Implication of Faster Neutrophil and Lymphocyte Recovery after Allogeneic Stem Cell Transplantation (SCT) in Children with Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4357-4357
Author(s):  
Dong Kyun Han ◽  
Hee Jo Baek ◽  
Ju Hee Yoo ◽  
Tai Ju Hwang ◽  
Hoon Kook

Abstract The repopulating neutrophils and lymphocytes after allogeneic SCT have an important role, not only on the prevention of serious infections in the early transplantation period, but on killing the residual leukemic cells by graft versus leukemia (GVL) effect. Previous studies have suggested that earlier neutrophil recovery was associated with less infections and better survival, while earlier lymphocyte recovery was associated with a lower relapse and a better survival in adult patients. The aim of this study was to compare the impact of neutrophil and lymphocyte recovery after SCT on predicting the survival, relapse, and GvHD in children with hematologic malignancies. We retrospectively evaluated 69 children transplanted for ALL (n=34: CR1, 22; CR2, 10; > CR2, 2), AML (n=26: CR1, 19; secondary AML, 4; > CR1, 3), chronic leukemia (n=7: CML, 6; CEL, 1) and JMML (n=2) at the Chonnam National University Hospital between Jan. 1996 and Mar. 2008. Conditioning regimes were TBI-based (n=41), and non-TBI based (n=28). Stem cell sources were: BM (n=46), PBSCs (n=10), UCB (n = 12), and BM + PB (n=1). Matched sibling donor was used in 26, while unrelated donors in 43. Three AML patients who received the 2nd allogeneic SCTs following autotransplants were included. The patients were grouped according to the absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) at D+21 and D+30. The best discriminating cutoff values for ANC and ALC were 1,000/μL and 500/μL, respectively. The groups were: Low ANC at D+21 (LNC21, n=25) vs. High ANC at D+21 (HNC21, n=44); Low ANC at D+30 (LNC30, n=15) vs. High ANC at D+30 (HNC30, n=54); Low ALC at D+21 (LLC21, n=28) vs. High ALC at D+21 (HLC21, n=41); Low ALC at D+30 (LLC30, n=19) vs. High ALC at D+30 (HLC30, n=50). The patients were 41 males and 28 females. The median age at transplant was 7.1 years (range, 0.4–18). The median day of neutrophil engraftment (≥ 1,000/μL) was D+21 for LLC21 vs. D+16 for HLC21 (P =.001); and D+20 for LLC30 vs. D+17 for HLC30 (P =.02), respectively. The median day of platelet engraftment (≥ 20,000/μL) was D+38 for LLC21 vs. D+19 for HLC21 (P =.04); and D+40 for LLC30 vs. D+22 for HLC30 (P =.07), respectively. The HNC21 and HNC30 group showed a better survival than LNC 21 and LNC30 group, but statistically not significant (69% vs. 58%; 67% vs. 59%, respectively). The HLC30 group exhibited a better 5 year overall survival (71% vs. 53%, P =. 04) and event free survival (72% vs 53%, P =. 06) than LLC30 group. The LNC21 group was associated with a high incidence of aGvHD (36% vs. 14%, P =. 03), but the incidence of Gr II-IV aGvHD and cGvHD was not different by the ALC counts. Relapse rate was not different between ANC and ALC groups. Six of 15 (40%) in LNC30 and 15 of 54 (28%) in HNC30 died, while 9 of 19 (47.4%) in LLC30 and 12 of 50 (24%) in HLC30 died (P = NS). In this study, we found that lymphocyte recovery ≥ 500/μL on D+30 was associated with better survival, faster myeloid and platelet engraftment without increasing the incidence of GvHD or mortality. Also faster neutrophil recovery ≥ 1,000/μL on D+21 was associated with a lower incidence of aGvHD. However, faster lymphocyte recovery was not translated into decreased relapse rate. Further studies incorporating larger number of cases and longer follow-up are warranted in children with leukemias.

Author(s):  
Dong-Woo Lee ◽  
So-Young Choi ◽  
Jin-wook Kim ◽  
Tae-Geon Kwon ◽  
Sung-Tak Lee

Abstract Background This study aimed to analyze the impact of COVID-19 on oral and maxillofacial fracture in Daegu by comparing the demographic data in 2019 and 2020, retrospectively. We collected data from all patients having trauma who visited the emergency room for oral and maxillofacial fractures. Methods This retrospective study was based on chart review of patients who visited the emergency department of Kyungpook National University Hospital in Daegu, South Korea from January 1, 2019, to December 31, 2020. We conducted a comparative study for patients who presented with maxillofacial fractures with occlusal instability during pre-COVID-19 era (2019) and COVID-19 era (2000) with demographics and pattern of injuries. Results After the outbreak of COVID-19, the number of monthly oral and maxillofacial fractures, especially sports-related oral and maxillofacial fractures, decreased significantly. Also, the number of alcohol-related fractures increased significantly. In addition, as the number of monthly confirmed cases of COVID-19 increases, the incidence of fracture among these cases tends to decrease. Conclusions The COVID-19 pandemic has changed the daily life in Korea. Identifying the characteristics of patients having trauma can provide a good lead to understand this long-lasting infectious disease and prepare for future outbreaks.


Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 311-316 ◽  
Author(s):  
Michel Attal ◽  
Philippe Moreau ◽  
Herve Avet-Loiseau ◽  
Jean-Luc Harousseau

AbstractMultiple myeloma (MM) is one of the key hematologic malignancies in which the impact of dose intensity has been demonstrated. Consequently, in 2005, MM was the most common disease for which autologous stem cell transplantation (ASCT) was indicated both in Europe and in the U.S. However, ASCT is not curative, and most patients relapse within a median of 3 years. Novel agents such as thalidomide (Thalidomid), bortezomib (Velcade), or lenalidomide (Revlimid) have been introduced to improve high-dose therapy, and promising results have been reported. Conversely, results from myeloablative allogeneic stem cell transplantation remain disappointing due to high transplantation-related mortality, justifying the exploration of strategies such as reduced-intensity conditioning, which have been shown to be feasible but for which proof of efficacy requires continued study.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4594-4594
Author(s):  
Angela Granata ◽  
Sabine Furst ◽  
Jean marie Boher ◽  
Luca Castagna ◽  
Patrice Chevallier ◽  
...  

Abstract Background: Since the first publication at the John Hopkins Hospital, (Luznik et al. BBMT 2008), Haploidentical T-cell replete Stem Cell Transplantation (HaploSCT) with post transplantation cyclophosphamide (PT-Cy) has become a reproducible and feasibility therapeutic option for many patients (pts) with hematologic malignancies , notably because of the low incidence of GVHD and infections, without increased graft failure. Initially, bone marrow (BM) was considered as the favorite source of hematopoietic stem cells in order to minimize the risk of GVHD. In a retrospective study, we previously showed no difference in terms of increased events (GVHD, NRM), regardless of the hematopoietic stem cell source (PBSC or BM) (Castagna et al. BMT 2014). Some recent publication seems to confirm this observation (Sugita J. BBMT 2015 , Solomon R. Adv in Hem. 2016), although no randomized study so far has been conducted. Here, we retrospectively analyze the incidence and the characteristics of GVHD in the setting of HaploSCT using PT-Cy, after infusion of PBSC. Methods: Inclusion criteria were: adult pts with hematologic malignancies receiving a PBSC HaploSCT from 2012 to 2015 in 4 centers (3 in France and 1 in Italy) with PT-Cy as part of the GVHD prophylaxis. PBSC infusion at day 0 was followed by PT-Cy 50 mg/kg on days +3 and +4 in association with calcineurin inhibitors (cyclosporine A or Tacrolimus) and mycophenolate mofetil (MMF), started at day +5. All patients received G-CSF support from day+5 until neutrophil recovery. Study end points were the cumulative incidences of acute (a) and chronic (c) GVHD, with a specific organ grading evaluation, non-relapse mortality (NRM), relapse (CIR) as well as progression free (PFS) and overall survival (OS). Additionally, we analyzed the composite endpoint "GVHD and relapse free survival" (GFRS) for which the occurrence of relapse, death or severe chronic GVHD was considered as relevant events. Correlation between CD 34+ and CD 3+ and the incidence of aGVHD and cGVHD was studied by a linear continuous variable. Results: Between March 2012 and December 2015, 192 pts with a median age of 57 years (range: 16-73) received T-cell replete PBSC HaploSCT for hematologic malignancies (myeloid: n= 55%; lymphoid: n=45%) in 4 centers. Patient's characteristics are shown in table 1. Pts received non myeloablative (according to Baltimore regimen) or busulfan-based reduced intensity conditioning, in 56% and 44% of cases, respectively. All, but 3 pts, engrafted, with a median time of 19 days (range, 14-47) to neutrophil recovery (ANC >500 x106/L) and 22 days (range, 14-252) to platelet recovery (PLT > 20 G x 109/L). The median CD34+ x 106/Kg and CD3+ x 106/Kg cells infused were 5.5 (range, 1.5-14.8) and 404 (range, 38-704), respectively. No relevant correlation was observed between the CD34+ and CD3+ infused cells and the incidence of GVHD, studied by linear continues variable. We noted only a trend to develop severe cGVHD with an increasing number of CD3+ cells infused. This result has to be considered with caution, because of the small events (6 pts affected by severe cGVHD). Complete donor T cell chimerisme was evaluable in 162 pts (83%) and achieved by day +30. The incidence of aGVHD was 38% at 100 days (all grades), whereas grade II-IV and III-IV were 24% and 10%, respectively. Concerning patients with aGVHD grade 2-4, the most affected organ was skin (19%), followed by gut (9%) and liver (2%). The incidence of 3-year cGVHD according to NIH classification was 15% (all grades). Three percent of pts developed severe cGVHD (lung n=1; liver, n=1). The most frequent involved organs were skin and mucosae (70%). No patient showed gut cGVHD. Finally, in univariate analysis, busulfan-based conditioning seems to negatively impact on severe cGVHD (p = 0.03; HR=3.37 [1.09 -10.46]) After a median follow up of 20 (range, 4 - 52) months, NRM at 100 days and 1 year was 10% and 20%, respectively. Three-year OS, PFS, CIR and GRFS were 63%, 55%, 25% and 49%, respectively. Conclusion: This retrospective study shows a very low incidence of severe cGVHD after HaploSCT even with PBSC as stem cell source, suggesting that the use of PT-Cy may overcome the anticipated increased incidence of cGVHD, contrary to as previously reported in the HLA identical setting (Mohty et al. Leukemia 2003). Similar to HLA identical sibling and unrelated donor transplantation, the most frequent organs involved are skin and mucosae Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sotaro Mori ◽  
Takuji Kurimoto ◽  
Yusuke Murai ◽  
Kaori Ueda ◽  
Mari Sakamoto ◽  
...  

Purpose. Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. Design. Retrospective observational study, clinical case series. Methods. We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. Results. Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy ( p = 0.02 ). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy ( p < 0.01 ). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. Conclusions. Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities.


Haematologica ◽  
2021 ◽  
pp. 0-0
Author(s):  
Ayala Tovy ◽  
Carina Rosas ◽  
Amos S. Gaikwad ◽  
Geraldo Medrano ◽  
Linda Zhang ◽  
...  

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. To establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and nonhematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3670-3670
Author(s):  
Neus Villamor ◽  
Olga Salamero ◽  
Jordi Esteve ◽  
Joaquim Carreras ◽  
Carol Moreno ◽  
...  

Abstract The absence of mutations in the VH gene (UM-VH) and the expression of ZAP-70 by leukemic cells are closely related adverse prognostic factors in CLL. Whether ZAP-70 should substitute VH gene analysis as prognostic predictor in patients with CLL is a matter of debate. We and others have shown that allogeneic but not autologous stem-cell transplantation may overcome the negative impact of the UM-VH on the outcome of patients with CLL. Herein we report on transplantation results based on ZAP-70 expression in leukemic cells. Thirty-seven patients (24 M/13 F; median age: 48 years, range: 29-63) received either an autologous (auto-SCT) (n=22) or an allogeneic (allo-SCT) (n=15) transplant. ZAP-70 was assessed by flow cytometry (19 cases), lymph node immunohistochemistry (10 cases) or both (8 cases). No discrepancies were observed in those cases in which both peripheral blood and lymph nodes were analyzed. Thirty-one patients were ZAP-70 positive and 6 ZAP-70 negative. ZAP-70 was positive in all UM-VH (n=24) and in 4 of 8 mutated VH patients. After a median follow-up of 62 months (range: 4 – 142), 5-year survival is 86% (66% to 100%) for allo-SCT and 50% (28% to 72%) for auto-SCT (p=NS), whereas 5-year disease-free survival (DFS) is 80% (54% to 100%) for allo-SCT and 37% (15% to 59%) for auto-SCT (p=0.03). Seventeen patients have relapsed: 16 of 31 of those being ZAP-70 positive and 1 of 6 of those ZAP-70 negative. In ZAP-70 positive patients the cumulative relapse rate at 5 years is 10% (2% to 65%) in the allo-SCT group and 53% (35% to 81%) in the auto-SCT group (p=0.04) (figure 1a). In addition, ZAP-70 positive patients submitted to allo-SCT have a trend for a longer DFS (76% at 5 years; 46% to 100%) than those receiving an auto-SCT (39% at 5 years; 15% to 63%) (p=0.07) (figure 1b). In summary, among transplanted patients those with ZAP-70 positive CLL have a better relapse rate and DFS if submitted to allo-SCT. Figure Figure


2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Hye-Rin Kang ◽  
Eui Jin Hwang ◽  
Sung A Kim ◽  
Sun Mi Choi ◽  
Jinwoo Lee ◽  
...  

Abstract Background The presence of cavities is associated with unfavorable prognosis in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, little is known about the characteristics of such cavities and their impact on clinical outcomes. The aim of this study was to investigate the size of cavities and their implications on treatment outcomes and mortality in patients with NTM-PD. Methods We included patients diagnosed with NTM-PD at Seoul National University Hospital between January 1, 2007, and December 31, 2018. We measured the size of cavities on chest computed tomography scans performed at the time of diagnosis and used multivariable logistic regression and Cox proportional hazards regression analysis to investigate the impact of these measurements on treatment outcomes and mortality. Results The study cohort comprised 421 patients (noncavitary, n = 329; cavitary, n = 92) with NTM-PD. During a median follow-up period of 49 months, 118 (35.9%) of the 329 patients with noncavitary and 64 (69.6%) of the 92 patients with cavitary NTM-PD received antibiotic treatment. Cavities &gt;2 cm were associated with worse treatment outcomes (adjusted odds ratio, 0.41; 95% CI, 0.17–0.96) and higher mortality (adjusted hazard ratio, 2.52; 95% CI, 1.09–5.84), while there was no difference in treatment outcomes or mortality between patients with cavities ≤2 cm and patients with noncavitary NTM-PD. Conclusions Clinical outcomes are different according to the size of cavities in patients with cavitary NTM-PD; thus, the measurement of the size of cavities could help in making clinical decisions.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3533-3533
Author(s):  
Mahmoud Aljurf ◽  
Hala Abalkhail ◽  
Amal Alseraihy ◽  
Mouhab Ayas ◽  
Abdullah Al-Jefri ◽  
...  

Abstract Abstract 3533 Background: Predicting relapse after hematopoietic stem cell transplantation (HSCT) in hematologic malignancies remains a challenge, especially when there is no specific molecular marker for the leukemic cells. Early detection of relapse and intervention prior to florid relapse will, in general, improve outcome. Donor chimerism has been extensively explored in predicting relapse, but specificity and sensitivity of this approach remain low. Currently, post-transplant chimerism evaluation is performed on all circulating cells or on subpopulation of the circulating cells. However, decrease in donor DNA (cells) can be caused by factors other than relapsing leukemic cells. Free circulating DNA in plasma has been used for diagnosis and prediction of cancer and for early detection of relapse. Leukemic cells have high turnover pouring their DNA into circulation at a higher rate than normal cells. Because of this higher rate of turnover, plasma is enriched by leukemia-specific DNA. We hypothesized that plasma chimerism analysis may detect leukemia relapse earlier than cell chimerism. We studied DNA chimerism in the plasma from patients with hematologic malignancies and compared the pattern with that of cell chimerism. Most of our patients had acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) and were all treated with allogeneic hematopoietic stem cell transplantation (HSCT). Methods: CD3+ cells were separated from the myeloid cells using beads. Chimerism analysis was performed on both populations to determine the relative ratio of donor DNA. In addition, DNA was extracted from the plasma from the same samples and chimerism evaluation was carried out in the same fashion as cells. Results: We first analyzed samples from patients who had aplastic anemia but treated with allogeneic HSCT (N=11). These samples demonstrated that the plasma DNA chimerism is comparable to that seen in the granulocytes and significantly different from the chimerism in the lymphocytes. Since these patients are physiologically normal, this suggests that the majority of the circulating plasma DNA is generated by the turnover of granulocytes. Then we analyzed patients transplanted as a treatment for leukemia (N=84) and had 100% donor DNA in their granulocytes. Of these, 16 (19%) patients had clinical evidence of relapse. All patients with relapse had >10% recipient DNA in the plasma reflecting the relapsing leukemic cells. One of these patients had a relapse only in testes without bone marrow involvement and his plasma chimerism was positive for recipient DNA while both lymphocytes and granulocytes showed 100% donor DNA. Only three of the 16 patients (19%) had more recipient DNA in the lymphocytes chimerism analysis. However, of the 84 samples, 16 samples (19%) showed more recipient DNA (>10%) in plasma than in granulocytes without evidence of relapse, but almost all these patients had neutropenia or thrombocytopenia. These patients are being followed up to determine if they will develop leukemia. Eight additional patients with mixed chimerism in granulocytes and lymphocytes were studied for DNA chimerism in plasma. Three of these patients had more recipient DNA in plasma than in granulocytes and the three patients had evidence of relapse, while the rest of the patients had no significant relative increase in recipient DNA (>10%) in plasma and had no evidence of relapse. Conclusion: Chimerism studies of plasma DNA might be useful in predicting early relapse after HSCT in patients with acute leukemia. Although further studies are needed, our data suggests that any increase above 10% in percentage of recipient DNA in plasma as compared to that in granulocytes should alert to potential relapse. This approach in predicting early relapse has significant advantage because it can be applied to all leukemias and does not require a leukemia specific marker. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4541-4541
Author(s):  
Kehinde U.A. Adekola ◽  
John P. Galvin ◽  
Vaibhav Sahai ◽  
Oluwatoyosi A. Onwuemene ◽  
Joanne Monreal ◽  
...  

Abstract Abstract 4541 Background: Allogeneic stem cell transplant (SCT) is currently the standard of care in the consolidative treatment of several hematologic malignancies. Typically after a stem cell transplant the monocytes engraft first, followed by the granulocytes, macrophages and then natural killer cells. Lymphocyte recovery is considered to be an indicator of immune reconstitution during SCT and correlation between rate of recovery of lymphocyte count and patient outcome has been reported in patients after a myeloablative allogeneic transplant. Studies suggest that early lymphocyte recovery may be a predictive marker of engraftment and survival post-myeloablative SCT. However, there is minimal data on lymphocyte recovery after reduced intensity conditioning allogeneic SCT. We report our institutional experience on the correlation between rate of absolute lymphocyte recovery and survival in patients with a hematological malignancy after a reduced intensity conditioning allogeneic SCT. Methods: We performed a retrospective review of all adult patients who underwent reduced intensity conditioning chemotherapy followed by an allogeneic SCT at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University from March 2001 to March 2008. We looked at the post- allograft absolute lymphocyte count (ALC) at 3 different time points – day 15, 21 and 28. Patients were then analyzed based on ALC cutoff values of 200/mm3, 500/mm3 and 1000/mm3. For each of the cutoff values, patients were divided into 2 groups: those with absolute lymphocyte count of less than or equal to the cutoff value and those with ALC of greater than the cutoff value. Results: A total of 131 consecutive patients were included in the analysis; 46.6% were male and 53.4% were female. 51.1% patients underwent matched sibling (MSD) while 48.9% had matched unrelated donor (MUD) SCT. Overall survival was determined in 117 patients; 14 patients were excluded due to incomplete data. At day 15 and 28, patients with an ALC of greater 200/mm3 had a statistically significant overall survival compared to those that were less than 200/mm3, p= 0.016 and p=0.05, respectively. An ALC of greater than 1000/mm3 at day 15 seemed to predict for a worse outcome compared to those with an ALC of less than 1000/mm3 (p=0.008). There were however six times more people in the group with ALC less than 1000/mm3 at day 15, compared to those with ALC greater than 1000/mm3. An ALC of greater than or less than 500/mm3did not significantly appear to affect overall survival at any of the time points evaluated. Conclusion: ALC of greater than 200/mm3 at day 15 and 28 in our patient population appears to be predictive of overall survival after a reduced intensity conditioning stem cell transplant in patients with a hematological malignancy. However, the relationship between ALC and outcome is inconsistent and needs to be explored further in the context of other prognostic factors. Disclosures: No relevant conflicts of interest to declare.


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