scholarly journals Incidence and Risk Factors of Invasive Fungal Infection in Adult Patients Receiving Allogeneic Hematopoietic SCT Recipients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2476-2476
Author(s):  
Yao-Chung LIU ◽  
Jyh-Pyng Gau ◽  
Cheng-Hwai Tzeng
Keyword(s):  
Risk Factors ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Chronic Gvhd ◽  
Prior History ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Blood And Marrow Transplantation ◽  
History Of

Abstract To investigate the incidence and risk factors for the occurrence of proven or probable invasive fungal infection (IFI) in adult patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), 421 patients undergoing HSCT between 2002 and 2013 in our hospital were retrospectively analyzed. Thirty-one patients with the median age of 42 years (range: 19-60) developed IFI after HSCT. The post-HSCT IFI incidence was 7.4% and median time from HSCT to the diagnosis of IFI was 139 days (range: 2-1809). The risk factors for the occurrence of IFI were analyzed using Cox regression models.Of the pretransplant factors, European Group for Blood and Marrow Transplantation (EMBT) risk>2 (P=0.001) and prior history of IFI (P=0.006) or DM (P=0.042) were the significant predictors for post-HSCT IFI by univariate analyses. In multivariate analysis, EMBT risk>2 (P=0.015) and prior history of IFI (P=0.006) retained significance. Of the post-transplant factors, acute graft-versus-disease (aGVHD) overall grade III-IV (P<0.001), extensive chronic GVHD (cGVHD) (P=0.002), post-transplant lymphoproliferative disorders (PTLD) (P=0.005) and the use of high-dose steroids (P<0.001) were statistically significant in univariate analyses. After multivariate analysis, high-dose steroids (P<0.001) and aGVHD overall grade III-IV (P=0.045) retained significance. These results suggest that risk group stratification prior HSCT and monitoring of IFI in patients with severe GVHD and receiving high-dose steroids is mandatory to decrease the risk of post-HSCT IFI, especially in those with prior history of IFI. Abstract 2476. Table 1.Possible factors for the occurrence of invasive fungal infection (IFI) after adult allogeneic HSCTIFIUnivariate analysisMultivariate analysisFactorsNo. of patientsN%HR95%CIP-valueHR95%CIP-valueEMBT risk=<216952.9>22522610.35.0381.930-13.1510.0013.3901.273-9.0290.015Prior history IFINo406276.6Yes15426.64.4571.551-12.8060.0065.8071.675-20.1290.006Prior history DMNo402286.9Yes19315.73.4901.045-11.6530.042aGVHDNo or Overall Gr. I-II379236.0Gr. III-IV42819.06.9363.046-15.796<0.0012.6271.023-6.7480.045High steroids*No367123.2Yes541935.111.1485.401-23.008<0.00111.1853.875-32.289<0.001cGVHDNo or limited364195.2Extensive571221.03.1311.518-6.4590.002PTLDNo405276.6Yes164254.6271.607-13.3200.005Abbreviations: CI = confidence interval; HR = hazard ratio; EBMT = European Group for Blood and Marrow Transplantation; HSCT = hematopoietic stem cell transplantation; GVHD = graft-versus-host disease; aGVHD = acute GVHD; cGVHD = chronic GVHD; Gr.= grade; PTLD = Post-transplant lymphoproliferative disorders. DM = Diabetes mellitus. High steroids* = post-HSCT high-dose steroid; Significant values (P<0.05) are given in bold. Figure 1 Incidence of post-HSCT IFI per year Figure 1. Incidence of post-HSCT IFI per year Figure 2 Overall survival of the patients with IFI Figure 2. Overall survival of the patients with IFI Disclosures No relevant conflicts of interest to declare.

Vaccine Response In Recipients of HLA Mismatched Unrelated Double Unit Cord Blood Transplantation (CBT).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1247-1247 ◽  
Author(s):  
Trudy N Small ◽  
Christine Scura Iovino ◽  
Michelle Abboud ◽  
Marissa Lubin ◽  
Esperanza Papadopoulos ◽  
...  
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Optimal Schedule ◽  
High Dose ◽  
Vaccine Response ◽  
Post Transplant ◽  
History Of

Abstract Abstract 1247 The use of CBT has increased steadily over the last decade, with recent studies showing long-term progression-free survival similar to that of unrelated volunteer donor transplant recipients. The ability of CBT survivors to respond to post-transplant immunizations may differ from other allogeneic transplant populations due to the lack of transfer of memory T- and B-cells with the graft. Limited data have been reported on vaccine responses following this treatment modality. We, therefore, analyzed responses to immunizations in 23 double-unit CB recipients (17 adults, 6 children) transplanted at our center from 10/05-12/08. Patients were transplanted at a median age of 34 years (range 7–61) for the treatment of acute leukemia (n=13), or lymphoma/CLL (n=8/2). They received high-dose myeloablative (n=11), reduced intensity myeloablative (n=5), or non-myeloablative (n=7) conditioning according to diagnosis, age, prior therapy, and co-morbidities. GVHD prophylaxis consisted of a calcineurin inhibitor and mycophenolate mofetil. No patient received ATG. The study patients had sustained engraftment with a 5/6 (n=12) or 4/6 (n=11) HLA-matched unit. Seven recipients received rituximab (median 4 doses, range: 4–8) as planned post-transplant therapy for B-cell malignancies (n=6) or treatment of an autoimmune hemolytic anemia (n=1). Eleven patients had a history of grade II-IV acute GVHD and 5 had ongoing late acute or chronic GVHD prior to vaccination. Criteria for vaccination were: CD4 cell count of at least 200 cells/ul, PHA of greater than 60% lower limit of normal and serum IgG level >500 mg/dl at least 6 weeks following the last dose of IVIG. The median time to vaccination was 1.26 years post-CBT; this time was significantly longer in patients treated with Rituximab compared to those who were not (1.6 years versus 1.2 years, p=0.02), due to delayed normalization of B-cell numbers in the former group (449 days vs 108 days, p=0.004).Pre-vaccination titers obtained at a median of 1 year post-CBT demonstrated that over 85% of patients lacked protection against Pneumococcus, H. influenzae, and Pertussis, and at least 50% lacked immunity against tetanus, measles, and mumps. Seroconversion or >3- fold rise in titer was observed in response to tetanus, diphtheria, H. influenzae, and Pneumococcus in 90% (18/20), 81% (13/16), 80% (16/20)and 90% (18/20) of patients and was not significantly different in patients with or without a history of acute or chronic GVHD. Whereas 90% (5/6) of patients without a history of GVHD responded to a series of Hepatitis B immunizations, only 22% (2/9) of those with prior acute and/or chronic GVHD did so (p=0.03). No patient was protected against pertussis following a single TDaP (n=14) and only 1 of 5 patients responded to the protein conjugated meningococcal vaccine. Immunization with a live attenuated vaccine was initiated in 7 seronegative patients, including all 6 children, at a median of 2.25 years (range 1.5–3.6) post-CBT (MMR, n=7, Varivax, n=3). Seroconversion against measles, mumps, rubella, or chickenpox was observed in 3/7, 2/7, 6/7, and 1/3 patients, respectively. There were no serious reactions to any vaccine. These data suggest that CBT recipients are capable of responding to tetanus, diphtheria, H. Influenza and pneumococcal vaccines similar to other transplant groups. Nonetheless, the sub-optimal response to pathogens associated with outbreaks in the community (Hepatitis B, Pertussis, meningococcus, measles, mumps, varicella) highlight the need to obtain pre- and post-vaccination titers to document response, as well as define the optimal schedule of post-transplant immunizations specifically in this transplant population. Disclosures: No relevant conflicts of interest to declare.

Prophylaxis and treatment of patients with aspergillosis: an overview, including the Royal Melbourne Hospital experience

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 75-80 ◽  
Author(s):  
Andrew Grigg
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Fungal Infection ◽  
Antifungal Prophylaxis ◽  
Resistant Organism ◽  
Prior History ◽  
High Dose ◽  
Allogeneic Bone ◽  
Royal Melbourne Hospital ◽  
Aspergillus Sp

Abstract Patients receiving allogeneic bone marrow transplants are at risk of developing Aspergillus infections. The pre-transplant risk factors for the development of invasive disease include prolonged neutropenia, colonization with Aspergillus sp. or a prior history of fungal infection. Post-transplant risk factors include severe graft-versus-host disease with concomitant high-dose corticosteroid therapy, and colonization with Aspergillus sp. The antifungal prophylaxis of selected high-risk pre-transplant patients at the Royal Melbourne Hospital includes granulocyte transfusions and AmBisome. In high-risk patients post-engraftment, prophylaxis consists of oral itraconazole, or if it cannot be tolerated, AmBisome. Antifungal prophylaxis is discontinued upon resolution of neutropenia, when prednisolone dose falls below 10 mg/day or when Aspergillus colonization disappears. Following this regimen, there has been only one death due to fungal infection in over 80 consecutive allograft patients. This patient was infected with an amphotericin B-resistant organism.

Risk Analysis for Invasive Fungal Infection after Living Donor Liver Transplantation: Which Patient Needs Potent Prophylaxis?

2018 ◽  
Vol 36 (1) ◽  
pp. 59-66
Author(s):  
Masashi Utsumi ◽  
Yuzo Umeda ◽  
Takahito Yagi ◽  
Takeshi Nagasaka ◽  
Susumu Shinoura ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Analysis ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Pathogens ◽  
Living Donor ◽  
Donor Liver ◽  
Candida Spp ◽  
Donor Liver Transplantation ◽  
Post Transplant

Background: Invasive fungal infection (IFI) is associated with high mortality after living donor liver transplant (LDLT). The aim of this study was to identify the risk factors for post-LDLT IFI for early diagnosis and improvement of antifungal treatment outcome. Methods: Risk analysis data were available for all 153 patients who underwent LDLT between January 2005 and April 2012. Results: During the follow-up period (1,553 ± 73 days, range 20–2,946 days), 15 patients (9.8%) developed IFI classified as “proven” (n = 8) and “probable” (n = 7) with fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p = 0.0026). Multivariate analysis identified model for end-stage liver disease score of ≥26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI. Conclusion: Preoperative recipients’ status and postoperative kidney dysfunction can affect an occurrence of post-transplant IFI. These risk factors would be taken into consideration for designation of proper antifungal therapy.

Incidence and Outcome of Non-CMV Viral Infections in 202 Consecutive Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1965-1965
Author(s):  
Christian Junghanss ◽  
Sebastian Rohde ◽  
Max Haversath ◽  
Guenther Kundt ◽  
Daniel Wolff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Fungal Infection ◽  
Viral Infections ◽  
Multivariate Analyses ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Infection Diagnosis

Abstract Background: Viral infections contribute significantly to morbidity and mortality following allogeneic HSCT. Whereas incidences and risk factors for CMV infections are well studied data for other viral infections are more limited. Here, we present data on 202 alloHSCT recipients that received predominantly reduced intensity conditioning (RIC). Patients and Methods: Data of 202 consecutive patients (pts) who received HSCT during 1/1999 to 12/2006 were retrospectively analysed with regards to viral infections caused by adenovirus (AdV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), epstein-barr virus (EBV) and BK-virus (BKV). Other factors included were gender, age, underlying disease, disease status, year of diagnosis, year of HSCT, time from diagnosis to HSCT, donor type, gender-matching between donor and recipient, stem cell source, conditioning-regimen, T-cell-depletion, prior autologous HSCT, acute and chronic GvHD, prior fungal infection, and viral serostatus of the recipients. Results: Median follow-up was 9.2mths (mean 21.7mths, range 8days to 95.3mths). Median pt. age was 45yrs (range 15 to 69yrs). Underlying diseases were ALL (n=20), AML (n=63), CLL (n=7), CML (n=32), MDS (n=21), MM (n=17), NHL (n=28), OMF (n=5), others (n=9). 137 pts received RIC most commonly based on treosulfan/fludarabine (n=112). 65 pts received myeloablative conditioning mainly based on 12Gy TBI containing regimen (n=48). GvHD-prophylaxis consisted of CSA/MTX (n=106), other CSA based regimen (n=83) or other (n=13). The overall infection incidences of AdV were 4.0%, of HSV 7.4%, of VZV 5.9%, of HHV6 8.9%, of EBV 4.5% and of BKV 5.4%. Median time of onset of AdV infections were 64 days after HSCT, of HSV 34 days, of VZV 542 days, of HHV6 97 days, of EBV 83 days, of BKV 50 days. Pts with AdV or HHV6 infections had a inferior survival compared to pts w/o the according viral infection (p=0.024 and p=0.048, respectively). 3/8 pts (37%) with AdV and 5/18 pts (28%) with HHV6 infections died within 30 days after infection diagnosis. Pts with EBV or BKV infections tended to have an inferior survival compared to pts w/o the according infection (p=0.084, p=0.152, respectively). 4/9 pts (44%) with EBV and 2/11 pts (18%) with BKV infection died within 30 days after infection diagnosis. Whereas pts with HSV infections had a similar survival compared to pts w/o infections, mean survival for pts with VZV infections was significantly better compared to pts w/o VZV infections (p=0.003). In multivariate analyses VZV infections remained to be associated with better survival (p=0.046, HR 0.132, CI 0.018–0.962). The other viral infections did not remain significant risk factors when analysed adjusted for competing risk factors. In order to determine the influence of late viral infections we performed an additional multivariate analyses solely including pts surviving beyond day 90. EBV infections (p=0.024, HR 2.807, CI 1.147–6.873) and HHV6 infections (p=0.013, HR 2.594, CI 1.227- 5.484) were significant risk factors for inferior survival besides unrelated donor HSCT (p=0.013), acute GvHD III/IV (p=0.001) and fungal infection prior to HSCT (p=0.005). Conclusion: Non-CMV viral infections are commonly observed following myeloablative and RIC alloHSCT. Since they are associated with significant mortality early broad viral screening seems advisable if virus infections are clinically suspected.

Long Term Infectious Complications Following Reduced Intensity Conditioning (RIC) Allogeneic HLA-Identical Sibling Transplantation (allo-SCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2850-2850
Author(s):  
Anne Etienne ◽  
Mohamad Mohty ◽  
Catherine Faucher ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
...  
Keyword(s):  
Low Dose ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Prior History ◽  
High Dose ◽  
Infectious Episode ◽  
Donor Bone Marrow ◽  
Increased Risk ◽  
History Of

Abstract In the setting of RIC for allo-SCT, long term outcomes are still poorly defined. Of note, the epidemiology of long term transplant-related infections is still sparse. This prospective report describes infectious complications occurring beyond 6 months after allo-SCT, in 159 consecutive patients who received a RIC allo-SCT from an HLA-identical sibling. Patients characteristics are as follow: median age was 50 (range, 18–68) years. 68 patients (43%) had a myeloid malignancy, whereas 66 patients (41%) had a lymphoid malignancy. The remaining 25 patients (16%) were treated for metastatic non-hematological malignancies. The majority of patients (n=126, 79%) had an advanced disease with high risk features precluding the use of myeloablative allo-SCT. 24 patients (15%) received donor bone marrow (BM), while the remaining 135 patients (85%) received PBSCs. In addition to fludarabine and busulfan, the RIC regimen included high dose ATG in 20 patients (13%) and low dose ATG in 95 (60%). 24 patients (15%) received fludarabine, busulfan and TLI, while the remaining 24 patients (15%) received fludarabine and low dose TBI. With a median follow-up of 19 (range, 6–90) months, 120 patients (75%) experienced at least one infectious episode (total number of episodes, 366) beyond the first six months after allo-SCT developing at a median of 8 (range, 6–34) months. In all, 212 infectious episodes (58%) required hospitalization (7% in the intensive care unit) for a median duration of 10 (1–91) days. 144 episodes (39%) could be documented (bacterial, n=48; viral, n=78; fungal, n=18). Microbiologically documented infections were distributed as follow: gram negative bacteria (18%), other bacteria (15%), CMV positive antigenemia (17%), HSV (19%), VZV (15%), other viruses (3%), aspergillus (6%), candida species (6%), other (1%). 76% of patients with an infection were under systemic immunosuppressive therapy for chronic GVHD at time of infection. Moreover, 85 patients (71%) experienced more than one infectious episode (median, 2; range, 1–12). In multivariate analysis, active or prior history of extensive chronic GVHD and the use of a BM graft were the strongest factors significantly associated with an increased risk of long term infections (P=0.0003; RR=2.04; 95%CI, 1.4–3.0; and P=0.005; RR=2; 95%CI, 1.2–3.2 respectively), highlighting the raising concern about the deleterious impact of severe chronic GVHD occurring after RIC allo-SCT, but also the protective effect of donor origin immunity based on graft origin and content. In this series of patients surviving at least 6 months after RIC allo-SCT, the overall long term transplant-related mortality was 11% (n=18), of whom 12 deaths were attributed to chronic GVHD and its complications including infections, and 5 deaths solely attributed to infections. In all, these results suggest that, despite reduction in early toxicity associated with the use of RIC regimens, long term debilitating chronic GVHD and its corollary of continuous immunosuppression and subsequent infections are still a matter of concern. Prospective efforts to develop optimal antimicrobial preventive strategies are needed to further improve the safety of the procedure and the overall benefits of RIC preparative regimens before allo-SCT.

Older Age, Use Of Myeloablative Regimens For Malignant Diseases and Chronic Graft-Versus-Host Disease Are Risk Factors For Avascular Necrosis Of Bone After Allogeneic Hematopoietic Cell Transplantation In Children and Adolescents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 917-917
Author(s):  
Xianxin Li ◽  
Ruta Brazauskas ◽  
Zhiwei Wang ◽  
Amal Al-Seraihy ◽  
K. Scott Baker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Unrelated Donor ◽  
Malignant Diseases ◽  
Graft Versus Host ◽  
History Of ◽  
Donor Source

Abstract Avascular necrosis (AVN) of the bone is a painful and debilitating complication of allogeneic hematopoietic cell transplantation (HCT) that is associated with significant morbidity and often requires surgery. Risk factors for its development in pediatric allogeneic HCT recipients are not well described. To assess risk factors for AVN in children and adolescents following allogeneic HCT, we conducted a nested case-control study with a matched cohort of 638 patients reported to the Center of International Blood and Marrow Transplant Research who were ≤ 21 years of age, received their first allogeneic transplant between 1990 to 2008 in the United States and had survived ≥ 6 months from HCT. Overall, 160 cases with AVN were identified. Each case was matched with up to 3 controls by same year of HCT, similar length of follow-up and by transplant center (478 controls). Cases and controls were confirmed via central review of radiology, pathology and/or surgical procedure reports. The median age for cases was 15 (range 2-21) years, 49% were male, 65% had acute leukemia, 65% had received high-dose total body irradiation (TBI) based conditioning regimen, and 65% had received unrelated donor HCT. Among cases, 18% had a history of acute graft-versus-host disease (GVHD) while 56% had a history of chronic GVHD prior to development of AVN. Median time from HCT to diagnosis of AVN was 14 (range <1-172) months. We evaluated age, gender, diagnosis, conditioning regimen, TBI, donor source and GVHD as risk factors for AVN. On conditional logistic regression, increasing age at HCT, female gender and chronic GVHD were significantly associated with increased risks of AVN. Compared to patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with non-malignant diseases and those who had received reduced intensity conditioning regimen for malignant diseases. (Table). Patients receiving unrelated donor transplant had lower risks of AVN compared to HLA-identical sibling donor HCT recipients; there was no significant interaction between donor source and GVHD status. Lack of data on pre- and post-HCT steroid exposure was a limitation of our study. Our findings suggest that children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to high-dose myeloablative conditioning regimens and immunosuppression post-HCT for the treatment of GVHD. Our study identifies important risk factors for AVN in a large cohort of pediatric HCT recipients. Future studies should evaluate the role of surveillance and preventive strategies for AVN in pediatric HCT recipients who are at high risk for development of AVN. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Secondary antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients with invasive fungal infection

2018 ◽  
Vol 12 (09) ◽  
pp. 799-805
Author(s):  
Mehmet S Pepeler ◽  
Şeyma Yildiz ◽  
Zeynep A Yegin ◽  
Zübeyde N Özkurt ◽  
Özlem G Tunçcan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Hematopoietic Stem Cell ◽  
Invasive Fungal Infection ◽  
Previous History ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem ◽  
History Of

Introduction: Invasive fungal infection (IFI) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. A previous history of IFI is not an absolute contraindication for allo-HSCT, particularly in the era of secondary antifungal prophylaxis (SAP). Prompt diagnosis and therapy are essential for HSCT outcome. Methodology: The charts of 58 allo-HSCT recipients [median age:29.5 (16-62); M/F:41/17] who had a previous history of IFI were retrospectively reviewed. Results: Possible IFI was demonstrated in 32 (55.2%), probable in 13 (22.4%) and proven in 13 patients (22.4%). All patients received SAP [liposomal amphoterisin B (n ꞊ 35), voriconazole (n ꞊ 17), caspofungin (n ꞊ 2), posaconazole (n ꞊ 1), combination therapy (n = 3)] which was started on the first day of the conditioning regimen. Treatment success was better in the voriconazole group when compared to the amphotericin B arm (100% vs 69.2%; p = 0.029). Development of breakthrough IFI was more frequent in patients on amphotericin B prophylaxis (42.4% vs 23.1%; p = 0.036). Clinical and radiological response were achieved in 13 of 18 patients (72.2%) who developed breakthrough infection. Overall survival of the study population was 13.5% at a median follow-up of 154 (7-3285) days. Fungal mortality was found to be 23%. Overall survival was better in the voriconazole arm, without statistical significance (90% vs 65.8%, p > 0.05). Conclusions: Secondary antifungal prophylaxis is considered to be an indispensible strategy in patients with pre-HSCT IFI history. Voriconazole seems to be a relatively better alternative despite an underlying necessity of larger prospective trials.

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.

Risk Factors and Clinical Outcome of Central Nervous System (CNS) Leukemia In Patients with Acute Promyelocytic Leukemia (APL) on Long-Term Oral Arsenic Trioxide Maintenance.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1082-1082
Author(s):  
Wing Y Au ◽  
Cyrus Kumana ◽  
Yok lam Kwong
Keyword(s):  
Risk Factors ◽  
Maintenance Therapy ◽  
Cell Count ◽  
Arsenic Trioxide ◽  
Clinical Course ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cns Relapse ◽  
History Of ◽  
Time Point

Abstract Abstract 1082 Background: The prognosis of patients with APL has improved with all trans-retinoic acid (ATRA) and arsenic trioxide (As2O3) therapy. An increasing frequency of isolated CNS relapse is reported in APL survivors and intrathecal prophylaxis has been proposed. We have used oral As2O3 as prolonged maintenance therapy for APL patients in first remission (CR1) and beyond. During oral As2O3 therapy, elemental arsenic penetrates the CNS at meaningful levels. The risk factors for CNS APL in this setting are unknown. Material and methods: From 2001 to 2009, consecutive APL patients in ATRA +/− chemotherapy-induced CR1, or As2O3 +/− chemotherapy-induced CR2 and beyond, were given As2O3 maintenance therapy, comprising oral As2O3 therapy (10mg daily) and ATRA (30mg twice daily), given two weeks every two months for two years. CNS leukemia was diagnosed by the presence of typical APL cells in the cerebrospinal fluid (CSF). Patients with CNS leukemia were treated with intrathecal methotrexate (12 mg twice weekly until clearing of CSF) and oral-As2O3, ATRA and ascorbic acid. Results: A total of 102 APL patients (46 men, 56 women) at a median age of 43 (13–43) years received oral As2O3 maintenance during CR1 (n=63) and CR2 or beyond (n=39). The median follow-up period was 55 (8–143) months. At initial presentation, the hematological parameters were hemoglobin: 8.5 (3–14.6) g/dL, white cell count: 10.1 (0.3–121) × 109/L (with 21 cases >10 × 109/L) and platelet count: 35 (3–162) × 109/L (with 67 cases <40 × 109/L). A total of 25 patients had a history of steroid treatment for APL differentiation syndrome. Leucocytosis (> 15 × 109/L) developing either during ATRA or As2O3 treatment occurred in 62 patients. For the whole cohort, the median peak leucocyte count at any time point in the clinical course was 29.3 (0.8–243) × 109/L. Eight patients (7 men, 1 woman, median age 49 years) developed CNS leukemia, at a median of 42 (1–56) months from commencement of As2O3 maintenance. All had a history of elevated peak WCC, at a median of 69.5 (26–123) × 109/L. Symptoms included headache (n=3), dizziness (n=2), confusion, blurred vision and leg weakness. The median CSF cell count was 35 (7–2500) × 106/L. Concurrent marrow morphologic relapse was found in 4 cases (first relapse, R1, n=1; R2, n=3). Four patients had normal blood counts and marrow morphology (still in CR1, n=1; CR2, n=3), although their peripheral blood cells were positive for PML-RARA by polymerase chain reaction. All patients responded completely to treatment initially, but recurrent CNS leukemia still occurred in 4 cases after 12–16 months. Additional treatment including cranial radiotherapy (n=6), systemic high dose cytarabine (n=2) and autologous hematopoietic stem cell transplantation (n=1). Three patients ultimately died of refractory APL at a median of 13 months after CNS relapse. On univariate analysis, risk factors for CNS relapse were male gender (RR 6.8, p=0.001), and leucocytosis at any time point (for WCC > 15×109/L, RR 8.4, p=0.004; for WCC > 20×109/L, RR 12.1, p<0.001). There was no significant relation to age, ATRA syndrome, hematologic parameters on presentation and disease status at commencement of oral As2O3 maintenance. Conclusions: With prolonged survival of APL patients, CNS leukemia is emerging as an important problem that curtails survival. Based on the use of oral As2O3 maintenance, patients who at any time point in the clinical course developing a leucocytosis of > 15–20 × 109/L are at high risk of CNS relapse and should be considered suitable candidates for CNS prophylaxis. Disclosures: Off Label Use: Oral arsenic trioxide for maintenance of APL in remission. Kwong:HKU: YL Kwong is an employee of the University of Hong Kong that holds a patent for oral arsenic trioxide.

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