Hematopoietic Stem ◽  
Air Leak Syndrome

Abstract Background: Air-leak syndrome (ALS) occurs when there is leakage of gas from the alveoli, which results in clinical symptoms including cough and sputum, dyspnea, and hypoxemia. ALS is rare but potentially life-threatening in patients who have received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is an independent prognosis factor of patients undergoing HSCT. However, the clinical features and risk factors for post-transplant ALS among pediatric patients have rarely been explored. Aims: This study analyzed the clinical characteristics, risk factors, clinical treatment options and prognosis to provide a scientific basis for ALS prevention and treatment for pediatric patients. Methods: We retrospectively reviewed patients who were diagnosed with ALS following allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in the prognosis of the HSCT. Results: A total of 2026 pediatric patients received an HSCT between January 2013 and December 2019. The ALS incidence rate was 1.4% (28 of 2,206 patients) with a survival rate of 64.3% (10 of 28 patients). The median overall survival (OS) time was 429 days (range: 55-1614 days). Sixteen patients were males and 12 were female. The median patients age was 12 years old (range: 1-16 years), and the median follow-up time was 871 days (range: 55-2973 days).We divided ALS into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). There was a significant difference in OS between the twogroups (80% among BOS patients versus 46% among IPS patients; P=0.037). Logical regression analysis showed that gender, an unmatched transplant donor and recipients (P=0.049), time to first occurrence of graft-versus-host disease after transplantation (P=0.021), and dosage of methylprednisolone >0.5mg/kg at the onset of ALS (P=0.049), were independent risk factors for poor prognosis in ALS. In addition, we found fluticasone, azithromycin, and montelukast (FAM) could significantly improve the prognosis following ALS (P=0.005). Compared with IPS, our results showed that some patients with BOS may benefit from imatinib (P=0.055), ruxolitinib (P=0.009), or pirfenidone (P=0.044). Conclusion: ALS is a rare manifestation of pulmonary complications following HSCT among pediatric patients. Our analysis demonstrates that early diagnosis and FAM treatment may improve the survival rate of ALS following HSCT among pediatric patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

SNP12 and SNP13 Variants of NOD2/CARD15 Gene of Donor and Recipient as Independent Risk Factors for Severe Intestinal and Pulmonary GVHD after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3242-3242
Author(s):  
Alexandra Holowiecka-Goral ◽  
Jerzy Wojnar ◽  
Sebastian Giebel ◽  
Elzbieta Grudziecka ◽  
Malgorzata Oczko ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Card15 Gene ◽  
The Impact ◽  
Grade Iii

Abstract Background: Presence of any of single nucleotide polymorphism (SNPs) of the NOD2/CARD15 gene have been recently proven to correlate with higher rate of GvHD after allogeneic hematopoietic stem cell transplantation - alloHSCT (Holler E et al; Blood2006,107,4189). Mutated variants lead to impaired antibacterial response. As NOD2/CARD15 is expressed not only in monocytets/macrophages but also in both intestinal and bronchial epithelial cells these organs seem to be a major target for developing advanced GvHD. Patients and methods: The impact of each single donor (D) and recipient (R) SNPs (8,12,13) of NOD2/CARD15 gene on the incidence of acute GvHD (grade II-IV, grade III-IV, intestinal), chronic GvHD (overall, extensive, pulmonary), survival, and non-relapse mortality was evaluated in a setting of 72 patients treated with alloHSCT in single BMT center in Katowice between Jan 2000 and Jun 2005. Median patient age was 33 (11–52) years. In 70/72 cases hematological malignancies were indication for alloHSCT. Conditioning regimen was myeloablative in all cases, bone marrow was used as the only source of stem cells in 74% of patients. GVHD prophylaxis consisted of CsA, Mtx and, in case of URD-HSCT - antithymocyte globulin. Results: In univariate and multivariate analysis, including other potential risk factors, the presence of SNP12 in the recipient was associated with increased incidence of intestinal acute GVHD (75% vs. 29%; RR 4,37, p=0,03), overall chronic GVHD (100% vs. 50%, RR 4,72; p=0,003), extensive chronic GVHD (80% vs. 24%; RR 5,12; p=0,02), and pulmonary chronic GVHD (47% vs. 9%; RR 5,97; p=0,02). SNP13 in the recipient resulted in increased incidence of grade III–IV acute GVHD (45% vs. 12%; RR 4,66; p=0,01), intestinal acute GVHD (64% vs. 24%; RR 4,21, p=0,005), and extensive chronic GVHD (55% vs. 25%; RR 3,59; p=0,03). SNP13D in the donor contributed to increased risk of pulmonary chronic GVHD (36% vs. 8%; RR 6,58; p=0,01). In this single centre analysis we were not able to demonstrate the impact of NOD2/CARD15 SNPs on survival. Conclusion: The presence of particular mutations of NOD2/CARD15 in the recipient and/or the donor is associated with increased risk of severe acute and chronic GVHD. In particular, intestines and lungs appear to be target organs of these complications. Our findings may contribute to optimization of immunosuppressive and gastrointestinal decontamination regimens based on individual risk assessment for GVHD.

scholarly journals Risk Factors for Acute and Chronic Gvhd after Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Relative Risks with Umbilical Cord Blood (UCB) and Matched Related Donors (MRD)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 189-189
Author(s):  
Aleksandr Lazaryan ◽  
Todd E. DeFor ◽  
Claudio Brunstein ◽  
Margaret L. MacMillan ◽  
Nelli Bejanyan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Lower Incidence ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Grade Iii

Abstract Despite continued improvement in outcomes after allo-HCT, acute (aGVHD) and chronic GVHD (cGVHD) remain major causes of morbidity and transplant related mortality (TRM). UCB has emerged as an important alternative donor source with clinical outcomes similar to those after HCT with 8/8 allele matched unrelated and related donor. While prior studies have indicated differences in risks and natural history of GVHD between hematopoietic stem cell (HSC) sources, we sought to provide a more detailed analysis taking advantage of the homogeneity in grading criteria, treatment plans, and graft selection criteria at a single center. To identify incidence and risk factors for acute and chronic GVHD, we retrospectively studied 1180 adult (≥18 years, n=801) and pediatric (n=379) recipients of single (sUCB, n=295), double (dUCB, n=416) UCB and MRD (n=469) allografts transplanted between 2000-2012. We estimated cumulative incidence of aGVHD and cGVHD with non-GVHD deaths modeled as competing risks. Analysis of risk factors for GVHD was performed separately in the three cohorts. sUCB, dUCB, and MRD differed in age (median 8, 44, 47 years, respectively), gender (54%, 63%, 62% males), conditioning (myeloablative in 80%, 40%, 55%; ATG was used in 60%, 23%, 16%), CsA/MMF GVHD prophylaxis (66%, 99%, 48%), total nucleated cells (median 0.5, 0.4, 7.7 x 108 cells/kg), CD34 dose (median 0.5, 0.5, 5.4 x 106 cells/kg), and CD3 dose (median 0.2, 0.1, 3.6 x 108 cells/kg). sUCB transplants had lower incidence of grade II-IV aGVHD (26%), grade III-IV aGVHD (7%) and cGVHD (7%) as compared to dUCB (56% aGVHD II-IV; 21% aGVHD III-IV; 26% cGVHD) and MRD (37% aGVHD II-IV; 16% aGVHD III-IV; 40% cGVHD) (all p<0.01, Figure). In competing risk multivariable analysis of sUCB allografts, age≥18 years was associated with higher incidence of grade II-IV aGVHD (HR=1.8, 95%CI, 1.1-2.9; p=0.01), grade III-IV aGVHD (HR=3.4, 95%CI 1.6-7.2; p<0.01) and cGVHD (HR=5.7, 95%CI 1.9-16.5; p<0.01). Better HLA match influenced grade II-IV aGVHD with lower incidence for 6/6 match (HR=0.5, 95%CI 0.2-1.0; p=0.04 vs. 4/6), but did not influence risks of grade III-IV aGVHD or cGVHD. GVHD prophylaxis with CsA/MMF was associated with reduced incidence of cGVHD (HR=0.3, 95%CI 0.1-0.9; p=0.03 vs. CsA/Steroid). In dUCB allografts, the use of ATG (HR=0.5, 95%CI 0.4-0.7; p<0.01) and year of transplant ≥2006 (HR=0.6, 95%CI 0.5-0.8; p<0.01) were associated with less grade II-IV aGVHD. Better HLA match limited both grade III-IV aGVHD (HR=0.3, 95%CI 0.1-0.9; p=0.03 for 6/6 vs. 4/6 match) and cGVHD (HR=0.6, 95%CI 0.4-0.9; p=0.02 for 5/6 vs. 4/6). Reduced intensity conditioning was associated with less grade III-IV aGVHD (HR=0.6, 95%CI 0.4-0.9; p=0.02) and cGVHD (HR=0.6, 95%CI 0.4-1.0; p=0.03). Prior grade II-IV aGVHD led to more frequent cGVHD (HR=2.0, 95%CI 1.3-3.1, p<0.01). In MRD analysis (79% received peripheral-blood stem cell [PBSC] grafts), risk of grade II-IV aGVHD (HR=2.5, 95%CI 1.1-5.5; p=0.02), grade III-IV aGVHD (HR=7.1, 95%CI 2.3-22.2; p=0.001) and cGVHD (HR=2.6, 95%CI 1.1-6.3; p=0.04) were higher in PBSC vs. marrow allografts. Older MRD recipients had higher risk of cGVHD (HR=5.8, 95%CI 1.7-19.8; p<0.01 for age≥18 vs. <18). This large analysis establishes contemporary incidence and prognostic determinants of GVHD for UCB in parallel to benchmark MRD allo-HCT. Our data argue that better HLA match may further mitigate the risks of grade III-IV aGVHD and cGVHD to maximize the benefits of dUCB transplantation. Increasing the UCB inventory or developing strategies (e.g., ex vivo expansion culture) that reduce the cell-dose threshold of 2.5 x 107 nucleated cells/kg and thereby increase the chance of identifying an adequately dosed, better HLA matched single UCB unit would further limit risks of acute and chronic GVHD after UCB transplantation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Phase II Study of Decitabine Followed By Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Patients with Myeloid Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2107-2107
Author(s):  
Christopher R. D'Angelo ◽  
Aric C. Hall ◽  
Kyungmann Kim ◽  
Ryan J. Mattison ◽  
Walter L. Longo ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for myelodysplastic syndrome (MDS) and high-risk acute myeloid leukemia (AML). Patients with high-risk disease have a markedly increased risk of relapse and death following transplant (Armand et al, Blood, 2014). Those who remain disease-free are at risk of severe morbidity from graft-versus- host-disease (GvHD). These issues highlight the importance of improved allo-HSCT platforms designed to reduce relapse rate without increasing risk of GvHD. Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases (Blum et al, PNAS, 2010). Use of post-transplant cyclophosphamide has demonstrated improved rates of GvHD following allo-HSCT using haplo-identical donors (Bashey et al, JCO, 2013). No studies have reported on outcomes in patients undergoing decitabine immediately prior to transplantation followed by post-transplant cyclophosphamide (PTCy). We hypothesized that the combination of decitabine induction prior to transplant and PTCy would be safe and result in improved disease control with low rates of GVHD, translating into improved survival in a high-risk transplant cohort. Methods In this single-arm, single institution trial, eligible patients received 10 days of IV decitabine at 20mg/m2 no sooner than 24 days and no later than 17 days prior to conditioning. Myeloablative conditioning included fludarabine (50mg/m2 day-5-2), busulfan (IV 3.2mg/kg/day -5-2), and 4 Gy total body irradiation on day -1. Patients above age 65 received a 25% busulfan dose reduction. Patients received a fully or partially matched related bone marrow graft on day 0. GvHD prophylaxis included 50mg/kg of IV cyclophosphamide on day +3-4. Patients with fully matched donors received only PTCy while those with partially matched donors also received mycophenolate mofetil through day +35 and tacrolimus through day +180. Results We enrolled 20 patients, fifteen patients with AML and 5 with MDS. The cohort had a median age of 64 (29-73) and was predominantly male (14/20, 70%). Eight (40%) patients scored as high risk by the HSCT comorbidity index. Eighteen patients (90%) had a high or very high-risk score by the refined disease risk index. All patients received decitabine and 18/20 (90%) underwent transplantation; 2 patients did not receive a transplant due to infectious complications. The majority of patients received a haplo-identical graft (13/18, 72%), and the remaining 5 received a matched related graft. Outcomes are reported in table 2 and figure 1. There were no engraftment failures. Five patients, 3 MDS and 2 AML, are long-term survivors with median follow-up over 3 years. One patient developed donor derived MDS and required a second transplant. Most transplanted patients (13/18, 72%) survived to day 100 with a median post-transplant survival of 138 days. There were 15 deaths on study with the majority due to underlying disease. Six patients (6/20, 30%) died of infectious complications or did not receive a transplant due to infection. Incidence of grade 3-4 acute GvHD was low among those surviving at least 40 days from transplant (3/17, 17%). There were also low rates of chronic GvHD among the 12 patients alive without ongoing GvHD at day 100 (2/12, 17%). Conclusions Decitabine induction followed by myeloablative conditioning in this high-risk population resulted in a high treatment related mortality of 40%. Still, outcomes fell into an expected range for high-risk myeloid disease in an elderly and comorbid population. Based on expected outcomes for high-risk patients from the literature (Armand et al, Blood, 2014), decitabine did not markedly improve overall survival outcomes, recognizing that no direct comparisons are available in our limited study population. Decitabine may increase the risk of peri-transplant infections by contributing to a cumulative immunologic insult combined with disease-related immunosuppression and transplant-related toxicity, highlighting the importance of strict vigilance for infections within this setting. Diligent monitoring may improve infectious outcomes as shown in the second half of the cohort; only two out of the latter 10 patients on protocol died of treatment related complications. There were no cases of engraftment failure. Rates of acute and chronic GvHD using a PTCy platform were low and support other studies reporting this benefit. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplant Recipients in High Endemic Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Muhammad Farhan ◽  
Qamar Un Nisa Chaudhry ◽  
Syed Kamran Mahmood ◽  
Tariq Ghafoor ◽  
Raheel Iftikhar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
High Viral Load ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Endemic Population ◽  
Cmv Reactivation

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

Risk Factors Analysis for Human Cytomegalovirus Viremia in Donor+/Recipient+ Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 51 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Rong Yang ◽  
Runan Zhang ◽  
Yanyue Zhang ◽  
Yaping Huang ◽  
Hanying Liang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Cumulative Incidence ◽  
Hematopoietic Stem

ABSTRACT Objective To assess the rate of, and risk factors for, human cytomegalovirus viremia (HCMV) in donor+/recipient+ (HCMV serostatus matched) hematopoietic stem-cell transplantation (HSCT) recipients. Methods HCMV DNA from 144 donor+/recipient+ HSCT recipients was examined by quantitative polymerase chain reaction (qPCR). Results The cumulative incidence of HCMV viremia was 69.4% (100/144) during the 48 weeks after HSCT. In a multivariate analysis, acute graft-versus-host disease (aGVHD) was discovered to be a risk factor for the occurrence of HCMV viremia (P = .006). The cumulative incidence of HCMV viremia and increasing DNA loads were significantly associated with aGVHD occurrence (P = .001 for each). The occurrence of late-term HCMV viremia was associated with aGVHD (P = .001) and a higher DNA load during the first 12 weeks after HSCT (P = .04). Conclusions aGVHD is a risk factor for HCMV viremia. Recipients with aGVHD who have a high HCMV DNA load should be strictly monitored to prevent HCMV activation.

A Prospective Cost Analysis of Non-Myeloablative Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2239-2239
Author(s):  
Chris Skedgel ◽  
Jo-Ann Edwards ◽  
Jean Roy ◽  
Andrea McNeil ◽  
Yvonne Gulliver ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hospital Admissions ◽  
Chronic Gvhd ◽  
Direct Costs ◽  
First Year ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The Cost

Abstract Hematopoietic stem cell transplantation (HSCT) is an intensive medical therapy used to treat both malignant and non-malignant conditions. Non-myeloablative transplantation (NMT) is an emerging transplant modality often performed on an outpatient basis. While NMT is associated with fewer acute complications compared to myeloablative HSCT, long-term complications, particularly chronic graft vs host disease (GvHD), are of concern. To our knowledge, there have been few economic evaluations of NMT and none in a Canadian healthcare environment. We prospectively developed and validated a process for capturing the costs and outcomes of NMT in order to estimate the cost per patient of NMT at a Canadian transplant centre. Ten consecutive patients undergoing NMT were followed from the first day of conditioning (Day −11) until either 1 year post-transplant or death. Donor costs were also recorded. All patient encounters, procedures and interventions during the study period were prospectively recorded. Nursing and other non-physician human resource costs were calculated based on recorded contact times and salaries. Physician costs were derived from Nova Scotia fee codes. Costs of hospital admissions were derived from Ontario Case Costing Initiative (OCCI) data and were specific to the primary diagnosis. Drug costs were based on acquisition costs at hospital and community pharmacies. Materials and equipment costs were based on costs at the QEII Health Sciences Centre, Halifax NS. The proportion of administrative costs to direct costs was derived from OCCI data and applied to local direct costs. All costs are in 2005 Canadian dollars ($CAN). Ten patients were followed for a median of 12 months (range 3.6–12) from September 2003 to April 2005. Eight patients were male and the median age of the cohort was 60 years (19–73). Five patients had AML; 3 had lymphoma and 2 had multiple myeloma.Cyclophosphamide and fludarabine were used as conditioning and tacrolimus and mycophenolate mofetil were used as GvHD prophylaxis. There were 7 hospital admissions among the 10 patients: 3 before day 100 and 4 after day 100. Eight patients survived at least one year post-transplant. No patients developed acute GvHD, while all 8 patients surviving to 1 year post-transplant developed chronic GvHD. Three patients relapsed within 1 year. The average cost per NMT was $CAN 43,377 of which $CAN 31,761 were recipient costs, $CAN 2,562 were donor costs and $CAN 8,675 were equipment and overhead costs. The key cost driver was hospital admissions for complications and/or palliative care at $CAN 9,793 per recipient. Physician fees ($CAN 6,958) and chemotherapy ($CAN 6,485) were also significant. Compared to published estimates of the cost of myeloablative HSCT, NMT appears considerably less costly in the first year post-transplant. Our analysis suggests that the lower cost of NMT was largely attributable to the limited amount of inpatient care these patients received. Further follow-up will be informative since the major complications of NMT including chronic GvHD and relapse may impact per transplant cost after the first year post-transplant. Direct comparison with myeloablative HSCT using our prospective costing method is also planned.

Risk Factors for Late Infections after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Related Donor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2848-2848
Author(s):  
Marie Robin ◽  
Raphaël Porcher ◽  
Renato De Castro Araujo ◽  
Régis Peffault de Latour ◽  
Agnès Devergie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Viral Infection ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
First Year ◽  
Hematopoietic Stem ◽  
Cmv Status

Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), late infections represent a major cause of morbidity and mortality but little has been previously reported. In a retrospective cohort study, late infections incidence was determined in 196 long-term survivors after matched related HSCT. Only patients transplanted for aplastic anemia, chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML) were included in this study. Median follow-up was 8 years. Among 30 patients who died beyond the first year, 9 patients died from graft-versus-host disease (GVHD) and 10 from infections. Bacterial late severe infections occurred in 30 patients, yielding an 8-year cumulative incidence of 15%. Late invasive fungal infection occurred in 8 patients corresponding to a cumulative incidence of 3.6%. Most viral infections were hepatitis C and VZV and overall late viral infection incidence was 35%. We identified 3 risk factors for bacterial infections in multiple analysis: CMV status (positive recipient and negative donor), irradiation based conditioning regimen and extensive chronic GVHD within the first year. Extensive chronic GVHD was the only risk factor of non-HCV viral infection in patients transplanted for AML or CML. Thus, late life threatening infections may occur in nearly a fourth of late survivors even after matched related transplantation and are associated not only with chronic GVHD but also with irradiation and to CMV status prior to transplantation.

Killer Immunoglobulin-Like Receptor and NOD2/CARD15 Polymorphisms Independently Influence Survival after Allogeneic Hematopoietic Stem Cell Transplanation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2167-2167
Author(s):  
Sebastian Giebel ◽  
Aleksandra Holowecka-Goral ◽  
Izabela Nowak ◽  
Tomasz Czerw ◽  
Jerzy Wojnar ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Kir Genes ◽  
Increased Risk ◽  
Grade Ii ◽  
Card15 Gene ◽  
Grade Iii

Abstract Background: Activating and inhibitory killer immunoglobulin-like receptors (KIRs) regulate function of NK cells and a subset of T cells. KIR genotype, in particular the content of activating KIR genes is highly polymorphic. NOD2/CARD15 protein is broadly expressed in APCs and lymphocytes. Single nucleotide polymorphisms (SNPs) of this gene have been reported to impair the pathogen elimination and trigger pathologic immunologic reactions like GvHD. The goal of this prospective study was to evaluate the impact of donor’s and recipient’s KIR and NOD2/CARD15 genotypes on outcome after allogeneic hematopoietic stem cell transplantation (alloHSCT). Pateints and methods: One-hundred-two consecutive patients with hematological malignancies, aged 32(18–58)y, treated with alloHSCT from HLA-matched related (n=34) or matched unrelated donor (MUD) (n=68) were included. The conditioning regimen was myeloablative, GVHD prophylaxis consisted of CsA, Mtx, and, in case of MUD-HSCT, pre-transplant ATG. Donors and recipients were tested for 11 KIR genes as well as SNP8,12,13 of the NOD2/CARD15 gene. In addition, immune reconstitution including KIR expression on T cells, was analyzed on days +28, +56, +100, +180, and +360. Results: Overall survival (OS) rate at 2y was significantly lower in alloHSCT with at least one activating KIR mismatch compared to transplants with full compatibility (62% vs. 86%, p=0.01). In particular, the presence of at least one activating KIR in the donor with its absence in the recipient (D+R−) was associated with decreased probability of OS (60% vs. 78%, p=0.01) and DFS (58% vs. 82%, p=0.005), as well as increased incidence of non-relapse mortality (NRM) (27% vs. 7%). KIR2DS1 and KIR3DS1 D+R− mismatches resulted in increased risk of grade II–IV acute GvHD, whereas KIR2DS3 and KIR2DS2 D+R− mismatches were associated with increased risk of chronic GvHD. The presence of at least one activating KIR D+R− mismatch was associated with increased CD8+/CD4+ T cell ratio up to day +100. In all cases of incompatibility regarding KIR2DS1, KIR2DS2 and KIR3DS1, T cells with expression of respective receptors could be detected up to 360 days after alloHSCT. The presence of SNP8 of the NOD2/CARD15 gene in the recipient was associated with decreased probability of OS (20% vs. 70%, p=0.005) and DFS (20% vs. 70%, p=0.01) as well as increased incidence of NRM (60% vs. 17%) and grade III–IV acute GvHD (67% vs. 8%). In a multivariate analysis including KIR and NOD2/CARD15 polymorphisms together with other potential risk factors, increasing number of D+R− activating KIR mismatches as a linear variable appeared to independently influence OS (HR: 1.3, p=0.02), DFS (HR: 1.3, p=0.008), NRM (HR: 1.4, p=0.02), grade II–IV acute GvHD (HR: 1.4, p=0.001), and chronic GvHD (HR: 1.2; p=0.02). Recipient SNP8 of NOD2/CARD15 was predictive for OS (HR: 5.5, p=0.003), DFS (HR: 4.4, p=0.008), NRM (HR: 5.9, p=0.006), grade III–IV acute GvHD (HR: 6.1, p=0.02), and chronic GvHD (HR: 3.7; p=0.03). Conclusions: Both activating KIR D+R− mismatches and recipient SNP8 of NOD2/CARD15 appear to enhance alloreactivity and independently influence survival after alloHSCT. Evaluation of these polymorphisms may contribute to better donor selection and optimization of the alloHCT procedure.

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